October 3-7, 2004 (Atlanta, GA)
(Accepted as: 2-plenary, 9-oral, 4-poster disc, 2-general poster)

ASTRO 2004 Booklet [PDF]

Pub #

Reference

Study #

Status/Type

2714/pending	Lawton, C. , DeSilvio, M., Lee, W., Gomella, D., Grignon, D., Gillin, M., Morton, G., Pisansky, T. and Sandler, H.: Results of a Prospective Multi-Institutional Phase II Trial (RTOG 98-05) of Transrectal Ultrasound Guided Permanent Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S184-185, Abs. #90, 2004.	9805	acc (oral pres)
2768/pending	Shaw, E., Seiferheld, W., Cairncross, G., Jenkins, R., Scheithauer, B., Brachman, D., Buckner, J., Fink, K., Souhami, L. and Curran Jr, W.: Radiation Therapy (RT) Alone vs Intensive Procarbazine-CCNU-Vincristine (I-PCV) Chemotherapy Followed by Radiation Therapy for Anaplastic Oligodendroglioma (AO) and Mixed Oligo-Astrocytoma (MOA): Results of Radiation Therapy Oncology Group (RTOG) - Intergroup Protocol 94-02. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S163, Abs. #57, 2004.	9402	acc (oral pres)
2769/pending	Werner-Wasik, Seiferheld, W., Michalski, J., Gilbert, M., Purdy, J., Simpson, J., Kresl, J.J., Curran Jr, W., Diaz, A. and Mehta, M.: Phase I/II Conformal Three-Dimensional Radiation Therapy Dose Escalation Study in Patients with Supratentorial Glioblastoma Multiforme: Report of the Radiation Therapy Oncology Group 98-03 Protocol. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S163-164, Abs. #58, 2004.	9803	acc (oral pres)
2770/pending	Mohiuddin, M., Winter, K., Mitchell, E., Hanna, N., Yuen, A., Nicholas, C., Shane, R., Hayostek, C. and Willet, C.: Results of RTOG-0012 Randomized Phase II Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S138-139, Abs. #16, 2004.	0012	acc (oral pres)
2771/pending	Greven, K., Winter, K., Underhill, K., Fontanesi, J., Cooper, J. and Burke, T.: RTOG 9708: Adjuvant Postoperative Irradiation Combined with Cisplatin/Taxol Chemotherapy Following Surgery for Patients with High-Risk Endometrial Cancer. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S212, Abs. #137, 2004.	9708	acc (oral pres)
2772/pending	Machtay, M., Pajak, T., Suntharalingam, M., Hershock, D., Stripp, D.C., Cmelak, A., Shenouda, G., Schulsinger, A. and Fu, K.: Definitive Radiotherapy +/- Erythropoietin for Squamous Cell Carcinoma of the Head and Neck: Preliminary Report of RTOG 99-03. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S132, Abs. #5, 2004.	9903	acc (plenary pres)
2773/pending	Rosenthal, D., Harris, J., Forastiere, A., Weber, R., Ridge, J., Myers, J., Garden, A., Kuettel, M., Sidhu, K., Schultz, C. and Ang, K.K.: Early Postoperative Paclitaxel Followed by Paclitaxel and Cisplatin Concurrent with Radiation Therapy (RT) (Phase II Trial RTOG H-0024) is Well Tolerated for Patients with Resected, High-Risk Squamous Carcinoma of the Head and Neck (HNSCC). Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S322, Abs. #1111, 2004.	0024	acc (poster disc.)
2775/pending	Movsas, B., Konski, A., Pajak, T., Coyne, J., Gwede, C., Garden, A., Spencer, S., Jones, C. and Watkins Bruner, D.: Quality of Life (QOL) Variables Influence Local Regional Control in Radiation Therapy Oncology Group (RTOG) Head & Neck Trials (9003 and 9111). Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S252, Abs. #199, 2004.	9003, 9111	acc (oral pres)
2776/pending	Roach, M., DeSilvio, M., Thomas Jr., C., Valicenti, R., Asbell, S., Lawton, C. and Shipley, W.: Progression Free Survival (PFS) after Whole-Pelvic (WP) vs. Mini-Pelvic (MP) or Prostate Only (PO) Radiotherapy (RT): A Subset Analysis of RTOG 9413, a Phase III Prospective Randomized Using Neoadjuvant and Concurrent (N&CHT). Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S264-265, Abs. #1014, 2004.	9413	acc (poster disc)
2777/pending	Abdel-Wahab, M., Berkey, B., Krishan, A., O'Brien, T., Hammond, E., Roach III, M., Lawton, C., Pilepich, M., Markoe, A. and Pollack, A.: Influence of Number of CAG Repeats on Local Control in the RTOG 86-10 Protocol. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S326, Abs. #1118, 2004.	8610	acc (poster disc)
2778/pending	Michalski, J., Winter, K., Roach III, M., Markoe, A., Sandler, H., Ryu, J., Parliament, M., Purdy, J., Valicenti, R. and Cox, J.: Clinical Outcome of Patients Treated with 3D Conformal Radiation Therapy 3D-CRT for Prostate Cancer on RTOG 94-06. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S169, Abs. #66, 2004.	9406	acc (oral pres)
2781/pending	Hartsell, W., DeSilvio, M., Watkins-Bruner, D., Scarantinio, C., Ivker, R., Roach III, M., Suh, J., Seider, M., Movsas, B., Petersen, I. and Konski, A.: Can Physicians Accurately Predict Survival Time In Patients With Metastatic Cancer? Analysis of RTOG 97-14. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S143-144, Abs. #25, 2004.	9714	acc (oral pres)
2779/pending	Zietman, A., DeSilvio, M., Slater, J., Rossi, C., Yonemoto, L., Slater, J., Berkey, B., Adams, J. and Shipley, W.: A Randomized Trial Comparing Conventional Dose (70.2GyE) and High-Dose (79. 2GyE) Conformal Radiation in Early Stage Adenocarcinoma of the Prostate: Results of an Interim Analysis of PROG 95-09. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S131-132, Abs. #4, 2004.	9509	acc (plenary pres)
2784/pending	Khor, L., DeSilvio, M., Al-Saleem, T., Hammond, E., Sause, W., Pilepich, M., Okunieff, P., Sandler, H. and Pollack, A.: MDM2 As A Predictor of Prostate Cancer Outcome: An Analysis of RTOG 8610. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S472-473, Abs. #2227, 2004	8610	acc (poster)
2785/pending	Gaffney, D., Winter, K., Fuhrman, C., Flinner, R., Greven, K., Ryu, J., Forbes, A., Kerlin, K., Nicholas, R. and Zempolich, K.: Feasibility of RNA Collection for Micro-Array Gene Expression Analysis in the Treatment of Cervical Carcinoma: A Scientific Correlate of RTOG 0128. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S479-480, Abs. #2239, 2004.	0128	acc (poster disc)
2786/pending	Kumar, P., Harris, J., Garden, A., Fu, K., Robbins, K.T., Pajak, T. and Ang, K.K.: Comparison of Intra-Arterial Cisplatin and Radiation Therapy to Other Radiation Therapy Oncology Group (RTOG) Regimens Using Standard or Accelerated RT with or without Concurrent Chemotherapy in Patients with Stage IV-T4 Head and Neck Cancer. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S495-496, Abs. #2266, 2004.	8117, 9003, 9615, 9703	acc (poster)
2780/pending	Watkins-Bruner, D., Winter, K., Hartsell, W., Konski, A., Curran Jr, W., Roach III, M., Doncals, D., Movsas, B., Lee, D. and Scarantinio, C.: Prospective Health-Related Quality of Life Valuations (Utilities) of 8 Gy in 1 Fraction vs. 30 Gy in 10 Fractions for Palliation of Painful Bone Metastases: Preliminary Results of RTOG 97-14. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S142, Abs. #23, 2004.	9714	acc (oral pres)

2714 Lawton, C, DeSilvio, M., Lee, W., Gomella, D., Grignon, D., Gillin, M., Morton, G., Pisansky, T. and Sandler, H.: Results of a Prospective Multi-Institutional Phase II Trial (RTOG 98-05) of Transrectal Ultrasound Guided Permanent Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S184-185, Abs. #90, 2004. Purpose/Objective: This prospective trial was opened by the Radiation Therapy Oncology Group (RTOG) in 1998 to evaluate the effectiveness of transrectal ultrasound guided permanent implantation of the prostate compared to historical data of prostatectomy or external beam radiotherapy within a cooperative group setting with special attention to the quality assurance standards of brachytherapy. Materials/Methods: One hundred and one patients were accrued to this protocol, which closed in April 2000. Accrued patients had low risk prostate cancer (T1-2, GS<6, PSA <10) and underwent an I125 permanent implantation of the prostate (145 Gy TG-43). Results: Of 101 patients, 97 are eligible and analyzable. Of the eligible patients, 96 had brachytherapy data and 95 had adequate follow up for evaluation. Median follow up was 41 months (range 4.5 months to 60.1 months). Ninety-four of the eligible patients had an implant that was delivered either per protocol or with an acceptable minor variation. The 3-year cumulative incidence rate of any failure is 9.8% per the protocol definition of failure (two consecutive rises above the nadir with the rise in PSA exceeding 1 ng/ml above the nadir or positive biopsy). The 3-year biochemical failure rates using the protocol definition and the ASTRO definition were 4.3% and 3.2% respectively. Acute grade 3 or higher toxicity was seen in eight patients, four of the eight were GU toxicity, 2 sexual, and the others hemorrhage. There were no grade 4 or grade 5 acute toxicities. Fifty patients experienced grade 2 toxicity, 44 of the 50 were genitourinary toxicities. Late grade 3 or higher toxicity was noted in 2 patients with grade 3 toxicity both genitourinary and no grade 4 or grade 5 toxicity. Conclusions: This prospective multi-institutional brachytherapy trial was completed successfully with acceptable quality assurance and early results comparable with single institution series. The toxicities are consistent with other reported series. With this trial, the RTOG has demonstrated its capacity to perform a prospective quality assured prostate brachytherapy trial and provides a positive outlook for the feasibility of subsequent cooperative group trials, including the active Phase III trial RTOG P-0232 examining the role of supplemental external beam radiotherapy for prostate brachytherapy.

2768 Shaw, E. Seiferheld, W., Cairncross, G., Jenkins, R., Scheithauer, B., Brachman, D., Buckner, J., Fink, K., Souhami, L. and Curran Jr, W.: Radiation Therapy (RT) Alone vs Intensive Procarbazine-CCNU-Vincristine (I-PCV) Chemotherapy Followed by Radiation Therapy for Anaplastic Oligodendroglioma (AO) and Mixed Oligo-Astrocytoma (MOA): Results of Radiation Therapy Oncology Group (RTOG) - Intergroup Protocol 94-02. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S163, Abs. #57, 2004. Purpose/Objective: The primary objective of the study was to determine whether pre-RT I-PCV improved the overall survival (OS) compared to RT alone in adults with AO or MOA; additional analyses included progression-free survival, treatment toxicity, and determining the prognostic relevance of 1p and 19q loss of heterozygosity (LOH) on OS. This abstract also addresses failure patterns. Materials/Methods: Eligibility criteria included AO or MOA by central review, age >=18 years, and KPS >=60. Tissue and blood were collected for 1p and 19q LOH analysis. RT consisted of 45 Gray (Gy) in 25 fractions to the tumor + edema + 2 centimeter (cm) margin defined on T2-weighted magnetic resonance imaging (MRI)(initial volume) followed by 14.4 Gy in 8 fractions to the tumor + 1cm margin defined on the T1 with contrast MRI (boost volume). I-PCV was given according to Cairncross, J Clin Oncol 12:2013–2021, 1994. For patients receiving pre-RT I-PCV, the pre-chemotherapy tumor volume was used for RT treatment planning. Pattern of failure (POF) data was determined for those patients who had pre- and post-treatment MRI scans available for central review. The POF was described as within or outside the boost volume. Results: 291 eligible patients were randomized, 143 to RT alone and 148 to I-PCV --> RT. Prognostic factors were balanced between the treatment arms (histology, age, KPS, and extent of surgical resection). The median survival time (MST) for I-PCV --> RT was 4.8 years vs 4.5 years for RT alone (p = 0.83, hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.74–1.45). The progression-free survival time was 2.6 years for I-PCV --> RT vs 1.9 years for RT alone (p = 0.053, HR 1.34, 95% CI 1.0–1.8). Of 206 patients with tissue/blood specimens, 46% had 1p19q LOH. MST was not reached with 1p19q LOH vs 2.8 years without 1p19q LOH (p < 0.001, HR 0.31, 95% CI 0.2–0.48), regardless of treatment. The incidence of acute grade 3–5 toxcity with I-PCV --> RT was 64%, including one treatment death, compared to 5% grade 3–4 toxicities (no grade 5) with RT alone. A subset of 40 patients had MRI scans available for POF analysis. 10/40 (25%) failed outside the boost volume, 6 (15%) within the initial volume and 4 (10%) outside the initial/boost volumes. Of 14 patients who received pre-RT I-PCV, 7 would have failed had the post- vs the pre-chemotherapy tumor volume been used for treatment planning. Conclusions: 1) Pre-radiation I-PCV did not significantly improve overall survival but may prolong progression-free survival; 2) 1p19q is an important prognostic factor in patients with anaplastic oligodedroglial tumors, regardless of treatment; 3) I-PCV is a moderately toxic regimen with 2/3 of patients experiencing grade 3–4 toxicity; 4) 25% patients failed outside the irradiated volume; and 5) Post-chemotherapy tumor volumes would not be appropriate for RT treatment planning.

2769 Werner-Wasik, M., Seiferheld, W., Michalski, J., Gilbert, M., Purdy, J., Simpson, J., Kresl, J.J., Curran Jr, W., Diaz, A. and Mehta, M.: Phase I/II Conformal Three-Dimensional Radiation Therapy Dose Escalation Study in Patients with Supratentorial Glioblastoma Multiforme: Report of the Radiation Therapy Oncology Group 98-03 Protocol. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S163-164, Abs. #58, 2004. Purpose/Objective: The phase I/II trial (RTOG 98–03) has evaluated feasibility and toxicity of escalating doses of conformal three-dimensional (3D) radiation therapy (RT) delivered with bis-chlorethyl nitrosourea (BCNU) chemotherapy (CT) in patients (pts) with supratentorial glioblastoma multiforme (GBM). Materials and Methods: Between 9/98 and 9/03, 209 pts with newly diagnosed GBM were entered. Eligible pts were >= 18 years of age, with KPS >= 60, neurological function (NF) 0-3, adequate organ function and histological proof of a unifocal radiosurgery-ineligible supratentorial GBM. The 3D treatment planning data were submitted digitally for all cases to the Image-Guided Therapy Center which facilitated quality assurance review of Gross, Clinical and Planning Target Volumes (GTV, CTV, PTV) and designated organs at risk contours, as well as dosimetry compliance. All pts received 46 Gy in 2 Gy fractions to PTV1, defined as GTV plus 1.8 cm margin. Subsequent boost was given to PTV2, defined as GTV plus 0.3 cm, to the following total doses: 66 Gy, 72 Gy, 78 Gy or 84 Gy. Pts were stratified by PTV2 (<75 cc, or Group 1 vs. >= 75 cc, or Group 2). All pts received BCNU 80 mg/m2 on days 1, 2, 3 and 56, 57, 58 of RT, then every 8 weeks for a total of 6 cycles. A total of 195 pts were analyzable for acute toxicity and a total of 153, for late toxicity. Potential follow up (FU) was shorter in higher RT dose levels than in the lower dose levels. The pretreatment patient characteristics, including age, gender, KPS, NF class, Recursive Partitioning Analysis (RPA) RTOG class, extent of surgery, Mini-Mental Status Exam results were well balanced between the two groups. Results: The CT and acute RT toxicities, late RT toxicities and frequency of tumor re-resection are listed in the table below. Two pts died within 90 days; 1 due to probable and 1 due to possible BCNU toxicity. No patients died of late RT toxicity to-date. Late Grade 3/4 RT toxicities included 2 severe headaches and 5 cases of RT necrosis at median interval of 6.4 months (mo). Acute and late grade 3/4 RT-related toxicities were no more frequent at higher RT dose levels and among larger tumors (Group 2) than at lower RT dose levels and among smaller tumors (Group 1). No dose-limiting toxicity (DLT), defined as >=30% Grade 3 or 4 irreversible CNS toxicity, was observed to date. Percentages of pts who underwent a second resection of tumor were similar between all dose levels (accounting for shorter FU in the highest dose levels). Number of progression-free pts who did not require steroids at 3 mo were as follows (Group 1 and 2, respectively): 5/12 and 2/10 (66 Gy); 4/11 and 3/8 (72 Gy); 5/17 and 3/14 (78 Gy); 4/7 and 2/4 (84 Gy). Conclusion: Conformal 3D RT dose escalation up to 84 Gy (boost given to PTV2) was feasible for pts with smaller or larger supratentorial GBM tumors. No DLT has been encountered so far. Updated results with longer FU will be presented.

2770 Mohiuddin, M., Winter, K., Mitchell, E., Hanna, N., Yuen, A., Nicholas, C., Shane, R., Hayostek, C. and Willet, C.: Results of RTOG-0012 Randomized Phase II Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S138-139, Abs. #16, 2004. Purpose/Objective: To evaluate in a randomized phase II study the rate of pathological complete response and toxicity of neoadjuvant chemoradiation for advanced T3/T4 distal rectal cancers. Materials and Methods: 1106 patients with clinical T3/T4 distal rectal cancers, 0–9cm from the dentate line, were randomized in a phase II study to receive combined neoadjuvant preoperative chemoradiation followed by surgical resection of disease. Patients were stratified by clinical stage and were randomized to receive either CVI 5-FU, 225 mg/m2 per day, 7 days per week plus pelvic Hyperfractionated radiation (HRT) 45.6 Gy at 1.2 Gy bid, >6 hour interval plus a boost to the tumor of 9.6 Gy for T3 and 14.4 Gy for fixed T4 cancers (Arm 1) or CVI 5-FU 225 mg/m2 per day Monday to Friday, 120 hours per week plus Irinotecan (CPT-11) 50 mg/m2 once weekly × 4 plus pelvic RT 45 Gy at 1.8 Gy per day and boost to the tumor of 5.4 Gy for T3 and 9 Gy for fixed T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks following completion of neo-adjuvant therapy. The primary end point of this study was assessment of pathological complete response (CR). Secondary end points included acute and late normal tissue morbidity. Results: 96 of the 106 patients were evaluable for response. 3 patients were ineligible and 7 patients did not undergo surgery (4 in Arm 1 and 3 in Arm 2) for either disease progression or patient/physician refusal for an overall respectability rate of 93%. The median time to surgery was 7 weeks. Patient characteristics were similar in both arms except for a higher percent of male patients (78% vs. 55%) and also a slightly higher incidence of T4 (32% vs. 25%) cancers in Arm 1. Overall tumor downstaging was observed in 78% of patients in both arms of the study. For all eligible patients who started treatment. The pathological complete response (pCR) rate was 26% (13/50) in Arm 1 and 26% (14/53) in Arm 2. For patients who had surgery the pCR rate was also the same in Arm 1, 28% (13/46) and 28% (14/50) in Arm 2. Acute and late toxicity in the two arms of the study was also similar. Grade 3s4 acute hematological and non-hematological toxicity occurred in 13% and 38% respectively in Arm 1 and 12% and 45% in Arm 2. Conclusions: Although the overall complete response rate and toxicity appears similar in both arm, this is the first multi institutional study to establish a 28% pathological complete response rate following neo-adjuvant therapy for T3/T4 rectal cancer and should be the standard for future trials in this disease.

2771 Greven, K., Winter, K., Underhill, K., Fontanesi, J., Cooper, J. and Burke, T.: RTOG 9708: Adjuvant Postoperative Irradiation Combined with Cisplatin/Taxol Chemotherapy Following Surgery for Patients with High-Risk Endometrial Cancer. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S212, Abs. #137, 2004. Purpose/Objective: Patients with completely resected high-risk endometrial cancer are at risk of disease recurrence even with the addition of adjuvant pelvic radiation. A phase II study was completed by the RTOG to assess the feasibility, safety, toxicity, and patterns of recurrence and survival when chemotherapy was combined with radiation for these patients. This report is an update of the late toxicity and patterns of recurrence and survival. Materials/Methods: Eligibility requirements included total abdominal hysterectomy and bilateral salpingo-oophorectomy no more than 8 weeks prior to radiotherapy that demonstrated grade 2 or 3 endometrial adenocarcinoma with either >50% myometrial invasion, cervical stromal invasion, or pelvic-confined extrauterine disease. This study was designed to administer 4500cGy in 25 fractions to the pelvis along with cisplatin (50mg/M2) on days 1 and 28. Vaginal brachytherapy with low dose rate (1 × 20Gy to surface) or high dose rate (3 × 6 Gy to the surface) applicator was performed after the external beam radiation. Four courses of cisplatin (50mg/M2) and Taxol (175mg/M2) were given at 4-week intervals following completion of radiotherapy. Results: Forty-six patients were entered between 10/97 and 4/99. Two patients were considered ineligible (one with a previous bladder cancer and one with surgery more than 8 weeks prior to start of RT). Follow-up times range from 6.9 to 61 months with a median of 4 years. Stage of disease was III, II and I in 61%, 16%, and 23% of patients respectively. Maximum late toxicity was grade 1 in 16%, grade 2 in 39%, grade 3 in 16%, and grade 4 in 5%. At 4 years pelvic, regional and distant recurrence rates are 2%, 2%, 19%, respectively. Six deaths occurred which were all due to recurrent endometrial cancer. Overall survival and disease-free (DFS) rates are 85% and 81% respectively. Four-year rates for survival and DFS for stage III patients are 77% and 72% respectively. There have been no recurrences for patients with stage IC, IIA, or IIB. Conclusion: As previously reported, the treatment protocol demonstrated a satisfactory completion rate and acute toxicity. Late toxicity is also acceptable. Local-regional control is excellent following combined modality treatment in all patients suggesting synergistic effects of chemotherapy and radiation. Distant metastases continue to occur in more advanced stage patients. This regimen appears reasonable to be tested for efficacy in randomized patients.

2772 Machtay, M., Pajak, T., Suntharalingam, M., Hershock, D., Stripp, D.C., Cmelak, A., Shenouda, G., Schulsinger, A. and Fu, K.: Definitive Radiotherapy +/- Erythropoietin for Squamous Cell Carcinoma of the Head and Neck: Preliminary Report of RTOG 99-03. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S132, Abs. #5, 2004. Purpose/Objective: Anemia has been associated with poor local-regional control and survival for squamous cell carcinoma of the head and neck (SCCHN). Recombinant human erythropoietin (Epo) elevates hemoglobin levels in anemic patients receiving radiotherapy. We thus designed a prospective randomized trial to determine if concurrent Epo administration with radiotherapy (±concurrent chemotherapy) could improve local-regional control in non-operative SCCHN. Materials/Methods: Eligible patients had non-metastatic, non-resected SCCHN, and a pre-treatment hemoglobin level between 9.0 g/dl and 13.5 g/dl (between 9.0 and 12.5 g/dl for women). Stratification was performed for stage, planned use of chemotherapy, pre-treatment hemoglobin level and gender. Randomization consisted of radiotherapy (XRT) alone (66–72 Gy) or XRT + Epo 40,000 units, subcutaneously injected, starting 7–10 days before the start of XRT. In the original protocol design, concurrent chemotherapy was not allowed; the study was later modified to allow (but not mandate) the use of concurrent high-dose intermittent cisplatin or weekly moderate dose platin/paclitaxel for Stage III/IV patients. Epo was continued throughout radiotherapy unless/until hemoglobin level reached 16 g/dl (14 g/dl for women); these “target” levels are above the package-insert labeling for erythropoietin. Epo was discontinued if hemoglobin exceeded these target levels and was restarted if hemoglobin fell below 13.5 g/dl (12 g/dl for women). Results: The study commenced June 2000. Upon recommendation of the RTOG Data Monitoring Committee, the study was permanently closed to accrual after 148 patients were enrolled; interim analysis revealed that it would be extremely unlikely that Epo would benefit local-regional control (LRC) or survival. There are 135 patients evaluable for this report and the median followup is 12 months. In the Epo arm, hemoglobin level increased by a mean of 1.59 g/dl, while in the control arm, hemoglobin level decreased by a mean of 0.19 g/dl (p = 0.0001 by t-test). However, as shown in the table below, there was no improvement in anti-tumor efficacy. There was no significant difference in the overall rate of Grade 3 + toxicity between the two arms. There was one fatal cardiovascular event attributed to Epo (suspected pulmonary embolism). Conclusions: Despite significantly improving patients’ hemoglobin levels, the addition of concurrent Epo to definitive radiotherapy does not improve local-regional control or survival for mildly/moderately anemic patients with SCCHN. Supported by RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the NCI as well as a grant from Ortho Biotech. This abstract's contents are the sole responsibility of the authors and do not necessarily represent the official views of the NCI or Ortho Biotech.

2773 Rosenthal, D., Harris, J., Forastiere, A., Weber, R., Ridge, J., Myers, J., Garden, A., Kuettel, M., Sidhu, K., Schultz, C. and Ang, K.K.: Early Postoperative Paclitaxel Followed by Paclitaxel and Cisplatin Concurrent with Radiation Therapy (RT) (Phase II Trial RTOG H-0024) is Well Tolerated for Patients with Resected, High-Risk Squamous Carcinoma of the Head and Neck (HNSCC). Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S322, Abs. #1111, 2004. Purpose/Objective: To test a regimen of early post-operative chemotherapy followed by concurrent chemoradiation. This approach was designed to combat the regenerative response of sub-clinical tumor clones persisting in a growth factor-rich postoperative tumor bed in patients receiving post-operative (post-op) RT for high-risk HNSCC. Materials/Methods: Eligible patients had grossly resected stage III/IV HNSCC with positive margins, extra-nodal extension, or multiple metastatic lymph nodes. Conformal RT (58–64 Gy/5.5-6W) started 28–35d post-op. Paclitaxel (80 mg/m2) was given once weekly during post-op weeks 2, 3, and 4 before beginning RT (induction). Paclitaxel (30 mg/m2) and cisplatin (20 mg/m2) were given once weekly during the last 3 weeks of RT (concurrent). The NCI Common Toxicity Criteria version 2.0 was used to score acute effects, and the RTOG/EORTC scale was used to score late effects. The primary endpoint was compliance (using RTOG 9501 as a reference), defined as delivering at least 90% of protocol RT dose, 3 doses of pre-radiation chemotherapy starting no later than post-operative day 18, and at least 2 of 3 doses of concurrent chemotherapy. The secondary endpoint is the rate of grade 5 and acute non-hematologic grade 4 toxicities. Results: Seventy patients entered between 3/5/2001 and 5/23/2003; 64 are analyzable. Forty-five (70%) had nodal risk, and 19 (30%) had positive margins. Primary tumor sites included: oropharynx 21 (33%), oral cavity 23 (36%), larynx 15 (23%), and hypopharynx 5 (8%). Primary tumor T-stages were: T4: 26 (41%), T3: 11 (17%), T2: 18 (28%), and T1: 5 (8%), Tis 2 (3%), and unknown 2 (3%). Fifty-five (86%) had N2, 6 (9%) had N1, and 2 (3%) had N0 disease; the nodal status of one was unknown. The estimated compliance rate is 71.9% [95% confidence interval (59.2%, 82.4%)]. There was one treatment-related death from myocardial ischemia. Six additional patients experienced grade 4 non-hematologic toxicities. There was one fistula, and no serious wound infections were reported. Conclusions: Early post-op induction chemotherapy followed by concurrent chemoradiation therapy is safe and well tolerated, and met compliance goals according to protocol definition. Outcome will be analyzed once each patient has been potentially followed for two years to determine if this new approach has promise to address the above biologic risk factors for recurrence.

2775 Movsas, B., Konski, A., Pajak, T., Coyne, J., Gwede, C., Garden, A., Spencer, S., Jones, C. and Watkins Bruner, D.: Quality of Life (QOL) Variables Influence Local Regional Control in Radiation Therapy Oncology Group (RTOG) Head & Neck Trials (9003 and 9111). Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S252, Abs. #199, 2004. Purpose/Objective: The purpose of this analysis was to evaluate the influence of QOL (via FACT-H&N, version 2.0) in addition to disease and socio-demographic factors on local regional control for patients treated on RTOG headsneck cancer clinical trials. Materials/Methods: 1510 patients treated on RTOG 9003 (locally advanced disease) and RTOG 9111 (laryngeal preservation) were potentially analyzable; baseline FACT-H&N data were available for 1093 patients. A Cox model stratified by protocol assessed which QOL measures (baseline FACT-G, its subscales or the H&N subscale) had an independent prognostic impact on local regional control after accounting for tumor and socio-demographic variables (T-Stage, N-Stage, age, gender, race, KPS, marital status, # in household, education level, household income and smoking status). The QOL measures were considered as continuous variables with higher scores associated with better QOL. Results: The mean FACT-G and H&N subscale scores were 86.4 and 21.2 with a standard error of measurement (SEM) of 5.3 and 4.3, respectively. Overall, patients with and without FACT-H&N had similar local regional control rates (HR = 1.094;p = 0.2827); by protocol, this was the case for RTOG 9003 (HR = 0.969;p = 0.7450), but not for RTOG 9111 (HR = 1.594;p = 0.0038). On univariate analysis, FACT-G, most of its subscales, and the H&N subscale showed significantly better local regional control for higher values. On multivariate analysis, T-sN-Stage and KPS were significant for local regional control, as expected. Socio-demographic variables found to have independent prognostic value were smoking status (HR = 1.413;p = 0.0007) and race (HR = 1.355;p = 0.0025). Moreover, FACT-G was prognostically significant when added to the fitted model (HR = 0.992;p = 0.0038). Of the subscales, functional (HR = 0.968;p < 0.0001) and emotional (HR = 1.028;p = 0.0359) well-being were found to be significant. Unlike the functional well-being scale, lower emotional well-being scores were unexpectedly associated with better local regional control. Conclusions: In conclusion, some baseline QOL and socio-demographic variables do have independent prognostic value for local regional control, which may identify patients requiring additional supportsearly interventions to improve outcome. (Supported by the Commonwealth Universal Research Enhancement (C.U.R.E.) Program ME-02-149 grant.)

2776 Roach, M., DeSilvio, M., Thomas Jr., C., Valicenti, R., Asbell, S., Lawton, C. and Shipley, W.: Progression Free Survival (PFS) after Whole-Pelvic (WP) vs. Mini-Pelvic (MP) or Prostate Only (PO) Radiotherapy (RT): A Subset Analysis of RTOG 9413, a Phase III Prospective Randomized Using Neoadjuvant and Concurrent (N&CHT). Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S264-265, Abs. #1014, 2004. Purpose/Objective: Despite the report of RTOG 9413 demonstrating a better PFS with WP compared to PO RT many physicians continue to favor smaller fields for the treatment of men with intermediate to high risk prostate cancer. This secondary analysis was performed to determine whether patients treated with MP RT had a PFS comparable to patients treated with WP RT, and whether patients treated with MP RT might have less toxicity than those treated with WP RT. Materials and Methods: Eligibility included histologically confirmed clinically localized adenocarcinoma of the prostate with an elevated prostate specific antigen (PSA) <100 ng/ml. Patients were stratified by T stage, PSA and Gleason Score (GS) and required to have an estimated risk of lymph node (LN) involvement >15%, based on the equation +LN = (2/3) PSA + [(GS - 6) × 10]. N&CHT consisted of flutamide 250 mg p.o. TID and either leuprolide or goserelin acetate depot preparations administered 2 months before and during RT. The study was activated on April 1, 1995 and closed June 1, 1999 with a total of 1323 cases. To avoid the bias due to total duration of treatment (4 mo. vs. 6 mo.), only patients treated on arms 1 and 2 were selected for this subset analysis. Three hundred twenty five men (arm 1), and 324 men (arm 2) were randomized to WP RT, and PO RT, respectively. Patients randomized to WP RT, were compared to subsets of patients randomized to PO RT (arm 2), dichotomized as PO with a radiation field size less than the median (i.e., 10cm × 11cm) vs. mini pelvic (MP) with a field size greater than or equal to the median. The Chi-Square and F tests were used to assess baseline imbalances among the three groups for proportions and continuous measures, respectively. Actuarial estimates for PFS were calculated using Kaplan-Meier methods. The log-rank test was used to test differences in the PFS curves among the radiation field size groups. Results: The median follow-up since study entry for all patients was 59.3 months. Pre-treatment characteristics were well distributed among the radiation field size groups with the exception of intercurrent disease favoring the PO group (p = 0.011). The 4-year PFS was 60% for the WP, 48% for the MP and 40% for the PO groups, respectively (see table 1 below). The log-rank test revealed a statistically significantly difference between the PFS distributions over time (p = 0.002). Pairwise comparisons showed that there were statistically significant differences in PFS between the WP and MP groups (p = 0.032) but no difference between PO and MP groups (p = 0.24). There were no significant differences in the incidence of late grade 2 and 3+ GI and GU between WP and MP RT (p > 0.05). Conclusions: WP RT is associated with an improvement in PFS compared to MP and PO RT in patients with a risk of LN involvement >15%. Late grade 3+ GI toxicity was similar with WP RT compared to MP RT, however both were higher than PO RT. This study supports WP RT as the standard of care for intermediate to high risk prostate cancer treated with RTsN&CHT. Longer follow-up is required to determine if this subset analysis eventually translates into a survival difference. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Outcomes Whole Pelvic RT "Mini-Pelvic" RT Prostate Only RT P Value 4 yr PFS (%) 60 48 40 0.0023 4 yr Grade 3+ GI 4.5% 1.5% 0% 0.023

2777 Abdel-Wahab, M., Berkey, B., Krishan, A., O'Brien, T., Hammond, E., Roach III, M., Lawton, C., Pilepich, M., Markoe, A. and Pollack, A.: Influence of Number of CAG Repeats on Local Control in the RTOG 86-10 Protocol. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S326, Abs. #1118, 2004. Purpose/Objective: To determine the influence of CAG repeat length on response to hormones in the RTOG 86–10 patients. The length of the CAG repeats in the N- terminal of the androgen receptor gene correlates inversely with AR transcriptional activity, and shorter CAG repeats are associated with a higher probability of developing prostate cancer. The effect of number of CAG repeats on outcome after androgen deprivation is less clear and will be studied. Materials/Methods: The cohort described was from RTOG 86–10, a phase III study in which patients were randomized to receive either radiotherapy (RT) alone or RT and short term androgen deprivation (RT + HT). Androgen receptor (AR) genotyping was done on archival diagnostic specimens with sufficient tissue. AR was also quantified by flow cytometry in a smaller subset of men to determine antigen density and percent positive receptors. The resultant values were studied for association with local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) in univariate and multivariate analyses. Results: Of the 456 analyzable cases in RTOG 86–10 (parent cohort), 94 (21%) had CAG repeat values determined (test cohort). The distributions of patients by pretreatment characteristics or assigned treatment (RT vs. H +RT) were not statistically significantly different between the parent and the test groups. However, cases with determined CAG values had a significantly higher risk of death (p =0.049), suggesting that the cases with determined CAG may not be representative of the entire cohort of patients on the study. The median CAG repeat was 19. The distribution of disease stage and assigned treatment were not significantly different in either the high or low CAG subgroups. There was a trend (p = 0.09) toward more Gleason 7–10 scores in both assigned treatments among the patients with CAG 19 or greater, but this trend was not seen in patients with CAG <19. CAG was not show be significant within the entire test cohort either in univariate or multivariate analysis of each of the four outcomes. However, subset analysis revealed that patients with CAG < 19 who received H+RT had improved LF compared to those who got RT alone (p = 0.026, 5-year rates 4.6% vs. 36.4%) and improved LF compared to patients with CAG 19 or greater that received H+RT (p = 0.028). No similar effect on OS was seen in these groups, but in the group with CAG 19 or greater, patients that received H+RT had improved OS compared to patients getting RT (p = 0.033, 5-year rates 69.0% vs. 53.1%). Conclusion: Measurement of CAG repeats may aid in selection of patients who achieve local control benefit from androgen deprivation.

2778 Michalski, J., Winter, K., Roach III, M., Markoe, A., Sandler, H., Ryu, J., Parliament, M., Purdy, J., Valicenti, R. and Cox, J.: Clinical Outcome of Patients Treated with 3D Conformal Radiation Therapy 3D-CRT for Prostate Cancer on RTOG 94-06. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S169, Abs. #66, 2004. Purpose: This is the first report of clinical outcome following 3D CRT for localized prostate cancer on RTOG 9406. Materials and Methods: RTOG 9406 is a Phase I/II multi-institutional dose escalation study of 3D CRT for prostate cancer. Patients with clinical stages T1 to T3 were eligible except T1b-c and T2a-b who had Gleason score <= 5 and PSA <= 4. Patients were registered on five sequential dose levels: 68.4Gy, 73.8Gy, 79.2Gy, 74Gy and 78Gy treating patients to a minimum dose of 1.8Gy per day (levels 1 through 3) or 2.0Gy per day (levels 4 & 5), respectively. For all cases entered, the 3-D treatment planning data were submitted digitally to the Image-Guided Therapy Center which facilitated QA review of GTV, CTV, PTV, and designated organs at risk contours and dosimetry compliance. Toxicity of treatment has previously been reported. Clinical criteria for local failure are progression (increase in palpable abnormality) at any time, failure of regression of a palpable tumor by two years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. For this study, unique biochemical definitions of local and non-local control were specified in the protocol prior to the establishment of the 1997 ASTRO consensus definition. PSA criteria for failure of local therapy is failure of PSA to fall below 4 ng/ml 12 months following the start of radiation therapy or two consecutive rises (at least one month apart) in PSA during first 12 months after start of treatment (or start of hormone therapy after one increase value). If PSA less than 4 ng/ml, a rising PSA to double nadir value or a rise of 1 ng/ml in the absence of clinical or bone scan evidence of this metastases is considered a local failure. Local failure was estimated using the cumulative incidence method. Disease-free survival was estimated using the Kaplan-Meier method. Results: Thirty-four institutions enrolled 1084 patients and 1055 patients are analyzable for outcome. Median follow up for levels 1, 2, 3, 4 & 5 was 6.4 years, 5.6 years, 5.1 years, 3.8 years, and 2.7 years, respectively. Using the unique 9406 protocol definition, the 5-year rates for failure of local therapy (including PSA criteria) for patients in levels 1, 2, & 3 were 44%, 53%, and 49%, respectively. The three-year incidence for the same endpoint for patients in levels 4 and 5 were 29% and 26%, respectively. When using a purely clinical definition (no PSA) the incidence of local failure at 5 years for levels 1, 2 & 3 was 5% for all groups. The 3-year local failure rate for levels 4 & 5 were 4% and 2%, respectively. The 5-year clinical disease-free survival (without 9406 PSA definition) for levels 1, 2 & 3 was 86%, 82%, and 81%, respectively. The 3-year disease-free survival for levels 4 & 5 was 90% for both levels. Conclusions: Previous reports from RTOG 9406 have demonstrated safety of dose escalation using 3D CRT for treatment to radiation doses as high as 79.2Gy and 1.8Gy per day or 78Gy and 2.0Gy per day fractions. The clinical disease-free survival (without 9406 PSA definition) appears comparable to other series using 3D CRT for localized prostate cancer. Analysis using ASTRO and other more sensitive and specific definitions of radiation therapy outcome will be presented. Analyses of outcome by prognostic factors including T-stage, initial PSA, Gleason score, and the use of neoadjuvant hormone therapy is planned.

2779 Zietman, A., DeSilvio, M., Slater, J., Rossi, C., Yonemoto, L., Slater, J., Berkey, B., Adams, J. and Shipley, W.: A Randomized Trial Comparing Conventional Dose (70.2GyE) and High-Dose (79. 2GyE) Conformal Radiation in Early Stage Adenocarcinoma of the Prostate: Results of an Interim Analysis of PROG 95-09. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S131-132, Abs. #4, 2004. Purpose/Objective: This trial was designed to test the hypothesis that increasing the radiation dose delivered conformally to men with early stage prostate cancer above conventional levels improves disease free outcome. Materials/Methods: From January 1996 to December 1999 393 patients with biopsy proven T1b-T2b prostate cancer and a PSA of <15ng/ml were recruited at two centers onto an IRB approved protocol. 75.3% had Gleason scores of 6 or less, 15.3% Gleason 7, and 8.4% Gleason 8–10. 61.2% had T1c tumors. The median age at diagnosis was 67 years and the median PSA was 6.3. Patients were randomized to receive an initial boost to the prostate alone using conformal protons (either lateral or perineal fields) of either 19.8 or 28.8 Gray equivalent (GyE). All patients then received 50.4Gy at 1.8Gy per fraction using 3-D conformal photons to the prostate, seminal vesicles, and peri-prostatic tissues. 197 patients were randomized to a total dose of 70.2 GyE (conventional dose) and 196 to 79.2 GyE (high dose). Of those assigned to high dose 12 received less than 77 GyE (5.6%). Of those assigned to conventional dose only 5 received doses above 71 GyE (2%). Median follow-up is 4 years. No patient received adjunctive androgen suppression therapy with their radiation. Local failure was defined using both direct and surrogate criteria: clinically through palpation, histologically after rebiopsy of a clinically benign prostate with a rising PSA, or biochemically by a PSA of >1ng/ml 2 or more years after treatment without rebiopsy. Biochemical failure was determined using the ASTRO definition. This trial originated with the Proton Radiation Oncology Group and received statistical and data management support from the American College of Radiology. Results: The distribution of PSA nadirs of either <0.5 or <1.0ng/ml was 36.7% and 73% after 70.2 GyE and 50% and 79.9% after 79.2 GyE. The cumulative incidence estimates of the five-year local failure rate using the surrogate of a PSA >1ng/ml 2 or more years after radiation were 63.6% (95% CI = 54.5% to 72.8%) for the 70.2 GyE group and 36.3% (95% CI = 26.5% to 46.0%) for the 79.2 GyE group (p = 0.0001). The five-year biochemical failure rates were 37.3% (95% CI = 28.4% to 46.3%) for the conventional dose group and 19.1% (95% CI = 11.1% to 27.1%) for the high dose group (p = 0.00001). This difference held true when only those with low risk disease were examined (T1b-2a, PSA <10, Gleason <6, n = 227, 58% of total). The 5-year biochemical failure rate was 34.9% in the conventional dose arm and only 17.2% in the high dose arm (p = 0.002). It was also significant for intermediate risk patients (39.5% vs 21.3% p = 0.01). At this time, there was no difference in the overall survival rates between the treatment arms (p = 0.83). Only 2% of patients receiving conventional dose and 1.5% receiving high dose radiation experienced acute urinary or rectal morbidity of RTOG grade >3. The respective proportions for those experiencing any grade 2 acute morbidity was 62 and 69%. So far only 1.5% and 0.5% respectively have experienced late morbidity of RTOG grade >3. Conclusions: This randomized controlled trial shows an advantage in terms of freedom from biochemical failure for men with low and intermediate risk prostate cancer receiving high dose versus conventional dose conformal radiation. This advantage was achieved without any associated increase in either acute or late urinary or rectal morbidity.

2780 Watkins-Bruner, D., Winter, K., Hartsell, W., Konski, A., Curran Jr, W., Roach III, M., Doncals, D., Movsas, B., Lee, D. and Scarantinio, C.: Prospective Health-Related Quality of Life Valuations (Utilities) of 8 Gy in 1 Fraction vs. 30 Gy in 10 Fractions for Palliation of Painful Bone Metastases: Preliminary Results of RTOG 97-14. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S142, Abs. #23, 2004. Purpose: To determine whether there is a difference in health-related quality of life (HRQL) valuations (utilities) for 8 Gy in a single fraction as compared to 30 Gy in 10 fractions for patients (pts) with painful bone metastases from breast or prostate cancers. Materials and Methods: Primary results of RTOG 97-14 are reported elsewhere. This analysis focuses on health utilities, assessed with the Health Utilities Index (HUI-III), which defines 972,000 health states using five or six functional capacity levels for eight attributes including vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. T-tests were used to compare HRQL scores between treatment arms as well as the change in HRQL scores and multi-attribute changes (3mos. - baseline) within treatment arms. Results: Of 898 eligible pts on the study, 363 have complete health utility information at both 3 mos. and pretreatment, on which this analysis is based. Median age was 66 years, with pts divided between prostate cancer (171) and breast cancer (192). Pt pre-treatment characteristics were equally balanced between the two treatment arms, with 56% having a weight bearing painful site, 66% having a pain score of 7-10 (severe pain), 30% receiving bisphosphonates and 60% having a solitary painful site, mirroring the study population as a whole. The 8Gy arm comprised 193 pts, with 170 in the 30Gy group. Acute toxicity was mild, grade 4 toxicity in 1 pt, grade 3 in 13; there was a higher rate of grade 2-4 acute toxicity in the 30Gy arm (36/170=21%) than with 8Gy (20/193=10%, p=0.0044). Median survival was 10.9 months with 45% of pts alive at one year. The mean total HUI-III-HRQL scores for the two treatment arms were compared separately at pretreatment and 3-months and no statistical difference was found at either time point. For Arm 1 (30Gy x 10 fractions), the mean change in total HUI scores (3mos - baseline) was statistically significant (p<0.0001) with a mean of 0.13 (95% CI 0.08, 0.18). For Arm 2 (8Gy x 1 fraction), the mean change in total HUI scores (3mos - baseline) was also statistically significant (p=0.0005) with a mean of 0.08 (95% CI 0.04, 0.13). Emotion and ambulation were the only individual multi-attribute utilities that differed significantly between arms, with emotion higher in the 30Gy arm at 3 mos. and ambulation higher in the 8Gy arm at 3 mos., each compared to baseline. (The Table shows only those HUI attributes that were significant at either pretreatment or 3 mos.) Congruent with the primary trial, the value placed on pain improvement with RT is highly significant in both arms at 3 mos. Conclusion: Based on this data, there is no difference in overall HUI-III-HRQL scores between the two treatment arms at baseline or at 3 mos. Utility scores increased significantly from baseline to 3 mos. for each of the treatment arms. The increased utility of changes in emotion on the 30Gy arm may indicate a benefit from increased social support gained with longer treatment time. Cognition decreases equally on both arms congruent with the literature on metastasis. Value added of utilities to standard quality of life and symptom assessment is a quantitative valuation of improvement.

2781 Hartsell, W., DeSilvio, M., Watkins-Bruner, D., Scarantinio, C., Ivker, R., Roach III, M., Suh, J., Seider, M., Movsas, B., Petersen, I. and Konski, A.: Can Physicians Accurately Predict Survival Time In Patients With Metastatic Cancer? Analysis of RTOG 97-14. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S143-144, Abs. #25, 2004. Purpose/Objective: To determine if physician prediction of survival time is accurate for patients with metastatic breast or prostate cancer. Materials/Methods: RTOG 9714 was a randomized comparison of two radiation therapy schedules for treatment of bone metastases from breast or prostate cancer. The treating physician was required to assign a baseline Karnofsky performance score (KPS) and to predict expected survival time as part of registration information. Study participants completed a baseline quality of life instrument, the Functional Assessment of Cancer Therapy (FACT). These three were evaluated to determine which correlates best with actual survival time. Spearman’s rank-order correlations were chosen since the variables of interest are continuous but not normally distributed. Results: 898 patients were eligible and analyzable. The actual median survival was 9.3 months. The median physician predicted survival was 12 months. The physician prediction of survival, KPS and FACT were all moderately correlated with actual survival time. The strongest correlation was between KPS and actual survival time. Patients with a higher KPS had a longer survival time (882 patients, Spearman’s rho = 0.259, p < 0.0001). Although this is a positive association, it is weak. The median survival time of the 618 expired patients is 6.5 months; the physician predicted survival for that group was a median of 12 months. The predicted survival was ±1 month of actual survival in 61 (10%) of this group, with 177 (29%) patients surviving >1 month longer than predicted and 375 (61%) surviving >1 month less than predicted. A univariate analysis of actual overall survival was performed, dividing the physician predicted survival into 3 groups; Kaplan-Meier estimates of actual survival are shown by the 3 predicted survival groups in the table below. Conclusions: KPS, FACT scores, and physician predicted survival all are correlated with actual survival. Physicians on this study were able to predict which patients would have longer survival times, although the prediction of survival was optimistic compared to actual survival by an average of 3 months.

2784 Khor, L., DeSilvio, M., Al-Saleem, T., Hammond, E., Sause, W., Pilepich, M., Okunieff, P., Sandler, H. and Pollack, A.: MDM2 As A Predictor of Prostate Cancer Outcome: An Analysis of RTOG 8610. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S472-473, Abs. #2227, 2004 Purpose/Objective: The MDM2 oncoprotein promotes p53 degradation via ubiquitin, establishing negative feedback control of p53 and consequently inhibiting cell-cycle arrest and apoptosis. Overexpression of MDM2 has been observed in over 30% of men with prostate cancer, but the clinical significance of this abnormality is unknown. In our prior experience (Mu et al, IJROBP 58:336–343, 2004), inhibition of MDM2 expression resulted in increased cell death of prostate cancer cells in vitro to radiotherapy (RT) and androgen deprivation (AD). To our knowledge, no study has previously examined the predictive value of MDM2 overexpression in men with prostate cancer who were treated with RT ± AD. We examined the association between MDM2 overexpression and local failure (LF), distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM) in men treated with RT alone or RT + short term AD (STAD) who were enrolled in Radiation Therapy Oncology Group (RTOG) protocol 8610. Materials/Methods: Of the 456 eligible and analyzable cases (parent cohort), archival diagnostic prostate biopsy tumor tissue from 109 patients had adequate, suitably-stained, tumor for MDM2 analysis (MDM2 cohort). Of these, 62 received RT alone and 47 received RT+STAD. Pretreatment characteristics of the parent and MDM2 cohorts were not statistically different. Expression levels were determined by immunohistochemical staining and reviewed under light microscopy. Actuarial estimates of OM were calculated using Kaplan-Meier methods and the cumulative incidence method was used to estimate LF, DM and CSM. Cox proportional hazards multivariate analysis (MVA) was used to determine the relationship of MDM2 to these endpoints. MDM2 staining was classified as positive manually if >5% of the tumor cells displayed nuclear staining by manual quantification. An image-analysis system (ACIS, Chromavision Medical Systems, Inc., San Juan Capistrano, CA) was also used to measure the percentage of cells with nuclear staining and the intensity of the staining. Results: Overexpression of MDM2 by manual counts was seen in 44% (n = 48) and was related to Gleason score 7–10 (p = 0.05). Of patients with MDM2 overexpression, 40 (83%) were classified as Gleason score 7–10 and 8 (17%) patients, Gleason score 2–6. MDM2 overexpression was not associated with age, clinical stage or assigned treatment (RT alone vs. RT+STAD) in univariate analyses. However, a non-significant trend was observed; MDM2 overexpression was associated with a 5-year distant metastasis rate of 43.8% versus 33.9% when MDM2 was not overexpressed (p = 0.14). In multivariate analysis (MVA), there were no trends observed for LF, CSM or OM. Similar relationships were observed with the ACIS counts of MDM2 overexpression. The median ACIS count was 3.0% (range: 0–26%). In univariate analysis, MDM2 overexpression in <=3% of tumor cells was associated with a 5-yr DM rate of 32.6% versus 45.8% when >3% showed overexpression (p = 0.057). MDM2 overexpression by ACIS was not found to be an independently significant predictor of LF, DM, CSM or OM in MVA. The intensity of MDM2 staining was also not significant. Conclusions: Positive MDM2 expression was associated significantly with Gleason score and, although not significant, an increased risk of distant metastasis. While the relationship of MDM2 overexpression to DM was not statistically significant, this observation may be clinically meaningful. The cohort examined was small and with larger patient numbers, MDM2 overexpression may emerge as a significant covariate. In addition, MDM2 overexpression, like p53, may potentially be more discriminating in men with more favorable risk prostate cancer.

2785 Gaffney, D., Winter, K., Fuhrman, C., Flinner, R., Greven, K., Ryu, J., Forbes, A., Kerlin, K., Nicholas, R. and Zempolich, K.: Feasibility of RNA Collection for Micro-Array Gene Expression Analysis in the Treatment of Cervical Carcinoma: A Scientific Correlate of RTOG 0128. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S479-480, Abs. #2239, 2004. Purpose/Objective: To determine the feasibility of RNA collection in a multi-institutional cooperative group setting to be utilized for micro-array gene expression analysis, and to describe the methodology. Materials/Methods: RTOG C0128, a phase I-II, protocol was designed to look at the safety and efficacy of external beam radiation therapy to 45 Gy with concomitant 5-FU and cisplatin chemotherapy, brachytherapy to deliver 85 Gy to point A, and Celecoxib at 400 mg twice daily for one year. Patients had the option of participating in a tissue collection portion of the protocol to be utilized for micro-array gene expression analysis. Fresh tissue was placed immediately into RNA Later solution, and then sent via overnight mail to the RTOG tissue repository. The tissue was divided with the large portion frozen in RNA Later and a small portion was placed into a paraffin block. An H&E slide was evaluated for presence of tumor, degree of necrosis, and grade. The total tissue was weighed and subsequently the total RNA was extracted. RNA quality was determined by two parameters: the absorbance ratio at 260 nm/280 nm, and by the ratio of the integrated peak of 28S RNA to 18S RNA after gel electrophoresis. Paired t test were used to evaluate differences between paired samples. Results: From August 2001 to March 2004, 83 patients were accrued to the trial, and tissue was obtained prior to initiation of therapy on 34 patients (41%). FIGO stages were IB (29%), II (47%), IIIA-IVA (21%), and unknown (3%). Additionally, biopsies were obtained at the time of the first implant from 22 of the accrued patients making paired samples available on 27% for RNA extraction and micro-array gene expression analysis. At the time of this writing, 71% of the samples have been analyzed. The mean amount of tissue obtained pretreatment was 110 ± 13 mg compared with 55 ± 10 mg for tissue obtained at the time of the first implant (p = 0.01). The mean total RNA extracted from the samples prior to treatment was 114 ± 15 ug versus 28 ± 4 ug at the time of the first procedure (p = 0.0004). The RNA quality was assessed via the absorbance ratio at 260 divided by 280 nm. The mean values pretreatment and post treatment were 1.96 ± 0.04 versus 1.78 ± 0.13, respectively (p = 0.03). Additionally, evaluation of the integrated peak of 28S RNA to 18S RNA after gel electrophoresis suggested higher quality RNA in the initial samples (p = 0.05). Conclusions: RNA extraction for gene expression analysis can be successfully performed in the multi-institutional cooperative group setting. Fresh tissue samples were obtained on 41% of accrued patients prior to treatment. The amount of biopsy material (p = 0.01) and the quantity of RNA extracted (p = 0.0004) were greater prior to treatment compared with the first implant. The quality of RNA was superior prior to treatment, as well. These results indicate that gene expression analysis is feasible in the cooperative group setting utilizing amplification techniques for the RNA. Hopefully, this will allow for improvement in prognosis, therapeutic development, and correlation with acute and late toxicities in patients with cancer.

2786 Kumar, P., Harris, J., Garden, A., Fu, K., Robbins, K.T., Pajak, T. and Ang, K.K.: Comparison of Intra-Arterial Cisplatin and Radiation Therapy to Other Radiation Therapy Oncology Group (RTOG) Regimens Using Standard or Accelerated RT with or without Concurrent Chemotherapy in Patients with Stage IV-T4 Head and Neck Cancer. Proc Amer Soc Thera Rad Onc (ASTRO), Atlanta, GA, Int J Radiat Oncol Biol Phys, [60] (1), pg. S495-496, Abs. #2266, 2004. Purpose/Objective: We compared overall survival (OS) and local regional control (LRC) in patients with stage IV-T4 disease originating from the oral cavity, oropharynx or hypopharynx among four RTOG head and neck cancer trials using RT with or without concurrent chemotherapy. Materials/Methods: The treatment regimens of the four RTOG protocols were as follows: 1. RTOG 8117--standard fractionated (SFX) RT [66.0-73.8 Gy] and 3 cycles of concurrent intravenous cisplatin (100 mg/m2 given on days 1, 22 and 43); 2. RTOG 9003 -- SFX RT (70 Gy in 7 weeks) alone [Arm 1], or 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) with intravenous daily cisplatin (10 mg/m2) and 5-FU (400 mg/m2 daily continuous infusion during last 2 weeks of RT) [Arm 1], concurrent SFX RT (70 Gy/13 weeks given every other week) alternating with every other week of intravenous 5-FU (800 mg/m2/d x 5 days)/Hydroxyurea (HU) [1 gm po bid x 6 days] [Arm 2], or concurrent SFX RT (70 Gy/7 weeks) with weekly intravenous cisplatin (20 mg/m2) and Taxol (30 mg/m2) [Arm 3]; and 4. RTOG 9615 --intra-arterial (IA) weekly cisplatin (100 mg/m2) x 4 weeks with SFX RT (70 Gy/7 weeks) [RADPLAT therapy]. Results: The estimated 2 year local regional control rates and overall survival are noted in Table 1. Using a Cox proportional hazards model stratified by RPA class, RADPLAT therapy reduced death rates by more than 50% when compared to Protocols 9003 and 8117, and by 21% when compared to arm 1 of Protocol 9703; there was virtually no reduction in death rates when compared to arms 2 and 3 of Protocol 9703 (0.8% and 1.8%, respectively). Conclusions: RADPLAT therapy significantly improves local regional tumor control rates when compared to RT alone (SFX or AFX-C) or intravenous daily cisplatin/5-FU combined with concurrent SFX RT. Overall survival is also significantly improved by RADPLAT therapy as compared to RT alone (SFX or AFX-C) or intravenous cisplatin (given every 3 weeks as a single agent or daily with 5-FU) and concomitant SFX RT. Additionally, local regional tumor control and overall survival using RADPLAT therapy appear comparable to contemporary concurrent chemoradiation regimens. Further testing in a phase III randomized trial comparing RADPLAT therapy to intravenous chemotherapy and RT is warranted in order to validate our findings.