2003 ASTRO Presenters Booklet [PDF]

Reference	Study Number
E. Shaw, W. Seiferheld, C. Scott, C. Coughlin, S. Leibel, W. Curran Jr and M. Mehta: Reexamining the Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) for Glioblastoma Multiforme (GBM) Patients. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S135-136, 2003. (pres as oral pres)	multi-studies (pres as oral pres)
M. Pilepich, K. Winter, C. Lawton, R. Krisch, H. Wolkov, B. Movsas, E. Hug, S. Asbell and D. Grignon: Androgen Suppression Adjuvant to Radiotherapy in Carcinoma of the Prostate. Long-Term Results of Phase III RTOG Study 85-31. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S172-173, 2003. (pres as oral pres)	85-31 (pres as oral pres)
D. Brat, W. Seiferheld, A. Perry, E. Hammond, K. Murray, A. Schulsinger, M. Mehta and W. Curran Jr: FISH Analysis of Genetic Markers of Prognosis for High Grade Astrocyotmas Using Tissue Micro-Arrays from RTOG Clinical Trials. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S135, 2003. (pres as oral pres)	multi-studies (pres as oral pres)
J. Michalski, K. Winter, J. Purdy, M. Parliament, H. Wong, C. Perez, M. Roach III, W. Bosch and J. Cox: Toxicity Following 3D Radiation Therapy for Prostate Cancer on RTOG 94-06 Dose Level V. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S151, 2003. (pres as oral pres)	94-06 (pres as oral pres)
S. Spencer, J. Harris, R. Wheeler, M. Machtay, C. Schultz, W. Spanos, M. Rotman, R. Meredith and K. K. Ang: Late Effects of RTOG-9610: Re-Irradiation and Chemotherapy in Patients with Squamous Cell Cancer of The Head and Neck. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S307, 2003. (pres as poster disc)	96-10 (pres as poster disc)
A. Pollack, M. DeSilvio, L. Khor, R. Li, T. Al-Saleem, E. Hammond, V. Venkatesan, R. Byardt, G. Hanks, M. Roach III, W. Shipley and H. Sandler: Ki-67 Staining Is a Strong Predictor of Patient Outcome for Prostate Cancer Patients Treated with Androgen Deprivation Plus Radiotherapy: An Analysis of RTOG 92-02. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S200-201, 2003. (pres as oral pres)	92-02 (pres as oral pres)
A. Chakravarti, W. Seiferheld, H. Robins, A. Guha, P. Sperduto, A. Choucair, D. Brachman and M. Mehta: Phase I Results from RTOG BR-0211, A Phase I/II Study of an Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), ZD 1839 (Iressa), with Radiation Therapy in Glioblastoma Multiforme (GBM). Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):s329, 2003. (pres as poster disc)	02-11 (pres as poster disc)
J. Bradley, M. Graham, K. Winter, J. Purdy, R. Komaki, W. Roa, J. Ryu, W. Bosch and B. Emami: Acute and Late Toxicity Results of RTOG 9311: A Dose Escalation Study Using 3D Conformal Radiation Therapy in Patients with Inoperable Non-Small Cell Lung Cancer. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S137, 2003. (pres as oral pres)	93-11 (pres as oral pres)
M. Werner-Wasik, C. Scott, B. Movsas, C. Langer, L. Sarna, N. Nicolaou, R. Komaki, M. Machtay, C. Smith, R. Axelrod and R. Byhardt: Amifostine As Mucosal Protectant in Patients with Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Receiving Intensive Chemotherapy and Thoracic Radiotherapy (RT): Results of the Radiation Therapy Oncology Group (RTOG) 98-01 Study. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S216, 2003. (pres as oral pres)	98-01 (pres as oral pres)
X. Tu, B. Berkey, H. Zhang, E. Hammond, J. Cooper, S. Spencer, A. Trotti, K. Fu, L. Milas and K. K. Ang: Impact of EGFR Expression on the Response of Advanced Head and Neck Carcinomas to Concomitant Boost Radiotherapy in a RTOG Phase III Trial (90-03). Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S157, 2003. (pres as oral pres)	90-03 (pres as oral pres)
W. Hartsell, C. Scott, D. Watkins Bruner, C. Scarantinio, R. Ivker, M. Roach III, J. Suh, W. Demas, B. Movsas, I. Petersen and A. Konski: Phase III Randomized Trial 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 Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S124, 2003. (plenary pres)	97-14 (plenary pres)
A. T. Turrisi, C. Scott, V. Rusch, K. S. Albain, F. Shepherd, C. Smith, Y. Chen, R. Livingston, D. Gandara, G. Darling, D. Johnson and M. Green: Randomized Trial of Chemoradiotherapy to 61 Gy [no S] Versus Chemoradiotherapy to 45 Gy Followed by Surgery [S] Using Cisplatin Etoposide in Stage IIIa Non-Small Cell Lung Cancer (NSCLC): Intergroup Trial 0139, RTOG (9309). Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S125-126, 2003. (plenary pres)	93-09 (plenary pres)
L. Hughes, K. Heydon, P. Edmonds, M. Roach III, H. Wolkov, S. Shah, A. Pollack, E. Hammond and A. Dicker: Vascular Endothelial Growth Factor (VEGF) Expression in Locally Advanced Prostate Cancer (LAPC): Secondary Analysis of Radiation Therapy Oncology Group (RTOG) 86-10. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S201-202, 2003. (pres as oral pres)	86-10 (pres as oral pres)
A. Konski, E. Sherman, M. Krahn, K. Bremner, J. Beck, D. Watkins Bruner and M. Pilepich: Monte Carlo Simulation of a Markov Model for a Phase III Clinical Trial Evaluating the Addition of Total Androgen Suppression (TAS) To Radiation Versus Radiation Alone for Locally Advanced Prostate Cancer (RTOG 86-10). Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S215-216, 2003. (pres as oral pres)	86-10 (pres as oral pres)
M. Graham, R. Paulus, D. Ettinger, J. Bradley, M. Pilepich, M. Machtay, R. Komaki, J. Atkins and W. Curran Jr: RTOG 9705, A Phase II Trial of Postoperative Adjuvant Paclitaxel/Carboplatin and Thoracic Radiotherapy in Resected Stage II and IIA Non-Small Cell Lung Cancer (NSCLC) Patients - Promising Long Term Survival Results. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S140-141, 2003. (pres as oral pres)	97-05 (pres as oral pres)
R. Komaki, S. Swann, D. Ettinger, B. Glisson, A. Sandler, B. Movsas and R. Byhardt: Phase I Dose-Escalation Study of Thoracic Irradiation with Concurrent Chemotherapy for Patients with Limited Small Cell Lung Cancer (LSCLC). Radiation Therapy Oncology Group RTOG. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S139, 2003. (pres as oral pres)	97-12 (pres as oral pres)

E. Shaw, W. Seiferheld, C. Scott, C. Coughlin, S. Leibel, W. Curran Jr and M. Mehta: Reexamining the Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) for Glioblastoma Multiforme (GBM) Patients. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S135-136, 2003. (pres as oral pres) Purpose/Objective: To determine whether the original RPA classification of malignant glioma patients (pts) could be improved upon by restricting the model to GBM pts, considering additional/different baseline variables, and by adding newer studies to the RTOG malignant glioma database. Materials/Methods: The new RPA considered 42 baseline variables and included 1672 GBM pts, compared to 32 variables and 1288 GBM pts (plus 290 AA) included in the original analysis. In the new analysis, radiation dose assigned rather than radiation dose received was used as the radiation treatment variable. The new analysis included two additional studies (RTOG 90-06 and 94-11), and excluded radiation treatment (RT) alone arms from the original database, such that all patients received BCNU plus RT. In order to compare the models, they were applied to a "test set" of 488 pts on six Phase II RTOG studies (76-11, 79-03, 80-07, 84-09, 95-13, 96-02), and evaluated by calculating explained variation (squared error loss), and determining whether the RPA classes provided statistically significantly distinct survival groups. Results: The original model explained more statistical variation than the new model in the test set of RTOG studies. However, RPA classes V and VI from the original model were not statistically significantly different when applied to the test set of studies, i.e., the variables mental status and radiation dose are no longer required. Therefore, we chose a simplified version of the original RPA model by combining classes V and VI, which results in three classes with statistically significantly distinct survival. This simplified model is easier to apply, since it involves only four variables: age, KPS, extent of resection (gross total or subtotal resection (G/STR) vs biopsy), and neurologic function (working (W+) or not working (W-)). Applying this simpler version of the original RPA model to the updated glioma database provided the results shown in the table and figure below. Conclusions: A simplified version of the original RPA model for only GBM patients combines RPA classes V and VI and results in three distinct prognostic groups defined by age, performance status, extent of resection, and neurologic function. The RTOG will use this simplified RPA classification in future clinical trials. RPA Class Definition Median Survival Time 1-Year Survival Rate 3-Year Survival Rate 5-Year Survival Rate III Age<50, KPS>=90 17.1 mos 70% 20% 14% IV Age<50, KPS<90 11.2 mos 46% 7% 4%   Age>=50, KPS>=70, G/STR, W+         V+VI Age>=50, KPS>=70, G/STR, W- 7.5 mos 28% 1% 0%   Age>=50, KPS>=70, Biopsy           Age>=50, KPS<70

M. Pilepich, K. Winter, C. Lawton, R. Krisch, H. Wolkov, B. Movsas, E. Hug, S. Asbell and D. Grignon: Androgen Suppression Adjuvant to Radiotherapy in Carcinoma of the Prostate. Long-Term Results of Phase III RTOG Study 85-31. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S172-173, 2003. (pres as oral pres) Purpose/Objective: RTOG (Radiation Therapy Oncology Group) Protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression using goserelin in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy. Materials/Methods: Eligible patients were those with Clinical Stage T3 or those with regional lymphatic involvement. Patients who have undergone prostatectomy were eligible if there was histologically documented penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement. Stratification was based on histological differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either radiotherapy and adjuvant goserelin (Arm I) or to radiotherapy alone followed by observation and application of goserelin at the time of relapse (Arm II). In Arm I the drug was to be started during the last week of radiation therapy and was to be continued for at least 2 years, preferably indefinitely or until signs of progression. Results: From 1987 to 1992 when the study was closed, 977 patients were entered: 488 on Arm I and 489 on Arm II. As of December 2002, the median follow-up for all patients reached 7.3 years and for live patients 10 years. The results are summarized on the table. Conclusions: Adjuvant androgen suppression has resulted in significant improvement in all end points including absolute survival.

D. Brat, W. Seiferheld, A. Perry, E. Hammond, K. Murray, A. Schulsinger, M. Mehta and W. Curran Jr: FISH Analysis of Genetic Markers of Prognosis for High Grade Astrocyotmas Using Tissue Micro-Arrays from RTOG Clinical Trials. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S135, 2003. (pres as oral pres) Purpose/Objective: Survival varies for patients with high grade astrocytomas. Aside from histologic grade, morphologic features do not reliably predict prognosis. Our goal was to determine if genetic losses from chromosomes 1p, 19q, 9p21, or 10q were associated with long or short survival in anaplastic astrocytoma (AA) and glioblastoma (GBM). We performed fluorescence in situ hybridization (FISH) analysis for these loci on tissue micro-arrays containing 106 high grade astrocytomas from Radiation Therapy Oncology Group (RTOG) clinical trials and correlated the findings with patient survival groups. Materials/Methods: Tissue micro-arrays were constructed using formalin-fixed, paraffin-embedded specimens from 18 AAs and 88 GBMs from RTOG protocols 74-01, 79-03, 79-18, 83-02, 90-06, 93-05, 94-04, 96-02, and 98-06. Cases were selected based on short or long survival. For AA, short and long survivals were <2 yrs and >4 yrs, respectively. For GBM, short and long survivals were <6 mos and >18 mos. Dual-color FISH was performed on 5 micron array sections. For chromosomes 1p and 19q, paired probes were directed at 1p32 and 19q13.4. Paired probes for chromosomes 9p21 and 10q were CEP9/9p21(p16) and CEP10/10q23(PTEN). "Deletion" was defined as >50% nuclei with only one fluorescent signal. Survivals were dichotomized into short- or long-term groups and chromosomal markers were defined as present or deleted. Data was analyzed using Fisher's exact test of association and logistic regression. AAs and GBMs, 1p and 19q deletions, and 9p21 and 10q deletions were analyzed separately and combined (adjusted p=0.025). Results: FISH analysis was possible on 65 to 85 tumors per micro-array depending on the marker. Chromosome 1p deletions were noted in 2 (17%) AAs and 0 GBMs, whereas 19q deletions were noted in 3 (20%) AAs and 7 (10%) GBMs. Combined 1p and 19q loss was detected in 2 (13%) AAs and 0 GBMs. Chromosome 9p21 loss was seen in 5 (63%) AAs and 39 (68%) GBMs. Chromosome 10q loss was detected in 4 (27%) AAs and 48 (71%) GBMs. 19q deletions were more frequent in long term than short term survivors for AAs (43% vs. 0%), GBMs (15% vs. 5%), and AA+GBM (20% vs. 4%). 10q deletions were more frequent in short term than long term survivors for AAs (38% vs. 14%), GBMs (75% vs. 66%), and AA+GBM (68% vs. 56%). 9p21 deletions were slightly more frequent in short term than long term survivors for AAs (67% vs. 60%), GBMs (72% vs. 64%) and AA+GBM (72% vs. 64%). No comparisons were statistically significant. Conclusions: We found that losses of chromosome 1p alone and the combined loss of 1p and 19q were rare events in high grade astrocytomas. This contrasts with oligodendrogliomas, in which combined 1p and 19q loss is frequent (60-70%) and predictive of prolonged survival. The long-term survival group of high-grade astrocytomas showed a trend towards a higher frequency of 19q loss (p=0.041). 9p21 and 10q deletions, generally regarded as late events in the progression to GBM, were slightly more frequent in short term survivors. Long and short-term survival groups of high-grade astrocytomas may have dissimilar frequencies of 19q, 9p21, and 10q deletions. A study of overall patient survival with these genetic markers could address prognostic significance more definitively.

J. Michalski, K. Winter, J. Purdy, M. Parliament, H. Wong, C. Perez, M. Roach III, W. Bosch and J. Cox: Toxicity Following 3D Radiation Therapy for Prostate Cancer on RTOG 94-06 Dose Level V. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S151, 2003. (pres as oral pres) Purpose/Objective: This is the first report of toxicity outcomes on dose level V (78 Gy) on RTOG 9406 for stage T1,2 adenocarcinoma of the prostate. Materials/Methods: Two hundred twenty-five patients entered on this cooperative group phase I/II 3D CRT dose escalation trial for localized (clinical stage T1,2) prostate cancer to a dose of 78 Gy (Level V); 216 patients analyzable for late toxicity. Minimum 2 Gy/fraction was prescribed to planning target volume (PTV). PTV margins of 5 to 10 mm were required. Patients were stratified according to risk of seminal vesicle invasion (SVI) based upon Gleason score and initial PSA. Group I patients had SVI risk of <15%. Group 2 patients had SVI risk of >=15%. Group 1 received 78 Gy to the prostate PTV. Group 2 received 54 Gy to the prostate and seminal vesicles PTV1 and a boost to prostate PTV2 to 78 Gy. Average months at risk after completion of therapy were 18.5 and 18.4 months for Group 1 and 2, respectively. Frequency of grade 3+ late effects 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 170 patients treated to dose level III (79.2 Gy in 1.8Gy/fraction) to see if fraction size influenced toxicity. Dose level III permitted narrower margins for the high dose volume compared to dose level V. Results: Acute toxicity at dose level V is remarkably low with grade 3 acute effects reported in only 2% of Group 1 and 4% of Group 2 patients. No grade 4 or 5 acute toxicities were reported. Late grade 3+ toxicity continues to be low compared to RTOG historical controls. Only 6 grade 3+ late effects were seen in Group 1 when 16.5 were expected (p=0.0095) and 6 in Group 2 when 13.5 were expected (p=0.042). Four patients in group 1 and 3 patients in Group 2 have experienced grade 3 bladder toxicity. Two patients in Group 1 and three patients in Group 2 experienced a grade 3 bowel toxicity. A single patient in Group 2 experienced a grade 4 bowel toxicity. No other grade 4 or 5 late effects have been reported. There were no statistical differences in rates of acute complications in patients who were treated in level III to 79.2 Gy at 1.8 Gy/fraction or in level V to 78 Gy at 2.0 Gy/fraction. However, the rates of late grade 2+ toxicities (any type) were 13% for level III vs 30% at level V for Group 1 patients (p=0.00085) and 9% at level III vs 35% at level V (p<0.0001) at 24 months. There is 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 although the differences were not statistically significant. The shorter follow-up on dose level V suggests these differences may increase with time. Conclusions: The rate of grade 3+ toxicity from 3DCRT with 78 Gy in 2.0 Gy fractions remains better than expected compared to historical controls. However, low-grade late toxicity is significantly higher in dose level V than dose level III. These differences may be dose and/or volume related.

S. Spencer, J. Harris, R. Wheeler, M. Machtay, C. Schultz, W. Spanos, M. Rotman, R. Meredith and K. K. Ang: Late Effects of RTOG-9610: Re-Irradiation and Chemotherapy in Patients with Squamous Cell Cancer of The Head and Neck. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S307, 2003. (pres as poster disc) Purpose/Objective: A phase II trial was conducted to identify and estimate the incidence of acute and late toxicities, and estimate long-term (2-year) survival in patients with recurrent squamous cell cancer of the head and neck (SCH&N) treated with combination chemotherapy and re-irradiation (RRT). The acute effects have already been presented. This is an initial report of the late effects observed. Materials/Methods: Eighty-six patients with second primary or recurrent SCH&N were registered between August 1996 and April 1999. Two patients were found ineligible, and 1 patient received no protocol therapy, leaving 83 analyzable patients. Seventy-five percent presented with recurrences, 23% with second primaries, and 1% with both. The median dose of prior RT was 64.4Gy, with a median of 2.4 years from prior RT. Patients were treated with daily concurrent 5 Fluorouracil IV bolus, Hydroxyurea and BID RT 60Gy total using 1.5Gy/fx for 4 weekly cycles each separated by 1 week of rest. Standard 2.0cm minimal margins were used around gross disease. The details have been reported previously. The cumulative incidence method was used to estimate late effects in patients that lived beyond 1 year. Results: Estimated 1- and 2-year survival rates are 42.6%(95% confidence interval 31.7, 53.5) and 17.3%(8.7, 25.8), respectively. Median survival is 9.3 months. There were 33 1-year survivors, including 11 2-year survivors. Estimated cumulative incidence of grade 3 or greater late toxicity (>1 year) was 12.3% by 24 months and 3.2% by 24 months for grade 4 toxicity. There were a total of 4 patients with late toxicity, with 2 reported between 1 and 2 years, and 2 post 2 years. Three of the 4 patients experienced mucosal and pharyngeal toxicity and 1 experienced grade 3 neurological toxicity described as hearing loss. Conclusions: The RTOG strategy of concurrent chemotherapy and RRT appears to remain a viable option in selected patients with unresectable recurrent SCH&N. The late effects observed thus far were noted in 4/33 patients who survived greater than 1 year. These results are encouraging and support the continued effort of the RTOG to identify more efficacious strategies. As we learn more about this population of patients, improved targeting techniques that limit dose to normal tissues should be considered.

A. Pollack, M. DeSilvio, L. Khor, R. Li, T. Al-Saleem, E. Hammond, V. Venkatesan, R. Byardt, G. Hanks, M. Roach III, W. Shipley and H. Sandler: Ki-67 Staining Is a Strong Predictor of Patient Outcome for Prostate Cancer Patients Treated with Androgen Deprivation Plus Radiotherapy: An Analysis of RTOG 92-02. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S200-201, 2003. (pres as oral pres) Purpose/Objective: The proportion of tumor cells stained immunohistochemically for the proliferation marker Ki-67, the Ki-67 staining index (Ki67-SI), has been associated with prostate cancer patient outcome. Few studies have studied radiotherapy (RT)-treated patients and no prior study has investigated patients treated with short term (STAD; 4 mo) or long term (LTAD; 28 mo) androgen deprivation plus RT. In this report, the association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomized between STAD+RT and LTAD+RT. Materials/Methods: There were 537 cases in RTOG 92-02 (35.5%) that had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Time events were measured from randomization. Unless mentioned, covariates were dichotomized in accordance with stratification and randomization criteria as follows: median Age (<=70, >70 years), initial pretreatment PSA (iPSA; <=30, >30 ng/ml), T-category (T2c, T3-T4), Gleason score (2-6, 7-10), and assigned treatment (STAD+RT, LTAD+RT). Results: Median Ki67-SI was 6.5% (range 0-58.2). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n=537) and other patients in RTOG 92-02 (n=977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (p=0.08), BF (p=0.0445), DM (p<0.0001), CSD (p<0.0001) and OD (p=0.0094). For these analyses iPSA was also included as a continuous variable. When categorical variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. In contrast, the 7.1% cut point was related to BF (p=0.09), DM (p=0.0008), and CSD (p=0.017). Ki67-SI was the most significant correlate of DM and CSD. In univariate analysis, the 5 year DM rate (95%CI) was 8.6% (5.2, 12.1%) for Ki67-SI <=7.1%, compared to 17.3% (12.2, 22.3%) for Ki67-SI >7.1% (p=0.0004). The 5 year CSD rates were 3.3% (1.2, 5.5%) and 12.0% (7.4, 15.9%) for Ki67-SIs <=7.1% and >7.1% (p=0.0041). In analyzing patients by assigned treatment, Ki67-SI was the strongest correlate of DM for each group. Because one of the principal effects of LTAD+RT over STAD+RT was the diminution of DM, a detailed analysis of the hazard rates for DM in all possible covariate STAD+RT subgroup combinations (n=16), as referenced to the most favorable LTAD+RT subgroup, was performed. The goal was to identify subgroups treated with STAD+RT that had the same DM rate as those who received LTAD+RT and would therefore not require LTAD. The 4 favorable subgroups identified had T2c disease, a Ki67-SI <=7.1%, a PSA<=30 or >30 ng/ml, and a Gleason score of 2-6 or 7-10. The 5 year DM rates were 5.2% and 3.6% for the favorable STAD+RT (n=63) and LTAD+RT (n=59) populations (p=0.69). Conclusions: Ki67-SI was the most significant determinant of DM and CSD, and was also associated with OD. The relationship of Ki67-SI to patient outcome is a continuous function, wherein the higher the Ki67-SI the greater the risk of an adverse result. The 7.1% cut point has been confirmed as correlating with DM and CSD, and appears to be useful in the selection of patients who will not benefit from LTAD+RT over STAD+RT. The KI67-SI should be incorporated into the stratification of patients in future trials.

A. Chakravarti, W. Seiferheld, H. Robins, A. Guha, P. Sperduto, A. Choucair, D. Brachman and M. Mehta: Phase I Results from RTOG BR-0211, A Phase I/II Study of an Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), ZD 1839 (Iressa), with Radiation Therapy in Glioblastoma Multiforme (GBM). Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):s329, 2003. (pres as poster disc) Purpose/Objective: EGFR protein overexpression and gene amplification has been associated with adverse outcome in the GBM patient population. There is accumulating preclinical evidence that EGFR can directly mediate resistance to radiation. Therefore, the RTOG has designed a Phase I/II study to determine whether radiation in combination with Iressa, a potent and selective EGFR-TKI, can safely enhance radiation response in GBM patients. This is a report from the Phase I component of RTOG 0211. Materials/Methods: Dose escalation of Iressa has been conducted separately for patients receiving enzyme-inducing anticonvulsants (EIACD) and for non-EIACD patients. EIACD dose escalations are being examined in the range from 250 to 750mg during RT (two escalations), followed by maintenance dose levels of 500mg, with escalation permitted up to 750mg. Non-EIACD dose escalations are being examined in the range of 250 to 500mg (one escalation), followed by maintenance dose levels of 500mg. As of 2/18/03, 23 patients have been accrued: 12 patients in the EIACD group and 11 patients in the non-EIACD group. Of these 23 patients, 16 have been evaluated to date for toxicity. Results: Using the standard 3+3 design, Iressa doses have been permitted to be safely escalated to 750mg in the EIACD group and to 500mg in the non-EIACD group, with these respective arms presently open for accrual. No Grade 4 non-hematologic toxicity attributable for Iressa + RT has been reported for either group. Grade 3 toxicities to date are as follows: One case of metabolic abnormalities (elevated liver enzymes) in the EIACD group at 500mg; and two cases of skin rash and one case of elevated liver enzymes in the non-EIACD group at 250mg. Conclusions: The combination of Iressa + RT appears to be well tolerated in both EIACD and non-EIACD patients in the dose levels examined thus far. Data for the 750mg arm in the EIACD group and 500mg arm in the non-EIACD group will be available at the time of the RTOG Annual Meeting. The Phase II component will then proceed at the maximum tolerated doses of Iressa for the EIACD and non-EIACD patients, respectively. This publication was supported by grant number (RTOG 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.

J. Bradley, M. Graham, K. Winter, J. Purdy, R. Komaki, W. Roa, J. Ryu, W. Bosch and B. Emami: Acute and Late Toxicity Results of RTOG 9311: A Dose Escalation Study Using 3D Conformal Radiation Therapy in Patients with Inoperable Non-Small Cell Lung Cancer. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S137, 2003. (pres as oral pres) Purpose/Objective: To prospectively evaluate acute and late morbidities from a multi-institutional 3-dimensional radiation therapy dose escalation study for inoperable non-small cell lung cancer. Materials/Methods: One-hundred and seventy-nine patients were enrolled in a Phase I/II 3-dimensional radiation therapy dose escalation trial. One hundred and seventy-seven patients were eligible. The use of concurrent chemotherapy was not allowed. Twenty-five patients received neoadjuvant chemotherapy. Patients were stratified at escalating radiation does levels depending on their V20 (the percentage of their total lung volume that would receive in excess of 20 Gy with the treatment plan). Patients with a V20 <25% (Group 1) received 70.9 Gy/33 fractions, 77.4 Gy/36 fractions, 83.8 Gy/39 fractions and 90.3 Gy/42 fractions, successively. The treatment arm for patients with a V20 > 37% (Group 3) closed early secondary to poor accrual (2 patients) and the perception of excessive risk for the development of pneumonitis. Toxicities occurring or persisting beyond 90 days following the start or radiation therapy were scored as late toxicities. Estimated toxicity rates were calculated based on the cumulative incidence method. Results: The Following acute > grade 3 toxicities were observed for Group 1; 70.9 Gy (one weight loss), 77.4 Gy (one nausea and one hematologic), 83.8 Gy (one hematologic), and 90.3 Gy (three lung). The following acute > grade 3 toxicities were observed for Group2; 70.9 Gy (none) and 7 7.4 Gy (two lung). No patients developed acute > grade 3 esophageal toxicity. Late developing toxicities are shown in the table below. The estimated rates of > grade 3 late lung toxicity at 18 months are 7%, 16%, 0%, and 13% for Group 1 patients receiving doses of 70.9, 77.4, 83.8, and 90.3 Gy, respectively. Group 2 patients have estimated late lung toxicity rates of 15% at 18 months for both 70.9 and 77.4 Gy dose levels. The estimated rates of late > grade 3 esophagus toxicity at 18 months are 7%, 0%, 3% and 6% respectively, for Group 1 patients and 0% and 4%, respectively, for Group 2 patients. Conclusions: Acute toxicity rates were acceptable for Groups 1 and 2. However, late toxicities were more pronounced. Late lung toxicity can be expected to occur at a rate of 15% for patients with a F20 <=% treated to radiation therapy dose levels of 77.4 Gy or greater without the use of concurrent chemotherapy. For patients with a V20 of 25-37%, late lung toxicity occurs at a rate of 15% for doses of 70.9 Gy or greater. The late esophageal toxicity rates should be interpreted with caution, as they are not controlled for esophageal dose or volume irradiated. A late death resulting from a TE fistula at the 90.3 Gy dose level is concerning. A more detailed analysis of esophageal toxicity will be presented.

M. Werner-Wasik, C. Scott, B. Movsas, C. Langer, L. Sarna, N. Nicolaou, R. Komaki, M. Machtay, C. Smith, R. Axelrod and R. Byhardt: Amifostine As Mucosal Protectant in Patients with Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Receiving Intensive Chemotherapy and Thoracic Radiotherapy (RT): Results of the Radiation Therapy Oncology Group (RTOG) 98-01 Study. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S216, 2003. (pres as oral pres) Purpose/Objective: RTOG conducted a Phase III randomized trial to evaluate the effect of amifostine (AMI) on reducing the incidence and severity of esophagitis and pneumonitis among patients (pts) with NSCLC receiving induction chemotherapy followed by concurrent hyperfractionated RT and chemotherapy. Patient symptom distress was also evaluated. Materials/Methods: Good-prognosis (minimal weight loss, KPS >70) patients with inoperable Stage II and unresectable Stage IIIA/B NSCLC received induction paclitaxel (P) 225mg/m2 IV day 1, 22 & carboplatin (C) AUC 6 day 1, 22 followed by concurrent weekly P (50mg/m2 IV) & C (AUC 2) & hyperfractionated RT (69.6 Gy/1.2 Gy BID) starting day 43 and were randomized at registration to receive AMI (500 mg iv once daily, four times per week to a total dose of 12,000 mg) during concurrent chemo-radiotherapy versus no AMI. AMI was given before the morning RT fraction (n=15) and later before the afternoon RT fraction (n=105). Toxicity was evaluated by health care providers with NCI-CTC and RTOG criteria (maximum toxicity and weekly Physician Dysphagia Log, PDL), as well as patients themselves using daily Patient Swallowing Diary (PSD), allowing calculation of area-under-the-curve (AUC) analyses of esophagitis. Results: A total of 243 pts were enrolled (9/98-3/02) and 242 were analyzable. Most were male (65%), with KPS >90 (79%) and <60 years (42%). One pt in each arm died due to hematologic toxicity (febrile neutropenia) and one pt in the control arm died of acute pneumonitis. Median Survival Time was 16.7 mo and not different between the arms. Mean length of esophagus in the RT field was not different between two arms (16.6 vs. 16.0 cm). AMI delivery was acceptable in 81% pts (per protocol: mean AMI dose delivered, 12,028 mg, in 29%; minor deviation: 10,614 mg, in 43%; major acceptable deviation: 7,070 mg, in 9%). Main reasons for stopping AMI prematurely were toxicity (15%) and patient refusal (13%). Maximum acute esophagitis Grade >3 incidence was 30% in the AMI arm vs. 34% in the control arm (NS). Time to development of Grade >3 esophagitis was no different between the arms. Esophagitis AUC based on physician evaluation (PDL) was not different between the arms (1.06 vs. 1.01; p=0.66). Based on patient assessment (PSD), maximum swallowing grade was not different between the arms, but the esophagitis AUC was improved in the AMI arm (2.19 vs. 2.34; p=0.025). This effect was particularly pronounced for pts younger than 65 years (2.09 vs. 2.42, p=0.003) and in females (2.1 vs. 2.49, p=0.006). The incidence of Grade >3 esophagitis in those pts who received AMI in the morning (n=15) was 13% vs. 40% in those concurrently randomized to the control arm (n=15; p=0.24); physician-derived esophagitis AUC was 0.98 vs. 1.32 (p=0.049) and patient-derived AUC was 2.19 vs. 2.42 (p=0.37). Late thoracic RT toxicities were as follows: 3 deaths from pneumonitis (1 in AMI arm); 18 grade 3 & 4 pneumonitis cases (8 in AMI arm); 5 grade 3 esophagitis (3 in AMI arm) and no higher grade late esophagitis. Conclusions: Amifostine did not decrease the incidence or severity of esophagitis or esophagitis AUC in the schedule and dose given. However, patient-based evaluation demonstrated a reduction in swallowing difficulty based on esophagitis AUC, but not maximum grade. Pneumonitis was not improved in the AMI arm. There was no evidence of compromised overall survival in patients receiving amifostine. Research supported by the NCI and Medimmune Oncology

X. Tu, B. Berkey, H. Zhang, E. Hammond, J. Cooper, S. Spencer, A. Trotti, K. Fu, L. Milas and K. K. Ang: Impact of EGFR Expression on the Response of Advanced Head and Neck Carcinomas to Concomitant Boost Radiotherapy in a RTOG Phase III Trial (90-03). Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S157, 2003. (pres as oral pres) Purpose/Objective: Our prior study showed that EGFR is a strong, independent prognostic indicator of survival and a predictor of local-regional relapse (LRR) after standard fractionated radiation (SFX; Ang et al. Cancer Res 2002;62:7350-6). This study was undertaken to confirm the prognostic-predictive value of EGFR expression in patients receiving accelerated fractionation with concomitant boost (AFX-C) and to determine whether EGFR is a marker for tumor clonogen proliferation. Materials/Methods: Unstained tumor biopsy slides were available from 147 of 268 analyzable patients randomized to receive AFX-C regimen in the 4-arm randomized RTOG trial evaluating the efficacy of altered fractionations (Fu et al. Int J Radiat Oncol Biol Phys 2000;48:7-16). The specimens were dewaxed, incubated after standard preparation with mouse monoclonal antibodies recognizing the extracellular domain of the EGFR molecule. The catalyzed product was visualized with DAB Chromogen Kit and lightly counterstained with Mayer's Hematoxylin. Quantitative EGFR-immunohistochemistry (IHC) was performed with SAMBA 4000 Cell Image Analysis System, without knowledge of the clinical outcome, to yield mean optical density (MOD), staining index (SI), and quick score (QS). These parameters were correlated with the T-stage, N-stage, combined stage grouping, and prognostic classes identified by recursive partitioning analysis (RPA). Subsequently, the EGFR parameters were correlated with overall survival (OS), disease-free survival (DFS), LRR, and distant metastasis (DM) rates. OS and DFS were estimated using the Kaplan-Meier method and compared by the log-rank test. Time to LRR and DM were computed using the method of cumulative incidence with testing by Gray's test. The median follow-up was 23.0 months for all analyzable and 72.7 months for living patents. Results: There were no significant differences in the pretreatment characteristics (T-stage, N-stage, RPA-class, tumor site, KPS, age, etc.) or in the outcome between patients with (n=147) and those without (n=121) EGFR assessment. The range and distribution of EGFR expression (MOD, SI, and QS) obtained from this AFX-C group were consistent with those found previously in the SFX group (e.g., median values: 31, 89.3, and 26 vs 29, 86.7, and 24). In concordance with our previous data, greater median EGFR expression was associated with a significantly lower OS, DFS, and LRR rates (p=0.0005, 0.0003, 0.001, respectively). In multivariate analysis, EGFR expression emerged as the strongest prognostic-predictive factor for all three endpoints. In contrast to the prior study, however, greater median EGFR expression was also correlated with a higher DM rate (p=0.017). Further analysis revealed that the magnitude of difference in LRR between lower and higher EGFR-expressing tumors was similar in SFX and AFX-C groups, which suggests that EGFR expression is not a marker for tumor clonogen proliferation during fractionated radiotherapy. Conclusions: The results of this study strengthen the evidence that EGFR expression is a strong prognostic factor and a robust predictor of poor tumor response to radiation. When practical assay kits become commercially available, EGFR expression can thus be used either as a selection criterion for enrollment of patients or as a stratification variable for treatment assignments in clinical trials evaluating the efficacy of EGFR antagonists. The data suggest that EGFR expression is not a marker for tumor clonogen proliferation.

W. Hartsell, C. Scott, D. Watkins Bruner, C. Scarantinio, R. Ivker, M. Roach III, J. Suh, W. Demas, B. Movsas, I. Petersen and A. Konski: Phase III Randomized Trial 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 Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S124, 2003. (plenary pres) Purpose/Objective: To determine whether 8 Gy in a single fraction provides equivalent complete pain relief compared to 30 Gy in 10 fractions for patients with painful bone metastases from breast or prostate cancers. Materials/Methods: In a multi-institutional cooperative group setting (RTOG and NCCTG), a randomized, prospective phase III study of palliative external beam radiotherapy (XRT) was conducted for patients with breast or prostate cancer and painful bone metastases. Eligible patients had worst pain score of >5 out of 10 on the Brief Pain Index (BPI), and radiographic evidence of bone metastasis at the painful site. Eligibility requirements included life expectancy >3 months, no prior surgery or XRT to that site, and no change in systemic therapy for 30 days prior. Patients were randomized to 8 Gy in a single fraction vs. 30 Gy in 10 fractions. Treatment could be given to as many as 3 painful sites. Randomization was stratified by solitary vs. multiple painful sites, weight bearing vs. non-weight bearing site, worst pain score and whether they were receiving bisphosphonates. Response was scored as complete (no pain), partial (improvement of >2 points in BPI), stable (+ 1 point change in BPI) or progressive (>2 point worsening of BPI). Results: A total of 949 patients were enrolled on the study from 1998-2002, of whom 897 are eligible and analyzable. Median age was 67 years, with patients evenly divided between men with prostate cancer (445) and women with breast cancer (452). Patient pre-treatment characteristics were equally balanced between the two treatment arms, with 56% having a weight bearing painful site, 72% having a pain score of 7-10 (severe pain), 27% receiving bisphosphonates and 57% having a solitary painful site. The 8 Gy arm comprised 454 patients, with 443 in the 30 Gy group. Acute toxicity was mild, with grade 4 acute toxicity in only 2 patients and grade 3 toxicity in 24; there was a higher rate of grade 2-4 acute toxicity in the 30 Gy arm (70/414=17%) than with 8 Gy (42/432=10%, p<0.0001). Late toxicity was rare (4%) in both treatment groups (grade 2-3 in 13/354 patients with 8 Gy vs 15/342 patients in 30 Gy). Median survival was 9 months with 41% of patients alive at one year. Pain relief was evaluated at 3 months using the BPI. For the entire group, complete response was seen in 17% and partial response in 49% for an overall response rate of 66%; only 10% of patients had progression of pain. The CR and PR rates for 8 Gy were 15% and 50%, compared to 18% and 48% for 30 Gy. For patients with solitary painful sites, the CR and PR rates were 18% and 52% for 8 Gy, and 25% and 46% for 30 Gy (p= 0.17). At 3 months, 33% of patients no longer required narcotic medications. Pain response was similar whether or not the patient was on bisphosphonates. Conclusions: Palliative external beam radiation therapy is very effective in providing pain relief, with complete or partial improvement in pain seen in 66% of patients. Pain and narcotic relief is equivalent for both 30 Gy in 10 fractions and 8 Gy in a single fraction. At 3 months follow-up, there is no difference between the two treatment arms, regardless of stratification. Treatment was well tolerated with few adverse effects. Acknowledgment: This study was supported by grant number (RTOG 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.

A. T. Turrisi, C. Scott, V. Rusch, K. S. Albain, F. Shepherd, C. Smith, Y. Chen, R. Livingston, D. Gandara, G. Darling, D. Johnson and M. Green: Randomized Trial of Chemoradiotherapy to 61 Gy [no S] Versus Chemoradiotherapy to 45 Gy Followed by Surgery [S] Using Cisplatin Etoposide in Stage IIIa Non-Small Cell Lung Cancer (NSCLC): Intergroup Trial 0139, RTOG (9309). Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S125-126, 2003. (plenary pres) Purpose/Objective: Optimal treatment for IIIa, N2 positive NSCLC needs definition from large randomized trials. Small phase III trials support the use of chemotherapy followed by [S]. Increasingly concurrent chemoradiotherapy produces substantial 2- and 3-year survival. SWOG 8805, a large phase II study employing cisplatin [P] etoposide [E] and 45 Gy thoracic radiotherapy (TRT) followed by resection demonstrated that patients achieving nodal complete response (CR) survived quite well. Intergroup 0139 tested the hypothesis that PE + concurrent 61 Gy TRT may be adequate, but [S] following induction therapy might either improve survival or increase morbidity/mortality. Study endpoints are progression free, median and overall survival, as well as pattern of failure. Materials/Methods: Pts. with proven IIIa NSCLC, pN2, confirmed M0, and medically fit for surgery randomized to [S] or no surgery [no S] at entry. All patients receive P -50mg/sq. meter, days 1,8; and E-50 mg/sq. meter d1-5 IV, every 3 weeks x 2 cycles, concurrent with 45 Gy TRT. Patients randomized to [S] are operated 4 - 6 weeks later. Patients randomized to [no S] continue without break off cord to 61 Gy. TRT target volume mandated initial sites of disease and subcarinal nodes in all fields. All patients were to receive two additional cycles of PE after initial therapy (Consol.). Four hundred twenty-nine patients randomized over 92 mo of study accrual; 18 were ineligible, this reports on 392 eligible patients, 201[S]; 191 [no S]. Results: Induction therapy delivered in 94% both arms; Consol 68% in [S] and 82% [no S], p = 0.037. Pts. received Induction and Consol Chemo: 58% [S], 79% [no S], p < 0.0001. RT delivery acceptable: 97% [S]; 82% [no S], p = 0.002. Local Failure (LF): 4% [S], 13% [no S]; LF+N+DM: 15% [S], 28% [no S]. Brain Mets: 10% [S], 18% [no S]. Median Survival (MS): 22.1 mo [S], 21.7 mo [no S], p= 0.51. Progression Free Survival (PFS): 14.0 mo [S], 11.7 mo [no S], p= 0.02. Cause of Death, Cancer: 71% [S], 81% [no S]. Cause of Death, Rx Complication: 11% [S], 2% [no S] p = 0.0655. In [S] patients, path CR (54 pts), MS: 36.7 mo vs. < CR (95 pts), MS, 22.1 mo, p=0.048. Conclusions: (1.) Surgery reduces progression, but is associated with more treatment death; (2.) Despite more chemotherapy, the [no S] group had more cancer death; (3.) LF was a component of failure in 15% [S] and 28% [no S]. (4.) Despite significantly improved PFS, surgery does not improve overall median survival, p =0.51 perhaps because of a strong trend to treatment related death. Patients with pathological CR at time of surgery survive better. While surgery in pathological + N-2 disease is not clearly established by these data, longer follow-up may demonstrate benefit since the curves cross and seem to plateau on the [S] arm. Both treatment arms perform well producing over 30% 3-year survival in each arm despite the older PE chemotherapy. Despite relatively simple TRT plans, the [no S] arm had significantly poorer protocol compliance to TRT fields. More active chemotherapy and better TRT targeting may improve chemoradiotherapy results and reduce surgical morbidity and mortality.

L. Hughes, K. Heydon, P. Edmonds, M. Roach III, H. Wolkov, S. Shah, A. Pollack, E. Hammond and A. Dicker: Vascular Endothelial Growth Factor (VEGF) Expression in Locally Advanced Prostate Cancer (LAPC): Secondary Analysis of Radiation Therapy Oncology Group (RTOG) 86-10. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S201-202, 2003. (pres as oral pres) Purpose/Objective: Vascular growth is controlled by a host of proangiogenic and antiangiogeneic factors working together to achieve homeostasis of the local environment. Angiogenesis allows for tumors to grow, invade and metastasize. This vascular growth process represents an opportunity for potential novel therapies. The mechanism of tumor angiogenesis is not fully known and appears to have a multitude of molecular regulators. VEGF, a potent direct-acting proangiogenic factor, was found to promote endothelial cell growth as well as increased vascular permeability. The angiogenic response to VEGF has been widely studied in vivo. Limited studies of small sample sizes have evaluated VEGF expression in prostate cancer. We have explored the potential value of VEGF as a predictive biomarker among men with prostate cancer enrolled on RTOG 8610. Materials/Methods: RTOG 8610, a phase III trial, randomized men with LAPC to radiation therapy (RT) alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and RT (STAD + RT) (Arm 2). Tissue samples from 118 men were evaluated from the RTOG tissue repository. The H&E slides were reviewed, and paraffin blocks containing the index case were chosen and immunohistochemically stained for VEGF expression. Individual slides had tumor identified and the percentage of the tumor staining for VEGF was recorded. The slides were evaluated for VEGF staining intensity and graded from 0-3. Univariate and multivariate analyses (with Cox regression models) were done. Results: Tissue samples were obtained from 118 (25%) of the 471 patients entered into RTOG 8610. Sufficient tumor material from 103 patients with known pretreatment characteristics was available for analysis. The majority of the patients had Gleason Score (GS) 7-10 (75%) with the remaining patients having a GS of 2-6 (25%). Tissue from 56% of samples examined was from men enrolled on Arm 1 and 44% were from Arm 2. Seventy-five percent of patients were under 75 years old. Clinical tumor stage was T3 (AUA Stage C) in 75% of patients and T2 (AUA Stage B) for the remaining 25%. Patients had a VEGF intensity score (IS) of 0-1 in 47% while 53% had an IS of 2-3. The distribution of VEGF IS by treatment arms was well balanced. Patients with VEGF IS 0-1 received RT alone in 54% and 46% received STAD_RT. Fifty-eight percent of the patients with VEGF IS 2-3 received RT alone and 42% received STAD_RT. More men with VEGF IS 2-3 had high GS then those with VEGF IS 0-1(GS 7-10 was 78% for VEGF 2-3, 71% for VEGF 0-1). This difference was not statistically significant. VEGF staining was present in essentially all of the tumor samples with 99% of the 103 samples having 100% staining. Univariate and multivariate analyses showed no statistically significant correlation between VEGF expression (0,1) and (2,3) for local failure, distant failure, disease-free survival or overall survival rates. Conclusions: This analysis represents one of the largest sample bases reviewed for VEGF expression in human prostate carcinoma patients. VEGF is highly expressed in this study population. Although no statistically significant correlation was seen between extent of VEGF expression and outcomes for patients randomized in RTOG 8610, VEGF will be further investigated as a high priority biomarker for patients from RTOG 9202 to add a broader distribution of prostate cancer patients with regard to GS for analysis. Further study will include biological correlation of VEGF IS with microvessel density in the RTOG 8610 patients.

A. Konski, E. Sherman, M. Krahn, K. Bremner, J. Beck, D. Watkins Bruner and M. Pilepich: Monte Carlo Simulation of a Markov Model for a Phase III Clinical Trial Evaluating the Addition of Total Androgen Suppression (TAS) To Radiation Versus Radiation Alone for Locally Advanced Prostate Cancer (RTOG 86-10). Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S215-216, 2003. (pres as oral pres) Purpose/Objective: The addition of hormone therapy to radiation has been shown to improve outcomes of patients with locally advanced prostate cancer. Increased cost and potentially more side effects accompany, however, the improved outcome. To S215 Proceedings of the 45th Annual ASTRO Meeting determine, by using a cost-utility analysis, the cost-effectiveness of the addition of hormone therapy to radiation for patients treated for adenocarcinoma of the prostate using a Monte Carlo simulation of a Markov Model. Materials/Methods: Radiation Therapy Oncology Group protocol 86-10 randomized patients to receive radiation alone (RT) or radiation plus total androgen suppression (RT Hormones) 2 months prior to and during the radiotherapy for the treatment of locally advanced prostate cancer. A Markov model was designed using Data Pro (Treeage Software) with the following states; No disease progression, Disease progression, Hormone unresponsive, and death. The analysis took a societal perspective. Allowed state to state transitions were No disease progression to Disease progression to Hormone unresponsive to death. Transition probabilities from one state to another were calculated from rates pertaining to RTOG 86-10 published in the literature. Cycle length for one state was 1 year. Markov termination condition was 20 cycles. Utility values for each health state and treatment were obtained from the literature and costs for each treatment were modeled or obtained from the literature. Costs and effectiveness were discounted at 3% per year. Utilities for the radiation treatments were obtained by 4 scaling methods; Standard Gamble, Rating Scale, Quality Well Being and Health Utility Index III from 141 prostate cancer patients. Distributions were sampled at random from the treatment utilities using a second order Monte Carlo simulation technique. This produced a distribution for incremental cost-effectiveness that was used to construct 95% uncertainty intervals and cost-effectiveness acceptability curves. One and two way sensitivity analysis was performed. Results: The mean expected cost for the RT only treatments was $55,703 (range: $55,656-$55,734). The mean effectiveness for the RT only treatment was 8.3 Quality-adjusted Life Years (QALYs) (range: 6.89-9.46). The mean expected cost for the RT Hormones was $49,325 (range: $49,311-$49,354). The mean effectiveness was 9.01 QALYs (range : 7.39-10.2). Incremental cost-effectiveness analysis showed RT Hormones to be the dominant strategy because it was cheaper and provided more QALYs. Incremental cost-effectiveness acceptability curves and sensitivity analyses will be presented. Conclusions: Our analysis shows that adding hormonal treatment to RT improves both health outcomes and lowers costs. The expected cost is lowered by preventing failures in the future and obviating the need for additional therapies, such as hormones and chemotherapy. Despite producing lower quality of life in the short term, hormonal therapy reduces the cost and morbidity associated with future treatment failures.

M. Graham, R. Paulus, D. Ettinger, J. Bradley, M. Pilepich, M. Machtay, R. Komaki, J. Atkins and W. Curran Jr: RTOG 9705, A Phase II Trial of Postoperative Adjuvant Paclitaxel/Carboplatin and Thoracic Radiotherapy in Resected Stage II and IIA Non-Small Cell Lung Cancer (NSCLC) Patients - Promising Long Term Survival Results. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S140-141, 2003. (pres as oral pres) Purpose/Objective: Determination of overall survival and progression-free survival and toxicity associated with adjuvant Paclitaxel/Carboplatin and thoracic radiotherapy (TRT) for completely resected Stage II and IIIA NSCLC patients. Materials/Methods: From July 1997 through June 1998, 93 patients were entered on this study; 88 were ultimately eligible. All eligible patients had a complete surgical resection with negative margins and pathologic stage II (44%) or stage IIIA(55%) disease. Patients received postoperative paclitaxel as a 3 hour infusion days 1, 22,43 and 64, 135 mg/m2(cycles 1 and 2) and 225 mg/m2(cycles 3 and 4) and carboplatin AUC=5, days 1, 22 (cycles 1 and 2) and AUC=6, days 43,64 (cycles 3 and 4). Concurrent TRT, 50.4 Gy/28 fractions/6 weeks (1.8 Gy/day, 5 days/week) was given during cycles 1 and 2. A boost of 10.8 Gy/6 fractions was given to patient with nodal extracapsular extension or T3 lesions. Patient characteristics included: 56% <60 years of age, 65% male, 82% with an initial KPS >90, 75% <5% weight loss, 57% adenocarcinomas. Eighty-six percent of patients completed all chemotherapy per protocol. Results: The median overall survival time was 56.3 months with one, two and three year survival rates of 86%, 70% and 61% respectively. The median progression-free survival time was 35.6 months with one, two and three year progression-free survival rates of 70%, 57% and 50% respectively. Brain metastasis as the sole site of first failure occurred in 22% and 17% failed in other metastatic sites as first failure. 46 patients ultimately failed with recurrent or metastatic disease. Local failure as a component of first failure accounted for 18% of patient who failed. One patient died during treatment with a septic neutropenic death during cycle 4. Grade 3/4granulocytopenia and thrombocytopenia occurred in 34.1% and 6% of patients respectively. Grade 3/4 esophagitis occurred in 16% of patients. Conclusions: The mature results of this trial suggest an improved overall and progression-free survival in this group of resected NSCLC patients compared with previously reported trials. (Table 1) A phase III trial comparing this treatment regimen with standard therapy appears warranted. The addition of prophylactic brain irradiation may be beneficial to this good prognostic group. Table 1 Comparison of RTOG 9705 to ECOG study* *Keller, et al, N Engl J Med 343: 1217-1222, 2000   RTOG 9705 TRT Alone Cisplat VP-16 & TRT Median Survival 56.3 mo 39 mo 38 mo Progression-Free Survival 35.6 mo 30.4 mo 26.1 mo 1 year survival 86% 79% 80% 2 year survival 70% 64% 64% 3 year survival 61% 52% 50% First site failure rate       Intrathoracic 18% 28% 29% Brain 22% 14% 14%

R. Komaki, S. Swann, D. Ettinger, B. Glisson, A. Sandler, B. Movsas and R. Byhardt: Phase I Dose-Escalation Study of Thoracic Irradiation with Concurrent Chemotherapy for Patients with Limited Small Cell Lung Cancer (LSCLC). Radiation Therapy Oncology Group RTOG. Proc Am Soc Thera Rad Oncol (ASTRO), Int J Radiat Oncol Biol Phys [57] (2):S139, 2003. (pres as oral pres) Purpose/Objective: Accelerated RT was shown to improve local control (LC) and survival among pts with LSCLC, but local failure was still unacceptably high. To improve without causing unacceptable acute toxicities, LC and survival, a multiinstitutional phase I radiation dose-escalation study was undertaken by the RTOG. Materials/Methods: Previously untreated, pathologically confirmed SCLC pts with limited stage and KPS > 70 were enrolled between 2/98 and 1/02. Pts originally received cisplatin (P), 60 mg/M2 IV and etoposide (E) 120 mg/M2 IV days 1-3, repeated every 3 wks x 4 cycles with concurrent thoracic radiation therapy (TRT) during the first 2 cycles of PE. TRT was given 1.8 Gy daily to 36 Gy followed by a small boost field encompassing only the gross disease. Boost TRT was delivered with escalations of 1.8 Gy twice daily (Bid) during the final days to establish the maximum tolerated dose (MTD). The first arm used a boost of 3 Bid Fx 1.8 Gy for a TD of 50.4 Gy. Escalations of Bid TRT during the last 5, 7, 9, and 11 days permitted TDs of 54 Gy 57.6 Gy 61.2 Gy and 64.8 Gy, all in a total time of 5 wks. A 50% rate of acute Gr 3 or 4 acute esophagitis was considered dose limiting. Results: Sixty-four pts were enrolled: 2 of the first 8 receiving 50.4 Gy developed Gr 3 acute esophagitis. Dose of E was changed to 240 mg/M2 PO on days 2 & 3 with same TRT dose of 50.4 Gy: 10 pts were treated with acceptable toxicity. Progressive dose escalations were possible until the 64.8 Gy arm when 3 of 8 pts (60%) had Gr 3 acute esophagitis. Therefore, the MTD was determined to be 61.2 Gy, in 34 Fx of 1.8 Gy when given concurrently with this regimen of PE, which has been proposed as a phase II study through RTOG. Conclusions: Accelerated thoracic radiotherapy, 61.2 Gy in 34 fractions of 1.8 Gy/Fx with concurrent PE in 5 weeks was considered to be MTD. This regimen will be open as a phase II trial through RTOG institutions to find the efficacy to be compared with accelerated Bid arm and PE in the future as a prospective phase III trial if phase II shows a promising outcome. This abstract reports investigations supported by grants to the RTOG (U10 CA 21661), CCOP (U10 CA37422), and Stat Center (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.