Search

External beam radiation therapy (EBRT) dose escalation has been tested in multiple prospective trials. However, the impact on patient reported outcomes (PROs) associated with higher doses of EBRT remain poorly understood. We sought to assess the differences in PROs between men treated with a dose of 70.2 Gy versus 79.2 Gy of EBRT for prostate cancer.The phase 3 clinical trial RTOG 0126 randomized 1532 patients with prostate cancer between March 2002 and August 2008 to 79.2 Gy over 44 fractions versus 70.2 Gy over 39 fractions. Eligible patients participated in the PRO data collection. PROs completed included the International Index of Erectile Function Questionnaire (IIEF), Functional Alterations due to Changes in Elimination (FACE), and the Spitzer Quality of Life Index (SQLI). The timepoints for the IIEF were collected pre-entry and at 6, 12, and 24 months. The FACE and SQLI were collected pre-entry and at 3, 6, 12, 18, and 24 months. The impact of EBRT dose to normal structures (penile bulb, rectum, and bladder) on PROs was also examined. Mixed effects models were used to analyze trends across time.In total, 1144 patients completed baseline IIEF forms and of these, 56%, 64%, and 61% completed the IIEF at 6, 12, and 24 months, respectively; 1123 patients completed the FACE score at baseline and 50%, 61%, 73%, 61%, and 65% completed all 15 items for the FACE metric at timepoints of 3, 6, 12, 18, and 24 months, respectively. Erectile dysfunction at 12 months based on the single question was not significantly different between arms (38.1% for the standard dose radiation therapy arm vs 49.7% for the dose escalated radiation therapy arm; P = .051). Treatment arm (70.2 vs 79.2) had no significant impact on any PRO metrics measured across all collected domains. Comprehensive dosimetric analyses are presented and reveal multiple significant differences to regional organs at risk.Compliance with PRO data collection was lower than anticipated in this phase 3 trial. Examining the available data, dose escalated EBRT did not appear to be associated with any detriment to PROs across numerous prospectively collected domains. These data, notwithstanding limitations, add to our understanding of the implications of EBRT dose escalation in prostate cancer. Furthermore, these results illustrate challenges associated with PRO data collection.

There is considerable interest in very short (ultrahypofractionated) radiation therapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience, and resource allocation benefits. Our objective is to demonstrate that detectable changes in health-related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline scores.xxxx is a nonblinded randomized phase 2 study of National Comprehensive Cancer Network low-risk prostate cancer in which each arm is compared with a historical control. Patients were randomized to 5 fractions (7.25Gy in 2 week and a day - twice a week) or 12 fractions (4.3Gy in 2.5 weeks- five times a week). Secondary objectives assessed patient-reported toxicity at 5 years using the Expanded Prostate cancer Index Composite (EPIC). Chi-square tests were used to assess the proportion of patients with a deterioration from baseline of5 points for bowel,2 points for urinary, and11 points for sexual score, RESULTS: The study enrolled 127 patients to 5 fractions (121 eligible) and 128 patients to 12 fractions (125 eligible). Median follow-up for all patients at the time of analysis was 5.38 years. The 5-year frequency for5 point change in bowel score were 38.4% (P=0.27) and 23.4% (= 0.98) for 5 and 12 fractions, respectively. The 5-year frequencies for2 point change in urinary score were 46.6% (P=0.15) and 36.4% (P=0.70) for 5 and 12 fractions, respectively. For 5 fractions, 49.3% (P=0.007) of patients had a drop in 5-year EPIC-50 sexual score of ≥11 points; for 12 fractions, 54% (P0.001) of patients had a drop in 5-year EPIC-50 sexual score of ≥11 points. Disease-free survival at 5 years is 89.6% (95% confidence interval:84.0-95.2) in the 5-fraction arm and 92.3% (95% confidence interval: 87.4- 97.1) in the 12-fraction arm. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity.This study confirms that, based on long-term changes in bowel and urinary domains and toxicity, the 5- and 12-fraction regimens are well tolerated. These ultrahypofractionated approaches need to be compared with current standard radiation therapy regimens.

PURPOSE: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). METHODS AND MATERIALS: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. RESULTS: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%−81.1%), numerically superior to the 3-year OS historical control of 54% (P < .001). The median survival time was 8.2 years (95% confidence interval, 5.6–9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. CONCLUSIONS: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.

PURPOSE/OBJECTIVE(S) To validate the association between body composition and all-cause mortality in men treated with radiation therapy for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to help classify patients by risk of all-cause mortality. MATERIALS/METHODS All participants of NRG/RTOG 9406 and NRG/RTOG 0126 with archived computed tomography that extended cranially to include the L4-L5 interface were included. Muscle mass and muscle density were estimated by measuring the cross-sectional area and average attenuation of the paired psoas muscles on a single slice at the level of L4-L5. Bone density was estimated by measuring the average attenuation of the vertebral body cancellous bone on a single slice at mid-L5. Adipose tissue density was estimated by measuring the average attenuation of the subcutaneous adipose tissue on a single slice at L4-L5. Survival analyses, including Cox proportional hazards models, were performed to assess the relationship between body composition variables and all-cause mortality. Recursive partitioning (RPA) was utilized to create a classification tree to classify NRG/RTOG 0126 participants by risk of death, and the discriminant ability of the classification model was validated using the NRG/RTOG 9406 data set. RESULTS Data from 2,066 men was included in this study (864 from NRG/RTOG 9406 and 1,202 from NRG/RTOG 0126). A total of 648 men died in the follow-up period and 51 (7.9%) were due to PCa. Psoas area, psoas density, and vertebral body density were individually associated with overall survival. In the final multivariable model, psoas area, comorbidity score, and age were associated with overall survival (Table). The RPA yielded a classification tree with 4 prognostic groups determined by age, comorbidity, and psoas cross-sectional area. When the RPA classification was applied to the NRG/RTOG 9406 validation set the discriminant ability was preserved (P < 0.001 groupwise log-rank). CONCLUSION The results of this study strongly support that body composition is related to all-cause mortality in men with localized PCa, with most deaths due to causes other than PCa. The inclusion of psoas cross-sectional area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction. This study also confirms the feasibility of performing body composition analysis using archived CT scans using NRG Oncology clinical trial data sets. These methods can be applied to other NRG Oncology data sets to further explore how body composition is related to patient outcomes.

Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power.Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ.From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis.The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P.001) and the study-hypothesized rate of 65%.

Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the numbermore » of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.« less

Purpose To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P P =.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity ( P =.099). Acute G2+ toxicity was associated with late G3+ toxicity ( P =.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race ( P =.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity ( P =.034). Conclusions Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT. The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70 Gy are associated with late rectal toxicity.

The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08.468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria.In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation.High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.

Purpose Because of the low alpha/beta value of prostate cancer, a therapeutic gain may be possible with a hypofractionated radiation scheme, and this gain may be further increased with the adjunct of hormone therapy. A Phase II study was undertaken to study the toxicity of such a treatment. Methods and Materials Forty-two patients with intermediate-risk prostate cancer were recruited for this study. Neoadjuvant and concomitant hormone therapy consisted of one injection of leuprolide acetate (4-month preparation) and 1 month of oral nonsteroidal, anti-androgen medication starting on the day of the injection. Radiation treatment was started 8 weeks after the injection and patients received 57 Gy in 19 fractions. Results Median follow-up was 46 months. The treatment was well tolerated and no interruptions occurred. The majority (59%) had Grade 0 or 1 acute genitourinary (GU) toxicity, whereas 36% had Grade 2 and 5% had Grade 3 acute GU toxicity. Only Grade 1 or 2 gastrointestinal toxicity was seen. All chronic toxicity was of Grade 1 or 2 except for 3 patients (8%) with Grade 3 toxicity. Sixty-eight percent (68%) of patients had no long-term side effects from the treatment. At time of analysis, 79% showed no sign of treatment failure. Conclusions Hypofractionated radiation with neoadjuvant and concomitant hormone therapy is well tolerated with no significant short- or long-term morbidity. Control for this risk group is good, and comparative Phase III studies should be undertaken to determine whether this treatment is superior to new evolving treatments.

Purpose Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk ( n = 152), intermediate-risk ( n = 142), or high-risk ( n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level ( p = .017) and National Comprehensive Cancer Network risk group ( p = .0022). On multivariate analysis, statin use was associated with a PSA level p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08–0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02–0.59, p = .02). Conclusion Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

Purpose To compare low (mean 0.44, SD ± 0.0163 mCi) with high source activity (0.61 ± 0.0178 mCi) in I 125 permanent seed brachytherapy regarding seed loss, dosimetric outcome, and toxicity. Methods and Materials The study included 199 patients with prostate cancer treated by permanent seed brachytherapy alone: the first 105 with seeds of lower activity (first cohort), the following 94 with higher seed activity (second cohort). The V100, V150, V200, and D90 were analyzed on the CT scan 30 days after implantation (CTD30). The V100, V150, and D2 of the rectum were also calculated on CTD30. Seed loss was determined 30 days after implantation. Urinary toxicity was measured with the International Prostate Symptom Score (IPSS) questionnaire. Results Lower seed activity was associated with lower V150 and V200 ( p = 0.01 and p ≤ 0.001, respectively) on CTD30. More patients had a V100 p = 0.098 for D90 and p = 0.029 for V100) on CTD30. There was no difference between cohorts in dose to the rectum ( p = 0.325–0.516) or difference in patients' IPSS score from baseline ( p = 0.0.117–0.618), although there was a trend toward more urinary toxicity at 4 and 8 months for high activity seeds. Seed loss as a percentage of implanted seeds was not different ( p = 0.324). Conclusions Higher seed activity (I 125 ≥ 0.6 mCi) results in at least equal V100 and D90 on CTD30. However, dose inhomogeneity and a trend toward more urinary toxicity at 4 and 8 months after treatment may lead to a higher long-term urinary complications.

Purpose To identify dosimetric parameters predictive of a good prostate seed I 125 quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperative (IO) inverse planning. Methods and Materials We analyzed 127 consecutively treated patients with primarily low-risk prostate carcinoma who underwent prostate permanent seed I 125 brachytherapy using an IO planning approach. The implant was done using the three-dimensional transrectal ultrasound (PRE-TRUS)-guided IO interactive inverse preplanning system. The TRUS was repeated in the operating room after the implant procedure was complete (POST-TRUS). The prostate was recontoured and postimplant dosimetry was calculated. Each patient underwent computed tomography scan on Day 28 (CT-D28) to evaluate implant quality. Area under the receiver operating characteristic curves (AUROC) was evaluated for models predictive of a V100 of ≥90% and a D90 of ≥140 Gy on the basis of CT-D28 values. Results On CT-D28, 72.4% of patients had a V100 of ≥90% and 74.8% had a D90 of ≥140 Gy. AUROC for a V100 of ≥90% was 0.665 ( p = 0.004) on PRE-TRUS and 0.619 ( p = 0.039) on POST-TRUS. AUROC for D90 of ≥140 Gy was 0.602 ( p = 0.086) on PRE-TRUS and 0.614 ( p = 0.054) on POST-TRUS. Using PRE-TRUS V100 cutoff of >97% gives sensitivity of 88% and a false-positive rate of 63%. A POST-TRUS D90 cutoff of >170 Gy resulted in a sensitivity of 62% and a false-positive rate of 34%. Conclusions Because of unacceptably high false-positive rates, IO preimplant and postimplant TRUS-based dosimetry are not accurate tools to predict for postimplant computed tomography–based dosimetry.

Patient-Reported Outcomes in NRG Oncology/RTOG 0938, a Randomized Phase 2 Study Evaluating 2 Ultrahypofractionated Regimens (UHRs) for Prostate Cancer H. Lukka, P. Stephanie, D. Bruner, J.P. Bahary, C.A.F. Lawton, J.A. Efstathiou, R. Kudchadker, L. Ponsky, S.A. Seaward, I.S. Dayes, D.D. Gopaul, J.M. Michalski, G. Delouya, I.D. Kaplan, E.M. Horwitz, M. Roach, III, W.H. Pinover, D.C. Beyer, H.M. Sandler, and L.A. Kachnic; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON, Canada, NRG Oncology Statistics and Data Management Center, Philadelphia, PA, Emory University, Atlanta, GA, Hopital Notre-Dame du CHUM, Montreal, QC, Canada, Medical College of Wisconsin, Milwaukee, WI, Massachusetts General Hospital, Harvard Medical School, Boston, MA, MD Anderson Cancer Center, Houston, TX, United States, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, Kaiser Permanente Northern California, Santa Clara, CA, United States, McMaster University, Hamilton, ON, Canada, Grand River Regional Cancer Centre, Kitchener, ON, Canada, Washington University School of Medicine, St. Louis, MO, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada, Beth Israel Deaconess Medical Center, Boston, MA, Fox Chase Cancer Center, Philadelphia, PA, University of California, San Francisco, San Francisco, CA, Abington Memorial Hospital, Abington, PA, United States, Foundation for Cancer Research and Education, Phoenix, AZ, Cedars-Sinai Medical Center, Los Angeles, CA, Boston Medical Center, Boston, MA

Hospitalization final 90 days of life 48.3% 64.0% .0004 Hospitalization final 30 days of life 31.5% 61.5%

Purpose To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma. Methods and materials Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of ≥60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m 2 of TMZ was given on Days 1–5 of RT. In Arm 1, 200 mg/m 2 of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m 2 of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles. Results A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose. Conclusion The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.

Purpose/Objective(s): To report the long-term survival and toxicity outcomes with the use of ultra-high-dose intensity modulated radiation therapy (IMRT) to a dose of 86.4 Gy for patients with localized prostate cancer. Materials/Methods: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified into prognostic risk groups based on the National Comprehensive Cancer Network risk-grouping system. Five hundred eighty-seven patients (59%) were treated with neoadjuvant and concurrent androgen-deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range 1-14 years). Results: The 5and 10-year actuarial prostate-specific antigen (PSA) relapse-free survival outcomes for low-, intermediate-, and high-risk groups were 98.8 and 96.3%, 89.1 and 75.4%, and 76.1 and 65.8% (p < 0.001), respectively. On multivariate analysis, T stage (p Z 0.002), Gleason score (p < 0.001), and pretreatment PSA (iPSA) (p Z 0.008) were predictors for biochemical relapse. The 5and 10-year actuarial DMFS for low-, intermediate-, and high-risk groups was 99.4 and 96.8%, 97.4 and 93.6%, and 90.1 and 74.4% (p < 0.001), respectively. On multivariate analysis, T stage (p < 0.001), Gleason score (p < 0.001), and iPSA (p < 0.033) were predictive for DM. No prostate cancer-related deaths were observed in the low-risk group. The 5and 10-year actuarial CSS for intermediateand high-risk groups was 99.4 and 93.8%, and 96.6 and 82.2% (p Z 0.008), respectively. On multivariate analysis, only T stage (p Z 0.016) and Gleason score (p Z 0.003) were predictive for prostate cancer-related death. The incidence of grade 2 or higher late gastrointestinal (GI) and genitourinary (GU) toxicities were 4.4% and 17.1%, respectively. Late grade 3 GI and GU toxicity was experienced in 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This represents the largest cohort of patients treated with ultra-high-dose radiation to 86.4 Gy using IMRT for localized prostate cancer with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes and is well tolerated with acceptable toxicity. Author Disclosure: D. Spratt: None. X. Pei: None. J. Yamada: None. M.A. Kollmeier: None. B. Cox: None. Z. Zhang: None. M.J. Zelefsky: None.

Objective : The aim of this work was to develop a parameter for use during fractionated stereotactic radiotherapy treatment planning to aid in the determination of the appropriate treatment volume and fractionation regimen that will minimize risk of late damage to normal tissue. Materials & Methods : We have used the linear quadratic model to assess the biologically effective dose at the periphery of stereotactic radiotherapy treatment volumes that impinge on the brain stem. This paper reports a retrospective study of 77 patients with malignant and benign intracranial lesions, treated between 1987 and 1995, with the dynamic rotation technique in 6 fractions over a period of 2 weeks, to a total dose of 42 Gy prescribed at the 90% isodose surface. From differential dose-volume histograms, we evaluated biologically effective dose-volume histograms and obtained an integral biologically-effective dose (IBED) in each case. Results : Of the 77 patiens in the study, 36 had target volumes-positioned so that the brain stem received more than 1% of the prescribed dose, and 4 of these, all treated for meningioma, developed serious late damage involving the brain stem. Other than type of lesion, the only significant variable was the volume of brain stem exposed. An analysis of the IBEDs received by these by these 36 patients shows evidence of a threshold value for late damage to the brain stem consistent with similar thresholds that have been determined for external beam radiotherapy. Conclusion : We have introduced a new parameter, the IBED, that may be used to represent the fractional effective dose to structures such as the brain stem that are partially irradiated with stereotactic dose distributions. The IBED is easily calculated prior to treatment and may be used to determine appropriate treatment volume and fractionation regimens minimizing possible toxicity to normal tissue.

Purpose: Results of treatment of patients with Stage I seminoma with orchiectomy and radiotherapy are excellent. Even without adjuvant radiotherapy, the relapse rate is only 15-20%; most of the patients fail in the retroperitoneum, with rare failures observed in the pelvis (0.5-2%). In 1991, we began a prospective study evaluating para-aortic lymph node radiation as the only adjuvant treatment for such patients. This paper reports our preliminary results. Materials & Methods: Between March 1991 and January 1996, 35 patients with histologically proven Stage I seminoma were entered in the study. Median age was 37.9 years (range: 27-65 years). A radical inguinal orchiectomy was performed in all patients. Staging workup consisted of a chest X-ray; B-HCG, α-fetoprotein, and CT scan of the abdomen and pelvis in all patients. Lymphangiogram was done in 23 (66%) of 35 patients for further evaluation of the retroperitoneal lymph nodes. Radiotherapy consisted of treatment to the para-aortic region only. Parallel opposed fields extending from the top of T11 to the bottom of L5 were used. The median field size was 8.7 x 21.8 cm (range: 7-11 X 18-26 cm). The median total dose, prescribed at midpoint, was 25 Gy given in 15 daily fractions of 1.66 Gy. Follow-up was performed every 3 months for the first year, every 4-5 months for the second and third years, and every 6 months thereafter. Chest X-ray, tumor markers, and CT scan of the pelvis were performed routinely as part of the follow-up investigation. Results: At a median follow-up of 39.7 months (range: 16-74 months), 34 (97.1%) of 35 patients are alive with no evidence of disease for an overall actuarial survival rate of 97.1% at 5 years and a cause-specific actuarial survival rate of 100%. Treatment morbidity was limited to Grade I-II acute side effects in 18 (51.4%) of 35 patients. No late side effects were seen. Conclusion: From our preliminary results, adjuvant radiation treatment limited to the para-aortic lymph node region, without ipsilateral pelvic irradiation, appears to be adequate treatment for Stage I seminoma. Such an approach in our patients resulted in minimal toxicity and excellent disease-free survival.

Radiation Therapy Oncology Group (RTOG) 9408: A Secondary Analysis of the Risk of Death From Second Cancers Comparing Whole Pelvic (WP) Radiation Therapy (RT) to Prostate Only (PO) RT and Neoadjuvant Hormonal Therapy (NHT) + RT to RT Alone M. Roach, D. Hunt, C.U. Jones, J. Bahary, K.L. Zeitzer, L. Souhami, M.H. Leibenhaut, M. Rotman, E.M. Gore, and H.M. Sandler; University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, RTOG Statistics, Philadelphia, PA, Radiological Associates of Sacramento, Sacramento, CA, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada, Albert Einstein Medical Center, Brooklyn, NY, McGill University, Montreal, QC, Canada, CCOP/SUNY Downstate, SUNY Downstate, NY, Medical College of Wisconsin, Milwaukee, WI, Cedars-Sinai, Los Angeles, CA

Anatomic recurrence patterns were classified as a local, lymphotropic, or osteotropic pattern if FFS and all subsequent RS were confined to the prostate/SVonly, LNs only, or bones only, respectively, for at least 2 years. The median follow-up (f/u) for all patients and those with BF was 7.0 and 10.1 years (yr), respectively. Median f/u after BF was 4.7 yr. Results: For the entire cohort, the 10 yr LF rate was 6%, 14%, and 17% for the LR, IR, and HR groups (overall p < 0.001). The 10 yr risk of isolated PLN relapse as a FFS was 0%, 1%, and 4%, respectively (p < 0.001). We next focused on outcomes following BF in the 602 patients with BF. At 5 yr, the rates of BM and PCSM were 42% and 19%. The most common FFS was local (42% of FFS), followed by bone (26%), PLN (17%), and retroperitoneal LN (7%). Patients displayed unique anatomic distributions of relapse, with local (31%), lymphotropic (7%), osteotropic (16%), and multiorgan patterns (22%). These anatomic patterns had markedly different prognoses, with 5 yr PCSM of 2%, 15%, 32%, and 48%, respectively (p < 0.001). Anatomic recurrence pattern was an independent predictor for PCSM (overall p < 0.001) and OS (overall p < 0.001) in MVA amongst patients with clinical failure. Gleason score 8-10, stage T34, and time to BF < 5 yr predicted for BM and PCSM following BF in MVA. Conclusions: In the dose escalation era, the most common first site of failure is within the prostate and SV, even for HR patients, suggesting improved local cancer eradication via addition of brachytherapy and/or radiosensitizers may be beneficial. On the other hand, patients treated without PLN EBRT have a relatively low risk of isolated PLN relapse. Failure patterns displayed a tropism for specific anatomic distributions, with divergent prognoses, suggesting underlying biological differences amongst different tumors. Author Disclosure: Z.S. Zumsteg: None. D.E. Spratt: None. P. Romesser: None. X. Pei: None. W. Polkinghorn: None. M. Kollmeier: None. Y. Yamada: D. Employment Other; Speakers Bureau, Institute for Medical Education. G. Consultant; Varian Medical Systems. M.J. Zelefsky: None.

Purpose: To determine the maximum acutely tolerable dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors or brain metastases. Methods and Materials: Between August 1990 and September 1993, 102 analyzable patients were entered on Radiation Therapy Oncology Group (RTOG) protocol 90-05, 38 of whom had recurrent primary brain tumors (median prior dose 60 Gy), and 64 of whom had recurrent brain metastases (median prior dose 30 Gy) ≤ 40 mm in maximum diameter. Unacceptable toxicity was defined as irreversible Grade 3, any Grade 4, or Grade 5 central nervous system (CNS) toxicity according to the RTOG CNS criteria, occurring in > 20% of patients per treatment arm within 3 months of radiosurgery. Results: Patients were initially entered onto one of three treatment arms according to the maximum diameter of the recurrent lesion. Twelve to 22 patients were entered on each arm. The dose levels were: arm 1, ≤ 20 mm, 18 Gy; arm 2, 21–30 mm, 15 Gy; and arm 3, 31–40 mm, 12 Gy. Subsequently, doses were escalated as follows: arm 4, ≤ 20 mm, 21 Gy; arm 5, 21–30 mm, 18 Gy; and arm 6, 31–40 mm, 15 Gy. Unacceptable acute toxicity secondary to cerebral edema occurred in 0, 7, and 5% of patients on Arms 1, 2, and 3, respectively, and in no patients on arms 4, 5, or 6. Multivariate analysis revealed that tumor volume ≥ 8200 mm 3 and a ratio of maximum dose to prescription dose (MD/PD) ≥ 2 were significantly associated unacceptable toxicity. Of 15 patients with both tumor volume ≥ 8200 mm 3 and MD/PD ≥ 2, unacceptable toxicity occurred in 2 of 4 treated with a single isocenter and 1 of 11 treated with multiple isocenters. Subsequently, operation for symptomatic radionecrosis was required in 6% of patients. Conclusion: We found that the incidence of acute toxicity was acceptable at 0–7% in patients with recurrent, previously irradiated primary brain tumors or brain metastases ≤ 40 mm in maximum diameter treated according to the protocol described.