Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer.

BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.

Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314.

Following documented evidence of the synergism of 5-fluorouracil (5-FU) and radiation therapy and an additive effect with mitomycin and irradiation, pilot studies have demonstrated the potential for definitive radiation therapy in the management of squamous cell and basaloid carcinomas of the anal canal, allowing sphincter preservation. Our study explored the long-term effectiveness of combined therapy at this disease site and examined the feasibility of a Radiation Therapy Oncology Group study involving concomitant radiation therapy and chemotherapy. Between 1983 and 1987, 79 assessable patients with any primary tumor stage of anal canal carcinoma were treated by external-beam irradiation combined with mitomycin given by bolus iv injection and 5-FU given by continuous infusion. Radiation was delivered to the perineum and pelvis to a total dose of 4,080 cGy in 4.5-5 weeks. The inguinal nodal areas received 4,080 cGy, calculated at a 3-cm depth in the center of the nodal area. A 96-hour infusion of 5-FU was started on days 2 and 28 of the irradiation at a dose of 1,000 mg/m2 over 24 hours, and a bolus injection of mitomycin was administered on day 2 at a dose of 10 mg/m2. The overall survival rates are 97% at 1 year and 73% at 3 years. Patients with lesions less than 3 cm in diameter and those treated strictly according to the protocol did significantly better than those with larger lesions and those whose treatment did not comply with the protocol. The interim outcome of the study demonstrates that this combined therapy is effective for patients with anal cancer and allows preservation of the sphincter and of sexual function.

Analysis of postoperative radiation therapy in stage I through III epithelial ovarian carcinoma.

A retrospective long-term analysis of the results of primary postoperative radiotherapy in 106 women with invasive epithelial ovarian carcinoma is presented. Forty-two women received open-field total abdominopelvic irradiation, and 64 received treatment by various subtotal abdominopelvic techniques. The mean follow-up of living patients in the two groups is 86 and 116 months, respectively. Women who had Federation International Gynecology and Oncology (FIGO) stages I through III-A with no postoperative residual disease, or less than 0.5-cm abdominal and/or less than 2-cm pelvic residual disease formed a favorable group in whom total abdominopelvic irradiation resulted in a 71% 10-year actuarial relapse-free survival rate compared with 40% for those treated by subtotal abdominopelvic techniques (P less than or equal to .0205). The survival improvement due to the total abdominopelvic technique in favorable patients became even more significant (P less than or equal to 0.003) after adjusting for differences in stage, grade, and postoperative residual disease volume (no, or favorable, gross). Increasing grade appeared to be associated with decreasing survival even among favorable patients treated with the optimal technique, although the differences did not approach statistical significance after adjusting for residual disease volume and stage. Surgical bowel complications were equivalent, 7.1% for total abdominopelvic v 8.1% for subtotal abdominopelvic techniques. The addition of intraperitoneal radioactive chromic phosphate increased the surgical bowel complication rate 33% over external pelvic irradiation alone without improving survival. Patients with unfavorable gross residual disease and/or FIGO stages III-B and IV were incurable by any radiation technique. Those with no, or favorable, gross residual tumor constitute a group in whom we believe open-field total abdominopelvic irradiation represents a potentially curative therapy modality.

Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study.

PURPOSE: In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities. METHODS: All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU. RESULTS: Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018). CONCLUSION: This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity.

Combination chemotherapy and radiation therapy in lung cancer.

This report outlines the principles and application of chemoirradiation in bronchogenic carcinoma. The emphasis is on the timing of treatment in small cell lung cancer and the Radiation Therapy Oncology Group trial in non-small cell lung cancer. The purpose of this report is to provide a framework for future trials.

Evaluation of the response of unresectable carcinoid tumors to radiotherapy.

Sixteen patients with unresectable primary or metastatic carcinoid tumors were treated with radiotherapy. Objective responses (CR + PR) were documented in 4 of 16 patients (25%). The median survival of the responders was 46 months following radiotherapy, as compared to the 10-month median survival of the entire group of 16 patients. There were five additional patients who improved symptomatically or had minor responses. The seven patients who received the highest doses of radiotherapy (greater than 29 GY), to local or regional treatment ports, had the best response rate (43%). Many patients eventually had objective evidence of relapse or tumor progression within the radiotherapy port, in part reflecting the relatively low radiotherapy doses used in the treatment of the nine patients with abdominal carcinoids. One patient remains disease free at 103 months. Patients who exhibited the carcinoid syndrome appeared to respond less frequently to radiotherapy than patients who did not have ectopic hormone secretion, although the number of patients with ectopic hormone secretion was too small to establish this point in a definitive manner. The results of this study demonstrate that carcinoid tumors respond to moderate doses of radiotherapy in a manner similar to many other epithelial tumors.

Breast irradiation following silicone gel implants.

Little information is found in the literature regarding breast irradiation in patients with reconstructed or augmented breasts. From November 1970 to October 1984, we treated ten patients with silicone gel prostheses with external radiation for recurrent disease, or as primary therapy. All patients were treated with megavoltage equipment. Technique and doses varied with the clinical situation, but generally, patients received 5000 rad in five weeks to the breast or mound with opposed tangential fields. The majority of patients had excellent cosmetic results with minimal late skin changes and no fibrosis or contracture. We conclude that, with proper surgical and radiotherapeutic techniques, good cosmetic results can be obtained in these patients, without compromising their therapy.

Randomized phase II chemotherapy and radiotherapy trial for patients with locally advanced inoperable non-small-cell lung cancer: long-term follow-up of RTOG 92-04.

PURPOSE: The standard treatment for patients with locally advanced inoperable non-small-cell lung cancer and good prognostic factors has become combined chemotherapy (ChT) and radiotherapy (RT). However, the sequencing of the two modalities, as well as fractionation of RT, has been controversial. The Radiation Therapy Oncology Group (RTOG) Study 92-04 was a randomized Phase II study designed to evaluate further the toxicity and efficacy of 2 different strategies of chemoradiation evaluated in 2 prior RTOG Phase II studies. METHODS: Patients with Stage II or III medically inoperable or unresectable non-small-cell lung cancer, good performance status, and minimal weight loss were enrolled into a prospective randomized Phase II RTOG study. Arm 1 consisted of induction ChT (vinblastine 5 mg/m(2) i.v. bolus weekly for the first 5 weeks, and cisplatin, 100 mg/m(2) i.v. on Days 1 and 29) followed by concurrent ChT/RT (cisplatin 75 mg/m(2) i.v. on Days 50, 71, and 92) during thoracic radiotherapy (63 Gy in 34 fractions during 7 weeks starting on Day 50). Arm 2 was concurrent ChT and hyperfractionated RT starting on Day 1 with a total dose of 69.6 Gy in 58 fractions during 6 weeks, 1.2 Gy/fraction b.i.d. ChT consisted of cisplatin, 50 mg/m(2) i.v. on Days 1 and 8, and oral VP-16, 50 mg b.i.d. for 10 days only on the days of thoracic radiotherapy repeated on Day 29. RESULTS: A total of 168 patients were entered between 1992 and 1994, and 163 patients were eligible for analysis. Eighty-one patients were treated in Arm 1 and 82 patients in Arm 2. Pretreatment characteristics, including age, gender, Karnofsky performance status, histologic features, and stage, were similar. The incidence of acute esophagitis was significantly higher among patients treated in Arm 2 than among those treated in Arm 1 (p <0.0001). The incidence of acute hematologic toxicity was significantly higher among patients treated in Arm 1 (p = 0.01 for anemia and p = 0.03 for other hematologic toxicities) than among those treated in Arm 2. Analysis of late toxicity showed that chronic esophageal toxicity was significantly more frequent in Arm 2 than in Arm 1 (p = 0.003). The time to in-field progression was significantly different (p = 0.009), favoring Arm 2 compared with Arm 1 (26% vs. 45% with failure in 2 years and 30% vs. 49% with failure in 4 years, respectively). The median 2-year and overall 5-year survival rates were similar between the two arms. CONCLUSION: Concurrent ChT and hyperfractionated RT resulted in a significant prolongation of the time to in-field progression, but with higher acute and chronic esophagitis. No other significant differences were observed between the two groups. Investigation with a chemoradio-protector is under way.

Is prolonged survival possible for patients with supraclavicular node metastases in non-small cell lung cancer treated with chemoradiotherapy?: Analysis of the Radiation Therapy Oncology Group experience.

PURPOSE: To determine if patients with non-small cell lung carcinoma (NSCLC) and positive supraclavicular nodes (SN+) have a similar outcome to other patients with Stage IIIB NSCLC (SN-) when treated with modern chemoradiotherapy. METHODS AND MATERIALS: Using the Radiation Therapy Oncology Group (RTOG) database, data were retrospectively analyzed from five RTOG trials studying chemoradiotherapy for NSCLC: 88-04, 88-08 (chemo-RT arm), 90-15, 91-06, 92-04. Comparisons were made between the SN+ and SN- subgroups with respect to overall survival, progression-free survival (PFS), and metastases-free survival (MFS) using the log rank test. Cox multivariate proportional hazards regression analysis was used to determine the effect of several potential confounding variables, including histology (squamous vs. nonsquamous), age (>60 vs. < or = 60), Karnofsky Performance Status (KPS) (<90 vs. > or = 90), weight loss (> or = 5% vs. <5%), and gender. RESULTS: A total of 256 Stage IIIB patients were identified, of whom 47 had supraclavicular nodes (SN+) and 209 did not (SN-). Statistically significantly more SN+ patients had nonsquamous histology (p = 0.05); otherwise, known prognostic factors were well balanced. The median survival for SN+ patients was 16.2 months, vs. 15.6 months for SN- patients. The 4-year actuarial survival rates were 21% and 16% for SN+ and SN- patients respectively (p = 0.44). There was no statistically significant difference in the 4-year PFS rates (19% vs. 14%, p = 0.48). The Cox analysis did not show the presence or absence of supraclavicular nodal disease to be a prognostic factor for survival, MFS, or PFS. The only statistically significant factor on multivariate analysis was gender, with males having a 40% greater risk of mortality than females (p = 0.03). There were no clinically significant differences in toxicity when comparing SN+ vs. SN- patients. Among the 47 SN+ patients, there were no reported cases of brachial plexopathy or other > or = Grade 2 late neurologic toxicity. CONCLUSIONS: When treated with modern chemoradiotherapy, the outcome for patients with supraclavicular metastases appears to be similar to that of other Stage IIIB patients. SN+ patients should continue to be enrolled in trials studying aggressive chemoradiotherapy regimens for locally advanced NSCLC.

Tolerance of pelvic normal tissues to hyperfractionated radiation therapy: results of Protocol 83-08 of the Radiation Therapy Oncology Group.

A prospective, centrally randomized Phase I/II trial of hyperfractionation in definitive radiation therapy for locally advanced squamous and transitional cell carcinoma of the bladder was conducted by the Radiation Therapy Oncology Group (RTOG) from April 1983 through June 1986. Patients with T3-4 and T2 N+ (AJC) histologically-confirmed cancer of the bladder received twice daily radiation therapy with 1.2 Gy per fraction and a minimum of 4 hr between fractions. All patients received a whole pelvic total dose of 50.4 Gy: Total doses to reduced volumes were 60.0 Gy, 64.8 Gy, or 69.6 Gy. Of 54 patients entered, 50 were eligible. An unbalanced treatment assignment was used: Nine patients received 60.0 Gy, 15 patients received 64.8 Gy and 26 received 69.6 Gy. Performance status (Karnofsky) was 90-100 in 72% of patients and 92% had transitional carcinoma. Eighty percent of tumors were T3 or T4. Observation of at least 18 months was available for 26 patients. Grade 3 acute reactions (within 90 days) were reported in eight patients (one at 60.0 Gy, three at 64.8 Gy and four at 69.6 Gy). Five patients experienced a total of seven major late effects--four Grade 3 and three Grade 4. The cumulative probability of Grade 3 and 4 late complications of treatment for the 46 patients at risk for late complications was 5% +/- 3% at 6 months, 7% +/- 4% at 12 months, and 10% +/- 5% at 18 and 24 months. The cumulative probability of Grade 3 or 4 late complications for patients who received a total dose of 69.6 Gy was 5% +/- 4% at 6 and 12 months and 11% +/- 8% at 18 and 24 months. Only one patient who experienced major late effects was also reported to have major acute reactions. Comparisons of survival of patients treated in the current study with those who received 60 Gy in 30 fractions in 6 weeks in RTOG Protocol 71-04, did not suggest any deleterious effects from hyperfractionated radiation therapy to the pelvis. The normal pelvic tissues tolerated hyperfractionated radiation therapy sufficiently well to justify exploring it, alone and with brachytherapy, in other pelvic tumors.

Phase I/II trial of accelerated fractionation in brain metastases RTOG 85-28.

PURPOSE: Radiation Therapy Oncology Group 85-28 represents a Phase I/II trial of accelerated fractionation in patients with brain metastases. METHODS AND MATERIALS: Patients entered had controlled or absent primary with metastases other than brain which were stable or only brain metastases with the primary uncontrolled. Karnosfky status was required to be greater than 60. Patients received 1.6 Gy twice daily separated by 4-8 hr delivered 5 days a week. The entire brain was treated to 32.0 Gy and the boost dose escalated from 16.0 Gy to 22.40 Gy and subsequently 32.00 Gy and 42.40 Gy. RESULTS: We observed no undue toxicity with escalating dose of irradiation. An incremental, although not statistically significant improvement in survival was noted with escalating doses. Median survival ranged from 4.2 months to 6.4 months with escalating dose of irradiation. Median survival also increased in patients with controlled primary tumors, non-lung primaries and solitary metastasis. CONCLUSION: The incremental improvement in survival in patients with good prognostic factors appeared encouraging. The Radiation Therapy Oncology Group will test the 54.4 Gy study against 30 Gy in 2 weeks in a Phase III trial based on the results of this trial.

Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group.

The Radiation Therapy Oncology Group in 1985 began a study of IORT plus external beam radiation therapy for patients with locally unresected, non-metastatic pancreatic cancer. Patients were treated with a combination of 2000 cGy of IORT and postoperative external beam radiation therapy to 5040 cGy in combination with IV 5-FU (500 mg/m2/day on the first 3 days of the external beam treatment). As patients were registered on study prior to exploration, it was expected that a number of patients would be excluded from further analysis at the time of surgery. Eighty-six patients were entered on study through 6/1/88 and analyzed through 4/90. Fifty-one patients were fully analyzable. Median survival time of the 51 patients was 9 months with an 18-month actuarial survival rate of 9%. Local control could not be adequately evaluated in this multi-institutional study. Major postoperative complications were not excessive and occurred in 12% of patients. Two patients had major late morbidity leading to death, one from duodenal bleeding and the second from biliary obstruction. Although this study does demonstrate the feasibility of IORT in a multi-institutional setting, it does not demonstrate any advantage of IORT over conventional therapy for this disease.

Fraction size in external beam radiation therapy in the treatment of melanoma.

RTOG 83-05 was a prospective randomized trial evaluating the effectiveness of high dose per fraction irradiation in the treatment of melanoma. Retrospective analysis suggested a dose response curve of melanoma to external beam irradiation as the dose per fraction is increased. RTOG 83-05 randomized patients with measureable lesions to 4 x 8.0 Gy in 21 days once weekly to 20 x 2.5 Gy in 26-28 days, 5 days a week. One hundred thirty-seven patients were randomized and 126 patients were evaluable: 62 patients in the 4 x 8.0 Gy arm and 64 patients in 200 x 2.5 Gy arm. Patient characteristics were essentially identical. Stratification was performed on lesions less than 5 cm or greater than or equal to 5 cm. The study was closed on May 31, 1988 when interim statistical analysis suggested that further accrual would not reveal a difference between arms. Response rate overall was complete remission 23.8%, partial remission 34.9%. The 4 x 8.0 Gy arm exhibited a complete remission of 24.2% and partial remission of 35.5%. The 20 x 2.5 Gy arm exhibited a complete remission of 23.4% and partial remission of 34.4%. There was no difference between arms.

Outcome for lymph node dissection negative T-1b, T-2 (A-2,B) prostate cancer treated with external beam radiation therapy in RTOG 77-06.

One hundred four patients with stage T-1b, T-2 N-O M-O prostate cancer were treated with external beam irradiation as part of RTOG 77-06. Lymph nodes were negative by lymph node dissection in 16 patients with T-1b and 88 patients with T-2 cancers. Survival exceeds age matched expected survival for the 10 years of observation (63% vs 59% at 10 years). Patterns of failure at 10 years show 87% of patients were free of isolated local recurrence, 79% free of metastatic failure, 67% free of any failure, and cause specific survival shows 86% free of cancer death at 10 years. The outcome of this group is equal or superior to reports of radical prostatectomy in similar stage patients.

Correlation of survival with quantitative tissue staining of prostate specific acid phosphatase in patients with prostate carcinoma by using microscopic image analysis: a preliminary report of correlative studies on RTOG protocols 75-06, 77-06, and 83-07.

PURPOSE: We have previously shown that the intensity (graded semiquantitatively as 1-4+) of tissue prostate-specific acid phosphatase (PSAP) staining determined immunocytochemically in a cohort of prostate carcinoma patients from Radiation Therapy Oncology Group Protocols (RTOG) protocols 75-06 and 77-06 correlated with survival. The extent of this staining was heterogeneous and was estimated. The extent of staining was not found to be significantly associated with survival. We undertook the present quantitative study to see if the improved precision and reliability of measurement of the intensity and extent of prostate specific acid phosphatase staining would confirm and extend our previous observations. METHODS AND MATERIALS: Patient cohorts representative of the entire group were obtained from RTOG 75-06 plus 77-06 and 83-07. The RTOG 77-06 plus 75-06 patients (No-Hormone population) did not receive preradiation hormonal therapy. RTOG 83-07 patients (Prehormone population) received one of two types of preradiation chemical androgen ablation. In this study, histologic slides of tumors were immunocytochemically stained for PSAP by the peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as a substrate and hematoxylin as a nuclear counterstain. The intensity and extent of immunocytochemical PSAP staining (IPSAP stain) was quantified using our dual wavelength and batch mode image process technique. RESULTS: Our study of 151 cases confirmed that overall survival of patients in both populations was positively correlated with the intensity and extent of IPSAP stain. Results of the two studies were similar. The statistical significance of the relationship of both extent and intensity was greater in the cohort from protocol 83-07, which was the patient group receiving pretreatment with hormones. In a Cox multiple regression analysis including clinical stage, Gleason and M. D. Anderson grades, and the cohort of patients (Prehormone or No-Hormone group) as covariables, both the intensity and extent of the IPSAP stain significantly correlated with survival along with M. D. Anderson grade of the tumor. CONCLUSION: Quantitative image analysis of the IPSAP stain predicts survival in patients treated with external beam radiotherapy with and without prior hormonal therapy.

Extended field (periaortic) irradiation in carcinoma of the prostate--analysis of RTOG 75-06.

From 1976 to 1983 the Radiation Therapy Oncology Group conducted a study of extended field (periaortic) irradiation in carcinoma of the prostate. Eligible patients were those with clinical Stage C tumor with or without evidence of pelvic lymph node involvement and also those with Stage A-2 and B with evidence of pelvic lymph node involvement. The stratification criteria included histological grade, clinical stage, absence or presence of hormonal manipulation, and method of lymph node evaluation (lymphangiogram vs. laparotomy vs. no nodal evaluation). The patients were randomized to either receive pelvic irradiation followed by a boost to the prostate or pelvic and periaortic irradiation followed by a boost to the prostate. The prescribed daily dose was 180-200 rad to a total midplane dose to the regional lymphatics to 4000-4500 rad. The prostatic boost target volume was to receive additional 2000-2500 rad bringing the total dose to that area to a minimum of 6500 rad. A total of 523 analyzable patients have been accessioned to the protocol. Four hundred forty-eight of these are known to have received treatment per protocol. Median follow-up is 4 years and 3 months. The analyzable patients were evaluated for the incidence of distant metastases, NED survival and survival as a function of treatment arm. No statistically significant differences between the treatment arms could be documented. Similarly, no significant difference between treatment arms could be documented within a number of subpopulations such as those characterized by a particular grade, hormonal status, stage, age, acid phosphatase level, etc. The results of the study revealed no apparent benefit of elective periaortic irradiation in patients with detectable disease confined to the pelvis.

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery: final report of an RTOG study.

This randomized RTOG study evaluated misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. One hundred and forty-six evaluable patients were treated with conventional radiation therapy to 60.00 Gy in 6-7 weeks plus BCNU 80 mg/m2/d for 3 days every 8 weeks (XRT + BCNU). One hundred and forty-seven evaluable patients were treated with misonidazole 2.5 gm/m2 once a week for 6 weeks, radiation therapy to 60 Gy and BCNU (MISO + XRT + BCNU). Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics was comparable among the treatment groups. The median survival for XRT + BCNU was 55.0 weeks, and for MISO + XRT + BCNU 46.0 weeks (p = 0.35). With patients on a minimum dose of dexamethasone of 3 mg/d, misonidazole neurotoxicity included 8.8% peripheral neuropathy, 2.7% CNS toxicity, and a 0.68% ototoxicity. BCNU pulmonary toxicity occurred in 9.3% of patients who received 902-2062 mg/m2 of BCNU.

Response, toxicity, failure patterns, and survival in five Radiation Therapy Oncology Group (RTOG) trials of sequential and/or concurrent chemotherapy and radiotherapy for locally advanced non-small-cell carcinoma of the lung.

PURPOSE: The purpose of this study was to assess response, toxicity, failure patterns, and survival differences in three chemotherapy (ChT)/radiation therapy (RT) sequencing strategies for locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Five completed Radiation Therapy Oncology Group (RTOG) trials for Stage II-IIIA/B inoperable NSCLC patients employed one of the three following strategy groupings: 1) sequential ChT followed by standard RT (60 Gy in 6 weeks); 2) combined sequential and concurrent ChT and standard RT (60 Gy in 6 weeks); or 3) concurrent ChT and hyperfractionated RT (69.6 Gy in 6 weeks). All five trials required KPS > or = 70; two trials (314 patients) required <5% weight loss and three trials (147 patients) had no minimum weight loss requirement. In all five trials the ChT used cisplatin with either vinblastine or oral etoposide. Combining data for the five trials yielded an evaluable group of 461 patients. The three methods of sequencing ChT and RT were evaluated for differences in response, acute and late toxicity, patterns of failure, and survival. Acute toxicity was defined as that occurring within 90 days from the start of RT. Late toxicity was defined as that occurring after 90 days from the start of RT. Acute or late toxicity > or = grade 3 was defined as severe. Site of first failure was recorded by date. In-field failure excluded distant metastasis as a failure and included only tissue in the RT treatment field. Overall progression-free survival (PFS) was defined as survival without evidence of intra- or extrathoracic tumor or death from any cause. RESULTS: Group 1 had a lower overall response rate (63%) compared to either Group 2 (77%) or Group 3 (79%), p = 0.03 and 0.003, respectively. Overall grade 4/5 acute toxicities were nearly equal between groups. The severe nonhematologic acute toxicities were significantly different by strategy group (p < 0.0001). Group 1 and 2 were not statistically different. Group 3 had significantly more patients with severe acute nonhematologic toxicity (55%) than either Group 1 (27%) or 2 (34%) with p < 0.0001 and p = 0.0005, respectively. This was due to a severe acute esophagitis rate of 34% for Group 3 versus 1.3% for Group 1 and 6% for Group 2 (p < 0.0001 for both comparisons). Overall grade 4/5 late toxicities did not differ by group. Severe late nonhematologic toxicities were different by group (p = 0.0098). Group 1 patients had significantly fewer severe late nonhematologic toxicities (14%) compared to patients in Groups 2 (26%) or 3 (28%) (p = 0.046 and 0.038, respectively). Severe late lung toxicity was 10% for Group 1 compared to 21% and 20% for Groups 2 and 3, respectively. Severe late lung toxicities differed by group (p = 0.033), but not severe late esophagitis (p = 0.077). There were no differences between the three strategy groups for patterns of first failure. The in-field failures were higher in Group 2 (71%) compared to Groups 1 (56%) and 3 (55%), p = 0.0478. Pairwise comparisons yielded p-values of 0.068 and 0.015 for Group 2 versus 1 and Group 2 versus 3, respectively. Three-year PFS was better in Group 2 (15%) and 3 (15%) compared to Group 1 (7%), but not statistically significant (p = 0.454). Similarly, in-field PFS was better in Group 2 (17%) and 3 (20%) than Group 1 (9%), but not significant (p = 0.167). There were improvements in 3-year survival for Group 2 (17%) and Group 3 (25%) compared to Group 1 (15%), but the differences were not statistically significant (p = 0.47). The same results were present for patients with less than 5% weight loss and patients with stage IIIA tumors. CONCLUSION: Thus, concurrent ChT and hyperfractionated RT had a higher incidence of severe acute esophageal toxicity. Severe late lung toxicity with concurrent ChT/hyperfractionated RT, as well as with induction ChT followed by concurrent ChT/standard RT, may be greater compared to sequential ChT/RT. (ABSTRACT TRUNCATED)

Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate.

PURPOSE: To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival. METHODS AND MATERIALS: The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2--T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II. RESULTS: As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific mortality (23% vs. 31%, p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2--6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7--10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival. CONCLUSION: In patients with Gleason score 2--6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.

Prostate-specific antigen levels are higher in African-American than in white patients in a multicenter registration study: results of RTOG 94-12.

PURPOSE: To compare serum prostate-specific antigen (PSA) levels in a national sample of African-American and white men with prostate cancer, and to attempt to explain any differences by using self-reported individual-level socioeconomic status adjustments. METHODS AND MATERIALS: During 4 1/2 months in 1994-95, 709 patients with nonmetastatic prostate cancer were enrolled in this prospective study; 17.5% were African-American and 82.5% were white. Information about clinical stage, tumor grade, pretreatment PSA, type of insurance, and educational and income status was obtained. Serum PSA levels were measured and racial differences were found; how the differences were influenced by other patient- or tumor-related factors and if the differences could be explained by socioeconomic status disparities were determined. In univariate analyses, factors associated with the mean PSA levels were studied; log-converted values were used to yield a normal distribution. Multivariate analyses were done on log-linear models for description of association patterns among various categorical variables; a perfectly fitted model should have a correlation value (CV) of 1.0. RESULTS: The mean PSA level was higher in African-Americans (14.68 ng/ml) than in whites (9.82 ng/ml) (p = 0.001). Clinical stage (p = 0.001), Gleason sum tumor grade (p = 0.0001), educational level (p = 0.001), and household income (p = 0.03) were also associated with mean PSA levels; age, type of biopsy, and insurance status were not. Disease stage (p = 0.0001), grade (p = 0.0001), education (p = 0.07), and income (p = 0.02) were all associated with PSA levels for whites, but none of these factors were important for African-Americans (all p values > 0.1). The best fitted log-linear model (CV = 0.99) contained PSA (< 10, 10-20, and > 20), Gleason sum grade (2-5, 6-7, and 8-10), race, and two interactions: PSA by race (p = 0.0012) and PSA by Gleason sum (p = 0.0001). Models replacing race for either income (CV = 0.82) or education (CV = 0.82) or both (CV = 0.78) did not fit as well. CONCLUSIONS: African-Americans with nonmetastatic prostate cancer have higher serum PSA levels at diagnosis than whites, implying a higher tumor cell burden. Individual-level household income, education, or insurance status alone or in combination account for racial differences, but only partially.