RTOG/ASCO Booklet [PDF]

Reference	Study Number
J. Bourhis, C. Amand and J.-P. Pignon: Update of MACH-NC (Meta-Analysis of Chemotherapy In Head & Neck Cancer ) Database Focused on Concomitant Chemotherapy. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):488, 2004.	9111
G. Cairncross, W. Seiferheld, E. Shaw, R. Jenkins, B. Scheithauer, D. Brachman, J. Buckner, K. Fink, L. Souhami and W. Curran Jr: An Intergroup Randomized Controlled Clinical Trial (RCT) of Chemotherapy plus Radiation (RT) versus RT alone for Pure and Mixed Anaplastic Oligodendrogliomas: Initial Report of RTOG 94-02. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):107, 2004.	9402
A. Chakravarti, W. Seiferheld, H. Robins, A. Guha, D. Brachman, W. Curran Jr, A. Choucair and M. Mehta: An Update of Phase I Data from RTOG 0211: A Phase I/II Clinical Study of Gefitinib + Radiation for Newly-Diagnosed Glioblastoma (GBM) Patients. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):124, 2004.	0211
A. Choucair, W. Seiferheld, C. Ford, J. Hansen, B. Dabbas, C. Schultz, A. Schulsinger, M. Mehta and W. Curran Jr: Long Term Survivors with Glioblastoma Multiforme (GBM) Treated on RTOG Protocols with Irradiation and Nitrosurea Have Higher Initial Expression of Ki-67. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):871, 2004.	multi
C. Ford, W. Seiferheld, A. Choucair, J. Hansen, B. Dabbas, C. Schultz, A. Schulsinger, M. Mehta and W. Curran Jr: Evaluation of Expression of DNA Repair Molecules as a Prognostic Factor for Long-Term Survivors with Glioblastoma Multiforme (GBM) Treated on RTOG Protocols with Irradiation and Nitrosoureas. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):109, 2004.	multi
A. Konski, T. Pajak, B. Movsas, J. Coyne, J. Harris, C. Gwede, A. Garden, S. Spencer, C. Jones and D. Watkins Bruner: Socio-Demographic Variables Influence Outcome in Radiation Therapy Oncology Group Head and Neck Trials. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):527, 2004.	9003,9111,9703
P. Kumar, J. Harris, A. Garden, K. Fu, K. T. Robbins, T. Pajak and K. K. Ang: Outcome Comparisons of Four Radiation Therapy Oncology Group (RTOG) Trials in Patients with Stage IV-T4 Head and Neck (H/N) Cancer: Encouraging Results Using Intra-Arterial (IA) Cisplatin (P) and Radiation Therapy (RT). Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):493, 2004.	multi
R. R. Kuske, K. Winter, D. Arthur, J. S. Bolton, R. Rabinovitch, J. White, W. Hanson and R. M. Wilenzick: A Phase II Trial of Brachytherapy Alone Following Lumpectomy for Stage I or II Breast Cancer: Initial Outcomes of RTOG 95-17. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):18, 2004.	9517
C. Langer, J. Harris, E. Horwitz, N. Nicolaou, M. Kies, W. Curran Jr, S. Wong and K. K. Ang: Phase II Trial Of Concurrent Split Course Hyperfractionated Radiotherapy (Hfx RT), Cisplatin (DDP) and Paclitaxel (P) in Patients with Recurrent, Previously Irradiated Squamous Cell Carcinoma of the Head and Neck (SCCHN): Results of RTOG 9911. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):488, 2004.	9911
W. Lee, M. DeSilvio, C. Lawton, M. Gillin, G. Morton, S. Firat, M. Baikadi, M. Kuettel, K. Greven and H. Sandler: A Phase II Study of External Beam Radiation Therapy Combined With Permanent Source Brachytherapy for Intermediate Risk Clinically Localized Adenocarcinoma of the Prostate: Preliminary Results of RTOG P-0019. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):397, 2004.	0019
E. Mitchell, K. Winter, M. Mohiuddin, N. Hanna, A. Yuen, C. Nicholas, R. Share, C. Hayostek and C. Willet: Randomized Phase II Trial of Preoperative Combined Modality Chemoradiation For Distal Rectal Cancer. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):254, 2004.	0012
H. Robins, M. Won, C. Schultz, A. Choucair, D. Brachman, W. Demas and M. Mehta: A Phase II Trial of Conventional Radiation Therapy (XRT) Plus High Dose Tamoxifen (TAM) for the Treatment of Supratentorial Glioblastoma Multiforme (GBM): RTOG Protocol BR-0021. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):114, 2004.	0021
G. Strauss, J. E. Herndon II, M. Maddaus, D. Johnstone, E. Johnson, D. Watson, D. Sugarbaker, R. Schilsky and M. Green: Randomized Clinical Trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in Stage IB Non-Small Cell Lung Cancer (NSCLC): Report of Cancer and Leukemia Group B (CALGB) Protocol 9633. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):2004.	9616

J. Bourhis, C. Amand and J.-P. Pignon: Update of MACH-NC (Meta-Analysis of Chemotherapy In Head & Neck Cancer ) Database Focused on Concomitant Chemotherapy. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):488, 2004.   Study Number 9111 Background: The MACH-NC Group have previously shown (Lancet; 2000) that chemotherapy (CT) improved survival (4% at 5 years) in non metastatic head and neck squamous cell carcinoma (HNSCC) treated by loco-regional treatment (LRT), with an higher benefit (8%) with CT concomitant to radiotherapy (RT). However the relatively important heterogeneity of the results limited the conclusions and prompted the MACH-NC to further confirm the results, by adding to the data base the data from the randomized trials performed between 1994 and 2000. Methods: Updated individual data from HNSCC patients randomized to LRT versus LRT + CT between 1965 and 2000 were included in this meta-analysis. The logrank-test, stratified by trial, was used for comparison and the hazard ratio (HR) of death was calculated. Results: 24 new trials, most of them on concomitant CT, were included totalizing 87 trials and more than 16,000 patients. The overall pooled HR was 0.88 (p<.0001) with an absolute benefit for CT of 5% at 5-years, and a significant interaction (p<.0001) between CT timing (adjuvant, neoadjuvant or concomitant) and treatment. The following analyses concern only the 50 concomitant trials. For this group, the HR was 0.81 (p<.0001) with an absolute benefit of 8% at 5-years. The results were identical for the 1994-2000 trials and the 1965-1993 trials, but without significant heterogeneity in the recent group. Similar results were obtained in the trials with postoperative RT (HR=0.80), conventional RT (0.83) and altered fractionated RT (0.73). No significant difference was seen between mono-CT (0.84) and poly-CT (0.77). The magnitude of the benefit was higher (p<0.01) for platinum-based CT (0.75) than for other CT (0.86). There was a decreasing effect of CT with age (p=.01). Conclusions: The benefit of concomitant chemotherapy was confirmed and was similar with both definitive and postoperative radiotherapy. The final analysis will be presented at the meeting. Unrestricted grants from ARC, Aventis, PHRC.

G. Cairncross, W. Seiferheld, E. Shaw, R. Jenkins, B. Scheithauer, D. Brachman, J. Buckner, K. Fink, L. Souhami and W. Curran Jr: An Intergroup Randomized Controlled Clinical Trial (RCT) of Chemotherapy plus Radiation (RT) versus RT alone for Pure and Mixed Anaplastic Oligodendrogliomas: Initial Report of RTOG 94-02. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):107, 2004. Study Number 9402 Background: Anaplastic oligodendrogliomas (AOs) and anaplastic oligoastrocytomas (AOAs) are treated with surgery and RT at diagnosis. They also respond to procarbazine, lomustine and vincristine (PCV), raising the possibility that PCV plus RT at diagnosis may improve outcome. Furthermore for AOs, response to PCV and long survival have been associated with 1p and 19q allelic loss. Methods: A RCT was conducted to test whether dose-intense, pre-RT PCV prolongs overall survival (primary endpoint) or progression-free survival (secondary endpoint) versus RT alone. Serious toxicity rates and quality of life were other endpoints. Patients with AOs or AOAs confirmed by central review, who were age >=18 years, had a Karnofsky score (KPS) >=60 and consented, were study-eligible. Tumor sections and peripheral blood were also collected. Results: 291 eligible patients were randomized; 60% were male, 68% were < age 50, 88% had a resection, 90% had a KPS >=80 and 70% had an AO. 148 patients had PCV plus RT and 143 had RT alone; the arms were balanced for prognostic factors. Median survivals were similar for both groups; 4.8 years for PCV plus RT and 4.5 years for RT (HR 1.04, 95% CI 0.74-1.45; p=0.830). Progression-free survival tended to be longer after combined treatment; 2.6 years for PCV plus RT versus 1.9 years for RT (HR 1.34, 95% CI 1.00-1.80; p=0.053). During PCV, 95 patients had grade 3 or 4 toxicity and one died. Grade 3 and 4 RT toxicities were infrequent in both groups. Tissues were available on 206 tumors; 92 (46%) had 1p and 19q loss. Irrespective of treatment, patients whose tumors lacked 1p and 19q lived longer than other patients; median survival not reached versus 2.8 years (HR 0.31, 95% CI 0.20-0.48; p<0.001). Longer follow-up is needed to ascertain treatment-specific outcomes for cases with 1p and 19q loss. Conclusions: Pre-RT PCV does not impart a survival advantage for histologically-defined AOs and AOAs, but may prolong progression-free survival at the expense of greater acute toxicity. As reported, 1p and 19q loss is a powerful prognostic marker in oligodendroglial tumors.

A. Chakravarti, W. Seiferheld, H. Robins, A. Guha, D. Brachman, W. Curran Jr, A. Choucair and M. Mehta: An Update of Phase I Data from RTOG 0211: A Phase I/II Clinical Study of Gefitinib + Radiation for Newly-Diagnosed Glioblastoma (GBM) Patients. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):124, 2004.   Study Number 0211 Background: The Radiation Therapy Oncology Group (RTOG) initiated a Phase I/II clinical study of the EGFR tyrosine kinase inhibitor, Gefitinib, in combination with radiation for newly diagnosed GBM patients. This report is an update of Phase I toxicity data. Methods: Patients entered on RTOG 0211 were stratified into two groups based on whether they were on enzyme-inducing anticonvulsant drugs (EIACDs:Group I) or not (non-EIACDs: Group II). The planned Gefitinib dose escalation during radiation was from 250 to 750mg in Group I and 250 to 500mg in Group II in 250 mg increments. A standard 3+3 design was used to evaluate dose-limiting toxicities (DLTs), which were defined as designated acute (<90 days) toxicity events. Results: A total of 18 patients in Group I (16 eligible and analyzable) and 13 patients in Group II (12 eligible and analyzable) were included in this update. In Group I, no DLTs were observed up to 750 mg. One subject in Group I had late (>90 days) Grade 3 elevation of SGOT. In Group II, one subject experienced a Grade 3 elevation of SGOT at the 250 mg dose level within 90 days. At the 500 mg dose level in Group II, one patient had late Grade 3 elevation of SGOT and one patient had acute Grade 4 elevation of SGOT. Other observed side-effects (e.g. fatigue, skin rash, headaches, seizures) did not fit the definition of DLTs or were deemed to be unrelated to Iressa. Conclusions: Gefitinib in combination with radiation appears to be well-tolerated in GBM patients at the dose levels examined. Further dose escalation is being planned for Group I, given the favorable side-effect profile in EIACD patients in this, as well as previously reported studies in the setting of recurrent disease. For non-EIACD patients, the Phase II component of the study has been initiated at the 500 mg dose level.

A. Choucair, W. Seiferheld, C. Ford, J. Hansen, B. Dabbas, C. Schultz, A. Schulsinger, M. Mehta and W. Curran Jr: Long Term Survivors with Glioblastoma Multiforme (GBM) Treated on RTOG Protocols with Irradiation and Nitrosurea Have Higher Initial Expression of Ki-67. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):871, 2004. Study Number multi Background: Ki-67 is a nuclear antigen that is upregulated during cellular proliferation. Ki-67 expression has been both positively and negatively associated with survival in a number of tumor primaries. Similarly, in patients with GBM, prior studies of the prognostic value of initial Ki-67 expression for overall survival have reported conflicting results with some suggesting a positive, others a negative, and others no correlation. Methods: In this study we compared the nuclear expression of Ki-67 using Mib-1 antibody between 28 long term (>18 months) and 35 short term (< 6 months) GBM survivors receiving irradiation and BCNU who were selected from RTOG Tissue Bank and who met the following criteria: eligibility requirements for the RTOG study on which they were enrolled, received the BCNU arm, and had survival <6 months or >18 months. Tumor cell expression was quantitated by performing immunohistochemistry on tumor array slides with determination of positively staining cells by use of the Chromovision automated cell imaging system. Results: % GBM cells + for Ki-67   Min. Max. Mean p(univariate) *p(multivariate) Short term survivors 0 29 6.1 0.007 0.016 Long term survivors 1 58 15.5 *Multivariate logistic regression with Ki-67, age, KPS and extent of resection. Conclusions: In this patient population, long term GBM survivors have a higher percentage of tumor cells expressing Ki-67. This suggests that further investigation of factors that are altered during the cell cycle may be of value in identifying prognostic factors for long term GBM survivors.

C. Ford, W. Seiferheld, A. Choucair, J. Hansen, B. Dabbas, C. Schultz, A. Schulsinger, M. Mehta and W. Curran Jr: Evaluation of Expression of DNA Repair Molecules as a Prognostic Factor for Long-Term Survivors with Glioblastoma Multiforme (GBM) Treated on RTOG Protocols with Irradiation and Nitrosoureas. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):109, 2004. Study Number multi Background: Adding BCNU to irradiation appears to modestly increase one and two year survival in GBM patients. BCNU attaches a chloroethyl adduct to the O6 position of guanine followed by formation of a DNA interstrand cross-link. These lesions may be repaired by alkyl-guanine transferase (AGT) and nucleotide excision repair (NER)/homologous recombinational repair (HRR) pathways, respectively. BCNU-initiated apoptosis signaling depends on intact DNA mismatch repair (MMR). Defects in MMR and intact NER/HRR and p53 expression may be linked to BCNU insensitivity. We hypothesized that these may also be prognostic factors in GBM. Methods: We compared the expression of AGT, ERCC1 (involved in the DNA nicking step of NER/HRR), the MMR proteins hMLH1 and hMSH2, and p53 between tumor samples, selected from the RTOG tissue bank, from 28 long term (>18 months) and 35 short term (< 6 months) GBM survivors receiving irradiation and nitrosoureas on RTOG protocols. Tumor cell nuclear expression was determined by immunohistochemistry using the Chromovision automated cell imaging system. Results: The two groups vary in age (p=0.003) and KPS (p=0.02) but not extent of resection (p=0.12). Factor Short Term Long Term p= (univariate) p=(multivariate)** AGT 10.2* 14.1 0.21 0.30 ERCC1 64.0 60.3 0.54 0.26 P53 31.0 33.6 0.68 0.42 hMLH1 40.2 49.8 0.16 0.85 Low AGT (< med) 29.9 45.1 0.18 0.46 hMSH2 17.0 19.4 0.48 0.88 Low AGT(< med) 9.3 14.6 0.19 0.49 *Mean % positive cells **Multivariate logistic regression analysis with factor, age, KPS, extent of resection. Conclusions: Within this patient population the levels of the DNA repair molecules examined do not predict for long term survivorship. No interaction between MMR and AGT was observed. Larger future studies should examine the expression of these and additional factors involved in the repair of nitrosourea induced DNA adducts.

A. Konski, T. Pajak, B. Movsas, J. Coyne, J. Harris, C. Gwede, A. Garden, S. Spencer, C. Jones and D. Watkins Bruner: Socio-Demographic Variables Influence Outcome in Radiation Therapy Oncology Group Head and Neck Trials. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):527, 2004.   Study Number 9003,9111,9703 Background: The specific aim of this study was to evaluate the influence of socio-demographic factors on local-regional (LR) control and survival of patients treated on RTOG head and neck cancer clinical trials. Methods: Patients treated on RTOG 9003, RTOG 9111 and RTOG 9703 were utilized. The model was stratified by protocol and a step-up procedure using a 0.05 significance level was initially used to build the model. The model was used to determine if any tumor or socio-demographic variables (age, gender, race, Karnofsky Performance Status (KPS), T-stage, N-stage, marital status, number of persons in household, education level, household income prior to cancer diagnosis, and tobacco use) are independent prognostic variables for LR control and/or survival. Results: A total of 1901 patients were entered onto the 3 RTOG trials of which 1822 were analyzable. Fifty-nine percent of the analyzable patients were from 9003, 28% from 9111 and 13% from 9703. In multivariate analyses T and N-Stage, and KPS were significant for both survival and LR control. Variables found to have prognostic value independent of disease related variables were gender, age, marital status and income for survival and marital status and race for LR control. A significant interaction between marital status and gender existed for both endpoints. Male patients currently married or a live-in partner, did significantly better than the other male patients, while no such effect was seen in the female patients. Tobacco use at protocol entry was evaluated in the multivariate model with only RTOG 9003 and 9111, and was significant for both endpoints. Conclusion: The socio-demographic variables race and marital status were found to have independent prognostic value for predicting LR control. Income and marital status were found to have independent prognostic value for predicting survival. These variables may identify patients requiring additional support and early interventions during the course of treatment to improve outcome.

P. Kumar, J. Harris, A. Garden, K. Fu, K. T. Robbins, T. Pajak and K. K. Ang: Outcome Comparisons of Four Radiation Therapy Oncology Group (RTOG) Trials in Patients with Stage IV-T4 Head and Neck (H/N) Cancer: Encouraging Results Using Intra-Arterial (IA) Cisplatin (P) and Radiation Therapy (RT). Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):493, 2004. Study Number multi Background: We conducted a comparison of overall survival (OS) and local-regional tumor control (LC) outcomes in patients with stage IV-T4 disease originating from the oral cavity, oropharynx or hypopharynx among 4 RTOG H/N trials using RT +/- chemotherapy. Methods: The four compared RTOG trials and their treatment regimens were as follows: 1. RTOG 8117-- standard fractionated (SFX) RT [66 - 73.8 Gy] & 3 cycles of concurrent IV P (100 mg/m2); 2. RTOG 9003 -- SFX RT (70 Gy in 7 weeks) alone [Arm 1], & accelerated fractionated (fx) RT with concomitant boost (AFX-C) [72 Gy in 42 fxs over 6 weeks] [Arm 4]; 3. RTOG 9703-- concurrent SFX RT (70 Gy/7 weeks in arms 1 and 3, and q other week over 13 weeks in arm 2] with IV daily P (10 mg/m2) / 5-FU (400 mg/m2 d/ CI last 2 wks of RT) [Arm 1], q other week of IV 5-FU (800 mg/m2/d x 5 days) / Hydroxyurea (1 gm po bid x 6 days) [Arm 2}, or weekly IV P (20 mg/m2) / Taxol (30 mg/m2) [Arm 3]; & 4. RTOG 9615 -- intra-arterial (IA) weekly P (100 mg/m2) x 4 weeks with SFX RT (70 Gy/7 weeks) [RADPLAT therapy]. Results: The estimated 2 year LC rates & OS are noted in Table 1. Using a Cox proportional hazards model stratified by RPA class, RADPLAT therapy reduced death rates by > 50% when compared with Protocols 9003 & 8117, and by 21% when compared to arm 1 of Protocol 9703; there was virtually no reduction in death rates when compared with arms 2 & 3 of Protocol 9703 (0.8% and 1.8%, respectively). Conclusions: RADPLAT therapy improves LC and OS when compared to RT alone (SFX or concomitant boost) and improves OS when compared to IV cisplatin and SFX RT. Additionally, LC and OS using RADPLAT therapy appear comparable to contemporary chemoradiation regimens. Further testing in a phase III randomized trial comparing RADPLAT therapy to IV chemotherapy and RT is warranted to validate our findings. TABLE 1. Comparison of Outcome of 4 RTOG Trials In Patients with Stage IV-T4 Head and Neck Cancer Protocol Regimen 2-Yr. LC (%) 2-Yr. OS (%)         8117 IV P + SFX Not Available 35.3 9615 IA P + SFX 53.9 58.8 9003-Arm 1 SFX 25.3 18.2 9003-Arm 4 AFX-C 34.8 29.5 9703-Arm 1 IV P/5-FU + SFX 43.1 47.9 9703-Arm 2 IV 5-FU/HU + SFX 50.0 52.0 9703-Arm 3 IV P/Taxol + SFX 53.5 56.0

R. R. Kuske, K. Winter, D. Arthur, J. S. Bolton, R. Rabinovitch, J. White, W. Hanson and R. M. Wilenzick: A Phase II Trial of Brachytherapy Alone Following Lumpectomy for Stage I or II Breast Cancer: Initial Outcomes of RTOG 95-17. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):18, 2004.   Study Number 9517 Background: In order to shorten the conventional 6-7 week radiation treatment time, and to treat only tissue at greatest risk for recurrence, this phase II trial evaluates partial breast irradiation with 4-5 days of interstitial brachytherapy as an alternative to external beam. Methods: Eligibility criteria included patients (pts) with invasive <= 3cm non-lobular carcinoma, 0-3 positive axillary nodes with no extracapsular extension and at least 6 nodes removed, negative surgical margins, no residual suspicious microcalcifications, no extensive intraductal component, and no collagen vascular disease. After lumpectomy and axillary dissection, pts were treated with either high (34 Gy in 10 fractions over 5 days) or low (45 Gy in 3.5-5 days) dose rate (HDR or LDR) brachytherapy. Treatment volume was the lumpectomy cavity plus 2cm, except where limited by chest wall or skin. Systemic therapy was given after brachytherapy at physician discretion. Endpoints included local and regional control, disease-free (DFS) and overall survival (OS). Results: One hundred pts were enrolled and one was ineligible because only a sentinel node was removed. Median follow-up is 3.7 years, range 0.6-5.7. Eighty-seven pts had T1 and 12 had T2 tumors. Seventy-nine were pathologically N0 and 20 were N1. The actuarial 4-year breast and nodal recurrence rate is 3% (3 pts, all HDR, T1N0 x2 and T1N1) and 3% (2 pts, both HDR, T1N0 x2), respectively. Distant metastasis occurred in 6 pts, 3 T1N0 and 3 T2N1, for an actuarial 4-year rate of 6%, HDR 8% and LDR 4%. DFS and OS were 85% and 93% at 4 years, (82% and 95% HDR, 90% and 90% LDR). Contralateral breast cancer developed in 3 pts, 1 HDR and 2 LDR. Six pts had non-breast second primaries, 4 HDR and 2 LDR. Conclusions: We conclude that partial breast brachytherapy on this RTOG trial yields excellent tumor control at this early analysis (<1% local failure per year), warranting support for a future phase III trial.

C. Langer, J. Harris, E. Horwitz, N. Nicolaou, M. Kies, W. Curran Jr, S. Wong and K. K. Ang: Phase II Trial Of Concurrent Split Course Hyperfractionated Radiotherapy (Hfx RT), Cisplatin (DDP) and Paclitaxel (P) in Patients with Recurrent, Previously Irradiated Squamous Cell Carcinoma of the Head and Neck (SCCHN): Results of RTOG 9911. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):488, 2004. Study Number 9911 Background: Recurrent SCCHN, if not curable by surgery or RT, is almost always fatal. Chemotherapy (CTx) alone (eg. DDP, 5FU) yields median survival times (MST) of 8-10 mos and 1 yr survival (OS) of < 35% at best. For limited relapse or patients (pts) with new unresectable SCCHN within previous RT portals, a potential role for re-irradiation combined with radiosensitizing CTx, exists. In a prior phase I trial of HFx RT/ DDP/ P, we observed >= 2 yr disease-free survival in 5 of 31 pts (ASCO 1999, A-1551), and therefore exported this regimen to RTOG for broader assessment. Methods: Eligibility stipulated recurrent SCCHN or second 1° tumors (SPT) in a previous RT field; measurable tumor; >= 75% of tumor volume previously treated to 45 Gy-75 Gy; >= 6 mos elapsed from prior RT, ECOG PS 0-1; ANC >=1500, plts >= 100K, bili < 1.5 mg/dl, creat < 1.5 mg/dl, and absence of distant mets. Pts received HFx RT (1.5 Gy/Fx BID x 5d every 2 wks x 4), in combination with DDP 15 mg/m2 IV QD x 5 and P 20 mg/m2 IV QD x 5 q 2 wks x 4. G-CSF was given days 6 through 13 of each 2 wk cycle. Results: 105 pts were entered between 3/00 and 6/03. We analyzed the first 60 eligible pts (min potential F/U of 1 yr): median age 59; 77% male; 60% PS 1. 22% had SPTs. Oropharynx (37%) and oral cavity (32%) were the predominant 1° sites. Median prior RT dose was 65.4 Gy (range, 45-73 Gy). 77% of pts received all 4 scheduled cycles of chemo. Gr ³ 4 acute toxicity (tox) occurred in 30%, Gr >= 4 acute heme tox in 27%. There were 4 fatal (Gr 5) toxicities: 2 in the acute period (dehydration, pneumonitis) and 2 late (carotid hemorrhage). In the full cohort of 105 pts, 7 Tx-related deaths (7%) occurred. At a median follow-up of 26.1 mos, MST is 13 mos with est. 1- and 2-yr OS rates of 53.2% (CI: 40.6, 65.9) and 27.5% (CI: 16.1, 38.9). Conclusion: Despite a fairly high inc. of Gr 5 tox, 1 and 2yr OS rates for split course HFxRT/DDP/P exceed results generally seen with chemotherapy alone. A phase III trial directly comparing CTx alone to concurrent CTx and re-irradiation is warranted.

W. Lee, M. DeSilvio, C. Lawton, M. Gillin, G. Morton, S. Firat, M. Baikadi, M. Kuettel, K. Greven and H. Sandler: A Phase II Study of External Beam Radiation Therapy Combined With Permanent Source Brachytherapy for Intermediate Risk Clinically Localized Adenocarcinoma of the Prostate: Preliminary Results of RTOG P-0019. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):397, 2004. Study Number 0019 Background: External beam radiation therapy is commonly combined with permanent source brachytherapy in the treatment of prostate cancer. The primary objective of this study is to estimate the rate of acute- and late-grade 3-5 genitourinary and gastrointestinal toxicity following treatment with external beam radiation therapy and permanent source brachytherapy in a multi-institutional, cooperative group setting. Methods: Between January 2001 and November 2001, 138 patients from 20 institutions were entered on this study. Acute toxicity information is available in 131 patients, and 127 patients are analyzable for late toxicity. All patients were treated with external beam radiation therapy (45 Gy/25 fractions) followed 2-6 weeks later by an interstitial implant using I-125 to deliver an additional 108 Gy. The median followup is 20 months. Median pretreatment PSA = 7.5. Results: The most commonly reported acute toxicity is urinary frequency and dysuria. Acute Grade 3 toxicity was documented in 10/131 (7.6%) patients. No Grade 4-5 acute toxicity has been observed. Late Grade 3 toxicity has been observed in six men (5 urinary, 1 bowel). The 18-month month estimate of late Grade 3 GU/GI toxicity is 3.3% (95% CI 0.1-6.5). No late Grade 4-5 toxicity has been observed. In the sixty-one men that reported no impotence at baseline and received no androgen deprivation, the 18-month rate of Grade 2-3 impotence is 45.5% (95% CI 32.6-58.5%). Conclusions: The acute and late morbidity observed in this multi-institutional, cooperative group study is consistent with previous reports from single institutions with significant prostate brachytherapy experience. The combination of external beam radiation therapy and permanent source brachytherapy is worthy of further study and is currently under evaluation in RTOG 0232, a phase III trial that compares permanent source brachytherapy as monotherapy to the combination of external beam treatment followed by brachytherapy.

E. Mitchell, K. Winter, M. Mohiuddin, N. Hanna, A. Yuen, C. Nicholas, R. Share, C. Hayostek and C. Willet: Randomized Phase II Trial of Preoperative Combined Modality Chemoradiation For Distal Rectal Cancer. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):254, 2004.   Study Number 0012 Background: Potential advantages of preoperative radiotherapy (RT) include increased resectability, sphincter preservation, local control, and overall survival. This randomized phase II study was designed to evaluate, pathologic complete response(pCR) to preoperative combined-modality chemotherapy with 5-fluorouracil (5FU) and RT, or with 5FU, irinotecan (I) and RT in patients with adenocarcinoma of the rectum. Methods: Patients with T3/T4 tumors located 0-9 cm from the dentate line, without distant metastases or extension to the anal canal, were stratified according to clinical staging and were randomized to receive :Arm 1 [(5FU/RT)-CVI 5-FU (225 mg/m²/d, 7 d/wk) + pelvic RT 45.6 Gy (1.23 Gy/bid, >=6-hour interval) + boost to tumor (9.6 Gy for T3 and 14.4 Gy for fixed T4)]; orArm 2 [(5FU/RT/I -CVI 5-FU (225 mg/m²/d, M-F,) +I(50 mg/m² once weekly x 4)+ pelvic RT 45 Gy (1.8 Gy/d) + boost to tumor (5.4 Gy for T3 and 9 Gy for fixed T4)]. Surgery was performed 4-10 weeks following completion of therapy. Primary endpoint was pCR, with an expected rate of >=20%. Secondary endpoints included acute and late normal tissue morbidity, patterns of failure, and complete resection rates. Results: 106 patients were enrolled (52 in Arm 1 and 54 in Arm 2); 3 were ineligible or never received protocol therapy, and 103 underwent surgery and were evaluable. Patient characteristics for Arm 1 and Arm 2, respectively, were: median age 56 and 59 years; 84% and 85% Caucasian; 70% and 83% Zubrod score 0; 68% and 75% stage T3; and 54% and 55% N0. Grades 3 and 4 acute hematologic and non hematologic toxicities occurred in 13% and 38%, respectively, in Arm 1 and 12% and 45% in Arm 2. Conclusions: Both regimens were well tolerated with acceptable grade 3/4 toxicities. The pathologic complete response rates of 30% with 5FU/RT and 26% with 5FU/RT/I were higher than in previous reports. Further study of these regimens should be considered.

H. Robins, M. Won, C. Schultz, A. Choucair, D. Brachman, W. Demas and M. Mehta: A Phase II Trial of Conventional Radiation Therapy (XRT) Plus High Dose Tamoxifen (TAM) for the Treatment of Supratentorial Glioblastoma Multiforme (GBM): RTOG Protocol BR-0021. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):114, 2004.   Study Number 0021 Background: Preclinical studies support the concept that inhibition of protein kinase C (PKC) by TAM should provide both anti-neoplastic effects and radiosensitization. Methods: High dose TAM (80 mg/m2 PO daily in divided doses) was given with and after conventional XRT to inhibit PKC mediated signaling, which is known to be enhanced in GBM. Patients (n=77) were accrued between 12/00-12/01; 75 patients were analyzable. Pretreatment characteristics included: 52%<60 years of age; 39% had a Zubrod score of 0, 70% had minor or no neurological symptoms; 65% were RTOG -recursive partition analysis (RPA) class III & IV. Results: A sample of 46 patients was reviewed for TAM delivery; 78% achieved acceptable dosing. Notable toxicity included: Late radiation Grade (G) G3 =2; Thrombo-embolic disease G2=2, G3=8, G4=3, G5=1 for an incidence of 18.7%, (which is lower than expected, based on the literature for DVT in GBM patients not receiving TAM). Median survival time (MST) was 9.7 months (M). This result was compared (using 3 different statistical methodologies) to the historical GBM control database of 1443 drug / XRT treated patients RPA class III, IV, & V. After controlling for RPA class IV, the MST was 11.3M, which compares to the historical RPA control of 11.2 M (p=0.38). Conclusions/Discussion: 1) The results obtained do not exhibit a substantial advance over previous studies with various XRT/drug doublets including BCNU. As TAM does not have significant overlapping toxicities with most other drugs, its testing in a combined modality approach with other medications may be justified in future clinical trails. 2) Historically the incidence of thrombo-embolic events in GBM patients is ~30%. The lower than expected incidence seen here has also been observed in other high dose TAM GBM studies. We speculate that TAM inhibited the PKC mediated phosphorylation of coagulation factors.

G. Strauss, J. E. Herndon II, M. Maddaus, D. Johnstone, E. Johnson, D. Watson, D. Sugarbaker, R. Schilsky and M. Green: Randomized Clinical Trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in Stage IB Non-Small Cell Lung Cancer (NSCLC): Report of Cancer and Leukemia Group B (CALGB) Protocol 9633. Submitted to Proc Am Soc Clin Oncol (ASCO), J Clin Oncol [23] (June 5-8, 2004):2004. Study Number 9616 Background: The value of adjuvant chemotherapy (CT) in resectable lung cancer is uncertain. The International Adjuvant Lung Trial (IALT) reported a modest but statistically significant survival advantage with cisplatin-based adjuvant CT in stage IA to III NSCLC. However, Adjuvant Lung Project Italy (ALPI ) failed to demonstrate a survival advantage for adjuvant CT. CALGB 9633 was designed to test adjuvant CT in T2N0M0, stage IB NSCLC. NCCTG and RTOG also participated. Methods: Within 4-8 wks of resection, patients were randomized to adjuvant CT with paclitaxel 200 mg/m2 /3 hrs and carboplatin AUC 6 day 1 every 3 wks for 4 cycles, or to observation. Eligibility requirements: age >18 yrs, histologically documented NSCLC, T2 primary lesion, lobectomy or pneumonectomy, absence of N1 or N2 nodes at surgery and/or mediastinoscopy. Results: Between 9/15/96 and 11/26/03, 344 patients were randomized. Median age-61 yrs (range 38-78 yrs); median follow-up-31 months; male-64%. Groups were well balanced with regard to age, gender, race, ethnicity, histology, tumor differentiation, and resection type. 79% underwent mediastinoscopy prior to resection. Lobectomy was performed in 89%, and pneumonectomy in 11%. Adjuvant CT was well tolerated with no CT-related toxic deaths. Grade III or IV neutropenia occurred in 51%. At a planned interim analysis in 11/03, the Data and Safety Monitoring Board found that the p-value for the log-rank test of survival was less than the prespecified stopping boundary for a positive impact on survival and recommended accrual suspension/study closure. Conclusions: This planned but still preliminary interim analysis indicates that adjuvant CT with paclitaxel and carboplatin significantly improves survival following resection of stage IB NSCLC. A full report will be available at the ASCO meeting in 6/04. Letters informing participating patients and physicians about these findings are being disseminated.