PFS or OS in patients who completed their prescribed course of radiation. Thus for patients with non-disseminated intracranialGCT we recommend histologic diagnosis followed by focal radiation without whole ventricle, whole brain or craniospinalradiation.

297 Secondary Analysis of RTOG 9310: An Intergroup Phase II Combined Modality Treatment of PrimaryCentral Nervous System Lymphoma with Chemotherapy and Hyperfractionated Radiotherapy

B.J. Fisher1, W. Sieferheld2, C. Schultz3, L. DeAngelis4, D. Nelson5, S.C. Schold6, W. Curran7

1Radiation Oncology, London Regional Cancer Centre, University of Western Ontario, London, ON, Canada, 2StatisticalUnit, RTOG Headquarters, Philadephia, PA, 3Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI,4Neurology, Memorial-Sloan Kettering, New York, NY, 5Radiation Oncology, Mayo Clinic, Rochester, MN, 6Neurology,Duke University Medical Center, Durham, NC, 7Radiation Oncology, Thomas Jefferson University, Philadelphia, PA

Purpose: To determine whether a hyperfractionated radiation schedule reduces the CNS morbidity for patients with primaryCNS lymphoma achieving a complete response after induction chemotherapy.

Materials and Methods: One hundred and two patients were registered on-study. Patients received 10 week course ofpreradiation chemotherapy with methotrexate, vincristine, procarbazine, leucovorin and decadron followed by whole cranialradiation followed by 2 cycles of intrathecal Ara-C. Radiation therapy was delivered by one of two schedules ie, 45 Gy/25fractions/5 weeks (RT) or 36 Gy/24 fractions/2.5 weeks b.i.d. (HFX). Tumor response after induction chemotherapy wasidentified through central review for 78 patients. Mini mental status exams (MMSE) were conducted at 8 months on 16/30 RTpatients and 9/15 HFS patients.

Results: Forty-five of the 78 patients achieved a complete response (CR) with 15 receiving hyperfractionated radiation therapy(HFX) and 30 receiving standard radiation therapy (RT). There were no notable differences in pretreatment patient character-istics between the RT and HFX groups. The rate of � grade 3 hematologic toxicities was similar between arms (RT�70%,HFX�67%). The rate of postradiation toxicity was nearly twice as high in the standard RT arm (23% vs 13%) but notstatistically different (p�0.46). There was no detectable difference in overall or progression-free (PFS) survival with mediansurvivals of 3.2 and 3.4 years and PFS of 1.5 and 1.4 years respectively.

The Mini Mental Status Exam (MMSE) improved at 8 months across all patients. Patients not experiencing a CR increased onaverage 0.79 points, while both RT and HFX arms each increased an average of 1.1 points. An analysis of the area under theMMSE curve at 8 months showed no statistically significant difference between RT and HFX groups (p�0.93). Overall, 2/10of HX patients (20%) and 8/23 (35%) of RT patients dropped to an MMSE score below 24 (dementia level). At two years, 90%of HFX patients, 68% of RT patients and 66% of non-CR patients� scores remained above 23.

Conclusion: Toxicity may be lower following post chemotherapy radiation in patients receiving the HFX radiation scheduleas compared with the RT schedule (45 Gy/25 fractions/5 weeks). Despite a 25% decrease in biologically effective tumor dosefor the HFX regimen, PFS and overall survival was not different. The HFX schedule will be further investigated in the futureintergroup PCNSL trial.

298 Practical Application of Biochemical Failure Definitions: What To Do and When To Do It

A.A. Martinez, MD FACR, L.L. Kestin, MD, F.A. Vicini, MD

Radiation Oncology, William Beaumont Hospital, Royal Oak, MI

Purpose: The post-treatment prostate-specific antigen (PSA) profile is often difficult to interpret following external beamradiotherapy (EBRT) for prostate cancer. We performed an extensive analysis of post-RT PSA profiles to determine the clinicalsignificance of biochemical failure (BF) and the correlation of BF with clinical failure (CF) and cause-specific death (CSD).

Materials and Methods: From 1987-1997, 727 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated withdefinitive EBRT and had at least 5 post-RT PSA levels and did not receive hormonal therapy for post-RT PSA elevations only(prior to evidence of CF). All patients received EBRT alone (no adjuvant hormonal therapy). Over 20 BF definitions were testedfor their correlation with CF (any local failure or distant metastasis) and CSD. All BF definitions were tested for sensitivity,specificity, accuracy, and positive and negative predictive value of predicting subsequent CF and CSD. The median follow-upwas 5.0 years.

Results: Three consecutive PSA rises yielded a 73% sensitivity, 76% specificity, and 75% overall accuracy for predicting CF.The 10-year CF rate (from the date of RT) for those 251 patients demonstrating 3 consecutive rises (BF) was 64% vs 14% forthose patients who did not have 3 rises (biochemically controlled). As expected, definitions requiring only 2 rises were moresensitive but less specific in predicting CF and CSD than those definitions requiring 3 or 4 rises. Defining BF as a post-nadirincrease to � 3 ng/ml above the nadir yielded the highest accuracy of 87%. In addition, this definition provided the greatestseparation in CF rates, 82% for BF vs 5% for BC at 10 years after RT. CF rates were also calculated from the date of BF (e.g.date of third rise). The CF rates at 6 months and 2 years after the third PSA rise were 9% and 27%, respectively (table). TheCF rates at 6 months and 2 years following an increase to � 3 ng/ml above the nadir were significantly higher at 23% and 54%,respectively. Once a patient was classified as a BF, regardless of the BF definition, the CF rate varied markedly depending onthe pre-treatment characteristics. For each BF definition, younger age at diagnosis, higher pre-treatment PSA, and higherGleason score independently predicted for CF after BF on multivariate analysis. For instance, patients with a pre-treatmentPSA � 4.0 ng/ml demonstrated an 11% CF rate at 2 years after the third PSA rise vs 46% after 3 rises with a pre-treatmentPSA � 20.0 ng/ml. Similarly, patients with Gleason 2-4 had a 2-year CF rate of only 3% following a nadir � 1.0 ng/ml vs 47%for Gleason 8-10 at 2 years after a nadir � 1.0 ng/ml. Although the CF rate after BF also correlated with pre-treatmentcharacteristics when using � 3 ng/ml above the nadir, CF rates remained high even for low-risk patients (e.g. 2-year CF of 48%for PSA � 10.0 ng/ml, 41% for Gleason 2-4).

166 I. J. Radiation Oncology ● Biology ● Physics Volume 51, Number 3, Supplement 1, 2001

Conclusion: Once the post-RT PSA profile reaches � 3 ng/ml above the nadir, there is a high risk of clinical failure withina relatively short time period for which treatment intervention should be strongly considered, regardless of pre-treatmentcharacteristics. Following a nadir � 1.0 ng/ml or 3 consecutive rises, some patients with low-risk pre-treatment characteristicscould be considered for further PSA observation before treatment intervention.

Definition6-Month

Clinical Failure2-Year

Clinical Failure5-Year

Clinical Failure2-YearCSD

5-YearCSD

Median Time toCF After BF

Median Time toCSD After BF

3 consecutive rises 9% 27% 79% 2% 18% 1.4 years 5.0 yearsnadir � 1.0 ng/m l4% 25% 52% 3% 16% 1.6 years 4.3 years� 1 ng/ml above nadir 11% 31% 70% 2% 20% 1.1 years 4.7 years� 3 ng/ml above nadir 23% 54% 96% 5% 32% 0.8 years 3.6 years

299 Adjuvant Pelvic Irradiation in 423 Patients with pT3N0 Prostate Cancer

Z. Petrovich1,2, G. Lieskovsky2,1, B. Langholz3, O. Streeter1, D.G. Skinner2

1Radiation Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 2Urology, Keck Schoolof Medicine, University of Southern California, Los Angeles, CA, 3Preventive Medicine, Keck School of Medicine,University of Southern California, Los Angeles, CA

Purpose: To evaluate treatment outcome in pT3N0 patients with adenocarcinoma of the prostate (CaP) treated with a plannedcourse of postoperative irradiation.

Materials and Methods: Over a period of 22 years a total of 423 pT3N0 CaP patients were treated in a single medical centerwith pelvic irradiation, which was the only adjuvant therapy given. There were the following patient characteristics: median age66 years; pathologic stage pT3aN0 in 296 (70%) and pT3bN0 in 127 (30%); Gleason score 2-4 in 12 (2.8%), 5-6 in 157 (37.1%),7 in 151 (35.7%), and 8-10 in 100 (23.6%); median and mean preoperative PSA level was 10 and 15.9 ng/ml, respectively.Radiotherapy consisted of a median dose of 48 Gy delivered to the prostatic fossa and its immediate vicinity. Median followup was 7 years.

Results: The 5- and 10-year actuarial survival was 92 and 73%, respectively and the 5-and 10-year disease-free survival(PSA�0.05 ng/ml) was 69 and 51%, respectively. In multivariate analysis Gleason score was the most important predictor forsurvival, p�0.00005 while pathologic stage and Gleason score were independently predictive of disease-free survival atp�0.00007 and p� 0.0003, respectively. The worst prognostic category was represented by pT3bN0, Gleason score 7-10patients who had 5.3 times greater risk of tumor recurrence than those with pT3aN0, Gleason score 2-6. A high (�25 ng/ml)preoperative PSA level was also a predictor of tumor recurrence, p�0.03. A total of 43 (10.2%) patients developed clinicalrecurrence. This included 30 (7%) patients with distant metastases alone and 13 (3%) with local recurrence, which included 2patients who also had distant disease. An additional 78 (18.4%) patients had PSA elevation (�0.05 ng/ml). This treatmentprogram was well tolerated with acute toxicity being common (65%) but of no clinical significance. No late or severe toxicitywas recorded.

Conclusion: Adjuvant pelvic irraddiation, as given in this study, appears to substantially reduce the expected incidence of localtumor recurrence in pT3N0 CaP patients. Treatment outcome was poor in pT3bN0 and Gleason score 7-10 patients, with morethan 80% showing evidence of clinical or PSA recurrence at 10 years following therapy. This group should be a target of aprospective trial of systemic therapy.

300 Evaluation of Ultrasound-Based Daily Prostate Localization during IMRT for Prostate Cancer

A. Chandra, L. Dong, E. Huang, D.A. Kuban, L.J. O’Neill, I.I. Rosen, A. Pollack

Radiation Oncology, MD Anderson Cancer Center, Houston, TX

Purpose: The NOMOS (Sewickley, PA) BAT Ultrasound System provides a means for correcting intertreatment prostatepositional variation. In this report, quality of the images, accuracy of the alignments, direction of the misalignments, andaverage shifts are described for 3509 procedures in 147 consecutive patients treated with IMRT for prostate cancer.

Materials and Methods: At the minimum, weekly port films were taken to ensure that the isocenter setup was based on bonylandmarks. BAT ultrasound alignments were done just prior to each IMRT treatment. If the shift was �1 cm, a second BATalignment was done and the physician was notified. Consistent shifts �1 cm usually precipitated a second planning CT-scan,which was used for future alignments (n�5 patients). BAT alignment images were stored and reviewed weekly by the treatingphysician. For this study, a single physician (A.C.) reviewed all images, and classified image quality and degree of prostatealignment in 6 directions on a 1-3 scale. Near perfect image quality or alignment was given a 1, fair image quality ormisalignment �5 mm (likely within the PTV) was given a 2, and unacceptable image quality or misalignment � 5 mm(potential to violate the PTV) was given a value of 3.

Results: IMRT was administered as a boost (median 17 fractions) in 79 patients or full treatment (42-44 fractions) in 68patients. Out of 4158 IMRT fractions administered, a BAT alignment was attempted in 84%. Among the 3509 attempted BATprocedures, quality was acceptable in 95%. In 22(0.6%) attempts no shift was made because the image was perceived to be toopoor by the treating radiation therapist. In 159 attempts (4.5%) a shift was made, but in retrospect the quality was judged tobe unacceptable, due mostly to poor bladder filling. Alignments could not be assessed on these patients. Of the remaining 3328BAT images, with quality scores of 1-2, shifts were unacceptable (�5 mm misalignment with CT-plan) in 3%. Of these, 51%were deemed unacceptable due to superior-inferior (SI), 55% due to anterior-posterior (AP), and 6% due to lateral (RL)misalignments. Eighteen procedures had major alignment errors in more than one direction. The Table shows the mean shifts

167Proceedings of the 43rd Annual ASTRO Meeting