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Committee Minutes-Advanced Technology Integration
Committee
ADVANCED TECHNOLOGY INTEGRATION COMMITTEE (January 2008)
Jeff Michalski, M.D., Chair

  1. Dr. Michalski introduced the new name of the committee. ATIC reflects the broader mission of the committee beyond image-guided therapies. The committee is involved in developing guidelines and protocols for a variety of new technologies including stereotactic therapy, image-guided radiation therapy and brachytherapy, proton therapy, adaptive radiation, lung heterogeneity, imaging for planning and disease response.

  2. Site Committee Liaisons. Several of the ATIC Liaisons to clinical sites described protocol activity in their respective committees.
    a. Lung Cancer Committee Liaison: Dr. Jeff Bradley reported RTOG 0117 has closed. The successor trial, RTOG 0617, is a randomized phase III comparison trial of standard dose (60 Gy) radiation therapy versus high dose conformal radiotherapy (74 Gy) with concurrent and consolidation Carboplatinum and Paclitaxel in stage IIIa/b NSCLC. It is an intergroup trial with support from NCCTG and CALGB. It has been activated but only 5 institutions have it cleared through their IRB AND have updated credentialing. He described RTOG 0515 compares GTV definition with or without PET in NSCLC which has nearly completed accrual. ACRIN/RTOG 6668/0235 is accruing well.
    b. Genitourinary Cancer Committee Liaison: In Dr. Roach's absence, Dr. Michalski described the active GU studies, including phase III 3D conformal radiation therapy trial RTOG 0126, the phase III prostate brachytherapy trial RTOG 0232, the high-risk prostate cancer study randomizing patients to standard hormone therapy versus the same with chemotherapy following radiation RTOG 0521 and, the phase III hypofractionation study RTOG 0415. A salvage protocol for post radiation failures using permanent seed brachytherapy has been activated RTOG 0526. There are three GU IGRT trials in development, including RTOG 0534, which is a salvage post-radical prostatectomy trial. Three other trials including two adjuvant or salvage trials using docetaxel RTOG 0621 or Sm53 RTOG 0622, respectively and a proton trial RTOG 0626 were described. A replacement for RTOG 0126 is in development. Two intermediate risk concepts have been proposed will involve high dose RT with either 3DCRT, IMRT, permanent or HDR brachytherapy.
    c. Gastrointestinal Cancer Committee Liaison: Dr. Laura Dawson updated the status of the liver trial. Accrual is 10/18 patients to date. Consideration is being given to extending the study with a dose per fraction escalation. The anal cancer IMRT trial RTOG 0529 was activated and the past 6 month's accrual has been good. There have been frequent modifications required in target volume definition and IMRT planning. It was suggested contours be reviewed before planning is done to make the process more efficient for participating institutions. Several developing trials were discussed including IMRT for rectum RTOG 0822, IMRT for postop pancreas RTOG 0714 and IMRT for locally advanced pancreas RTOG 0823. A PET study for esophageal cancer is being discussed.
    d. Breast Cancer Working Group Liaison: Dr. Julia White reported RTOG 0413 has increased its accrual to 4300 patients but the rate of accrual has slowed. 3DCRT accounts for 71% of registrations and 23.5% Mammosite. A phase II hypofractionated 3D/IMRT trial RTOG 0713 with concomitant boost stage 0, I or II breast cancer proposed is proposed. An atlas for breast IMRT has been developed. A proposal for 3dCRT or IMRT for local recurrence in breast cancer RTOG 0715 his being developed. There is considerable enthusiasm for treatment of "oligometastatic" breast cancer in a prospective phase i/ii trial allowing SBRT to lung and liver and short course therapy to bone metastases.
    e. Gynecology Cancer Working Group Liaison: Two protocols remain active. RTOG 0418 continues to accrue patients with cervical cancer whereas the endometrial cases have met their accrual target. RTOG 0417 has 10 patients registered. The goal is to develop a library of MRI for future target definitions. According to Bill Straube of ITC, there has been no voluntary MRI submission. Several proposals involving brachytherapy and IMRT for vaginal, cervical and endometrial sites are being discussed.
    f. Sarcoma Committee Liaison: Dr. Dian Wang updated the group on an IMRT/3D trial for preoperative treatment of sarcoma. The trial will utilize daily image guided therapy. It is about to be activated. IORT was raised as a possible boost modality but the ATIC and ATC leadership felt this would be too resource intensive with little expected gain.
    g. Brain Tumor Committee Liaison: No report.
    h. H&N Cancer Committee Liaison: No report.

  3. ATC Report: The ATC is made up of ITC, RTOG, RPC and QARC. The goals of the ATC are to support the infrastructure for technology research through development, coordination and service. The ATCs developmental priorities are 1. Electronic exchange of planning data, 2. Web-based tools to facilitate data review, 3. Archiving of planning, verification and imaging data, 4. Development of methods for data analysis, 5. Compatibility with EMR and digital health standards including CaBIG and DICOM-RT. The ATCs new development strategy is to emphasize commercial and open source products for QA management and review. It is expected 'thin-client' applications will allow distributed QA review. ATC is working with CaBIG and NCIA. ATC coordinates QA effort and data sharing. They help insure appropriate and uniform QA procedures are implemented across cooperative groups. They assist in protocol development and credentialing. The service objective involves credentialing, data submission and data integrity QA. As of this month 6190 complete volumetric data sets have been submitted over 14 years using the ATC Quality Assurance Submission Analysis and Review System (i.e. QuASAR, formerly method 1). Compliant TRP systems are listed at http://atc.wustl.edu/credentialing/atc_compliant_tps.html . The ATC is also supporting trials by NABTT, EORTC, JCOG, and industry.

  4. Brachytherapy Report: Dr. Hsu discussed the open brachytherapy trials RTOG 0232, 0417 and the salvage prostate trial. The Genitourinary Cancer Committee plans to allow HDR and permanent seeds on the successor trials to RTOG 0126. Several GYN protocols are planned with vaginal brachytherapy and eventually a move to prescribing dose to tumor/target rather than to 'point A'.

  5. Stereotactic Radiotherapy Subcommittee Report: Dr. Bradley updated the status of SBRT trials for Dr. TImmerman. The brain SRS trial RTOG 0320 remains open. RTOG 0236 toxicity data was presented at ASTRO 2007. The liver trial RTOG 0438 remains open with 18 patients registered. Another lung cancer trial RTOG 0618 for medically operable cases has been activated and involves identical credentialing and treatment techniques as RTOG 0236. Several concepts remain in development including a Phase I trial RTOG 0633 from Dr. Andrea Bezjaka regarding treatment of central lung tumors. The proposed a phase II trial for pulmonary metastases was not approved by RTOG strategy. The proposed phase I/II trial of SBRT for solitary spinal metastases is undergoing revision. A hepatoma trial is being considered.

  6. Medical Physics Report. Dr. Gillin reported progress on implementation of protons in ATI trials. A survey requesting information on the use of PET for planning has been distributed. Heterogeneity corrections are required for RTOG 0617. Convolution algorithms are allowed but other algorithms may require additional testing. It has been proposed the lung benchmark for convolution algorithms be eliminated. Guidelines for radiation dose to patients from in-room monitoring are being developed. The sarcoma trial is the first (nonSBRT) IGRT trial is about to open.

  7. Radiologic Physics Center. Dr. Geoff Ibbott updated the group on the status of the RPC QA phantoms. Modification of the prostate phantom is planned to allow testing of proton therapy. They are working with Dr. Deasy to use CERR to evaluate phantom data. He reiterated the lung benchmark would be dropped for plans done with the convolution algorithm. TLDs have been mailed to all 5 proton centers. On site dosimetry check is planned.
ADVANCED TECHNOLOGY INTEGRATION COMMITTEE (June 2007)
Jeff Michalski, M.D., Chair

  1. Site Committee Liaisons. Several of the IGRT Liaisons to clinical sites described protocol activity in their respective committees.

    1. GI Cancer Committee Liaison: Dr. Laura Dawson updated the status of the liver trial. Accrual is low with only 7 patients to date. The IMRT anal cancer trial RTOG 0529 was activated in the past 6 months and accrual has been good. An SBRT concept for hepatocellular cancer was proposed by Dr. Dawson. A study of organ motion by 4D CT or volumetric imaging was also being considered.

    2. Breast Cancer Working Group Liaison: Dr. Julia White reported RTOG 0413 has increased its accrual to 4300 patients but the rate of accrual has slowed now that only high risk cases are eligible. A phase II hypofractionated IMRT trial RTOG 0715 with concomitant boost stage 0, I or II breast cancer proposed is proposed. An atlas for breast IMRT is being developed. A proposal for 3DCRT or IMRT for local recurrence in breast cancer has been made. There is some enthusiasm for treatment of "oligometastatic" breast cancer in a prospective phase I/II trial.

    3. Sarcoma Committee Liaison: Dr. Dian Wang updated the group on an IMRT/3D trial for preoperative treatment of sarcoma. The trial will utilize daily image guided therapy. It has been sent to CTEP along with the new IGRT guidelines.

    4. GU Cancer Committee Liaison: In Dr. Roach's absence, Dr. Michalski described the active GU studies, including phase III 3D conformal radiation therapy trial RTOG 0126, the phase III prostate brachytherapy trial RTOG 0232, the high-risk prostate cancer study randomizing patients to standard hormone therapy versus the same with chemotherapy following radiation RTOG 0521 and the phase III hypofractionation study RTOG 0415. A salvage protocol for post radiation failures using permanent seed brachytherapy has been activated RTOG 0526. There are three GU IGRT trials in development, including RTOG 0534, which is a salvage post-radical prostatectomy trial. Three other trials including two adjuvant or salvage trials using docetaxel RTOG 0621 or Sm53 RTOG 0622, respectively and a proton trial (RTOG 0626) were described. A replacement for RTOG 0126 is in development. Two intermediate risk concepts have been proposed. It is possible both could be run by the group.

    5. Lung Cancer Committee Liaison: Dr. Jeff Bradley reported RTOG 0117 is about to close and will be replaced by RTOG 0617, a randomized phase III comparison trial of standard dose (60 Gy) radiation therapy versus high dose conformal radiotherapy (74 Gy) with concurrent and consolidation Carboplatinum and Paclitaxel in stage IIIa/b NSCLC. It is an intergroup trial with support from NCCTG and CALGB. Dose will be prescribed as a minimum to the PTV. IMRT will be allowed. Dr. Bradley then described RTOG 0515 compares GTV definition with or without PET in NSCLC. An amendment was proposed that requires THREE physicians to define the GTV in order to avoid treating patients without the use of the PET data. While the amendment may adversely affect accrual due to the added work, it was felt treatment of patients should include the available PET data.

    6. Brain Tumor Committee Liaison: No report.

    7. H&N Cancer Committee Liaison: No report.

  2. ATC Report: Dr. Purdy announced the ATC grant has been renewed for 5 years. The ATC is made up of ITC, RTOG, RPC and QARC. As of this month 5706 complete volumetric data sets have been submitted over 13 years using the ATC Quality Assurance Submission Analysis and Review System (i.e. QuASAR, formerly method 1) Compliant TRP systems are listed at http://atc.wustl.edu/credentialing/atc_compliant_tps.html. There are plans to improve the DICOM database RT archive with TeraMedica Evercore system and improve functionality for case reviews and data analysis. The ATC is making an effort to work with CaBIG, QRRO and the planning system developed by UNC. The ITC is also seeking assistance from RTP vendors. ITC is striving to maximize the integrity of digital data submission with minimal human interventions. The ATC is also supporting trials by NABTT, EORTC, JCOG, and industry. Data use requests from MSKCC and industry (CMS) for research and development have been made.

  3. Stereotactic Radiotherapy Subcommittee Report: Dr. Bradley updated the status of SBRT trials. An abstract from RTOG 0236 has been accepted for oral presentation at ASTRO 2007. The liver trial RTOG 0438 remains open with low accrual. Several SBRT concepts remain in development including a Phase I trial RTOG 0633 from Dr. Andrea Bezjak regarding treatment of central lung tumors. The phase SBRT II trial RTOG 0624 for medically inoperable stage IB NSCLC with concurrent systemic therapy had its LOI rejected by CTEP. Dr. Timmerman has proposed a phase II trial for medically operable stage I cancers. RTOG 0618, the proposed phase II trial for pulmonary metastases was not approved by RTOG research strategy. The proposed phase I/II trial of SBRT for solitary spinal metastases was disapproved by DCP. Two SBRT liver trials are being considered for hepatoma and metastases.

  4. Medical Physics Report. Dr. Michael Gillin presented Medical Physics Report to the Advanced Technology Integration Committee. The Committee has recommended superposition/convolution dose calculation algorithms are accepted for heterogeneous dose calculations without needing a 'dry run' test. Alternative algorithms will need to pass a dry run phantom dosimetry test. Guidelines for Image Guided Radiation Therapy have been developed and approved by Advanced Technology Integration Committee and the Medical Physics Committee. These will be posted on the necessary websites. Testing of IGRT phantoms will be conducted by TJU and MCW physicists. Using different delivery and couch systems. Proton guidelines have been drafted and will be used for cooperative group trials. The RTOG will require digital data submission for proton RTP data. A small group from MGH and MD Anderson Cancer Center will draft a proton amendment for RTOG 0415. The Medical Physics Committee believes radiation dose from daily imaging associated with IGRT needs to be examined. A task group will be formed to study this issue. Dr. Michalski suggested Dr. Steiber be included as a clinical representative to the task group.

  5. Radiologic Physics Center. Dr. Geoff Ibbott updated the group on the status of the RPC QA phantoms. They are currently working with medical physics and the ITC to develop guidelines on dose calculation algorithms for SBRT and lung IMRT.

  6. Brachytherapy Report. The new brachytherapy co-chair for the Advanced Technology Integration Committee is Dr. Joe Hsu from UCSF.
IMAGE GUIDED RADIATION THERAPY COMMITTEE(FEBRUARY 2007)
Jeff M. Michalski, M.D., Chair

  1. Site Committee Liaisons: Several of the IGRT Liaisons to clinical sites described protocol activity in their respective committees.

    a.      GU Cancer Committee Liaison: In Dr. Roach's absence, Dr. Michalski described the active GU studies, including phase III 3D conformal radiation therapy trial RTOG 0126, the phase III prostate brachytherapy trial RTOG 0232, the high-risk prostate cancer study randomizing patients to standard hormone therapy versus the same with chemotherapy following radiation RTOG 0521 and, the phase III hypofractionation study RTOG 0415. There are currently two GU IGRT trials in development, including RTOG 0534, which is a salvage post-radical prostatectomy trial and a salvage protocol for post radiation failures using permanent seed brachytherapy RTOG 0526. Three other trials including two adjuvant or salvage trials using docetaxel RTOG 0621 or Sm53 RTOG 0622, respectively and a proton trial RTOG 0626 were described.

    b.      Lung Cancer Committee Liaison: Dr. Jeff Bradley reported that RTOG 0117 is about to close and will be replaced by RTOG 0617, a randomized phase III comparison trial of standard dose (60 Gy) radiation therapy versus high dose conformal radiotherapy (74 Gy) with concurrent and consolidation Carboplatinum and Paclitaxel in stage IIIa/b NSCLC. It is an intergroup trial with support from NCCTG and CALGB. Dr. Bradley also described RTOG 0515 compares GTV definition with or without PET in NSCLC.

    c.      Brain Tumor Committee Liaison: Dr. Volker Steiber discussed an MR spectroscopy study for Glioblastoma multiform.

    d.      Breast Cancer Working Group Liaison: Dr. Julia White reported RTOG 0413 has increased its accrual to 4500 patients. A proposal for 3dCRT or IMRT for local recurrence in breast cancer has been made. A phase II hypofractionated IMRT trial with an incorporated boost in early stage breast cancer proposed by Dr. Gary Freedman has been proposed.

    e.      GI Cancer Committee Liaison: Dr. Paul Okunieff updated the status of the liver trial. Only 3 institutions have made the effort to be credentialed. Accrual is low. One reason for low enthusiasm is that some felt they were not ready for this study without gating.

    f.      Sarcoma Working Group Liaison: Dr. Dian Wang proposed an IMRT/3D trial for preoperative treatment of sarcoma. The trial would also utilize daily image guided therapy.

  2. ATC Report: Dr. Purdy acknowledged the effort and support of the members of the ATC team ITC, RTOG, RPC, QARC, RCET and James Dye at the NCI. As of this month 4974 complete volumetric data sets have been submitted over 13 years using the ATC method 1. Eight (8) commercial vendors and 15 treatment planning systems have implemented ATC compliant export. These systems are listed at http://atc.wustl.edu/credentialing/atc_compliant_tps.html. Brainscan and Tomo/HiART have compliant software but have limited release of their data exchange. Accuracy, Philips Pinnacle and Prowess are developing exchange capabilities. Four hundred and eighty-six (486) institutions can submit data to the ITC. Eleven RTOG trials (includes one NSABP/RTOG) are currently open and supported by the ATC and another 10 have been completed. Eleven abstracts (posters and/or presentations) were presented at the 2006 AAPM and 5 abstracts at the 2006 ASTRO meetings. An ATC workshop was held at the 2006 AAMD annual meeting to educate dosimetrists on the technical issues regarding protocol data submission. Dr. Purdy again encouraged the membership to take advantage of the volumetric treatment planning datasets for secondary analysis. The ATC is examining the credentialing process for all protocols and plans to develop a more efficient mechanism for credentialing of image-guided trials. It has been suggested to move to a modality specific credentialing rather than a protocol specific credentialing.

    Challenges: The ATC would like to see a formal mechanism developed to decide which trials will be supported by ATC funding. There need to be ATC compliant SRS and SBRT planning systems and an efficient credentialing process. Methods to receive quantitative PET, MR and fusion QA need development. In-room monitoring data of EPI, MV and kV CT needs to be accommodated. Finally Adaptive RT will lead to more data submission and the mechanism to review and analyze this data needs to be developed. Proton beam RT will be supported.

    Priorities: Increase publications referencing the ATC grant. Move toward integration of method 1 to industry and CaBIG compliance. Move QA scoring to RTOG HQ. Simplify the credentialing process for ATC supported studies. Develop QA process for multimodality imaging.

  3. Adaptive Radiation Therapy: Dr. Larry Kestin described a protocol concept of a companion trial for RTOG 0415. The hypofractionation study currently being conducted by Dr. Robert Lee requires daily imaging for prostate localization. Dr. Kestin has proposed a companion study would collect image data used to localize patients on a daily basis. Initially it was intended to collect any daily imaging modality but due to the limited usefulness of 2D images (US and/or MV-KV set up films) it was felt it may be more valuable to target volumetric datasets in the form of in-room CT imagining with kV or MV sources. This data could then be used to estimate actual dose delivery to the target and help the RTOG develop the methods and tools to conduct dose recalculation for true Adaptive Radiation Therapy trials.

  4. Medical Physics Report: Dr. Michael Gillin presented Medical Physics Report to the IGRT Committee. They have recommended the adoption of guidelines for PET imaging used in RTOG protocols that address the general performance of the imager, criteria for registration of PET with the planning CT and baseline standards for PET quantitative parameters (e.g. SUV). At a recent NCI workshop an ad hoc committee has been charged with developing criteria for the utilization of protons within NCI supported cooperative group trials. A draft is expected by May 2007. The Medical Physics Committee proposes clearer use of terminology to describe processes in radiation oncology. Some examples include: Image Guided Radiation Therapy - a general term. There is a RTOG IGRT Committee. IGRT has both broad and specific meaning. Adaptive Radiation Therapy - daily adjustments of treatment parameters based upon pre-treatment evaluation (images or signals or …) Registration of different image data sets - the process which translates the spatial orientation of one data set to a second data set, e.g. CT to CBCT or PET to CT. Fusion - the process which data elements from one data set, e.g. target, are deposited onto a second data set, e.g. GTV from PET/CT to simulation CT. Fusion is a process performed after registration.

    There continues to be significant discussion regarding acceptance of various heterogeneity correction algorithms with a continuum of improvement from Clarkson to Superposition/Convolution and Monte Carlo. Pressure needs to continue on vendors to update their algorithms with modern accurate calculation algorithms.

    The Medical Physics Committee supports the proposal to move towards a modular credentialing process for IGRT related trials.

  5. Radiologic Physics Center: Dr. Geoff Ibbott reported that there are currently 4 prostate IMRT and 25 H&N IMRT phantoms in service. There are 2 cranial stereotactic radiosurgery phantoms, 3 thoracic with 6 more under construction, and 3 liver stereotactic body radiotherapy phantoms in service. The stereotactic liver phantom is a mobile phantom to account for gating or tracking. The initial failure rate of institutions attempting the phantoms is approximately 30%. The most common reasons for failure include inadequate beam modeling at leaf ends and setup errors during phantom irradiation. New phantoms will include fiducial markers for anatomy or marker-based alignments.

    Dr. Ibbott reported the RPC currently evaluates dose delivered to TLDs within +/- 0.05 and distance to agreement (DTA) of +/- 5mm at all sides of the target. This methodology neglects dose variations across the target and he is proposing to include criteria to evaluate this. When evaluating dose across the target, some heterogeneity correction algorithms do not satisfactorily model the dose delivered to the volume. This problem is currently under discussion by the Lung, the Medical Physics and the IGRT steering committees.

    The RPC has visited proton facilities at PTC-H and UF-Jacksonville to inspect and measure beam output and depth dose characteristics. They have evaluated various radiochromic films for proton beam evaluation. The RPC is encouraging a uniform adoption of calibration protocols for proton therapy with traceability to NIST. The RPC is participating with the AAPM Work Group on Particle Beams. They intend to implement an Eclipse workstation at RPC for independent review of dose distributions.

  6. Brachytherapy Report: Dr. Ibbott reported on behalf of Dr. Robert Lee, who was unable to attend. There are currently 4 brachytherapy protocols open and they include cervix RTOG 0116 & 0417, prostate RTOG 0232, and breast RTOG 0413. RTOG 0116 is expected to complete its accrual in the next several months. A prostate protocol in in-development for salvage brachytherapy of external beam failures.

  7. Stereotactic Radiotherapy Subcommittee Report: Dr. Timmerman updated the status of SBRT trials. Several SBRT concepts have been proposed including a Phase I trial from Dr. Andrea Bezjak regarding treatment of central lung tumors, a phase SBRT II trial for medically inoperable stage IB NSCLC with concurrent systemic therapy. Dr. Timmerman has proposed a phase II trial for medically operable stage I cancers. This trial is similar to the recently completed RTOG 0236 trial but extending the treatment to better performance status patients. Dr. Volker Stieber has proposed a phase II trial for pulmonary metastases. Sam Ryu from Henry Ford Hospital has proposed phase I/II trial of SBRT for solitary spinal metastases that would entail the delivery of a single dose of 16 Gy to the vertebral body. Primary endpoints would involve pain control. Dr. Tracy Schefter has proposed an SBRT phase I/II trial for oligo-metastases and Dr. Laura Dawson a trial for SBRT in localized hepatoma.

  8. Dr. Dorfman from the cancer imaging program gave a presentation on NCI initiatives in Image Guided Interventional therapies to the broad RTOG membership. He came to the IGRT session for questions and answers. There may be mechanisms to support "Device Trials" through the Cancer Imaging Program.
IMAGE GUIDED RADIATION THERAPY COMMITTEE(June 2006)
Jeff Michalski, M.D., Chair

IGRT Steering Committee. Dr. Jeff Michalski called the meeting to order. He reported the IGRT Steering Committee has teleconferences monthly and also meets at the semi-annual meeting in advance of the larger IGRT session. The Steering Committee reviews protocols in development and assures proper communication between the quality assurance centers, the investigators and the RTOG. At this semi-annual meeting a scientific session was held devoted to Image Guided Radiation Therapy. In the session invited speakers described their institutional experience of in room monitoring for patient localization and organ motion management. Hopefully this session will promote concepts to be evaluated by the RTOG in the years to come.

Radiologic Physics Center. Dr. Geoff Ibbott reported there are currently 4 prostate IMRT and 15 H&N IMRT phantoms in service. Ten additional H&N phantoms are under construction. There are 2 cranial stereotactic radiosurgery phantoms, 3 thoracic, and 3 liver stereotactic body radiotherapy phantoms in service. The stereotactic liver phantom is a mobile phantom to account for gating or tracking. The average return time for the phantoms after being sent to institutions is 28 + 12 days. As of June 15, 67 mailings of phantoms had been delivered this year. Priority for mailing phantoms is given to institutions that have IRB approval of a specific protocol and an ITC account.

The pass rate of institutions using irradiation phantoms is approximately thirty-four percent (34%). It appears the pass rate has been improving in most recent years and will continue to improve in the future years.

There is significant variability in the heterogeneity correction algorithms used by various vendors. The ratio of heterogeneity to homogeneity corrections varies from 12% (CMS Xio, Super Physician/Convolution) to 21% (Brain Lab, Clarkson and Pencil Beam). The ratio of TLD dosimetry to dose calculated with heterogeneity algorithms varies from .92 (Render plan) to .99 (Pinnacle, Precise). There are currently 416 institutions credentialed for RTOG 0413/NSABPB-39 Partial Breast Irradiation Protocol. The majority of patients enrolled and physicians and institutions credentialed are for 3D conformal radiation therapy. The RPC reviews brachytherapy cases, whereas the RTOG reviews the 3D cases. RPC is also working with institutions that have proton beam capabilities to develop quality assurance processes for this modality.

Brachytherapy Report. Dr. Ibbott reported on behalf of Dr. Robert Lee, who was unable to attend. There are currently 3 brachytherapy protocols open and they include cervix RTOG 0116, prostate (RTOG 232, and breast (RTOG 412). The prostate HDR protocol (RTOG 0321) has completed accrual. Two additional studies are in development and include one study for cervix (RTOG 0417) and another for recurrent prostate cancer (RTOG 0526). A protocol concept has been submitted to use Gliasite brachytherapy followed by external beam radiation therapy for newly-diagnosed Glioblastoma multiforme. It is expected credentialing will be required for the brachytherapy component. As this protocol moves forward efforts will be spent developing specific criteria for this modality.

Medical Physics ReportM. Dr. Michael Gillin presented Medical Physics Report to the IGRT Committee. The ATC has developed guidelines for the use of IMRT, including intrathoracic treatments, and distributed these guidelines for comment on May 31, 2006. The guidelines require cooperative groups to define criteria for acceptability for dose algorithms, motion control and credentialing. The dose must be prescribed to a volume and include tissue heterogeneities.

It is expected Medical Physics may be able to make recommendations to eliminate some of the current credentialing for 3D conformal radiation therapy in preparation for new credentialing, including motion control and image-based treatment set-ups. The ATC has requested input into defining priorities to which studies should receive ATC support. It is the opinion of the Medical Physics Committee extra cranial stereotactic radiotherapy should receive higher priority than stereotactic radiosurgery. He described there are several challenges for imaging protocols in RTOG. Protocols are developing faster than the cooperative group quality assurance mechanisms. There are at least three major divisions of imaging. These include: (1) Fusion and target definition; (2) in-room imaging for patient set-up; and (3) 4D CT. In the next grant the RTOG will require significant infrastructure development. The ITC is currently receiving 5 Gigabytes of data per week. In the next grant this could easily exceed 100 Gigabytes per week. The infrastructure needs to address issues regarding memory, band width, distributed architecture and “middle ware”. Some basic questions will need to be addressed, such as what data should stored and where should it be stored. It will also be a challenge to make the remote review process user friendly for the oncologists and scientists.

In the next grant, Dr. Gillin suggested there are opportunities regarding imaging with respect to treatment planning (CT, MR, MRS, and PET). There will also be opportunities to evaluate patient set-up using 2D/2D and 3D/3D patient matching. It is possible to use imaging for dose response evaluation and finally imaging for the control of organ motion. He also feels there will be an important role for the Medical Physics Committee to evaluate heavy charge particles, particularly proton therapy.

ATC Center Report. Dr. Walter Bosch presented the ATC Report. The Advanced Technology QA Consortium (ATC) is made up of the Image Guided Therapy QA Center (ITC), Resource Center for Emerging Technologies (RCET), the RTOG Headquarters Dosimetry, the RPC, and the Quality Assurance Review Center (QARC). It is supported by the NIH U24 Grant CA81647. A new CRA was hired at the ATC to assist in the increasing workload (Anna Eccher). The ITC network has been reconfigured and the ITC is now part of the Washington University Clinical Operations Network (WUCON) and it will be submitted to the ITC by secure FTP methodology. The transition to this new system occurred over May 27-29 weekend. Instructions for users of this specific treatment planning system are available on the ATC web site. As of June 22, 2006, 3,913 complete protocol case digital datasets have been submitted to the ATC over the past 12 years. Thirteen commercial RTP systems have implemented export capability and 418 institutions are able to submit data. The rate of data submission to the ITC has been growing over the past 18 months, in large part related to the partial breast irradiation protocol. The ATC compliant treatment planning systems are listed on the ATC web site (http://ATC.wustl.edu). The ITC continues to work with vendors to develop data exchange compliance. CMS Xio 4.3.1 was released in early June and has DICOM export, which has been tested successfully by the vendor. No data from a clinical site has yet been received by the ITC using this version. The TomoTherapy Hi-ART system has successfully submitted data to the ITC both by the vendor and also from the UC Davis Center. Simuplan for Mammosite has submitted DICOM test data as of May 11, 2006. This system is not yet ‘vendor complete’, as only CT images were readable by the ITC. The ITC is also working with MD Anderson to test Varian Eclipse and Massachusetts General Hospital to text CMS Xio, with respect to proton beam data exchange. To date the ITC has supported 19 RTOG digital data exchange protocols, 14 of which remain open as of June 22, 2006. As of June 7, RTOG 0413/NSAPB 39 has accrued 1,446 of 3,000 expected patients. The ATC also supports other cooperative groups, including the COG, ACASOG, CALGB, JCOG and are planning a collaboration with the URTC. The ATC works with CDRP institutions to facilitate credentialing for advanced technology trials. Five to six cancer disparity institutions have been credentialed for at least one ATC supported protocol. ATC has requested a formal mechanism to decide which clinical trials should receive ATC support. In the past, ATC encouraged all investigators to utilize their services. Now, with growing protocol utilization, the ATC must work with the RTOG and other cooperative groups to optimize the use of all of their resources. Working with NCI, the Medial Physics Committee and the ATC, guidelines for use of IMRT, including intrathoracic treatments, have been developed as described in Dr. Gillin’s report. ATC continues to work towards facilitation of data exchange. The ATC has hosted an IHE-RO Technical Committee meeting in April 2006 in St. Louis. Representatives from the ATC also have attended the AAMD Annual Meeting in Vancouver, British Colombia in June 2006. Abstracts have been submitted to the AAPM Annual Meeting for July 2006 and for the ASTRO Meeting in November 2006. The ATC also is one of the funded participants in the CaBIG in vivo imaging workspace. ATC members are participating in the following special interest groups (SIG): Test bed SIG, Standards in Interoperability SIG, and Software SIG. Challenges and opportunities the ATC-supported clinical trials include: Development of a formal mechanism to allocate ATC resources; development of ATC treatment planning stereotactic radiosurgery or stereotactic radiotherapy systems; the utilization of quantitative PET data import and image fusion for quality assurance; the use of 4D CT (exceeding several hundred megabytes); image guided radiation therapy (portal imaging, cone beam CT, megavoltage CT) and adaptive radiation therapy (daily confirmation and/or adjustment using onboard imaging). On the next meeting cycle, the ATC expects increased use of ATC Method 1 at QARC, successful implementation of RCET software, increased integration with endotreatment informatics efforts. ATC has continued to work with industry to improve integration in their informatic efforts. They are also working to develop CaBIG compliant software and also the ATC grant renewal corresponds tightly with the RTOG grant renewal in 2007.

Stereotactic Radiotherapy Subcommittee Report. Dr. Robert Timmerman reported there is currently a single active brain stereotactic radiosurgery protocol (RTOG 0320) is examining stereotactic radiotherapy alone versus the same with Temozolomide or Erlotinib. There currently are no brain stereotactic radiosurgery protocols in development. There are several active stereotactic body radiation therapy (SBRT) protocols. The first is RTOG 0236, which is using SBRT for medically inoperable lung cancer. RTOG 0438 is using the same for patients with liver metastases. There are four SBRT protocols in development. The first is a phase I study for medically inoperable lung cancer patients with central tumors. The eligibility mirrors those of RTOG 0236 but allow treatment for patients with tumors in the central tracheobroncheal tree. RTOG 0624 also emulates RTOG 0236 using SBRT for Stage I medically inoperable lung cancer but including adjuvant systemic therapy as well. RTOG 0618 will be a phase II SBRT protocol using 60 Gy in 3 fractions in patients with medically operable lung cancer. Finally, a phase II SBRT protocol has been submitted in concept for patients with pulmonary metastases. Dr. Laura Dawson will discuss a primary liver cancer protocol using stereotactic body radiotherapy in patients with localized hepatoma and, finally, Dr. Ryu has proposed a single fraction stereotactic body radiosurgery treatment for patients with spinal metastases.

Site Committee Liaisons. Several of the IGRT Liaisons to clinical sites described protocol activity in their respective committees.

In addition to the stereotactic body radiotherapy protocols previously discussed, Dr. Jeff Bradley described a randomized phase III comparison trial of standard dose (63 Gy) radiation therapy versus high dose conformal radiotherapy (74 Gy) with concurrent and a consolidation Carboplatinum and Paclitaxel in patients with stage IIIa/b non-small cell lung cancer. It is expected that this will become an intergroup trial. The targeted accrual will be five hundred and twelve (512) patients with the primary endpoint being overall survival.

Dr. Bradley also described the RTOG 0515 protocol, which is a comparative study of GTV definition with or without PET fusion for patients with non-small cell lung cancer. This study has recently opened for accrual and seeks to register 48 patients.

Dr. Michalski described the active GU studies, including phase III 3D conformal radiation therapy trial (RTOG 0126), the phase III prostate brachytherapy trial (RTOG 0232), the high-risk prostate cancer study randomizing patients to standard hormone therapy versus the same with chemotherapy following radiation (RTOG 0521) and, finally, the recently-opened phase III hypofractionation study (RTOG 0415). There are currently two GU IGRT trials in development, including RTOG 0534, which is a salvage post-radical prostatectomy trial. The other protocol in development is the salvage protocol for post radiation failures using permanent seed brachytherapy (RTOG 0526). With recent completion of the HDR trial, Dr. Joe Hsu has proposed two concepts, including a dose seeking trial of HDR brachytherapy monotherapy, as well as a randomized trial of HDR versus LDR for low-risk prostate cancer patients. Finally an IGRT registry will be discussed later by Dr. Kestin.

Dr. Volker Steiber discussed a bioanatomic radiation therapy concept for patients with Glioblastoma multiform. It is hoped newer imaging modalities and novel contrast agents may allow better targeting of primary brain tumors. This study may require further investigation of imaging capabilities available within the RTOG.

Dr. Lorraine Portelance described IGRT activities in the Gynecology Cancer Working Group. RTOG 0418 is a phase II study utilizing post-operative pelvic IMRT for patients with endometrial or cervical cancer. An anatomical Atlas for pelvic IMRT was developed by the Gynecology Cancer Working Group and is now available on the RTOG web site. The next study (RTOG 0417) is a phase II study of radiotherapy plus Cisplatinum and Bevacizumab in advanced cervical cancer. Drs. Tracey Schefter and Beth Erickson are principal investigators for this trial. In the study attempts are being made to collect MRI- or CT-based brachytherapy for future analysis. It is hoped to develop a brachytherapy image databank from this trial.

Dr. Julia White updated the group regarding IGRT studies in breast cancer. The first concept is a phase II multi-center trial to evaluate repeat breast preserving surgery and 3D conformal partial breast radiation therapy for patients who have developed a local recurrence in breast cancer proposed by Dr. Bruce Haffty. Two additional protocols will seek to introduce IMRT in the treatment of breast cancer. Prior to further development of those concepts, Dr. Frank Vicini has offered to work with the RTOG Breast Cancer Working Group to develop guidelines for defining appropriate treatment planning and dose delivery parameters for the utilization of IMRT in various stages of breast cancer. This may lead to a phase II hypofractionated IMRT trial with an incorporated boost in early stage breast cancer proposed by Dr. Gary Freedman and an IMRT or 3D CRT protocol of nodal irradiation for stages II and III breast cancer.

Dr. Larry Kestin described a protocol concept of a companion trial for RTOG 0415. The hypofractionation study currently being conducted by Dr. Robert Lee requires daily imaging for prostate localization. Dr. Kestin is proposing a companion study that would collect image data used to localize patients on a daily basis. The data could come from CT images (KV helical, MV helical, KV cone beam, or MV cone beam), ultrasound images, or X-ray images with fiducial markers. It is felt this registry trial is a first step toward the development of studies designed to test the clinical benefit of adaptive radiation therapy using in-room monitoring.

Dr. Sam Ryu from Henry Ford Hospital presented a protocol concept for the use of stereotactic radiosurgery in the treatment of solitary spinal metastases. This study would entail the delivery of a single dose of 16 Gy to the vertebral body in patients with spinal metastases. Primary endpoints would involve pain control. Radiosurgical guidelines would be developed that would require a 16 Gy marginal dose delivered with stereotactic radiosurgical precision. Spinal cord dose would be kept to < 10 Gy to < 10% of the spinal cord volume.

Dr. Laura Dawson presented a concept for the use of SBRT in unresectable hepatocellular carcinoma. This protocol would require immobilization planning and delivery similar to that currently being done in RTOG 0438 (liver metastases). Data image guidance would be required. Study design would be a phase II study with 5 fractions of stereotactic body radiotherapy in liver cancer. There would be 3 cohorts based on liver volume required to be irradiated (Veff). Primary endpoint would be progression of disease-free survival. The credentialing would require a dry run and confirmation that institutions could create a stereotactic body radiation therapy plan and conduct a Veff calculation. The liver phantom would need to be irradiated and IGRT data submission would need to be demonstrated. At lease one repeat CT in the treatment position per patient would be required.



IMAGE GUIDED RADIOTHERAPY COMMITTEE (January 2006)
Jeff Michalski, M.D., Chair

  1. IGRT Steering Committee - Dr. Jeff Michalski announced the IGRT Committee has formed a Steering Committee composed of Site Committee Liaisons and representatives from Medical Physics, ATC and RTOG Headquarters. The Steering Committee will meet at each semi-annual meeting, prior to the larger IGRT General Session. Liaisons will also present at the General Session an update regarding IGRT related activities and the oversight committees.


  2. ATC Center Report - Dr. James Purdy gave the Advanced Technology Consortium Activity Report (see text elsewhere in the meeting book). The ATC digital data submission procedures are now documented and posted on the ATC website. To date 3,026 completed data sets have been submitted over an eleven year period using the ATC method I. Sixteen commercial RTP systems have implemented export capability and 331 institutions have been able to submit digital data. The ITC has received compliant data from Brain Lab brain scan and TomoTherapy High Art clinical users. Brain Lab (12/06) and TomoTherapy (3/29/05) have declined website posting of their data exchange capability due to limited distribution of export-capable systems. TomoTherapy has indicated, until they have implemented the DICOM export in their system, it will make a workstation capable of submitting data by RTOG data exchange format available for customers who wish to participate in ITC clinical trials. The ITC has received RTOG data objects from both M.D. Anderson and Massachusetts General Hospital Proton Facilities using Varian Eclipse and CMS Xio, respectively. The ITC is working with the NCI caBIG program on image data transfer. PET image data for RTOG 0515 will be submitted to the ITC. PET data for RTOG 0522 will be submitted to ACRIN Core Lab. A formal mechanism is being proposed to request ATC data for research purposes.

    The challenges continue to face the ATC support of clinical trials include an increasing number of patient's registrations, ATC compliance, Stereotactic radiosurgery, radiotherapy treatment planning systems and daily imaging for verification (cone beam or megavoltage CT).


  3. Medical Physics Report - Dr. Michael Gillin presented Medical Physics Report to the IGRT Committee. The ATC has drafted a preliminary report for the use of IMRT in thoracic tumors. The Medical Physics Committee is circulating the report within the RTOG and will provide the ATC with comments. The Medical Physics Committee discussed the need for an updated approach for credentialing various RTOG protocols. The goal is to develop a tiered approach, which ranges from simple to more complex. The Physics Committee is in support of the ATC proposal to develop mechanisms to allow access to digital data, which is now managed by the ITC. The Physics Committee is in support of a 2-hour workshop for an upcoming RTOG meeting entitled, "Quality Assurance for Clinical Trials". While the workshop will be to review current issues and to define solutions for current and future QA issues, including data transmission, protocol specific data, etc. The Committee posed the question, "When will the RTOG protocols not be permitted to submit hard copy, paper and film and transition to a complete digital data submission methodology?" In the next grant they feel RTOG should emphasize imaging. The RTOG should be encouraged to develop a radiotherapy PAC system and establish standards for imaging for patient positioning to include cone beam CT, megavoltage and KV images. There is a need to develop RTOG standard image analysis tools as well as establish bench marks and quality assurance standards for image fusion and data sets that currently do not have standards such as respiratory traces and quantitative images.


  4. Radiologic Physics Center and Brachytherapy Report - Dr. Geoff Ibbott presented an overview of the RPC monitoring program. More than 1400 institutions have been monitored by the RPC program. They visit approximately 40 institutions per year. He described the RPC priority for site visits. This is largely driven by patient accrual but TLD problems or charting problems also contribute to priority for RPC visits. He reported that 70% of institutions receive at least one significant dosimetry recommendation as a result of an on-site dosimetry review. The RPC recently acquired the Eclipse Brachyvision treatment planning system that will allow them to receive plans electronically through the ATC. The RPC expects placement of an ITC server at the RPC in the near future, which will allow them to receive digital data for RTOG protocols to participate in rapid reviews for RTOG 0413, receive digital data from GOG members and to facilitate credentialing of NCCT members.


  5. The RPC is involved in credentialing patients for image guided brachytherapy trials. More than 274 institutions are credentialed for the RTOG 0413 partial breast irradiation study, 228 for 3D conformal, 137 for mammocyte and 30 for multicatheter brachytherapy. For RTOG 0232, 87 applications for credentialing have been submitted and 64 institutions have been credentialed. Nine dry run/benchmark cases are pending. The active brachytherapy protocols include RTOG 0116 for cancer of the cervix, RTOG 0232 for cancer of the prostate, RTOG 0321 for cancer of the prostate with high dose rate brachytherapy, and RTOG 0413 for partial breast irradiation. Developing brachytherapy protocols include RTOG 0417 for cancer of the cervix a and RTOG 0526 for recurrent prostate cancer.

    The RPC currently has phantoms for IMRT credentialing, including 8 of the head and neck, 2 of prostate, 3 of lung and 2 of liver. One hundred and twenty two RTOG institutions are credentialed for head and neck IMRT, 16 for prostate (institutions credentialed for head and neck are automatically credentialed for prostate), 6 for lung and 2 for liver. The RPC is currently developing standards for proton beam calibration. There currently exists no NIST traceability for proton beams. The RPC also is developing a QA program for multi-institutional trials of proton therapy.


  6. Stereotactic Radiotherapy Subcommittee Report - Dr. Robert Timmerman discussed three ongoing protocols using stereotactic radiosurgery or stereotactic radiotherapy. Protocols RTOG 0320 for brain metastases, RTOG 0236 for clinically inoperable early stage lung cancer and RTOG 0438 for liver metastases are currently accruing patients. The accreditation process requires a site questionnaire, phantom radiation and special data submission. Each of these requires a dry run or benchmark case and the first case (RTOG 0263 & 0438) must be approved prior to the treatment delivery. The ITC remote review tool allows stereotactic cases to be reviewed prior to treatment delivery in a timely fashion. There is currently a trial in development, RTOG 0618, to allow stereotactic body radiotherapy for medically operable lung cancer. In the study it is expected the dose prescription will use heterogeneity corrections.


  7. IGRT Data Set Research - Dr. Joseph Deasy from Washington University gave a presentation on the use of dose volume data from the RTOG clinical trials and ITC databases. Using data from RTOG 9311 he was able to develop a prognostic scoring system for the development of radiation pneumonitis. He described differences between dose volume outcomes modeling and conventional outcomes analyses. He emphasized the size of the database for dose volume modeling extends in the gigabytes rather than kilobytes for conventional outcomes analysis. Also very labor and time intensive procedures sometimes taking as much as 1 FTE per year for a single good analysis. Possible methods of incorporating dose volume outcomes analysis into RTOG trials include planning for dosimetry outcomes as part of the protocol planning up front, developing a cost plan to pay for analyses under the RTOG grant or acquisition of separate grants such as the R01 or R03.


  8. Site Committee Liaisons

    1. Nancy Lee reported three head and neck trials are currently open involving IMRT or 3D treatment planning. The most recent opened trial is RTOG 0522, which allows IMRT and is also using PET CT scanning for treatment planning and outcomes assessment. She is developing a protocol of nasopharyngeal carcinoma, which will replace RTOG 0225. This will incorporate IMRT and VEGF inhibitors.


    2. Dr. Bradley reported an update of lung cancer trials involving IGRT, including RTOG 0117, 0236, 0235, and 0515. RTOG 0515 recently was approved and will open soon. This will test the benefit of PET fusion for target volume definition in patients with non small cell lung cancer. A new concept for stereotactic body radiotherapy for operable non small cell lung cancer has been proposed.


    3. Dr. Alan Katz reported RTOG 0438, the phase I trial for liver metastasis, was recently opened. Another study for anal cancer using IMRT is in development by Dr. Lisa Kachnic.


    4. Dr. Michalski updated the Committee on the active GU protocols. These include RTOG 0126 and 0232. The phase III chemotherapy trial also involves IMRT or 3D conformal treatment planning. Two studies are under development, including a salvage EBRT trial which will allow 3D and IMRT and a salvage brachytherapy trial.


    5. Dr. Lorraine Portlance reported new study activity in the Gynecology Cancer Working Group. These include RTOG 0418 phase II study of IMRT +/- Cisplatinum for postoperative endometrial or cervical cancer and RTOG 0417 a phase II trial of Cisplatinum and Avastin for cervical cancer. This latter study will develop an image guided brachytherapy library.


    6. Dr. Julia White reported good progress on RTOG 0413, the phase II partial breast radiation trial. An atlas for regional nodal radiation for locally advanced breast cancer is in development.




  9. Adaptive RT - Dr. Alvaro Martinez from William Beaumont Hospital described their institutional experience in the management of prostate and lung cancer using frequent imaging and replanning during the course of external beam radiation therapy. He presented as an argument the biggest gain in margin reduction and conformality occurs with customizing the PTV margin according to the patient's unique uncertainty characteristics. Dr. James Dye from NCI expressed significant interest in developing a concept testing the advantage of using adaptive radiation therapy for external beam radiation therapy of either prostate or lung cancer. He suggested Dr. Martinez or his designate could make a presentation to CTEP members to gauge their enthusiasm for research in this area.


IMAGE GUIDED RADIOTHERAPY COMMITTEE (June 2005)
Jeff Michalski, M.D., Chair

1. IGRT RETREAT - Dr. Jeff Michalski reported the members of the IGRT Committee met six weeks ago in Philadelphia to begin planning the IGRT research strategy for the upcoming renewal. While the grant is not due for nearly two years, it is time to begin developing our strategy for the next six years. He outlined some of the accomplishments that have been achieved since the grant was awarded nearly three years ago. The Committee appears to be meeting and, in some cases, even exceeding milestones set forth in the grant. From the Retreat many new ideas have been generated and will be discussed in this IGRT session today.

2. ATC CENTER REPORT - Dr. James Purdy gave the Advanced Technology Consortium activity report (see text elsewhere in the meeting book). The ATC held a Steering Committee meeting in Washington, DC, on April 6, 2005. The ATC has a semi-annual face-to-face meeting prior to the RTOG or other cooperative group meetings. The next ATC meeting is scheduled prior to the COG this fall. He described the ATC digital data submission methods are now documented and posted on the ATC website. To date, 2,441 complete digital data sets have been submitted over an eleven-year period using ATC Method 1. Fifteen commercial RTP systems have implemented export capability and 215 institutions have been able to submit digital data. Recently the number of institutions participating in the ATC trials has increased related to the partial breast irradiation trial. Several other treatment planning systems have implemented export capability but have not yet had a user submit data, including Hi-Art from TomoTherapy and Xio from CMS. Furthermore, several vendors are currently developing data transfer capabilities, including 3D Line (ERGO), Brain Lab (brain scan), AccuRay (Cyberknife), Nucletron (Oncentra) and Siemens (Dosimetrists Work Space/CONRAD). The challenges continue to face the ATC’s support of clinical trials include increasing the number of ATC-compliant stereotactic radiosurgery or radiotherapy treatment planning systems. PET fusion in a quantitative manner with CT for plan evaluation remains a challenge. In the future, 4D CT will increase the volume of data submitted to the ITC. Other challenges include image guided radiotherapy using electronic portal imaging devices, cone beam CT and helical tomotherapy. Adaptive radiotherapy using daily adjustment and confirmation of treatment position will be expected.

3. MEDICAL PHYSICS REPORT - Dr. Michael Gillin reported there has been significant progress in the implementation of high technology protocols in RTOG. He has made an effort to make sure a physics investigator is named on each protocol. The Medical Physics Committee has facilitated the credentialing process for many of the technology trials. They have also assisted in the definition of appropriate dosimetry standards and assured conformance with the NCI IMRT guidelines. It is the opinion of the Medical Physics Committee image guidance for both treatment planning and treatment delivery should be a major theme for the upcoming grant renewal. Major physics imaging issues include quality of images themselves and the quality of the final product of image manipulation. The current challenges in the RTOG include 4D CT image registration, quantitative PET, cone beam CT and the correlation of images and treatment outcome. Future challenges will be the use of deformable image registration, 4D PET and tailored therapies depending on specific image data. Finally, Dr. Gillin stressed the need for RTOG to work with ACRIN and the importance of the Medical Physics Committee in other RTOG Committees to increase their interactions and opportunities that are provided with new developments in radiation oncology imaging.

4. BRACHYTHERAPY REPORT - Dr. Geoff Ibbott highlighted the activities of the RPC. They monitor over 1300 institutions and have visited approximately 49 RTOG institutions in the past two years. They are involved in the credentialing for five brachytherapy protocols, three IMRT protocols and one stereotactic body radiotherapy protocol. The RPC is an important member of the ATC and reviews and approves credentialing requirements for brachytherapy. Dr. Ibbott reported 70 distinct institutions are credentialed for participation in RTOG 0413 (partial breast irradiation), 58 for 3D, 34 for Mammosite and 12 for multicatheter brachytherapy. At those institutions there are 115 oncologists credentialed for 3D, 59 for Mammosite and 28 for multicatheter brachytherapy. The RPC has developed credentialing criteria for stereotactic body radiotherapy in the lung. This includes a TLD to institution dose ratio of between 0.92 and 1.02, a distance agreement of < 5 mm. The PTV must receive > 95% of the prescribed dose of 20 Gy and > 99% must be received by > 90% of the prescribed dose (18 Gy). The mobile phantom for liver stereotactic therapy has been developed and has been shipped to Princess Margaret. They have tested it and it will soon be shipped to University of Rochester. Finally a phantom is being developed for the possibility of mesothelioma IMRT clinical trial and a separate phantom is being developed for Gyn IMRT.

5. PROTOCOLS IN DEVELOPMENT

RTOG 0438 - Dr. Alan Katz updated the group on the status of RTOG 0438, the trial of highly conformal radiation therapy for unresectable hepatobiliary cancer or liver metastases. The liver phantom has been received and tested by Dr. Laura Dawson at Princess Margaret Hospital. It is soon to be shipped to the University of Rochester, where Dr. Katz and his team will test it themselves. The protocol is scheduled to be submitted to CTEP within the next week. He and others have every expectation that the study will be open within the next few months.

RTOG 0515 - Dr. Jeff Bradley reported RTOG 0515, comparative study of target volume delineation with or without PET scanning is soon to be open. This study involves sending qualitative PET CT images to the ITC for review. The study will not involve quantitative PET analyses. He reported Dr. Komaki’s trial, RTOG 0523, will likely require 3D conformal radiation therapy. This is a phase III randomized trial of concurrent chemotherapy for inoperable stage III non-small cell lung cancer. Patients are randomized to receive chemo-radiotherapy alone versus the same with Cetuximab. Patients will receive conformal therapy without elective nodal irradiation. There is some consideration for the allowance of IMRT in the future. This will be considered once mechanisms for IMRT QA in the thorax are resolved.

RTOG 0418 - Dr. Anuja Jhingran reported RTOG 0418 will be evaluating IMRT in the postoperative setting for patients who have undergone hysterectomy for cervical or endometrial cancer. A group of gynecologic radiation oncologists met earlier this week to establish guidelines for pelvic and boost target volume delineation.

RTOG 0521 - Dr. Seth Rosenthal reported RTOG 0521, a randomized trial for patients with high-risk prostate cancer, has received tentative CTEP approval. This trial will require 3D conformal or IMRT radiation therapy for high-risk prostate cancer patients. IMRT to the pelvic lymph nodes will be an option.

RTOG 0528 - Dr. Lisa Kachnic reported significant progress on the development of a trial utilizing IMRT for the treatment of anal canal carcinoma. RTOG 0528 is a phase I/II study intending to use IMRT for the reduction of toxicity of patients receiving chemo-radiotherapy for this disease. She demonstrated examples of target volumes and a fractionation regimen that gives the high-dose PTV 50 Gy in 25 fractions of 2 Gy per day. Elective nodal areas would receive 1.8 Gy to 45 Gy in 25 fractions with the exception of the inguinal lymph nodes receiving 41-42 Gy in 165 cGy fractions.

Dr. James Galvin reported the RTOG Head and Neck Cancer Committee are currently developing two trials which will allow IMRT or 3D conformal radiation therapy for Head and Neck cancer. One of these is evaluating an oral agent that is expected to reduce mucositis. The other trial is Dr. Ang’s randomized study of radiation chemotherapy + or – Cetuximab for laryngeal and hypopharyngeal cancers. This trial will allow IMRT and if patients receive treatment, their data will be submitted digitally to the ITC. It was felt for the former trial; evaluating the drug to prevent mucositis, while IMRT credentialing would be required the data would not require digital submission to the ITC.

6. PROTOCOL CONCEPTS

ADAPTIVE RT - Dr. Larry Kestin presented results of a study from William Beaumont Hospital using adaptive radiation therapy for the treatment of prostate cancer. This protocol entails the use of daily CT scans during the first five fractions of radiation therapy for patients receiving treatment for localized prostate cancer. The margin of the PTV was then calculated for the individual patient using their data reflected their individual set-up and internal organ motion variability. In their hands they were able to significantly reduce the margin for the majority of patients receiving either 3D conformal radiation therapy or IMRT. He proposed a randomized trial where patients would be treated with daily localization or customized target volumes based on their specific organ motion assessment. The control arm would be patients treated with a set margin of 1 cm. The group felt, while adaptive radiation therapy should be explored, it may be difficult for institutions and patients to accept randomization to an arm would prevent them from receiving the benefits of the technology available at that institution. It was felt a trial first evaluates the ability for the RTOG to do on-line correction and/or margin reduction may be more appropriate.

RTOG 0413 - Dr. Julia White updated the group on the status of the phase III breast trial, RTOG 0413

NSABP B-39. Accrual to the study has taken off quickly and, as mentioned above, more than 70 sites are already credentialed. She reinforced the importance of on-line quality assurance for patients registered to this trial. She then discussed two early concepts the Breast Cancer Working Group is exploring regarding the use of IMRT for the treatment of breast cancer. The first concept would be for low-risk and early-stage breast cancers would employ IMRT with concomitant boost to the tumor bed to reduce the overall treatment time. The second concept would be the use of IMRT to create a more homogeneous radiation dose distribution for patients receiving elective nodal irradiation.

RTOG 0236 - Dr. Jeff Bradley reported Dr. Timmerman’s trial (RTOG 0236) is accruing at a good rate for the early months of the protocol. Dr. Timmerman is also proposing a similar trial be conducted for patients who have operable lung cancer.

OTHER CONCEPTS - Dr. Leland Rogers discussed a concept involving the use of IMRT for the treatment of meningioma. He proposed a phase I/II feasibility study of IMRT for intermediate and high-risk meningiomas and observation for low-risk meningiomas. Treatment would entail either conformal external beam up to a dose of 54 Gy in 30 fractions or possibly stereotactic radiosurgery with a dose of 12-15 Gy.

OTHER COMMENTS - Dr. Shipley encouraged development of a clinical trial comparing IMRT to the pelvis versus conventional XRT to the pelvis. Quality of Life endpoints could be compared. Dr. Cox asked that IGRT trials allow proton therapy. Dr. Michalski reported at the IGRT Retreat, Dr. George Chen raised this same issue. The IGRT Committee felt this was a good idea.
IMAGE GUIDED RADIOTHERAPY COMMITTEE (January, 2005)
Jeff Michalski, M.D., Chair

1. ATC Report:

Dr. James Purdy gave the Advanced Technology Consortium activity Report (see text elsewhere in the meeting book). Dr. Purdy pointed out the ATC website (http://atc.wustl.edu) has been modified to make navigation easier. To date, 2,180 complete data sets have been submitted to the ATC over the past 10 years using method 1. There are now 14 commercial RTP systems that have been able to implement data export capabilities. 166 institutions have been able to submit data to the ITC for review. A list of the ATC compliant treatment planning systems is available on the web site. Of note, in the past year Nucletron’s HDR system has been able to demonstrate compliant data submission. Varian’s BrachyVision has been able to demonstrate submission by the vendor. In addition, Rosses and RTek have been able to demonstrate submission data for permanence prostate seed implants by both vendor and user. The ATC has been able to receive data from CMS, XiO, Tomotherapy High Art, and Varian’s BrachyVision. They are still awaiting receipt of data from a non-vendor related user. In addition, five other treatment-planning systems are working with the ATC to develop the data exchange capabilities.

Dr. Purdy then went through the ATC Priority List:

1) To provide daily operational support for ongoing ATC supported protocols.
2) Facilitate outcome analysis and data mining for ATC supported closed protocols.
3) Implementation of ATC Method 1 at QARC.
4) Continue to interface with RTP vendors to foster implementation of ATC compliant DICOM expert capabilities.
5) Develop, test and implement ATC Method 2 with support from RCET.
6) Develop, test and implement ATC Method 3 at the NCI Canada.
7) To provide expertise in areas of protocol design, credentialing, monitoring and analysis for new clinical trials that use advance technology requiring digital data submission.
8) To develop formal interface mechanisms with other cooperative groups including the NSABP, NCIC, JCOG, COG, PBTC, SWOG, CALGB and EORTC.
9) To develop BrachySys software to facilitate RPC supported clinical trials.
10) Increase the ATC profile in radiation oncology community through presentations and publications.

The ATC is developing a mechanism of PET CT data transfer and review. Currently the ATC interactions with cooperative groups involving digital data exchange include the RTOG and JCOG. Other groups have approached the ATC regarding digital data submission including the NSABP, NCIC, COG, PBTC, and NABTT. A list of ongoing RTOG studies, as well as, completed studies was then presented to the group. Dr. Purdy also described the involvement of the ATC with the Japanese Cooperative Oncology Group (JCOG) regarding a study involving stereotactic body radiation therapy for patients with T1 non-small cell lung cancer. The ATC has initiated an effort to provide quality assurance for the NSABPB-39 and RTOG 0413 study involving partial breast radiation. This study will utilize the ATC Method 1. QARC will continue to work with the COG regarding their radiation therapy trials including ACNS0331 - Medulloblastoma and ACNS0126 - High Grade Glioma. The average turn around for successful completion of IMRT dry runs is 95 days. This is partly related to some institutions being outliers with turn around exceeding 300 days in a few instances. This contrasts with the successful completion of dry runs for the Partial Breast Radiation trial, which averaged approximately 20 days.

2. Medical Physics Report

Dr. Michael Gillin reported the RTOG Lung Cancer Committee and Medical Physics Committee now endorse the use of heterogeneity corrections using modern algorithms. Recommendations of the RTOG are consistent with the AAPM TG65. They recommended the incorporation of heterogeneity corrections be performed for all future RTOG studies involving thoracic radiation.

They identified it is important to identify the next generation of Physicists who will be active in the RTOG and other cooperative groups. They are working on methods to attract younger physicists from major institutions for the June 2005 meeting.

New NCI deadlines have been distributed for the use of IMRT and clinical trials. There are 14 protocol requirements listed in the guidelines. Of note, they state the planning should be conducted using 3D Imaging Data and there should be adoption of the NCI IMRT working group and ICRU reports 50 and 62 and the protocol must provide a rationale for the choice of margins (IM and SM) to be used for the expansion of the CTV to the PTV. The protocol must require heterogeneity corrected dose distribution for plan evaluation and dose prescription. The use of IMRT for intrathoracic should be permitted only when correction for heterogeneity and accounting for organ motion are addressed in the design of the protocol.

The Medical Physics Committee also recognizes there is significant institutional effort related to quality assurance. They point out there is evidence the average length of time to complete the credentialing process has decreased significantly. As IMRT for specific sites becomes routine, some of these processes may be phased out. It is important, however, to point out the first time failure rate for the RTOG or QARC IMRT credentialing process still is in the range of 25%. The Medical Physics Committee passed the motion either the RPC Phantom or the QARC Benchmark be acceptable methods for credentialing institution in the event IMRT is being used for the external beam portion of RTOG 0232, the Phase III Prostate Brachytherapy protocol.

The RTOG Medical Physics Committee continues to study electronic imaging devices, immobilization devices, and breathing control devices. Dr. Galvin has started a study regarding reproductivity for patients treated on RTOG 0236.

3. Brachytherapy Report

Dr. Robert Lee discussed the brachytherapy activities in the RTOG. He described both the closed and open studies. The current open studies include the RTOG 0232 Prostate Brachytherapy protocol; RTOG 0321 Prostate HDR protocol, and the RTOG 0116 Cervix protocol. The RTOG 0413 Breast Phase III study will open soon. He encouraged members to contact him about any other ideas they have regarding implementing brachytherapy studies in the RTOG.

4. Protocols in Development

Dr. Michalski informed the members the Liver Stereotactic protocol (PIs - Dr. Alan Katz and Dr. Laura Dawson) is expected to open up within the next few months. The protocol will require credentialing with a phantom that incorporates organ motion.

The PET for Lung Cancer for planning study (RTOG 0515) is expected to open soon. This study is evaluating the use of PET Imaging for radiation therapy treatment planning.

The Cervix/Endometrium Post-op IMRT study (RTOG 0418) was discussed briefly by Dr. Michalski, since Dr. Jhingran was unavailable. The Gynecology Cancer Committee still considers this to be a high priority study for them.

The Prostate Hypofractionation study was discussed by Dr. Lee. The NCI reviewed the initial concept and felt a non-inferiority study was not appropriate. Dr. Lee is working with the Genitourinary Cancer Committee membership to develop a stronger rationale for hypofractionation and the possibility of this study being converted to an equivalence trial is being considered.

Dr. Christina Tsien presented a clinical trial exploring either IMRT for unresectable or gliasite brachytherapy for glioblastoma multiforme. This study would employ a novel hypo fraction regimen for glioblastoma multiforme.

Dr. Craig Stevens discussed a concept using IMRT for treatment of Mesothelioma. This protocol would require significant effort and cooperation between the radiation oncologist, medical physicist and thoracic surgeon. Dr. Craig Stevens suggested a conference call between the principal investigators and the treating physician would occur in advance of each patient’s treatment to address appropriate quality control for this very complex treatment plan.

Dr. Schultz presented RTOG 0421. This is a Phase III trial for local recurrent previously radiated head and neck cancer. IMRT will be an option on this protocol. Dr. Schultz did not feel central Quality Assurance of the IMRT would be necessary for the re-irradiation protocol. He did feel, however, institutions providing IMRT on this protocol should be credentialed for other head and neck IMRT protocols.

Dr. Vicini was not available for discussion of the RTOG 0413/NSABP B39. This 3000 patient randomized study will require institutional credentialing for either 3D Conformal, Intersitial Brachytherapy, and or MammoSite brachytherapy for partial breast radiation. This study is anticipated to require pre-treatment review target volumes and treatment planning by one of the study PI’s or his designate.

5. Open/Ongoing Clinical Trials

Dr. Timmerman updated the group with respect to the lung stereotactic radiotherapy protocol. This study currently has 2 patients registered. Dr. Timmerman briefly discussed the credentialing and quality assurance review mechanism for the trial.

Dr. Joe Hsu discussed the Prostate HDR protocol. Two sites are credentialed for participation in the study. A second program has been approved to allow patient participation (Varian’s BrachyVision). Dr. Alvero Martinez asked if the constraint for the minimum number of catheters could be reduced. Dr. Hsu felt this was reasonable and plans to make an amendment to the protocol. Dr. Martinez also asked if guidelines and a mechanism could be developed to allow ultrasound based interactive planning to be used in lieu of CT based treatment planning.

Dr. Brad Prestidge updated the group on RTOG 0232. This randomized trial has had slow accrual to date. The projected monthly accrual was 25.3 cases per month and the average monthly accrual for the past six months was 6.8 cases per month. We discussed the possibility the credentialing process is an obstacle to registering patients on a trial. It was pointed out the number of institutions credentialed exceeds 50 and the RPC and ITC were working on methods to reduce the burden of the credentialing process. In addition, two more treatment-planning systems are now able to allow institutions to participate in a clinical trial (Rosses and RTek). There was a brief discussion about hormone therapy being allowed on the protocol and as it stands up to two months of hormone therapy is allowed prior to registration. Patients may receive six months of hormone therapy. Finally, it was agreed IMRT be allowed on this trial. For the purpose of this study central Quality Assurance of the IMRT is not allowed. Institutions have the option of either being credentialed using IMRT for any of the RTOG studies using the RPC Phantom or using the QARC Benchmark tool.

Dr. Michalski updated the group regarding RTOG 0126. Accrual for this study has improved over the past six months.

Dr. Bradley discussed the RTOG 0117 Lung Cancer trial. This study is currently in the Phase II of its investigation. They need approximately 42 more patients to complete the trial of 74 Gy and 2.0 Gy fractions delivered 3D radiation therapy in concurrent chemotherapy.

IMAGE GUIDED RADIOTHERAPY COMMITTEE (June, 2004)
Jeff M. Michalski, M.D., Chair

1. ATC Report - Dr. James Purdy gave the Advanced Technology Consortium (ATC) activity report (see full text elsewhere in meeting book).

Most digital data is being submitted to the ITC in RTOG data exchange format (aka Method 1). More than 1900 datasets have been submitted. It is expected this year may set a record for datasets submitted to the ITC for QA purposes. Efforts to develop a robust data exchange using the application relies on DICOM and RCET developed Websys/Netsys software (aka Method 2) has been problematic. A more rigid software development, testing and production system has been emphasized. Those systems are compliant with the various elements of data exchange are posted on the ATC web site. (atc.wustl.edu or itc.wustl.edu) This next meeting cycle the ATC will work on distributing the remote review tool server to others such as the QARC and NCIC.

IMRT requires dosimetry verification using phantoms available through the RPC. A head and neck phantom is available to credential institutions for RTOG 0022 and RTOG 0225. A prostate phantom is available for RTOG 0126, although prior approval with the H&N phantom will allow approval for the prostate study. Approval for IMRT with the prostate phantom is not sufficient for approval to do H&N IMRT because of the greater complexity of treatment to that site.

The ATC has begun collaborations with other cooperative groups in the US, Canada, Japan and Europe. These efforts will allow further testing of the data exchange and contribute to a growing volume of treatment planning data captured from cooperative group studies.

2. Brachytherapy Report - Dr. Robert Lee summarized brachytherapy activities in the RTOG. There is currently one phase III trial open RTOG 0232 is testing the benefit of adding EBRT to permanent seed implants for prostate cancer. The HDR trial for localized prostate cancer will open soon (see below). The outcome of patients treated on prior prostate brachytherapy trials have been or will be presented this year at ASCO or ASTRO. The RTOG 9517 partial breast study is undergoing analysis and writing now. The new phase III trial for whole breast vs partial breast RT will open soon. The cervix cancer trials are moving toward digital data exchange. Dr. Lee requested any investigator wishing to explore brachytherapy in the RTOG might contact him for assistance.

3. Medical Physics Report - Radiological Physics Center is working on phantoms for IMRT and Extracranial SRT. H&N IMRT phantom: 61 institutions met the dose and distribution criteria and 30 institutions did not. However, only 19 of the 61 institutions finished the credentialing process by also submitting the dry run to the ATC. There is no delay in shipment of the H&N phantom or the prostate phantom for RTOG institutions. Medical Physics Committee recommends institutions who wish to participate in RTOG IMRT protocols be prepared to complete both the phantom and the dry run promptly, e.g. one month. In the future, the entire team (physicians and physicists) will be informed regarding their institution’s progress in this process.

4. Lung Heterogeneity Dose Prescriptions: The Medical Physics Committee is working on a model density corrected dose prescription. The current concept includes: (1) Dose to a volume, not a point, (2) Use of modern algorithms, (3) Allowable energy < 12 MV, (4) Explicit definition of expansion from GTV to CTV to PTV. Next steps - Have a limited number of institutions calculate density corrected dose distributions following a proposed approach in order to determine the effect of implementing a density corrected dose distribution. Task Group 65 of the Radiation Therapy Committee of the American Association of Physicists in Medicine, Tissue Inhomogeneity Corrections for Megavoltage Photon Beams is in press. TG 65 “recommends heterogeneity corrections be applied to treatment plans and dose prescriptions” provided there is sound clinical and physics understanding of the consequences of migrating from a homogeneous model to a heterogeneous model.

5. Medical Physics Committee is currently working on maintaining consistency for extra-cranial SRT protocols – with respect to respiratory correlated protocols, Specification/Definition and QA.

Protocols In Development:

1. Dr. Timmerman reported that RTOG 0236, the lung Stereotactic radiotherapy trial has been approved by CTEP and will open soon. The study requires both digital data submission and a phantom treatment by ATC before patients can be registered.

2. Dr. Dawson updated the group on the progress of RTOG 0245, Dr. Alan Katz’s liver Stereotactic radiotherapy trial. This study is nearly ready to be finalized and approved. Like the lung trial, it will require both a phantom (with motion in development by RPC) and digital data submission.

3. Dr. Hsu presented an update on the development of the RTOG 0321 study for prostate cancer using HDR brachytherapy. Nucletron has completed development of digital data exchange as of the time of this meeting. Dr. Hsu will provide the manufacturer with a list of institutions wishing to participate in this trial and the breast cancer trial.

4. Dr. Bradley is completing the development of RTOG 0238. This trial is planning to test the utility of PET scanning in treatment planning for lung cancer.

5. Dr. Christina Tsien discussed a concept for glioblastoma multiforme radiation dose escalation. Unlike RTOG 9803, this trial will increase dose to the planned target volume by incrementally increasing the dose per fraction. She has proposed seven dose bins starting at 2.2 Gy per fraction and ending at 3.0 Gy per fraction. Patients will receive adjuvant Temozolomide on this protocol. Due to the positive results of the concurrent RT and Temozolomide study presented at ASCO, there is more enthusiasm for this trial in the Brain Tumor Committee.

6. Dr. Jhingran updated a concept to evaluate IMRT in the treatment of patients with carcinoma of the cervix and endometrium. This would be a Phase II study testing the feasibility of administering IMRT for gynecologic malignancies in a cooperative group setting. End points would be an assessment of acute and late toxicities.

7. Dr. Robert Lee presented a protocol concept of a Phase III trial of standard versus hypo fractionated radiation therapy for low risk localized prostate cancer. This study would allow the use of 3D CRT or IMRT. Patients would be randomized to receive 70.2 Gy in 39 fractions versus 65 Gy in 25 fractions. This has a high priority in the Genitourinary Cancer Committee.

8. Dr. Doug Arthur updated the group on the phase III breast trial. It will require digital data submission. It was suggested institutions should be re-credentialled for partial breast radiation; however it was felt the small change in target volume definitions would not require complete recredentialling unless an institution chose some other form of therapy (e.g. 3D or mammosite if previously credentialed only for interstitial).

Ongoing Clinical Trials:

1. Dr. Seth Rosenthal is developing an amendment for RTOG 9902, the high-risk prostate cancer trial. He intends to allow IMRT for the boost portion of the therapy. In addition, he will allow a range of total doses from 70.2 to 73.8 Gy. Because the radiation therapy is not a key component of the trial, it was felt digital data submission should not be required, however institutions must have been credentialed on another RTOG IMRT trials. There was debate as to whether IMRT to the pelvic lymph nodes would be allowed. Because there is no standard on pelvic node IMRT, it was felt this should not be allowed.

2. Dr. Prestige announced accrual remains slow on RTOG 0232 – the randomized study for brachytherapy plus external beam radiation therapy versus brachytherapy alone for early stage prostate cancer. He encouraged institutions to get credentialed for electronic data submission of permanent brachytherapy treatment plans. Dr. Michalski pointed out there was some interest from institutions in the UK to participate.

3. Dr. Michalski summarized progress on other current open clinical trials:

4. The two head and neck studies, RTOG 0225 and 0022, are accruing at a good pace. The nasopharyngeal carcinoma trial (RTOG 0225) has accrued ten patients since activation last year.

5. The randomized prostate cancer trial (RTOG 0126) had the IMRT amendment approved by the NCI last fall. Accrual has improved this past meeting cycle.

6. The breast cancer clinical trial RTOG 0319 is accruing at a good pace and will likely be closed before the next meeting. This trial will be followed by a randomized study of limited volume radiation therapy using mammosite, HDR brachytherapy or 3D CRT versus whole breast radiation therapy and conventional techniques.
IMAGE GUIDED RADIOTHERAPY COMMITTEE (January, 2004)
Jeff Michalski, M.D., Chair

Brachytherapy Report. - Dr. Geoff Ibbott summarized Brachytherapy activities in the RTOG. Abstracts for RTOG 9517 (breast cancer), 9805 (prostate), and 0019 (prostate) have been reported at ASTRO meetings in 2002 and 2003. The randomized study RTOG 0232 (Brachy +/- EBRT) is currently being supported by the ATC and is relying on digital data submission. The ACOSOG “SPIRIT” trial is also supported by the ATC. Accrual targets for that trial have been changed from 1400 to 600 patients with a PSA endpoint being used. Most of the 54 patient accrual has come from PMH. Two cervical cancer trials (0016 and 0128) are registering patients at a good rate and will likely complete accrual in the next year. The HDR prostate trial is near activation. The data submission for QA may need to start in hard copy, as digital submission is not currently implemented by commercial HDR planning systems. A 3000 patient randomized trial for whole breast vs. partial breast radiation therapy is being developed by RTOG and NSABP. The study will allow 3DCRT, Mammosite, or interstitial Brachytherapy. The study will be supported by the ATC.

ATC Report - Dr. James Purdy gave the Advanced Technology Consortium (ATC) activity report (see full text elsewhere in meeting book). The ATC has full group meetings at the semi-annual RTOG and COG meetings to maintain a close working relationship with the cooperative groups. The ATC has monthly conference calls to review progress on various QA projects. Developmental efforts are focused on electronic data exchange of planning, verification and diagnostic imaging data between the ATC QA centers and participating institutions.

Most data is being submitted to the ITC in RTOG data exchange format (aka Method 1). The ATC is developing a secure data exchange that will rely on DICOM and RCET developed Websys/Netsys software (aka Method 2). Several institutions are working on submitting data in this manner and providing feedback to ATC regarding its reliability and ease of use. The compliant RTP systems using the RTOG data exchange are CMS focus, Philips (ADAC) Pinnacle, Philips (Marconi) AcQplan, Nucletron Helax TMS, Nucletron TheraplanPlus, Elekta Precise Plan, University of North Carolina RTP system, University of Michigan RTP system, and Memorial Sloan Kettering RTP system. Nomos Corvus can submit data but requires a “work around” procedure to allow submission of targets and organs at risk that have not been cutoff by the PTV generation tool. The work around procedure has been posted on the ITC website. Varian Eclipse is the first DICOM system that has been able to submit data digitally with an approved “dry run”. Several other RTP systems are developing a DICOM data submission method including Varian variseed, Elekta precise plan, Nucletron, Siemens. Another workshop for data exchange development is scheduled for May 2004 in conjunction with the DICOM working group. Treatment planning vendors are invited to these meetings in order to facilitate the integration of DICOM data exchange into their treatment planning systems.

Information about data exchange or institutional credentialing for IGRT trials can be obtained from the ATC or ITC websites (atc.wustl.edu or itc.wustl.edu).

IMRT requires Dosimetry verification using phantoms available through the RPC. A head and neck phantom is available to credential institutions for 0022 and 0225. A prostate phantom is available for 0126, although prior approval with the H&N phantom will allow approval for the prostate study. Approval for IMRT with the prostate phantom is not sufficient for approval to do H&N IMRT because of the greater complexity of treatment to that site.

Medical Physics Report - Dr. Michael Gillin presented the Medical Physics Report. A symposium on lung cancer radiation therapy was held on Friday, January 16th. Topics of discussion included the use of heterogeneity corrections for lung cancer Dosimetry and prescription and the use of technology to address organ motion related to respiratory ventilation.

The Medical Physics Committee is discussing the issues regarding quality assurance of in room target localization devices such as: ultrasound guidance and/or electronic portal imaging devices. Dr. Gillin described the developing trials and the credentialing process for participation. There are currently two stereotactic radiotherapy protocols proposed for lung and liver cancer respectively. Each of these protocols will require a credentialing process and dry run submission. The lung cancer trial will require a rapid target volume and Dosimetry review prior to the first patient being treated by each institution. Both protocols will require electronic digital submission of treatment plans. Technological management for organ motion will be recommended for the lung cancer trial and required for the liver tumor trial.

Protocols in Development - Dr. Hsu presented an update on the development of the P03T1 study for prostate cancer using HDR Brachytherapy. The treatment-planning vendor has not completed development of digital data exchange as of the time of this meeting. In order to allow the protocol to move forward Dr. Hsu is willing to accept hard copy Dosimetry for quality assurance purposes for this limited institution Phase I trial.

Dr. Bradley updated the group regarding L0235. Dr. Mitch Machtay is the principal investigator for this study being managed by ACRIN. All patients undergo pre-treatment PET scan followed by combined chemotherapy and radiation therapy with a post-treatment PET scan used to assess treatment response.

Dr. Bradley is completing the development of L0238. This trial is planning to test the utility of PET scanning in treatment planning for lung cancer.

Dr. Christina Tsien discussed a concept for glioblastoma multiforme radiation dose escalation. Unlike RTOG 9803, this trial will increase dose to the planned target volume by incrementally increasing the dose per fraction. She has proposed seven dose bins starting at 2.2 Gy per fraction and ending at 3.0 Gy per fraction. Patients will receive adjuvant Temozolomide on this protocol.

Dr. Jhingran presented a concept to evaluate IMRT in the treatment of patients with carcinoma of the cervix. This would be a Phase II study testing the feasibility of administering IMRT for gynecologic malignancies in a cooperative group setting. End points would be an assessment of acute and late toxicities.

Dr. Robert Lee presented a protocol concept of a Phase III trial of standard versus hypo fractionated radiation therapy for low risk localized prostate cancer. This study would allow the use of 3D CRT or IMRT. Patients would be randomized to receive 70.2 Gy in 39 fractions versus 65 Gy in 25 fractions.

Dr. Ross Abrams presented RTOG 0223. This trial is a Phase I/II study for postoperative adjuvant chemotherapy and radiation therapy for pancreatic cancer. This study will be using 3D conformal radiation therapy and the ATC will be providing quality assurance support.

Ongoing Clinical Trials - Dr. Michalski summarized progress on the current open clinical trials.

P0232 – the randomized study for Brachtherapy plus external beam radiation therapy versus Brachtherapy alone for early stage prostate cancer is accruing at a slow rate while institutions get credentialed for electronic data submission of permanent Brachtherapy treatment plans.

The two head and neck studies, RTOG 0225 and 0022, are accruing at a good pace. The nasopharyngeal carcinoma trial (RTOG 0225) has accrued ten patients since activation last year.

The randomized prostate cancer trial (RTOG 0126) had the IMRT amendment approved by the NCI last fall. Accrual to the study has slowed while institutions submit the amendment to their IRB’s and complete credentialing requirements for IMRT. It is expected that accrual to this study will pick up once the regulatory requirements have been completed at the participating institutions and once RTOG 9910 closed to accrual.

The breast cancer clinical trial RTOG 0319 is accruing at a good pace and will likely be closed before the next meeting. This trial will be followed by a randomized study of limited volume radiation therapy using either mammosite, HDR Brachytherapy or 3D CRT versus whole breast radiation therapy and conventional techniques.
IMAGE GUIDED RADIOTHERAPY COMMITTEE (June, 2003)
Jeff M. Michalski, M.D., Chair

1. ATC Report. Dr. James Purdy gave the Advanced Technology Consortium (ATC) activity report. The ATC had a full group meeting at this RTOG meeting. They intend to meet on a regular basis, generally during semi-annual cooperative group meetings (RTOG, COG, etc…). In addition, the group has monthly conference calls to review progress on various QA projects. Developmental efforts are focused on electronic data exchange of planning data between ATC QA centers and participating institutions. Web based software tools are being developed and refined to facilitate QA reviews by RTOG, QARC, and RPC protocol related data submissions and allow archiving of treatment planning and QA databases. There are currently six trials that are actively accruing patients and are supported by the ATC (RTOG 9803, 0022, 0117, 0126, 0225, 0232). In addition, they are involved in development of QA guidelines and support of several other IGRT trials.

Most data is being submitted in RTOG data exchange format. Several sets of “dry-run” data have been submitted in DICOM format with at least one of them being approved. The compliant RTP systems using the RTOG data exchange are CMS focus, Philips (ADAC) Pinnacle, Philips (Marconi) AcQplan, Nucletron Helax TMS, Nucletron TheraplanPlus, Elekta Precise Plan, University of North Carolina RTP system and University of Michigan RTP system. Nomos Corvus can submit data but requires a “work around” procedure to allow submission of targets and organs at risk that have not been cutoff by the PTV generation tool. The work around procedure has been posted on the ITC website. In addition, study chairs may be required to recontour some structures that are cutoff by the PTV generation algorithm. Varian Eclipse is the first DICOM system that has been able to submit data digitally with an approved “dry run”. Several other RTP systems are developing a DICOM data submission method including Varian variseed, Elekta precise plan, Nucletron, Siemens and Memorial Sloan Kettering (in house system). Workshops for data exchange development have been held by the ATC as recently as May 2003.

Information about data exchange or institutional credentialing for IGRT trials can be obtained from the ATC or ITC websites (atc.wustl.edu or itc.wustl.edu).

2. Medical Physics Report. Dr. Michael Gillin reviewed the results of the RPC/RTOG phantom exercise for IMRT credentialing. Nineteen institutions have submitted data to RPC using the IMRT phantom. Based upon the first 10 data sets, it is their recommendation that institutions will be considered successful in the phantom exercise if the measured dose to the PTV agrees to within 7% of the planned dose and the maximum shift between the calculated dose and the measured dose in the region of the “Organ at Risk” is =<4mm. This distance criteria for the OAR is more practical than an absolute or relative dose due to the fact that there is rapid fall off of dose in these areas. Based upon these criteria, 6 of the next 8 submitted phantom exercises would have passed. These criteria will continue to be examined as more data is acquired.

3. New Technology Discussion. Dr. Robert Timmerman and Dr. Alan Katz gave presentations on the use of extracranial focused high-dose radiation therapy for lung and liver tumors, respectively. Each updated the committee on the status of their developing clinical trials.

4. Protocols in Development. As described above, the two extracranial radiosurgery trials for liver and lung tumors are being developed. It is hoped that they both can be activated by the time of the next meeting.

Dr. Joe Hsu reported progress on HDR brachytherapy with EBRT for patients with localized prostate cancer. Two fractions of 950cGy in addition to external beam RT to 45 Gy (before or after implant) are planned. Credentialing will be done by the RPC. Digital data exchange with HDR RTP software is not available from any vendor. This protocol has been given high priority by the GU committee

The breast cancer limited volume 3D CRT trial has been developed and may be ready to open by the time of the next meeting. IMRT is not allowed and probably not necessary for this trial. This will be an important phase II study to lead to a phase III trial of limited volume RT (3D or brachy) vs full breast irradiation.

Dr. Christina Tsien has proposed a follow-up trial to RTOG 9803 of hypofractionated 3DCRT for GBM. This trial will likely be a new study and not an amendment to RTOG 9803 due to the changed fractionation scheme, PI, statistician and chemotherapy.

5. Ongoing Clinical Trials. Dr. Brad Prestidge reported that RTOG 0232 has been opened. This randomized trial of EBRT + brachy vs brachy alone for prostate cancer will require digital data submission to the ATC for quality assurance review. Institutions will need to demonstrate ability to submit data to the ATC prior to registering their first case.

RTOG 0023, the fractionated SRS protocol for GBM, will close immediately after this semi-annual meeting. RTOG 9803, the 3DCRT protocol has nearly met its accrual and will likely close within the next few months.

RTOG 0117 has reopened and accrual has been slow on the amended protocol. The study was suspended September 2002 due to toxicity in 2 of 7 patients. A Phase I proposal to “de-escalate” was submitted to NCI with a planned 9 patients to be treated to 74Gy in 2Gy then 70Gy in 2Gy with concurrent Carboplatin and paclitaxel. The MTD from this phase I component would then be followed by a phase II to accrue 43 patients. If this treatment plan were tolerable and effective, the Lung Cancer Committee would plan to conduct a phase III trial with this regimen vs the best arm of RTOG 9410.

The two H&N IMRT protocols are accruing slowly. As stated above, a work around for NOMOS data submission has been developed and procedures are available at the ITC website. The nasopharyngeal carcinoma trial just recently opened. Investigators were encouraged to enroll patients on both of these important clinical trials.

Dr. Michalski reported that RTOG 0126, the randomized trial of high dose versus standard dose conformal radiation therapy for intermediate prostate cancer would soon allow IMRT. The decision was made to drop the need for two separate target volumes for patients receiving IMRT. Instead, a single target volume that encompasses the proximal seminal vesicles will be used. For patients treated with forward planned 3DCRT, an optional volume reduction after 55.8 Gy will be allowed. The prescription point was changed to a minimum dose to the PTV, rather than an ICRU reference dose.
IMAGE GUIDED RADIOTHERAPY COMMITTEE (January, 2003)
Jeff Michalski, M.D., Chair

1. Intergroup Image Guided Brachytherapy Report - Dr. Subir Nag described efforts undertaken by members of several cooperative groups on proposed criteria for implementation of image based Brachytherapy for cervical cancer. Recommendations include the use of MRI for treatment planning and standardization of nomenclature for describing target volumes, dose prescription, and dose reporting. It is anticipated that this information will be published in the near future.

2. ATC Report - Dr. James Purdy gave the Advanced Technology Consortium (ATC) activity report. The ATC represents a re-organization of the various quality assurance groups funded by the NCI to provide services to cooperative groups administering radiation therapy. The Image-Guided Therapy QA Center (ITC) (along with RPC, QARC and RTOG HQ Dosimetry) and the Resource Center for Emerging Technology (RCET) have been funded independently to provide QA for radiotherapy studies. To avoid duplication of services and to take advantage of the strengths of each group, these two independent groups were integrated under the umbrella of the ATC.

Over the past year, the ITC has continued to credential institutions for participation in Brain, Lung, H&N and Prostate trials. They continue to enhance some of the remote review tools for investigators to review patient data on the various image-guided clinical trials. They are currently working on implementation of DICOM 3.0 for quality assurance data exchange. They are working with vendors to develop compliance and implementation of DICOM rules. Another workshop is planned to aid RTP vendors to implement DICOM data exchange. Two vendors have been successful in submitting data to the ITC, using DICOM format (Elekta Precise Plan and Varian Variseed). However, no clinical user has successfully submitted data to the ITC using these DICOM tools. RTP systems that are currently using the RTOG exchange standard include Adac Pinnacle, CMS Focus, Helax TMS, PTI Render Plan 3D, and Theraplan Plus. The Nomos CORVUS system is able to exchange data to a limited degree and the Marconi AcQPlan, which had previously been approved, has recently been suspended because of new problems related to data exchange. Recently, accrual to IMRT studies with the Nomos CORVUS systems was temporarily suspended to allow resolution of problems that were discovered related to target volume growth and the impact on organ at risk volumes. A solution has been proposed and a task group will meet following the IGRT session to discuss it before announcing it to RTOG membership. It is anticipate that Corvus plans will be allowed on IMRT studies within one month of this meeting.

The NCI has circulated a letter to cooperative group members describing the use of IMRT for clinical trials. Unless IMRT guidelines have been described in the clinical trial, including mechanism for QA, this modality is not allowed.

Individuals seeking information about Image Guided Radiation Therapy Quality can visit the ITC web site at http://itc.wustl.edu.

3. Medical Physics Report - Dr. Michael Gillin reviewed the results of the RPC/RTOG phantom exercise for IMRT credentialing. Nineteen institutions have submitted data to RPC using the IMRT phantom. Based upon the first 10 data sets, it is their recommendation that institutions will be considered successful in the phantom exercise if the measured dose to the PTV agrees within 7% of the planned dose and the maximum shift between the calculated dose and the measured dose in the region of the “Organ at Risk” is =<4mm. This distance criteria for the OAR is more practical than an absolute or relative dose due to the fact that there is rapid fall off of dose in these areas. Based upon these criteria, 6 of the next 8 submitted phantom exercises would have passed. These criteria will continue to be examined as more data is acquired.

4. Closed Clinical Trials - Dr. Michalski reported that RTOG 9406 dose level IV was presented at ASTRO last fall. As with previous dose levels, this dose of 74 Gy at 2 Gy per day is tolerable in patients with localized disease.

5. Ongoing Clinical Trials - Dr. Robert Cardinale reported that more than 40 of 76 patients have been registered to date. This study entails the delivery of four stereotactic fractions for 5 or 7 Gy per fraction.

Dr. Bradley reported that he has been appointed the Principal Investigator for the lung cancer dose escalation trial RTOG 0117. The study was suspended September 2002 due to toxicity in 2 of 7 patients. A Phase I proposal to “de-escalate” was submitted to NCI with a planned 9 patients to be treated to 74Gy in 2Gy then 70Gy in 2Gy with concurrent Carboplatin and Paclitaxel. The MTD from this phase I component would then be followed by a phase II to accrue 43 patients. If this treatment plan were tolerable and effective, the Lung Cancer Committee would plan to conduct a phase III trial with this regimen vs the best arm of RTOG 9410.

Dr. Nancy Lee reported that the nasopharyngeal carcinoma IMRT trial RTOG 0225 is soon to be opened. This trial is for patients with stage I-IV nasopharyngeal carcinoma. Patients with stages III and IV will receive chemotherapy. The patients will receive 2.12 Gy per day to dose of 70 Gy to the primary target volume and the secondary target volume will receive 1.8 Gy per day to dose 59.4 Gy.

Dr. Eisbruch discussed the RTOG 0022 protocol, which has been open for nearly one year. It currently has been accruing patients slowly. This trial is for oropharyngeal carcinoma and treats the primary target volume to 66 Gy at 2.2 Gy per day fractions and the secondary target volume to 60 Gy in 2 Gy fractions.

Dr. Michalski reported that the GBM trial RTOG 9803 dose level IV (84 Gy to PTV2) has been opened for both PTV size stratifications with some accrual already. A poster describing favorable tolerance to XRT on the first two dose levels was presented at the Society of NeuroOncology in November, 2002.

Dr. Michalski reported that (RTOG 0126), the randomized trial of high dose versus standard dose conformal radiation therapy for intermediate prostate cancer, has opened. Twenty-eight patients have been registered since November. Institutions previously credentialed to participate in RTOG 9406 remain credentialed for this trial, unless there has been a change in treatment planning systems. A draft amendment to allow IMRT has been circulated to several institutions with various treatment planning systems to determine if proposed dose constraints can be achieved. Two separate plans for PTV1 and PTV2 will be required. This is necessary to avoid fractionation differences between the two arms for the initial PTV1 (prostate and seminal vesicles). Additional comments from other members will be sought to confirm that the dose limits are practical before the amendment is finalized.

6. Protocols in development - Dr. Bradley updated the group on RTOG 0238. This trial will test the value of PET scanning and defining target volumes for patients with non-small cell lung cancer.

Dr. Robert Timmerman presented his concept on the treatment of localized lung cancer using extracranial stereotactic radiosurgery. Significant progress has been made since the last meeting. In this trial, patients will receive three fractions of 2000 cGy prescribed to the 60-90% isodose curve. Test cases from IU should be submitted to finalize data submission and QA rules. Issues regarding patient repositioning and organ motion are currently being defined. Institutions must demonstrate an ability to reposition patients using CT data prior to the first treatment.

Dr. Okunieff updated Dr. Katz’s proposed liver metastasis trial. This concept is for hypofractionated radiation therapy for primary liver cancer and liver metastases. The objective of this trial is to determine the maximum tolerable dose of radiation that can be safely delivered with small volume large fraction of radiation therapy. Details regarding patient immobilization, breath holding, and portal imaging is to be resolved.

Dr. Joe Hsu reported a phase I concept of HDR brachytherapy with EBRT for patients with localized prostate cancer. Two fractions of 950cGy in addition to external beam RT to 45 Gy (before or after implant) are planned. Credentialing will be done by the RPC. Digital data exchange with HDR RTP software is not available from any vendor. Nucletron has attended the ITC data exchange workshops in the past and are considering implementing a DICOM for clinical trial support. RTOG members are encouraged to demand this feature if purchase is anticipated for trial participation.

Dr. Mack Roach presented a concept to examine portal imaging for prostate cancer daily EBRT localization. Nearly half of the committee attendees felt such a study would be worthwhile and had EPID capabilities.
3D-CRT COMMITTEE (June, 2002)
Jeff M. Michalski, M.D., Chair

1. Radiosurgery Report - Dr. Luis Souhami presented a report of activities in the Radiosurgery Committee. The RTOG BR-0023 trial continues to accrue patients. Later in the meeting, Dr. Robert Cardinale reported that accrual has been at a good pace with good quality control. Quality of strengths for this study is currently being done using the old hard copy paper documentation. At today’s plenary session, Dr. Paul Sperduto will report the positive results of the randomized trial of radiosurgery in the management of patients with 1 to 3 brain metastases on RTOG 93-05. A protocol is currently under development to evaluate extra cranial radiosurgery by Dr. Robert Timmerman and this is discussed below.

2. Brachytherapy Report - Dr. Laurie Gaspar reported that Dr. Robert Lee is proceeding with the Quality Assurance patients entered on P-0019. Quality Assurance for RTOG 98-05 is now complete. Dr. Kuske will be reporting on preliminary results for RTOG 95-17, the Breast Brachytherapy Protocol, before today’s plenary session. Two protocols are under development. P-1084, a randomized trial of external beam radiation therapy plus brachytherapy boost versus brachytherapy alone. A strong endorsement for digital-based quality assurance data management was made. Another protocol testing HDR brachytherapy for localized prostate cancer by external beam radiation therapy was proposed by Dr. Hsu. Some interest was expressed regarding the possibility of conducting a brachytherapy trial in ocular melanoma. Dr. Nag will be investigating the interest of the RTOG membership for this trial.

3. ITC Report - Dr. James Purdy gave the 3D QA Center activity report. Over the past year, the ITC has continued to credential institutions for participation in Brain, Lung, H&N and Prostate trials. They are currently working on implementation of DICOM 3.0 for quality assurance data exchange. They are working with vendors to develop compliance and implementation of DICOM rules. They have also enhanced some of the remote review tools for investigators to review patient data on the various image-guided clinical trials. IMRT guidelines have been developed for clinical studies. The ITC continues to manage data on two closed trials (RTOG 94-06 and 93-11) and have been conducting treatment planning data management on four open trials ( RTOG 98-03, L-0117, H-0022 and T-0126).

The ITC currently accepts treatment data using the RTOG data exchange format. They are working with RTP vendors on the implementation of the DICOM 3.0 standards for participation in multi-institutional clinical trials. Two vendors have been successful in submitting data to the ITC, using DICOM format (Elekta Precise Plan and Varian Variseed). However, no clinical user has successfully submitted data to the ITC using these tools. RTP systems that are currently using the RTOG exchange standard include Adac Pinnacle, CMS Focus, Helax TMS, PTI Render Plan 3D, and Theraplan Plus. The Nomos CORVUS system is able to exchange data to a limited degree and the Marconi AcQPlan, which had previously been approved, has recently been suspended because of new problems related to data exchange.

The ITC has been working with QARC and the RPC to develop common credentialing and documentation for cooperative group participation in prostate brachytherapy. Recent guidelines for the use of intensity modulated radiation therapy in clinical trials have been proposed to the NCI’s Radiation Research Program. These will soon be published.

Dr. Purdy reported that in 1999 the NCI funded two advanced technology QA centers, including the Resource Center for Emerging Technology (RCET) at the University of Florida and the Advanced Technology QA Consortium organized by the ITC (ITC, RPC, QARC and RTOG Headquarters). This past year, the NCI has restructured this ATC grant creating one advanced technology QA consortium with RCET being merged into the existing consortium. This consortium of quality assurance centers is working to provide services to the RTOG, CALGB, COG, SWOG, and other cooperative groups.

Individuals seeking information about image guided radiation therapy quality can visit the ITC web site at http://itc.wustl.edu.

4. Medical Physics Report - Dr. Michael Gillin reported that quality assurance for the prostate brachytherapy trials RTOG 98-05 and P-0019 are nearing completion. Significant progress has been made on developing quality assurance mechanisms for RTOG 02-36, the stereotactic body radiosurgery trial for early stage lung cancers. Issues that currently need to be addressed for the study include the use of a body frame and serial CT-based repositioning studies. He confirmed that intensity modulated radiation therapy will not be allowed on RTOG trials unless specifically described in the clinical trial with prescription and quality assurance issues clearly defined. The next challenge for the Medical Physics Committee may be the implementation of prescription quality assurance guidelines for prostate high dose rate brachytherapy.

5. Closed Clinical Trials - Dr. Michalski reported that RTOG 94-06, the dose escalation trial for prostate cancer, has enough follow-ups for the submission of an abstract to this Fall’s ASTRO meeting for dose level IV. As with previous dose levels, this dose of 74 Gy at 2 Gy per day appears to be tolerable in patients with localized disease.

Dr. Robert Cardinale reported that twelve institutions are currently accruing to BR-0023 the fractionated stereotactic radiotherapy trial for glioblastoma. Twenty-four of the 76 patients have been registered to date. This study entails the delivery of four stereotactic fractions for 5 or 7 Gy per fraction.

Dr. Bradley reported that he has been appointed the Principal Investigator for the lung cancer dose escalation trial L-0117. Drs. Byhardt and Govindan are the Co-PI’s. Eight patients have been registered to date. Most of these have been in the past two months. One fatal toxicity of radiation pneumonitis was reviewed. Subsequently it was felt that the death was related to infection. Additional patients need to be treated at the first dose level and, if tolerable, we will move to the next dose level. An amendment will be presented to the NCI deleting chemotherapy arm D. A single escalation will be performed from the current level of 75.25 Gy at 2.15 Gy per day to a dose of 80.5 Gy at a rate of 2.3 Gy per day. In addition, the dosimetry criteria will be relaxed for the esophagus and weight loss limit will be added for the eligibility criteria.

Dr. Nancy Lee reported that the nasopharyngeal carcinoma IMRT trial (RTOG 02-25) is soon to be opened. This trial is for patients with stage I-IV nasopharyngeal carcinoma. Patients with stages III and IV will receive chemotherapy. The patients will receive 2.12 Gy per day to dose of 70 Gy to the primary target volume and the secondary target volume will receive 1.8 Gy per day to dose 59.4 Gy.

Dr. Chao discussed the H-0022 protocol, which has been open for nearly one year. It currently has accrued six patients from three institutions. This trial is for oropharyngeal carcinoma and treats the primary target volume to 66 Gy at 2.2 Gy per day fractions and the secondary target volume to 60 Gy in 2 Gy fractions.

Dr. Michalski reported that the randomized trial of high dose versus standard dose conformal radiation therapy for intermediate prostate cancer has opened. Already two patients have been accrued. Institutions previously credentialed to participate in RTOG 94-06 remain credentialed for this trial, unless there has been a change in treatment planning systems. An amendment describing handling of pathology for central review and the tumor tissue bank will be submitted shortly. The amendment also covers some issues regarding patient immobilization.

6. Protocols In Development - Dr. Bradley updated the group on RTOG 02-38. This trial will test the value of PET scanning and defining target volumes for patients with non-small cell lung cancer. Dr. Mitchell Machtay described another protocol that we use PET to allow physicians to predict response to chemo-radiation therapy for non-small cell lung cancer. This trial will likely require support from both ACRIN and the ITC.

Dr. Robert Timmerman presented his concept on the treatment of localized lung cancer using extracranial stereotactic radiosurgery. Significant progress has been made since the last meeting. In this trial, patients will receive three fractions of 2000 cGy prescribed to the 60-90% isodose curve. A minimum of seven fields will be used. Issues regarding patient repositioning and organ motion are currently being defined. We may ask an institution to demonstrate an ability to reposition patients using CT data prior to the first treatment.

Dr. Dawson presented a concept of Dr. Katz’s in his absence. This concept is for hypofractionated radiation therapy for primary liver cancer and liver metastases. The objective of this trial is to determine the maximum tolerable dose of radiation that can be safely delivered with small volume large fraction of radiation therapy. Details regarding patient immobilization, breath holding, and portal imaging are to be resolved.

Tracey Schelter, from University of Colorado, presented a similar trial of extracranial stereotactic radiosurgery for liver metastases. In this trial, patients would receive three fractions of 7 to 10 Gy each. It was felt by many that the two liver trials represented a continuum of dose escalation for this disease. It might be appropriate to combine these two concepts into one.
3D-CRT COMMITTEE (January, 2002)
Jeff Michalski, M.D., Chair

Radiosurgery
Dr. Luis Souhami presented a report on the activities of the Stereotactic Radiosurgery Committee. There is currently only a single trial, BR-0023, a trial of fractionated stereotactic radiosurgery. Several trials are in development including 1044, a phase II trial of RSR13 + radiosurgery and 1002, a phase III trial of radiosurgery alone vs radiosurgery + WBRT for patients with 1-3 brain metastases. Another concept (1081) has been proposed to test radiosurgery plus Gd-Texaphyrrin. RTOG 95-08 will be analyzed with all patients (1 to 3 metastases) included. RTOG 93-05 has been analyzed and an abstract will be submitted to ASCO. The study did not demonstrate an advantage for SRS boost in GBM.

Brachytherapy
Dr. Laurie Gaspar reported on activities of the Brachytherapy Subcommittee. Quality assurance for P-0019 (Prostate Brachytherapy) is anticipated soon. Interobserver variation in the definition of prostate target volumes amongst experienced brachytherapists was discussed. How this will affect future quality assurance review and dosimetric analyses is uncertain. Dr. Gaspar suggested that examples of appropriate target volumes be posted on the ITC website. This will be considered if agreement on target volume can be made.

QA of cases on RTOG 98-05 (prostate brachytherapy) is nearly complete. The breast brachytherapy trial (RTOG 95-17) is nearly ready for analysis with 2 years of median follow-up.

A randomized trial of permanent seed implant vs. external beam radiation therapy plus implant for prostate cancer (1084) is under development. Follow-up analysis of the trial’s predecessor, P-0019 is holding up moving this study forward. An HDR protocol for prostate cancer is being developed. A concept for endobronchial brachytherapy with p53 adenovirus was submitted from MD Anderson.

Medical Physics Committee Report
Dr. Michael Gillin reported from the Medical Physics Committee. In part due to NCI concerns, the RTOG has chosen not to allow IMRT on protocols that do not explicitly allow this treatment modality. If a PI wishes to allow this treatment, an amendment must be submitted that explains IMRT prescription issues, including normal tissue dose constraints, AND mechanisms for Quality Assurance. This amendment must be approved by the RTOG and NCI. Any questions as to what constitutes IMRT must be directed to members of the medical physics committee.

The IMRT workshop on Friday was well attended and early feedback suggests it was a success. Institutions wishing to participate with IMRT on RTOG 99-11 must be credentialed by medical physics. QA review on RTOG 98-05 is near completion. QA on P-0019 is starting soon.

Quality Assurance
Mr. Bill Harms submitted the 3D QA center activity report. The name of the center has changed to the Image-Guided Therapy Center (ITC). Fifty-three institutions are currently credentialed for participation in prostate cancer trials, twenty-six in lung cancer trials, and thirty-eight in GBM trials. The oropharyngeal IMRT study, H-0022 has four institution credentialed to register patients.

Six vendors have RTOG data exchange that allows institutions to submit 3DCRT treatment planning data to the ITC for QA review. Nomos and Varian Cadplan are working on developing exchange capabilities. The Nomos system does create problems with generation and QA of PTV margins. Three vendors are working on DICOM data exchange including Elekta (3D and IMRT), MDS Nordion (3D and IMRT) and Varian Variseed (Prostate seeds). Only Variseed and CMS focus have implemented a data exchange system for seed implants. To date, a user has not tested the Variseed DICOM exchange. The SGI Prowess treatment planning company has declined all efforts to implement exchange on their program. A DICOM workshop for development of data exchange is scheduled for March at the ITC. Vendors have been invited. The ITC has been working on receipt of DICOM data sets as an alternative to RTOG data exchange.

Prostate brachytherapy currently is being reviewed at the Medical College of Wisconsin. It is expected that the phase III brachytherapy trial will use a digital data exchange mechanism can allow centralized computer based review of plans. This may be supplemented by hardcopy data submission for institutions that do not have exchange capability on their seed implant planning software.

Members interested in participating in radiosurgery, brachytherapy or 3D-CRT are urged to visit the RTOG website which lists significant information regarding requirements of participation for these studies. The Image Guided Therapy Quality Assurance Center is working to implement DICOM which will facilitate future institutional and vendor participation in imaged guided radiotherapy trials.

Clinical Studies
For the sake of time, discussion was limited to protocols in development.

P-0126 will be a randomized trial of high dose conformal radiation therapy versus standard dose conformal radiation therapy. The trial will evaluate patients with any intermediate risk prostate cancer. The dose prescription will be 82.28 Gy to the ICRU reference verses 72 Gy to the same point in the standard dose arm period. These numbers represent the central dose on the third dose level of RTOG 94-06. No hormonal therapy is planned for this trial period. IMRT will be added as an amendment once the trial has begun. If data from dose level V suggests this is tolerable, then the protocol may be modified for this higher BED prescription.

Robert Timmerman presented a concept for a Pilot/phase I extracranial body radiosurgery for T1 or T2 lung cancer. Treatment would consist of 3 fractions of 16 to 20 Gy to a very small target volume. Issues with respect to immobilization and organ motion were discussed. It was argued that the technical issues related to this new technology should be worked out in the context of a working group by the time of the next meeting.

Jeff Bradley presented a concept testing the use of PET scanning in 3D CRT of Lung cancer. He wishes to evaluate the impact of PET on target volume definition and treatment plan quality. Patients would have a treatment plan created based upon CT and other diagnostic tests then separately with the same studies and a PET scan. An important element will be the ability to register and “fuse” PET and treatment planning CT data. The resources of the ITC may be required to collect and compare dosimetric information.

Mitch Machtay presented a concept on the use of PET to predict and assess early response to patients with NSCLC. Patients would undergo a pretreatment PET scan followed by standard chemoradiotherapy. A follow up PET scan 2 to 3 months post therapy would then be acquired to assess response. The hypothesis is that the intensity of PET uptake prior to therapy sill predict for treatment response and the follow-up PET can serve as a surrogate to local tumor response and control. ACRIN may be a resource for funds to perform the second PET as well as interpret the imaging data.

Alan Katz presented a concept for a phase I/II study of hepatic irradiation for liver metastases. The treatment would consist of >300cGy fractions to a limited volume of tumor plus a PTV margin. Total dose would be escalated by increasing the dose per fraction. Eligibility and dose to normal structures would be limited by normal tissue constraints derived from dose escalation trials reported from institutions such as University of Michigan as well as the data from University of Rochester.

Frank Vicini described the results of HDR brachytherapy and partial breast irradiation for early stage breast cancer. The NCI Milan is currently conducting a randomized trial of single fraction intraoperative radiation therapy versus standard breast irradiation. Dr. Vicini proposes a study to test 3DCRT or IMRT for short course partial breast irradiation. Eventually this could be compared to standard whole breast irradiation. Details of treatment planning and management of venilatory motion need to be resolved before carrying forward to clinical trial.
3D-CRT COMMITTEE (November, 2001)
Jeff Michalski, M.D., Chair

A brief update on the recent grant submission and site visit was delivered by Dr. Michalski. He noted that as the group, in general, did very well in its review, so did the IGRT committee. Strengths of the committee included its activity in prostate cancer, lung cancer and brain tumors. They also plotted the recent efforts in putting together the neck trial period. An area of weakness was identified to be gastrointestinal tumors.

Radiosurgery

Dr. Luis Souhami presented a report on the activities Stereotactic Radiosurgery Committee. He announced, once again, that RTOG 93-05 and RTOG 95-08 have closed. A protocol testing fractionated SRS radiotherapy in brain metastases is currently being developed. A different discussion about BR-0023 was deferred to Dr. Robert Cardinale who will present later in the session.

Brachytherapy

Dr. David Raben presented a report from the brachytherapy in Dr. Gaspar’s absence. He summarized Lung Cancer State of the Science meeting held at that NIH early this month. At the meeting issues of small early lung cancers and their management were discussed. Surgical options as well as radiotherapy options including brachytherapy and body stereotactic radiosurgery were discussed. Dr. Robert Timmerman has proposed a body reduced surgery treatment protocol for cancer of the lung.

The Phase II study of external beam radiation plus brachytherapy is accruing at a rapid pace. It is hoped that the next study will be a randomized study between brachytherapy alone vs external radiation and brachytherapy. Efforts are being given to allow centralized quality assurance with the resources from the 3D QA center. Dr. Hsu from UCSF intends to put forth a protocol using high dose rate brachytherapy in the management of prostate cancer. This will be discussed more fully in the GU strategy and Research Strategy sessions.

Quality assurance

Mr. Bill Harms submitted the 3D QA center activity report. They too have changed their name to the Image Guided Therapy Quality Assurance center (IGTQAC). Fifty-three institutions are currently credentialed for participation in prostate cancer trials, twenty-six in lung cancer trials, and twenty-nine in GBM trials. The oropharyngeal IMRT study, H022 has recently opened and four institutions are working on credentialing. A deficiency in the NOMOS Corvus treatment planning system was identified. In order to perform quality assurance, planning target volumes need to be displayed and this currently is not possible in the current version of Corvus. Dr. Purdy has discussed this with one of the software developers at NOMOS who feels that a correction to this can be forthcoming in the very near future.

Prostate brachytherapy currently is being reviewed at the Medical College of Wisconsin. As mentioned above when the next protocol is open it is hoped that a digital data exchange mechanism can allow centralized computer based review of plans.

Members interested in participating in radiosurgery, brachytherapy or 3D-CRT are urged to visit the RTOG website which lists significant information regarding requirements of participation for these studies. The Image Guided Therapy Quality Assurance Center is working to implement DICOM which will facilitate future institutional and vendor participation in imaged guided radiotherapy trials.

Clinical Studies

Dr. Graham presented the two lung cancer trials. RTOG 93-11 has been submitted for oral presentation at the 2001 ASTRO meeting. The objective of identifying maximally tolerated dose based upon acute toxicity has not yet been met. Despite this, it is planned to close this and open up the next trial L-0117. This is a dose intensification of radiation using increasing dose per fraction for a biologically more aggressive treatment.

Dr. Robert Cardinale presented BR-0023. This is a protocol using fractionated stereotactic radiation therapy in a boost delivered weekly during fractionated external beam radiation. QA will be performed by Dr. Michael Gillin at the Medical College of Wisconsin.

Dr. Nancy Lee from UCSF presented a concept for the treatment of nasopharyngeal carcinoma using IMRT. She was urged to submit her protocol to the Image Guided Therapy QA Center for their review and possible commentary.

Dr. Michalski presented RTOG 98-03 a phase I/II study using radiation dose escalation applying Conformal Radiation Therapy in Supratentorial Glioblastoma Multiforme. It recently completed its accrual to the second dose level. We will need to wait three to four months for maturation of toxicity before determining whether or not it is safe to open the third dose level period.

RTOG 94-06 was discussed briefly. This protocol was closed in October 2000. The third dose level has been analyzed and been presented as a poster at ASCO. It is to be presented for fall presentation at ASTRO.

H0022 for oropharyngeal cancer has opened and credentialing of institutions is underway.

P-O126 will be a randomized trial of high dose conformal radiation therapy versus standard dose conformal radiation therapy. The trial will evaluate patients with any intermediate risk prostate cancer. The dose prescription will be 82.28 Gy to the ICRU reference verses 72 Gy to the same point in the standard dose arm period. These numbers represent the central dose on the third dose level of RTOG 94-06. No hormonal therapy is planned for this trial period.

Dr. Donald Chapman from Fox Chase Cancer Center discussed briefly the results of a workshop held earlier this week on functional imaging. He specifically described the use of hypoxic imaging agents to identify areas of tumor ready resistance. This was followed by a brief discussion of PET imaging with FDG Glucose for tumor targeting by Dr. Wade Thorstad.

3D-CRT COMMITTEE (June, 2000)
Jeff Michalski, M.D., Chair

Mr. Bill Harms presented the 3D-QA Center activity report. There are now forty-one institutions approved to participate in RTOG 94-06, nineteen in 93-11 and fifteen in RTOG 98-03. As of June 2000, 941, 137 and 39 patients have been entered on each of these studies, respectively. Five commercial vendors currently provide software for RTOG 3D-QA data exchange. These vendors are Adac, Pinnacle, CMS Focus, Helax TMS, PTI Rendor Plan and Theratronics Theraplan PLUS. Four additional systems remain in the implementation-testing phase and they include Arts, Varian Cad Plan, Marconi Acqplan and Nomos Corvus. The QA Center has developed guidelines regarding quality assurance procedures for Intensity Module Radiation Therapy (IMRT) and permanent prostate brachytherapy. CMS Focus certainly provides a data exchange for prostate seed brachytherapy. Varian is working on the implementation of the data exchange for prostate brachytherapy. Prowess currently has no plans to implement data exchange.

Dr. Michalski updated the committee on the progress of RTOG 94-06. Dose level 5 has 61 patients registered. Patients on dose level 5 require PTV dose of 78 Gy. Enough follow up has elapsed on patients treated to the first two dose levels to allow an updated late toxicity analysis. This data has been submitted to ASTRO and will be presented in the fall at an oral presentation of ASTRO.

Dr. Graham talked about RTOG 93-11. The patients in the lowest risk group will soon complete accrual to the highest dose level. No unexpected toxicity has been identified in this group of patients. Patients in the intermediate dose level continue to accrue at the second dose level and it is expected that the third and highest dose level will be open in the near future.

Dr. Avraham Eisbruch presented RTOG 1065, which involves either 3D Conformal Radiation Therapy or IMRT for cancer of the oral pharynx. The final version of the protocol has been submitted to the NCI for approval. It is hoped that patient accrual will be begin within the next six months. In the meantime the QA Center is developing anatomical atlas for assistance in treatment planning as well a benchmark or dry run case to be downloaded by institutions wishing to be credentialed for participation in this trial.

Dr. Michalski presented the concept for a phase III randomized study of 3D-CRT in prostate cancer. RTOG developing 1077 protocol will randomize patients between receiving the maximum tolerated dose of radiation as defined by RTOG 94-06 versus a standard dose of 70 Gy also with 3D Conformal Radiation Therapy. Patients with intermediate risk prostate cancer will be used to complete this trial.

Dr. Christopher Crane presented a concept on the use of 3D Conformal Radiation Therapy in patients with resected carcinoma of the stomach. He was urged to develop objectives upon which a clinical trial can be built.

Dr. Graham presented her concept of dose escalation with concurrent chemotherapy for non-small cell lung cancer. This study will replace RTOG 93-11. The patients on this study will receive concurrent chemotherapy with one of two different regimens of Carboplatin and Taxol. Regimen A patients will receive daily infusions of chemotherapy where in Regimen B chemotherapy is every three weeks. An interesting aspect of this protocol involves decreasing over all treatment time by increasing the dose per fraction. Through the use of conformal radiation therapy normal tissue doses will be constrained while the dose at the target volume will be escalated in a biological fashion by increasing dose per fraction with decrease overall treatment time. The issue regarding the use of new adjuvant chemotherapy was raised and will be addressed by Dr. Graham. In addition, a representative from ACRIN is interested in acquiring follow up CT data in patients treated on this dose escalation trial.

The session closed with a didactic presentation by Dr. Jack Fowler. In this presentation he described the rationale for increased dose per fraction of overall treatment time as a method of dose escalation for patients with non-small cell lung cancer as described in the trial by Dr. Graham.
3D PROSTATE CONSORTIUM
Jeff Michalski, M.D., for James D. Cox, M.D., Chair

This special meeting was called by Dr. James Cox to discuss future directions of the 3D RTOG 94-06 dose escalation study using three dimensional conformal radiation therapies for prostate cancer. This study has nearly met its accrual for groups 1 & 2 patients at all three planned dose levels. Patients in group 3 (stage C) continue to accrue at the second dose level of 73.8 Gy. Accrual has been slow to this group since the opening of the study and this rate has not changed appreciable over the past year.

Because new publications suggest an advantage to adjuvant hormone therapy in this high risk group, discussion was held regarding the possible continuance of hormone therapy for patients on this study. As this study has already been amended to allow neoadjuvant hormonal therapy, it was felt appropriate to make a formal amendment to allow continuance of hormones on RTOG 94-06. These data are already being collected so that appropriate subgroup analyses can be made if necessary.

A long discussion was held regarding adding a fourth dose level to this study in anticipation that no chronic toxicity would be identified even at the 79.2 Gy level. Dr. Perez and others felt that ten weeks of radiation therapy was a significant financial burden and time commitment that make the study unacceptable for many patients. An 84.6 Gy dose level (three additional fractions at 1.8 Gy) would require 47 treatment visits. Because many institutions treat patients at 2 Gy per day fractions, it was felt reasonable to consider a new arm with this dose per fraction. With biologically equivalent dose models, it was calculated that 74 Gy at 2 Gy per day provided an equivalent dose roughly intermediate to that of 73.8 Gy and 79.2 Gy at 1.8 Gy fractions. Because this dose intermediate level did not require 18 month follow up information from the recently closed 79.2 Gy level, this arm could start accrual as soon as the statistical section was amended. The possibility of adding this dose arm will be discussed with Drs. Cox, Curran and Pajak. Once accrual and follow up at each of these dose levels is complete, a decision regarding further dose escalation could be made in the future using either 1.8 Gy or 2 Gy per day fractions.

Limiting the dose to the rectum at this opposed 74 Gy dose level was felt to be important. Just as in the 79.2 Gy level it was felt to be appropriate to restrict the dose to the PTV to 72 Gy while prescribing a GTV dose of at least 74 Gy. Patients in group two who require “conedown” of treatment volume will have that take place at 54 Gy to spare the seminal vesicles. The suggested amendments may change how the prescription dose is reported and also the amount of heterogeneity that is allowed on this protocol. Recommendations regarding the dose prescription issues will be written up by Dr. Purdy and circulated among the 3DOG RTOG members.