RTOG/ASTRO Presenters Booklet [PDF]

2002 Accepted ASTRO References [PDF]

2002 ASTRO Abstracts [PDF]

Reference	Study Number
Ang, K. K., Harris, J., Garden, A., Jones, C., Trotti, A., Cheng, J., Spencer, S. and Weber, R.: Concomitant Boost Radiation And Concurrent Cisplatin For Advanced Head And Neck Carcinomas: Preliminary Results Of A Phase II Trial Of The RTOG (99-14). Proc Am Soc Thera Rad Oncol (ASTRO), New Orleans, LA, Int J Radiat Oncol Biol Phys, [54] (2) pg. 71, Abs. #118, 2002. (oral pres.)	99-14
J. Cooper, T. Pajak, A. Forastiere, J. Jacobs, B. Saxman, J. Kish, H. Kim, A. Cmelak, M. Rotman, M. Machtay, J. Ensley, C. Chao, C. Schultz, N. Lee and K. Fu: Patterns of Failure for Resected Advanced Head & Neck Cancer Treated By Concurrent Chemotherapy and Radiation Therapy: An Analysis of RTOG 95-01/Intergroup Phase III Trial. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):2, 2002. (plenary pres)	95-01
P. Eifel, K. Winter, M. Morris, C. Levenback, P. Grigsby, R. Stevens, M. Rotman, D. Gershenson and D. Mutch: Pelvic Radiation with Concurrent Chemotherapy versus Pelvic and Para-Aortic Radiation for High-Risk Cervical Cancer: An Update of RTOG 90-01. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):1, 2002. (plenary pres)	90-01
B. Eldridge, R. Rabinovitch, B. Berkey, D. Raben, K. K. Ang and K. Fu: The Impact of Baseline Nutritional Support on Treatment Outcome in Patients with Locally Advanced Squamous Cell Cancer of the Head And Neck Treated with Definitive Radiotherapy: Report of The Radiation Therapy Oncology Group (RTOG) Trial 90-03. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):115, 2002. (oral pres)	90-03
L. Hughes, K. Heydon, P. Edmonds, E. Hammond and A. Dicker: Cyclooxygenase 2 (COX-2) Expression in Locally Advanced Prostate Cancer: Secondary Analysis of Radiation Therapy Oncology Group (RTOG) 86-10. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):271-272, 2002. (general poster pres)	86-10
R. Kuske, K. Winter, D. Arthur, J. S. Bolton, R. Rabinovitch, J. White, W. Hanson and R. M. Wilenzick: A Phase I/II Trial of Brachytherapy Alone Following Lumpectomy for Select Breast Cancer: Toxicity Analysis of Radiation Therapy Oncology Group 95-17. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):87, 2002. (oral pres)	95-17
W.R. Lee, C. Scott, C. Lawton, G. Morton, T. Pisansky, M. Baikadi, D. Bruner and H. Sandler: Health-Related Quality of Life (HRQOL) in Men Treated with Prostate Brachytherapy Alone on Radiation Therapy Oncology Group (RTOG) Trial 98-05. Submitted to Proc of Am Soc Ther Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):47-48, 2002. (oral pres)	98-05
M. Maor, B. Berkey, A. Forastiere, R. Weber, H. Goepfert, W. Morrison, B. Glisson, A. Trotti, J. Ridge, C. Chao, G. Peters, D. Lee, A. Leaf, J. Ensley and K. Fu: Larynx preservation and tumor control in stage III and IV laryngeal cancer: a three-arm randomized intergroup trial; RTOG 91–11. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):2-3, 2002. (plenary pres)	91-11
J. Michalski, K. Winter, C. Perez, J. Purdy, J. Ryu, M. Parliament, R. Valicenti, M. Roach III, H. Sandler, A. Markoe and J. Cox: Toxicity Following 3D Radiation Therapy For Prostate Cancer On RTOG 94-06 Dose Level IV. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):107, 2002. (oral pres)	94-06
W. Regine, F. Schmitt, C. Scott, C. Dearth, R. Patchell, R. Nichols Jr., E. Gore, R. Franklin III, J. Suh and M. Mehta: Feasibility of Neurocognitive Outcome Evaluations in Patients with Brain Metastases in a Multi-Institutional Cooperative Group Setting: Results of Radiation Therapy Oncology Group (RTOG) Trial BR-0018. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):49, 2002. (oral pres)	BR-0018
W. Seiferheld, A. Chakravarti, K. K. Ang, X. Tu, E. Hammond, W. Curran Jr and M. Mehta: Overexpression of the Epidermal Growth Factor Receptor (Egfr), as Determined by EGFR Immunostaining on Tissue Microarrays, Fails to Demonstrate Prognostic Value for Patients with Glioblastoma Multiforme: A Report from RTOG 74-01, 79-18, 83-02, 84-09, 90-06, 93-05, 96-02, and 98-06. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):96, 2002. (oral pres)	74-01, 79-18, 83-02, 84-09, 90-06, 93-05, 96-02, and 98-06
L. Souhami, L. Souhami, C. Scott, D. Brachman, E. Podgorsak, M. Werner-Wasik, R. Lustig, C. Schultz, W. Sause, P. Okunieff, J. Buckner, L. Zamorano, M. Mehta and W. Curran Jr: Randomized Prospective Comparison Of Stereotactic Radiosurgery (SRS) Followed By Conventional Radiotherapy (RT) With BCNU To RT With BCNU Alone For Selected Patients With Supratentorial Glioblastoma Multiforme (GBM): Report Of RTOG 93-05 Protocol. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):94-95, 2002. (oral pres)	93-05
P. Sperduto, C. Scott, D. Andrews, M. Schell, A. Flanders, M. Werner-Wasik, W. Demas, J. Ryu, L. Gaspar, J.-P. Bahary, L. Souhami, M. Rotman and W. Curran: Stereotactic Radiosurgery With Whole Brain Radiation Therapy Improves Survival In Patients With Brain Metastases: Report Of Radiation Therapy Oncology Group Phase III Study 95-08. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):3, 2002. (plenary pres)	95-08
C. Thomas Jr., B. Berkey, B. Minsky, L. Gaspar, A. Herskovic , T. Rich and L. Gunderson: Recursive Partitioning Analysis (RPA) Of Pre-Treatment Variables For 416 Patients With Loco-Regional Esophageal Cancer Treated With Concomitant Chemoradiotherapy (CT-RT) On Intergroup And Radiation Therapy Oncology Group (RTOG) Trials. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):131, 2002. (oral pres)
R. Valicenti, K. Winter, J. Cox, H. Sandler and J. Michalski: The Effect On Toxicity Of Induction Hormonal Therapy In Prostate Cancer Patients Receiving Dose Escalated 3D Conformal Radiation Therapy On RTOG 94-06. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):133-134, 2002. (oral pres)	94-06

2679 Ang, K. K., Harris, J., Garden, A., Jones, C., Trotti, A., Cheng, J., Spencer, S. and Weber, R.: Concomitant Boost Radiation And Concurrent Cisplatin For Advanced Head And Neck Carcinomas: Preliminary Results Of A Phase II Trial Of The RTOG (99-14). Proc Am Soc Thera Rad Oncol (ASTRO), New Orleans, LA, Int J Radiat Oncol Biol Phys, [54] (2) pg. 71, Abs. #118, 2002. (oral pres.) Purpose/Objective: A phase II trial was undertaken to assess the feasibility, acute and late toxicity, rate of local-regional control (LRC), and survival of the combination of accelerated fractionation by concomitant boost (AFX-CB) and cisplatin for the treatment of patients with locally advanced head and neck squamous cell carcinomas (HNSCC). Materials/Methods: Between April and November 2000, 84 patients with histologic proof of stage III or IV carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx and having Zubrod performance status of 0-1 and adequate hematologic, hepatic, and renal functions were registered. Three patients were found to be ineligible, 1 did not receive protocol therapy, and 3 had no follow up data resulting in a total of 77 (92%) analyzable patients. Age ranged from 40 to 76 with a median of 57 years. Sixty-one (79%) patients were men, 51 (66%) had oropharyngeal cancer, 64 (83%) had stage IV disease. The radiation dose was 72 Gy in 42 fractions over 6 weeks, delivered in one daily fraction of 1.8 Gy during the first 3.5 weeks and two fractions per day, 1.8 Gy and 1.5 Gy separated by > 6 h interval, during the last 2.5 weeks. Cisplatin, 100 mg/m2, was given in short iv infusion at week 1 and week 3 or 4. Tumor status and side effects were assessed every 2-3 months the first year and subsequently 3-4 months. Results: Of the 77 analyzable patients, 92% received radiation dose within 5% of the protocol guideline and 89% received both cycles of cisplatin. Overall, 51 (66%) patients had grade 3 acute reactions, 19 (25%) had grade 4 toxicity, and 3 patients (4%) died of sepsis or pneumonia. Dysphagia, bone morrow suppression, nausea, and vomiting were the most common side effects, which were mainly associated with cisplatin administration. Grade 3 and 4 acute mucositis occurred in 39 (51%) and 2 (3%) patients, respectively. At the time of analysis, 63 (82%) patients were still alive. At a median follow-up of 1 year for patients at risk, the estimated 1-year survival rate was 81.3% (95% confidence interval: 71.8-90.7). Grade 3 and 4 late toxicities developed in 17 (23%) and 6 (8%) patients, respectively, with chronic dysphagia being the leading problem. Conclusions: Results of phase III trials in patients with locally advanced HNSCC showed that AFX-CB improved the likelihood of LRC and cisplatin given concurrently with SF yielded better LRC and survival rates relative to SF radiotherapy. This phase II study was launched to test the feasibility of combining AFX-CB and cisplatin in patients with advanced HNC. The data showed that the acute and late toxicities of the combination of AFX-CB with cisplatin were similar to those observed with other concurrent radiation-chemotherapy regimens (e.g., cisplatin-5FU given during the boost phase of SF, hydroxyurea-5FU plus split-course radiation, and cisplatin-taxol and SF as studied in RTOG 97-03). The 1-year survival rate of 81.3% is encouraging given that 83% of patients had stage IV disease. Therefore, a phase III trial comparing AFX-CB plus cisplatin with SF plus cisplatin will be activated to test whether accelerated fractionation provides an additional benefit in the concurrent radiation-chemotherapy setting.

2671 J. Cooper, T. Pajak, A. Forastiere, J. Jacobs, B. Saxman, J. Kish, H. Kim, A. Cmelak, M. Rotman, M. Machtay, J. Ensley, C. Chao, C. Schultz, N. Lee and K. Fu: Patterns of Failure for Resected Advanced Head & Neck Cancer Treated By Concurrent Chemotherapy and Radiation Therapy: An Analysis of RTOG 95-01/Intergroup Phase III Trial. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):2, 2002. (plenary pres) Purpose/Objective: Local-regional recurrence of disease has been the most common mode of failure of treatment of advanced, head and neck cancer despite grossly or microscopically complete surgical resection and post-operative radiation therapy. We primarily sought to learn whether the addition of concurrent cisplatin (CDDP) chemotherapy to radiation therapy (RT) would improve the likelihood of local-regional control of disease. Associated secondary endpoints measured the anatomic pattern of first failure and the time course of local-regional relapse. Materials/Methods: Between 9/95 and 4/00, 459 patients who had resected, high-risk (2 or more involved lymph nodes, extra-capsular disease and/or microscopically involved mucosal margins of resection) squamous cell carcinomas of the head and neck region were enrolled in a prospectively randomized phase III trial. Following gross total resection of all visible and/or palpable disease, 231 patients were randomly assigned to RT alone (60–66 Gy /30–33 fractions/ 6–6.6 weeks) and 228 patients were randomly assigned to identical RT plus CDDP (100 mg/m2 i.v. on days 1, 22 & 43). Local-regional (L-R) recurrence of disease was the primary endpoint of this study. Results: With a median follow-up of 26.6 months, the 2-year L-R control rate is 74% for those assigned to RT and 79% for the RT plus CDDP group (p=0.16). Ninety-six patients are alive at 3 years; 81 of the 96 (84%) do not have local-regional recurrence. Local-regional recurrence as the first site of treatment failure decreased from 25% in the group receiving RT only to 17% in the group receiving concurrent therapy (p=0.041, crude incidence). Distant metastasis as the first site of failure occurred in 22% and 15% respectively (p=0.076, crude incidence). The two-year actuarial estimate of disease-free survival was significantly improved (43% vs. 54%, P=0.049), but overall survival was not (57 % vs. 63%, P=0.51). None of the patients treated by RT experienced protocol-related fatal toxicity, whereas 3% of the patients treated with concurrent chemoradiotherapy did. The risk of local-regional recurrence began to favor combined therapy only after six months of follow-up had passed. No local-regional recurrences were observed after 36 months of follow-up. Conclusions: The concurrent addition of single agent cisplatin chemotherapy to post-operative radiation therapy (without any subsequent adjuvant chemotherapy) decreases local-regional recurrence as the first evidence of treatment failure and decreases distant recurrence to almost the same degree. Our findings also suggest that three-year follow-up may be adequate to assess the ultimate rate of local-regional recurrence when concurrent chemotherapy and radiation therapy are used post-operatively.

2673 P. Eifel, K. Winter, M. Morris, C. Levenback, P. Grigsby, R. Stevens, M. Rotman, D. Gershenson and D. Mutch: Pelvic Radiation with Concurrent Chemotherapy versus Pelvic and Para-Aortic Radiation for High-Risk Cervical Cancer: An Update of RTOG 90-01. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):1, 2002. (plenary pres) Purpose/Objective: To report mature results of a randomized trial that compared extended field radiotherapy (EFRT) with chemoradiation (CT-RT) in women with loco-regionally advanced carcinomas of the uterine cervix. Materials/Methods: Between 1990 and 1997, 403 women were randomized to receive either EFRT (45 Gy to the pelvis and paraaortic nodes followed by low dose-rate intracavitary radiation (ICRT)) or CT-RT (45 Gy pelvic RT and ICRT with 3 cycles of concomitant 5-FU and cisplatin). Patients with cervical cancer were eligible if they had stages IIB–IVA, stages IB2–IIA with tumor diameter > 5 cm, or positive pelvic lymph nodes. Paraaortic lymph nodes (PAN) were evaluated with either lymphangiogram or lymphadenectomy. To achieve balance between the treatment arms, patients were stratified by stage (IB–IIB and III-IVA) and by method of lymph node evaluation. Overall, 96 patients (25%) had positive pelvic lymph nodes and 118 (30%) had stages III-IVA disease. For patients with stages IB–IIA the median tumor diameter was 6 cm. Median follow-up of surviving patients was 5.8 years. Results: Of 403 patients randomized, 195 and 194 could be evaluated in the EFRT and CT-RT arms, respectively. Overall 5-yr survival rates for patients treated with EFRT and CT-RT were 52% and 72%, respectively (p < 0.0001). Disease-free survival rates were 43% and 67%, respectively (p < 0.0001) and pelvic recurrence rates were 34% and 18%, respectively (p < 0.0001). The rates of PAN recurrence were not significantly different for patients treated with EFRT and CT-RT (4% and 7%, respectively; P = 0.15). However, other distant metastases were significantly more frequent for patients treated with EFRT (31% vs. 18%, P = 0.001). Although the study was not powered to detect a treatment difference within the stratified subgroups, of the 272 patients with stages IB–IIA those treated with CT-RT had a significantly better OS than those treated with EFRT (78% vs. 55%, p < 0.0001); of the 117 patients with stages III-IVA, there was a trend toward better OS for those treated with CT-RT (59% vs. 47%, P = 0.066). The 5-yr rates of late grade 3 or higher treatment-related toxicity were comparable for patients treated with EFRT and CT-RT (12% and 14%, respectively; P = 0.65). Conclusions: Mature analysis confirms that the addition of 5-FU and cisplatin to radiation therapy significantly improved the survival rate of women with locally advanced cervical cancer, decreasing both local and distant recurrences without significantly increasing the rate of late treatment-related side effects.

2624 B. Eldridge, R. Rabinovitch, B. Berkey, D. Raben, K. K. Ang and K. Fu: The Impact of Baseline Nutritional Support on Treatment Outcome in Patients with Locally Advanced Squamous Cell Cancer of the Head And Neck Treated with Definitive Radiotherapy: Report of The Radiation Therapy Oncology Group (RTOG) Trial 90-03. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):115, 2002. (oral pres) Purpose/Objective: This analysis was performed to determine whether nutritional support affects treatment related toxicity, local-regional control and overall survival in patients treated with definitive radiotherapy alone for locally advanced squamous cell cancer of the head and neck (HNSCC). Materials/Methods: Data was evaluated on the 1073 patients treated on RTOG 90-03, a randomized trial comparing 4 definitive radiotherapy (RT) fractionation schemes for locally advanced cancer HNSCC (standard fractionation, hyperfractionation, accelerated hyperfractionation with planned split, and accelerated fractionation with concomitant boost). Information retrieved from the database included pretreatment patient characteristics (primary tumor site, weight loss 6 months prior treatment, T, N, and AJCC stage), specific nutrition support (including oral nutrition supplementation and tube feeding use at baseline, during treatment, and 3- and 6-months following treatment), and incidence and severity of dysphagia and KPS (baseline, during treatment, 3- and 6-months follow-up), and incidence and severity of mucositis (during treatment, 3- and 6-months follow-up). Uni- and multivariate analyses were performed to determine if these factors were significantly correlated with treatment outcome. Results: Prior to initiation of RT, 293 patients (27%) were receiving baseline nutritional support (BSN) of some kind (50%-oral supplements alone, 27%-supplementation via tube feeding, and 23%-various combinations of oral+/or tube+/or IV supplementation). During treatment, nearly all patients (86%) required nutritional support. Patients receiving BNS had significantly poorer distributions of KPS, T, N, and overall AJCC stages (all p<0.0001) compared to those patients who did not. BNS patients had significantly increased weight loss in the six months prior to RT than those who did not receive BNS (means of 8kg and 3kg, respectively). Patients with moderate-severe dysphagia at baseline were more likely to require BSN (p<0.0001). Patients with moderate-severe dysphagia at baseline that did not receive BSN were more likely to require nutritional support during treatment (p=0.015) than those who had no-mild dysphagia at study entry, regardless of whether they received standard or altered fractionation. However, dose delivered and overall elapsed days of treatment were not significantly different for BNS patients than others. Patients receiving BNS had a trend toward less Grade 3-4 mucositis (p=0.057) after completion of treatment (adjusting for baseline dysphagia and standard versus altered fractionation). However, patients receiving BNS had a significantly increased actuarial rate of local-regional failure (71% vs. 44%, p<0.0001) and a significantly decreased actuarial rate of overall survivial (16% vs. 39%, p<0.0001) compared to all other patients at 5 years post-randomization. A multivariate analysis demonstrated that T stage, N stage, KPS, weight loss, and BNS were all significant independent predictors of local-regional control and overall survival. Conclusions: Patients with locally advanced HNSCC who receive BNS, despite their associated poorer KPS and increased pre-treatment weight loss, are just as likely to complete a full course of definitive radiotherapy in the prescribed time frame. Patients with BNS have inferior rates of local-regional control and overall survival that is independent of their greatly advanced stage. Further research will be beneficial in identifying the cause of the poorer prognosis for this population, which will lead to improved design and analysis of clinical trials.

2676 L. Hughes, K. Heydon, P. Edmonds, E. Hammond and A. Dicker: Cyclooxygenase 2 (COX-2) Expression in Locally Advanced Prostate Cancer: Secondary Analysis of Radiation Therapy Oncology Group (RTOG) 86-10. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):271-272, 2002. (general poster pres) Purpose/Objective: Cyclooxygenase (COX) catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX-mediated synthesis of PGs. While COX-1 is constitutively expressed in a wide range of tissues, COX-2 is cytokine inducible. Enhanced COX-2 expression has been attributed a key role in the development of inflammation and related processes observed in pathologically altered disease states. Cyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid to prostaglandins, is overexpressed in a variety of different tumors, including colon, pancreatic, lung and head and neck cancers. COX-2 is also observed within human tumor neovasculature, suggesting that COX-2 derived prostaglandins contribute to tumor growth by inducing formation of new blood vessels. There are limited studies with small sample sizes that have evaluated COX-2 expression in prostate cancer. We have explored the potential use of COX-2 as a biomarker in tissue samples from patients with prostate cancer enrolled on RTOG 86-10. Materials/Methods: RTOG 86-10, a phase III trial, randomized locally advanced prostate cancer patients to radiation therapy alone versus radiotherapy and hormonal cytoreduction. Tissue samples from 106 individual patients were evaluated from the tissue repository at the RTOG. The H&E slides were reviewed, and the representative paraffin blocks containing the index case were chosen and immunohistochemically stained for COX-2 expression. Individual slides had tumor identified and the percentage of the tumor staining for COX-2 was recorded. The individual slides were evaluated for COX-2 intensity staining and graded from 0-3. The staining patterns in the samples were homogeneous allowing for intensity to be rated as whole numbers. Univariate and multivariate methods were done using Cox regression. Results: Characteristics of the sample population were evaluated. Age distribution revealed 76% of the patients were less than 75 years of age. Clinical stage of the samples revealed 25% of the patients were staged as T2 and 75% were T3. Gleason Score (GS) distribution revealed 25% of patients were 2–6 and 75% were 7–10. The assigned treatment arms were radiotherapy (RT) alone with 56% of patients while 44% of patients received RT and hormonal cytoreduction. There were an overwhelming number of tumor samples (99%) which stained for COX-2. A large percentage (78%) stained with intensity graded as 2 or 3. Samples with GS 7–10 had 81% COX-2 expression intensity graded as 2 or 3 while GS 2–6 had only 69% expression (2,3). Multivariate and univariate analysis showed no statistically significant difference between COX-2 expression (0,1) versus (2,3) in local failure, distant failure, biochemical failure, disease-free survival or overall survival. The lack of significance may be due to the tissue sample size and homogeneity of the patient group. Conclusions: This analysis represents the largest sample base reviewed for COX-2 expression in prostate carcinoma patients. COX-2 is highly expressed in this study population. Patients with GS 7–10 locally advanced prostate cancer had greater intensity of COX-2 expression when compared with their lower GS counterparts. Due to the large degree of COX-2 expression seen in prostate carcinoma, COX-2 will be a high priority biomarker when evaluating samples from RTOG 92-02.

2626 R. Kuske, K. Winter, D. Arthur, J. S. Bolton, R. Rabinovitch, J. White, W. Hanson and R. M. Wilenzick: A Phase I/II Trial of Brachytherapy Alone Following Lumpectomy for Select Breast Cancer: Toxicity Analysis of Radiation Therapy Oncology Group 95-17. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):87, 2002. (oral pres) Purpose/Objective: Wide-volume breast brachytherapy delivers accelerated partial breast irradiation (APBI) over 4-5 days compared to 5-6 weeks conventional whole breast external beam (EBRT). RTOG 95-17 is the first prospective cooperative group trial of APBI alone following lumpectomy in select breast cancers. Toxicity rates are reported for both low (LDR) and high dose-rate (HDR) APBI on this trial. Materials/Methods: Between August 1997 and March 2000, 100 women were enrolled in this study with invasive < 3cm non-lobular carcinomas after lumpectomy with negative surgical margins (no ink on tumor) and axillary dissection with 0-3 positive axillary nodes without extracapsular extension. Extensive intraductal component or collagen vascular diseases were exclusions. Patients were treated with APBI utilizing either LDR (45 Gy in 3.5-5 days) or HDR (34 Gy in 10 BID fractions over 5 days) APBI. The target volume was defined as 2cm beyond the lumpectomy cavity peripherally and 1cm superficial and deep. Chemotherapy (no earlier than 2 weeks following APBI) and/or tamoxifen could be given at the discretion of the treating physicians. Of the 100 cases, one was excluded for having only sentinel node mapping. Thirty-three women were treated with LDR and 66 HDR APBI. Twenty-one were younger than 50 years, 45 between 50 and 69 years, and 33 were age 70 or older. There were 88 T1, 12 T2, 79 node-negative, and 21 node-positive tumors. The median follow-up for all patients is 2.7 years (0.6-4.4). Results: Toxicities reported to be due to surgery included breast edema (n=16), hematoma (n=8), arm edema (n=7), cellulitis (n=6), skin necrosis (n=5), abscess (n=3), wound dehiscence (n=2), breast distortion (n=2), and other (n=15). Four patients had grade 3 or 4 and 31 had grade 1 or 2 surgical toxicities. Toxicities reported during APBI, during follow-up, and at last follow-up are shown in table below. Patients receiving chemotherapy, a non-protocol therapy, had 55 percent (n=6) and 14 percent (n=2) grade 3 toxicities during follow-up for LDR and HDR, respectively, in contrast to 0 and 2 (4 percent) without chemotherapy. Conclusions: Acute toxicity for this partial breast radiation technique was acceptable realizing that a learning curve for each institution was expected. In addition, catheter placement techniques have improved since the study was designed, with potential to reduce treatment toxicity. The 5 percent, 10 percent, and 4 percent grade 3 or 4 toxicity rates (during APBI, at any follow-up, or at the last follow-up, respectively) may well be acceptable to women who would otherwise be unable to undergo breast conservation due to time or transportation issues necessary for conventional EBRT. Toxicity during APBI Toxicity at any follow-up Toxicity at last follow-up LDR(n=33) HDR(n=66) LDR(n=33) HDR(n=66) LDR(n=33) HDR(n=66) Grade 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 Infection 0 1 1 4 4 2 0 0 1 0 2 0 0 0 0 0 0 0 Erythema 11 2 1 23 11 0 5 3 0 12 5 0 2 2 0 2 1 0 Ulceration 0 2 0 2 2 0 0 1 0 1 1 0 0 0 0 0 0 0 Thickening 0 0 0 3 0 0 12 7 3 21 3 1 5 3 1 10 0 0 Fibrosis 0 0 0 2 0 0 8 11 4 20 3 2 7 3 2 6 0 1 Dehiscence 0 1 0 0 0 0 0 1 0 0 0 1 0 0 0 0 1 0 Breast edema 3 6 0 13 14 0 6 4 0 17 6 0 0 0 0 4 2 0 Arm edema 0 1 0 3 0 0 4 3 0 6 6 0 1 0 0 0 2 0 Breast pain 0 3 1 12 7 0 8 2 0 9 7 2 2 0 0 0 1 0 Tenderness 5 2 0 15 3 0 12 2 0 26 4 0 6 0 0 4 1 0 Bleeding 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Pneumothorax 0 0 1* 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Telangiectasia 0 0 0 0 0 0 5 3 2 17 6 0 4 1 2 7 2 0 Max toxicity/pt 8 11 3 27 27 2 8 15 6 33 23 4 11 4 3 18 8 1 % toxicity/pt 24 33 9 41 41 3 24 45 18 50 35 6 33 12 9 27 12 2 *One patient required a chest tube for a pneumothorax after catheter insertion (scored as grade 4).

2667 W.R. Lee, C. Scott, C. Lawton, G. Morton, T. Pisansky, M. Baikadi, D. Bruner and H. Sandler: Health-Related Quality of Life (HRQOL) in Men Treated with Prostate Brachytherapy Alone on Radiation Therapy Oncology Group (RTOG) Trial 98-05. Submitted to Proc of Am Soc Ther Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):47-48, 2002. (oral pres) Purpose/Objective: To prospectively assess health-related quality of life (HRQOL) during the first year after treatment with prostate brachytherapy (PB) alone for T1c-2a prostate cancer. Materials/Methods: Ninety-eight patients from 24 institutions were eligible and properly entered on this study. All patients were treated with PB alone using I-125 (Amersham Model 6711). The prescription dose was 145 Gy. Three separate HRQOL questionnaires (Functional Assessment of Cancer Therapy-Prostate: FACT-P, Sexual Adjustment Questionnaire: SAQ and International Prostate Symptom Score: IPSS) were self-administered before and after PB (baseline; 3, 6, 9 and 12 months following PB). The Standard Error of Measurement (SEM) was used to analyze changes in HRQOL scores over time. Patients that improved greater than the SEM were categorized as Improved; patients that declined greater than the SEM were categorized as Declined; patients were otherwise categorized as Stable. All changes are measured using the pretreatment HRQOL score as baseline. Results: The percentage of men who reported the ability to have an erection decreased from 73% at baseline (65% unassisted, 8% assisted) to 57% at one year (36% unassisted, 21% assisted). The rate of urinary incontinence increased to 14% at six months but had decreased to 1% at the 12-month follow-up. At one year after PB, 80% of men reported decreased sexual functioning according to SAQ scores. More than 60% of men reported decreased urinary function at 12 months compared to baseline. Changes in HRQOL at 12 months for the subscales of FACT-P are illustrated in the table. Conclusions: The rate of incontinence is low one year following PB but many men have persistent urinary symptoms. Of those men potent at baseline, roughly 80% maintain the ability to have an erection one year following PB although 80% of men also report a decline in sexual function according to the SAQ. At one year more men reported a decline in PWB, PCS and SFWB subscales but more men reported an improvement in the EWB, FWB and RWD subscales. Acknowledgement: This work was made possible by an unrestricted grant from Amersham Health. Subscale of FACT-P Improved Stable Declined Physical Well-being (PWB) 11% 58% 31% Social/Family Well-being (SFWB) 20% 55% 25% Emotional Well-Being (EWB) 44% 53% 4% Functional Well-being (FWB) 36% 47% 16% Relationship with Doctor (RWD) 18% 80% 2% Prostate Cancer Symptom (PCS) 16% 53% 32%

2682 M. Maor, B. Berkey, A. Forastiere, R. Weber, H. Goepfert, W. Morrison, B. Glisson, A. Trotti, J. Ridge, C. Chao, G. Peters, D. Lee, A. Leaf, J. Ensley and K. Fu: Larynx preservation and tumor control in stage III and IV laryngeal cancer: a three-arm randomized intergroup trial; RTOG 91–11. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):2-3, 2002. (plenary pres) Purpose/Objective: To evaluate induction chemotherapy followed by radiation (control) versus concomitant chemotherapy and radiotherapy versus radiation therapy alone in the treatment of stage III and low-volume stage IV glottic and supraglottic cancers. Endpoints for evaluating the trial were laryngectomy free-survival (LFS), laryngectomy preservation rate (LPR), patterns of relapse, treatment-related adverse events, and overall survival. Materials/Methods: Between August 1992 and May 2000, 547 patients were enrolled in our study. Patients were eligible for the study if they had a new diagnosis of a potentially resectable stage III or IV squamous carcinoma of the glottic or supraglottic region; patients with a T1 or a high-volume T4 tumor were excluded from the study. Patients were randomly assigned to 3 treatment arms. Patients in arm 1 received 3 cycles of induction cisplatin 100 mg/m2 once and 5-fluorouracil 1000 mg/m2 /day for 5 days every 3 weeks. In responding patients, this treatment was followed by 70 Gy of radiation in 35 fractions for 49 days. Patients in arm 2 received concurrent cisplatin 100 mg/m2 on days 1, 22, and 43 of radiation treatment (70 Gy/35 fractions for 49 days). Patients in arm 3 received radiation only at 70 Gy/35 fractions for 49 days. Patients with a neck node > 3 cm or with multiple neck nodes underwent a neck dissection 8 weeks after completion of therapy. After excluding 30 patients from the study, 517 remained for analysis (173 in arm 1, 172 in arm 2, and 172 in 3). Sixty eight percent of the 517 patients had supraglottic cancer. Pretreatment patient and tumor characteristics were very similar in the 3 treatment arms. Results: At 2 years, LFS for the patients treated with concomitant chemotherapy and radiotherapy was significantly better than for patients treated with radiotherapy alone (p = 0.018). The LPR was significantly greater in arm 2 compared with arms 1 and 3. The number of laryngectomies at 2 years was 43, 21, and 49 for the induction, concomitant and radiotherapy arms respectively. Loco-regional control at 2 years for patients in arm 2 (78%) was significantly better than either arm 1 (61%), or arm 3 (56%), p < 0.01. Ten patients in the study died of treatment toxicity; 5 died in the induction chemotherapy arm and 5 died in the concomitant chemotherapy and radiation arm. Acute grade 4 and 5 toxicity was 31%, 21%, and 5% in treatment arms 1, 2, and 3 respectively (<0.0001). Late grade 4 and 5 toxicity was 9%, 8% and 10% in the 3 arms (not significant). Overall survival was very similar for the patients in the 3 treatment arms (~75% at 2 years). Conclusions: Concomitant chemotherapy and radiotherapy was superior for LPR and loco-regional control compared with induction chemotherapy followed by radiotherapy and compared to radiotherapy alone. Patients on concomitant treatment had a superior LFS compared to patients treated with radiation alone. There was no significant difference between induction chemotherapy and radiotherapy alone using these criteria. Better local control with the concomitant treatment arm did not improve survival.

2675 J. Michalski, K. Winter, C. Perez, J. Purdy, J. Ryu, M. Parliament, R. Valicenti, M. Roach III, H. Sandler, A. Markoe and J. Cox: Toxicity Following 3D Radiation Therapy For Prostate Cancer On RTOG 94-06 Dose Level IV. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):107, 2002. (oral pres) Purpose/Objective: This is the first report of toxicity outcomes on dose level IV (74 Gy) on RTOG 9406 for stage T1,2 adenocarcinoma of the prostate. Materials/Methods: 262 patients were entered on this cooperative group, phase I/II dose escalation trial of 3DCRT for localized carcinoma of the prostate to a dose of 74 Gy (Level IV). 256 patients at this dose are analyzable for toxicity. The daily fraction size was 2 Gy and was prescribed to the minimum isodose surface that encompassed the planning target volume (PTV). Patients were stratified according to risk of seminal vesicle invasion (SVI) based upon Gleason score and presenting PSA. Group I patients had clinical stage T1,2 tumors with SVI risk of <15%. Group 2 patients had clinical stage T1,2 tumors with SVI risk of > 15%. PTV margins between 5 to 10 mm were required. Patients in Group 1 received 74 Gy to a PTV encompassing the prostate. Patients in Group 2 received 54 Gy to a PTV1 encompassing the prostate and seminal vesicles followed by a boost to a PTV2 encompassing prostate only to 74 Gy. Average months at risk following completion of therapy were 23.9 and 19.7 months for Group 1 and 2, respectively. The frequency of late effects grade > 3 was compared to a similar cohort of patients treated on RTOG studies 7506 and 7706 with length of follow-up adjustments made for the interval from completion of therapy. A second comparison was made to 206 patients treated to dose level II (73.8 Gy in 1.8Gy/fraction) to see if fraction size influenced toxicity. Results: Acute toxicity at dose level IV is remarkably low with grade 3 acute effects reported in only 1% of Group 1 and 3% of Group 2 patients. No grade 4 or 5 acute toxicities were reported. Late toxicity continues to be low compared to RTOG historical controls. One patient in group 1 and 4 patients in Group 2 have experienced grade 3 bladder toxicity. A single patient in Group 2 experienced a grade 3 bowel toxicity. No grade 4 or 5 late effects have been reported. The rates of late grade 2 toxicities (any type) were 22% and 15% in Groups 1 and 2, respectively. Table 1 summarizes the observed versus expected > grade 3 late effects using historical RTOG controls with adjusted follow-up intervals. There was no statistical difference in rates of acute or late complications in patients who were treated to 73.8 Gy at 1.8 Gy/fraction or 74 Gy at 2.0 Gy/fraction. There was a trend that patients treated with the larger 2.0 Gy fractions had more grade 3 or greater toxicity than patients treated with 1.8 Gy fractions (2% vs 1%, P=0.09). The longer follow-up on dose level II suggests these differences may increase with additional follow-up. Conclusions: Tolerance to 3DCRT with 74 Gy in 2Gy fractions remains better than expected compared to historical controls. The magnitude of any effect from fraction size requires additional follow-up. This work was supported by RTOG grant (U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115) from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Late Effects > Grade 3 # Patients Total # Months at Risk Average # Months at Risk # Observed # Expected p-value Dose Level IV Group 1 100 2750 239 1 18.1 < 0.0001 Group 2 141 2760 19.7 5 19.6 0.001

2678 W. Regine, F. Schmitt, C. Scott, C. Dearth, R. Patchell, R. Nichols Jr., E. Gore, R. Franklin III, J. Suh and M. Mehta: Feasibility of Neurocognitive Outcome Evaluations in Patients with Brain Metastases in a Multi-Institutional Cooperative Group Setting: Results of Radiation Therapy Oncology Group (RTOG) Trial BR-0018. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):49, 2002. (oral pres) Purpose/Objective: A multi-institutional trial was conducted by the RTOG to test the feasibility of performing a neurocognitive test battery consisting of 5 measures and a quality of life instrument in patients with brain metastases. Materials/Methods: Major eligibility requirements included: 1) histological proof of a primary malignancy, 2) measurable single or multiple brain metastases, 3) Zubrod performance status 0–1, 4) neurological function status 0–2, and 5) ''certification'' for administration of neurocognitive assessments. This certification process required either attendance at an RTOG neurocognitive assessment training workshop, or review of an instructional video, followed by submission of an audio of mock/simulated test sessions for central review. The test battery included the following measures: 1) Mini-Mental State Exam (MMSE), 2) Hopkins Verbal Learning Test (HVLT), 3) Verbal Fluency/Controlled Word Association Test (COWAT), 4) Ruff 2 and 7 test ( 2 & 7 ), 5) Trailmaking Test (TMT), and 6) Profile of Mood States Short Form (POMS-SF). The primary objective of this trial was to establish whether patients were able to complete this test battery. Compliance was defined as successful completion of a test measure based on available data, as data for all patients was not available at this time. The test battery was to be administered just prior to, at completion of, and at 1 month following whole brain radiation therapy to 37.5 Gy at 2.5 Gy per fraction once daily. Between November 2000 and August 2001, 59 patients were enrolled to the trial. Results: Patient characteristics included: 32% > 65 years; 44% performance status 0; 81% with multiple brain metastases. Patient compliance with the test battery at the three time points is summarized in the table below. Overall compliance was >90%. The most common causes of non-compliance were patient related factors (e.g. performance status or inability to understand test instructions) and not institutional error. Conclusions: Neurocognitive evaluation of patients with brain metastases in a multi-institutional and cooperative group setting appears feasible using the test battery and certification process employed in this study. This battery and certification process will be incorporated into future RTOG brain tumor trials. Updated analyses will be presented at the ASTRO meeting.   MMSE HVLT COWAT Ruff 2 & 7 TMT-A TMT-B POMS-SF Pretreatment Forms Compliance (%) 51/51 (100) 47/49 (94) 49/50 (98) 45/48 (94) 49/50 (98) 47/49 (96) 49/51 (96) End of Treatment Compliance (%) 40/42 (95) 40/42 (95) 40/42 (95) 38/41 (93) 42/43 (98) 38/41 (93) 38/41 (93) One Month Follow-Up Compliance (%) 33/34 (97) 27/31 (87) 29/32 (91) 23/29 (79) 23/29 (79) 23/29 (79) 29/32 (91)

2683 W. Seiferheld, A. Chakravarti, K. K. Ang, X. Tu, E. Hammond, W. Curran Jr and M. Mehta: Overexpression of the Epidermal Growth Factor Receptor (Egfr), as Determined by EGFR Immunostaining on Tissue Microarrays, Fails to Demonstrate Prognostic Value for Patients with Glioblastoma Multiforme: A Report from RTOG 74-01, 79-18, 83-02, 84-09, 90-06, 93-05, 96-02, and 98-06. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):96, 2002. (oral pres) Purpose/Objective: The epidermal growth factor receptor has previously been found to be overexpressed in 50% of patients with glioblastoma multiforme (GBM). Prior studies on other tumor types and also on GBMs using either genomic methods or quantitative Western analysis suggest that EGFR amplification/overexpression may be associated with adverse outcome. However, whether EGFR immunostaining carries independent prognostic value on multivariate analysis with RTOG recursive partitioning analysis (RPA) factored in has yet to be reported and was the primary objective of this study. Materials/Methods: The study population comprised of 156 GBM patients from RTOG studies 7401, 7918, 8302, 8409, 9006, 9305, 9602, and 9806 in whom sufficient pretreatment tumor biopsy specimens were available for immunohistochemical assay (IHC). Quantitative EGFR-IHC was done with SAMBA 4000 Cell Image Analysis System, without knowledge of clinical outcome, to yield mean optical density (MOD), staining index (SI), and quick score. These EGFR-IHC parameters were correlated with the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) classes and, subsequently, with overall survival. Results: The data revealed that GBM exhibited a wide variation in EGFR expression (MOD:7.63-165.33, SI: 5.6-99.9, and QS: 0.47-162.2) with a relatively strong correlation between MOD and SI (r: 0.67). There was no correlation between EGFR expression and RPA classes (r: 0.08-0.10). The overall survival of patients with high EGFR expressing tumors (>median MOD) was not noticeably different than those of patients with lower EGFR expression tumors (median survival time 10.8 mo. vs. 12.6 mo., P=0.71). Other cutpoints were also investigated with similar results. Multivariate analysis including RPA class, MOD, and SI also indicated that neither MOD nor SI predict survival (each with a hazard ratio of 1.0). Conclusions: EGFR expression, as determined by immunohistochemistry, does not appear to have prognostic value for GBM patients, although it has yet to be determined whether this is an artifact of EGFR detection by immunohistochemistry compared to genomic/quantitative Western analysis.

2662 L. Souhami, C. Scott, D. Brachman, E. Podgorsak, M. Werner-Wasik, R. Lustig, C. Schultz, W. Sause, P. Okunieff, J. Buckner, L. Zamorano, M. Mehta and W. Curran Jr: Randomized Prospective Comparison Of Stereotactic Radiosurgery (SRS) Followed By Conventional Radiotherapy (RT) With BCNU To RT With BCNU Alone For Selected Patients With Supratentorial Glioblastoma Multiforme (GBM): Report Of RTOG 93-05 Protocol. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):94-95, 2002. (oral pres) Purpose/Objective: RTOG 9305 was a prospective randomized trial evaluating upfront SRS followed by RT with BCNU to RT with BCNU to compare survival, patterns of failure, toxicity and quality of life between the two arms, in selected patients (pts) with GBM. Materials/Methods: Between February 1994 and September 2000, 203 selected pts with GBM were entered on this phase III trial. Eligible pts were > 18 years of age, KPS > 60, with histological proof of a unifocal (< 4 cm) GBM. Pts were stratified by age and KPS. Pts were randomly assigned to receive: 1) 60 Gy/ 30 fractions/2 Gy once daily plus BCNU 80 mg/m2 days 1, 2, 3 of RT then q 8 weeks for a total of 6 cycles (Arm 1), or 2) SRS (15-24 Gy) followed by the same RT and BCNU (Arm 2). A total of 186 pts enrolled were analyzable (4 pts in Arm 1 and 17 in Arm 2 excluded). The primary reason for ineligibility on the SRS arm was due to the tumor being too large at time of SRS. The pretreatment patient characteristics, including age, KPS, RTOG RPA class and pre/post surgery tumor size, were well balanced between the arms. The Spitzer Quality of Life index was used to measure general quality of life (QOL) and the Mini Mental Status Examination (MMSE) was used for cognitive functioning. We used the standard error of measurement (SEM) to determine clinically meaningful change in the scores. Results: At a median follow-up time of 44 months, the median survival for Arm 1 was 14.1 months (95% CI: 11.0, 14.9) and it was 13.7 months (95% CI: 11.3, 15.2) for arm 2, P = 0.5328. The 24 and 36 months survival rates were 22% and 16% vs 18% and 8% for Arm 1 and 2, respectively. Similarly, there was no difference in survival between the arms when analyzed by RTOG RPA classes III or IV (median survivals of 14.7 and 14.2 for Arms 1 and 2, respectively). Compliance was very good for conventional RT and chemotherapy but 18% of the SRS pts had unacceptable deviations. Five pts died on Arm 1 due to chemotherapy toxicity compared to two pts on the Arm 2. Acute and late grade 3 RT-related toxicities were more frequent on Arm 2 and there were no grade 4 toxicities. The patterns of failure were similar between the arms with more than 90% of the pts presenting a component of local failure. QOL deterioration (Spitzer index) at the end of therapy, compared to baseline, was similar between the arms (40% on Arm 1 and 50% on Arm 2, P = 0.4606). Using the MMSE only, approximately 30% of the pts, in each arm, had a cognitive decline in that timeframe. There was no difference in quality-adjusted survival between the two arms. Conclusions: As used in this trial, the results show that the use of upfront SRS followed by RT and BCNU does not lead to an improved survival nor changes patterns of failure in this group of selected pts with GBM. Furthermore, there was no difference in general QOL and cognitive functioning between the arms.

2620 P. Sperduto, C. Scott, D. Andrews, M. Schell, A. Flanders, M. Werner-Wasik, W. Demas, J. Ryu, L. Gaspar, J.-P. Bahary, L. Souhami, M. Rotman and W. Curran: Stereotactic Radiosurgery With Whole Brain Radiation Therapy Improves Survival In Patients With Brain Metastases: Report Of Radiation Therapy Oncology Group Phase III Study 95-08. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):3, 2002. (plenary pres) Purpose/Objective: To determine if stereotactic radiosurgery (SRS) after conventional whole brain radiation therapy (WBRT) improves overall survival when compared to WBRT alone in patients with 1–3 brain metastases. Secondary objectives include a comparison of sites of recurrence and cause of death. Materials/Methods: Between 1/96 and 6/01, 333 patients from 34 institutions were randomized to receive WBRT + SRS or WBRT alone. The WBRT was given at 250cGy/fraction to 3750 cGy in 3 weeks. The SRS dose was based on tumor size and was delivered within one week of completion of WBRT. The study was designed to detect a 50% improvement in median survival time (MST) with 80% statistical power for all patients and a 75% improvement in MST in patients with solitary metastases. Central radiology review of local control and salvage therapy analyses will be presented. Results: There was a statistically significant survival advantage with WBRT + SRS for the following patients: solitary brain metastases (MST 6.5 vs 4.9 months, P=0.04), RPA class I (MST 11.6 vs 9.6 months, P=0.05), age < 50 (9.9 vs 8.3 months, P=0.04) and patients with non-small cell lung cancer or any squamous cell carcinoma (5.9 vs 3.9 months, P=0.05). Also, patients with initial KPS of 90–100 appeared to benefit (10.2 vs 7.4 months) without reaching statistical significance (p=0.07). Furthermore, all patients in the WBRT + SRS group were more likely to have a stable or improved performance status (KPS) at 3 months (50% vs 33%, P=0.02) and at 6 months (43% vs 27%, P=0.03). There was no significant difference in cause of death but there was a significant difference in local control as reported by the treating institution (82% vs 71% at one year for WBRT + SRS vs WBRT alone, respectively (p=0.01). Toxicities were comparable between the two treatment groups. Conclusions: WBRT + SRS provided a survival advantage compared to WBRT alone in each of the following patient categories: 1) solitary brain metastasis; 2) RPA class I ; 3) age < 50; 4) non-small cell lung cancer or any squamous cell carcinoma. Furthermore, all subsets of patients in the WBRT + SRS group were more likely to have a stable or improved performance status than those in the WBRT alone group. Systemic disease remained the primary cause of death (>2/3) in both groups and improved systemic therapies are needed.

2677 C. Thomas Jr., B. Berkey, B. Minsky, L. Gaspar, A. Herskovic , T. Rich and L. Gunderson: Recursive Partitioning Analysis (RPA) Of Pre-Treatment Variables For 416 Patients With Loco-Regional Esophageal Cancer Treated With Concomitant Chemoradiotherapy (CT-RT) On Intergroup And Radiation Therapy Oncology Group (RTOG) Trials. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):131, 2002. (oral pres) Purpose/Objective: Specific aims of this analysis were to analyze the relative contributions of uniformly collected pre-treatment patient (pt) and tumor-related variables to survival and to identify terminal nodes via RPA that could be utilized as stratification variables for future phase 3 trials. Materials/Methods: From two Intergroup trials (85-01, N=130; 94-05, N=218) and one RTOG trial (92-07, N=68), we identified 416 pts who were treated with concomitant cisplatin-based CT-RT and were analyzed for survival by RPA in order to define prognostic classes. The following pre-treatment factors were evaluated: histology, age, weight loss, KPS, gender, race, T-stage, tumor location and size, N-stage, and degree of dysphagia. The entire dataset was considered as the initial node. The criteria for split points was the smallest p-value less than unadjusted 0.05. Results: Of 416 pts, 336 (81%) were dead at the time of the analysis. RPA identified only one significant split: pre-treatment weight loss in the prior 6 months <10% vs. > 10% (Figure). Within the <10% weight loss cohort we observed a trend toward improved survival in pts with a KPS 90-100 compared to those with a KPS 50-80 (p=0.098). Conclusions: Unlike our experience with malignant glioma, brain metastases, and locally advanced non-small cell lung cancer, RPA failed to identify novel prognostic information that could be incorporated into the stratification scheme of future CT-RT trials for esophageal cancer. The lack of endoscopic ultrasound as an adjunct to the initial staging work-up precludes an accurate determination of T-stage and should be incorporated into the staging algorithm of future cooperative group trials. Furthermore, our analysis may validate % weight loss as a stratification variable for esophageal cancer. Finally, this parameter may be utilized when comparing pt. cohorts that have been treated with definitive CT-RT versus those pts. where surgery has been a component of therapy. This Abstract was supported by grant number RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115 from the National Cancer Institute (NCI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI. Figure: Overall survival by weight loss in last six months

2669 R. Valicenti, K. Winter, J. Cox, H. Sandler and J. Michalski: The Effect On Toxicity Of Induction Hormonal Therapy In Prostate Cancer Patients Receiving Dose Escalated 3D Conformal Radiation Therapy On RTOG 94-06. Submitted to Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [54] (2):133-134, 2002. (oral pres) Purpose/Objective: This study determines the effect on toxicity by the addition of induction hormonal therapy (HT) to 3D conformal radiation therapy (3D CRT) in RTOG 94-06. Materials/Methods: Between 8/94 and 2/00, 583 eligible prostate cancer patients enrolled on the first three dose levels of RTOG 94-06, a phase I/II dose escalation 3D CRT trial. Two hundred and seven men initiated HT between 2 to 3 months prior to 3D CRT, and completed all HT no longer than 3 months after radiotherapy. 36 continued HT more than 3 months after completing radiotherapy and were excluded. The 547 patients evaluable for this analysis of toxicity were treated at dose level I (68.4 Gy), level II (73.8 Gy), or level III (79.2 Gy). All dose prescriptions were to the minimum isodose surface encompassing the planning target volume (PTV) (dose levels I and II) or the clinical target volume (CTV) (dose level III). Men were stratified into 3 risk groups according to their relative risk of seminal vesicles (SV) invasion:<15% (Group I) vs. >15% (Group II) or to T stage (T1, 2 vs. T3 tumors (Group III). In Group II patients only, there was a CTV reduction to treat only the prostate after delivery of 55.8 Gy to a PTV including the SV. All HT consisted of an LHRH agonist with or without a non-steroidal anti-androgen. The rates of acute and late effects > grade 2 were compared between groups of patients receiving induction HT or no HT in addition to 3D CRT. Results: The distribution of patients according to group, dose level, and induction HT is summarized in Table 1. The majority of men (50%) were treated on dose level II to 73.8 Gy. On univariate analysis, induction HT significantly increased the likelihood of acute GU effects > grade 2 (22% to 32%, P=0.009). Hormonal therapy did not have a significant effect on any other acute or late toxicity. On multivariate analysis, the variable: percent of the bladder receiving > the reference dose (< 30% vs. >30%) was an independent predictor of acute GU effects (p=0.0009, RR=2.07, CI:1.88-2.28). Although induction HT was not a significant predictor in itself, its interaction with adverse baseline urinary status was a significant factor (p=0.011, RR=4.31, CI: 1.68-5.29). Neither dose level or disease group were significant factors in the multivariate analysis. Conclusions: Induction HT did not have an independent effect on the risk of side effects after 3D CRT. However, induction HT combined with 3D CRT significantly increased the risk of acute GU effects compared to 3D CRT alone in men with poor baseline urinary function. In patients receiving 3D CRT, no more than 30% of bladder volume should exceed the prescribed reference dose. Supported by Grants No. RTOG CA21661, CA60267, and Stat U10CA32115 from the NCI. Table 1. Dose Level Group 1 Group II Group III All Groups (subtotal) Total HT No HT HT No HT HT No HT HT No HT I (68.4 Gy) 6 67 4 30 1 2 11 99 110 II (73.8 Gy) 17 77 49 58 62 12 128 147 275 III (79.2 Gy) 29 73 39 21 0 0 68 94 162 All Dose Levels (Subtotal) 52 217 92 109 63 14 207 340   Total 269 201 77   547