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.

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.

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.

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.

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.

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.

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.

Elective pelvic irradiation in stage A2, B carcinoma of the prostate: analysis of RTOG 77-06.

From 1978 to 1983 the Radiation Therapy Oncology Group conducted a study to evaluate the role of elective pelvic lymph node irradiation in carcinoma of the prostate. Eligible patients were those with clinical Stage A2 (occult disease with more than 3 positive chips and poorly differentiated tumor) and Stage B without clinical (lymphangiogram) or biopsy evidence of lymph node involvement. The patients were randomized to receive 6.5 weeks of either prostatic bed irradiation only 6500 cGy at 180-200 cGy per treatment or pelvic node irradiation to 4500 cGy with a boost of 2000 cGy to the prostatic bed bringing the total dose to 6500 cGy. As of February, 1988, the median follow up has been 7 years and there were 445 analyzable cases who were evaluated for local control, incidence of distant metastases, ned (no evidence of disease) survival and survival. The results of the study revealed no statistically significant benefit of elective pelvic irradiation.

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.

Analysis of preoperative intracavitary cesium application versus postoperative external beam radiation in stage I endometrial carcinoma.

Two groups of patients with surgical Stage I endometrial carcinoma treated at the LDS Hospital in Salt Lake City are analyzed. Group 1 comprises 112 patients treated from 1974 through 1976, during which time preoperative intracavitary cesium was routinely used in all patients. Group 2 comprises 117 patients treated 1981 through 1983 under the treatment policy of hysterectomy without preoperative cesium. High risk patients from each group (grade 3 and/or deep myometrial invasion) generally received similar postoperative external beam pelvic radiotherapy (4500-5000 cGy). While 5-year actuarial disease-free survival rates were similar in each group (94% Group 1 vs 91% Group 2), multivariate analysis by the Cox Regression Method revealed that inclusion within treatment Group 2 carried independent adverse prognostic significance (p = 0.018). Other independent predictors of adverse 5-year disease-free survival included deep myometrial invasion and increasing histologic grade. Group 1 patients with grade 3 lesions had a superior 5-year actuarial disease-free survival (76% vs 53%) compared to those from Group 2. Group 1 patients with deep myometrial invasion also had a superior 5-year disease-free survival (84% vs 69%). The remaining low risk patients (grade 1 or 2, less than 1/3 myometrial invasion) had an excellent 5-year disease-free survival with or without preoperative cesium. Immediate preoperative intracavitary cesium was well tolerated, did not obscure pathologic findings and in our experience, reduced the probability of recurrence in high risk Stage I endometrial carcinoma patients.

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.

Correlation of pre-treatment transurethral resection and prognosis in patients with stage C carcinoma of the prostate treated with definitive radiotherapy--RTOG experience.

Four hundred and ninety-four patients with clinical Stage C carcinoma of the prostate, who were entered onto a phase III RTOG study, have been analyzed as to the potential effect of the pre-treatment transurethral resection (TUR) of the tumor. Treatment consisted of definitive irradiation to the prostate (6500-7000 cGy) and regional lymphatics (4500-5000 cGy). A total of 202 patients underwent pre-treatment TUR. This population was compared with the remaining 292 patients as to the rate of locoregional failure, incidence of distant metastases, disease-free survival, and survival. The TUR population fared significantly worse for all four end-points. To account for uneven distribution of recognized prognostic factors the results were then adjusted using stratified Mantel-Haenszel tests. The stratification process resulted in a reduced level of significance in the differences between the two populations. However, a trend toward a higher incidence of distant metastases could be observed within most strata. The trend was most pronounced in subpopulations characterized by Gleason score 6-7 and normal serum acid phosphatase (SAP). For the population characterized by Gleason score 6-10 and normal SAP, the differences in the incidence of distant metastases retained statistical significance. Whether these findings are secondary to tumor dissemination during TUR or are due to incompletely identified selection biases remains to be demonstrated in future (prospective) studies.

Correlation of radiotherapeutic parameters and treatment related morbidity--analysis of RTOG Study 77-06.

The current report is an updated and detailed analysis of treatment related morbidity in RTOG 77-06, a Phase III randomized study comparing prostatic irradiation versus pelvic irradiation followed by a prostatic boost, in patients with Stage A2 and B carcinoma of the prostate without evidence of nodal involvement. A total of 453 analyzable cases were accrued from 1978 to 1983, when the study was closed. All cases of treatment related morbidity were classified as to severity (using a clinical severity grading system). The data were then correlated with a number of radiotherapeutic parameters including treatment volumes (fields), doses, and techniques. Overall, pelvic irradiation, compared to prostate irradiation only, was not associated with a significantly increased incidence of treatment related morbidity. Within the range of pelvic doses used in this study a significant dose effect could not be detected. Total doses to the prostate of more than 7000 cGy were associated with an increased risk of rectal bleeding. Certain treatment techniques, (AP/PA irradiation of the pelvic lymphatics) were associated with an increased incidence of bowel complications.

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.

Comparison of pathologic and clinical evaluation of lymph nodes in prostate cancer: implications of RTOG data for patient management and trial design and stratification.

RTOG 77-06 and 75-06 were studies of nodal irradiation in prostate cancer, for which the status of nodes was determined by lymph node dissection (LND), lymphangiography (LAG), or computer assisted tomography (CT) based on investigator preference. Actuarial 5 year endpoints of survival, NED survival, local recurrence and distant metastasis have been determined by stage for 805 eligible patients with a comparison of pathologic vs clinical (imaging test) determined nodal status. Patients with pathologically negative lymph nodes show significantly improved 5 year survival (Stage T-2 (B) 84% vs 77%, Stage T-3,4 (C) 82% vs 65%) and NED survival (Stage T-2 (B) 72% vs 63%, Stage T-3,4 (C) 64% vs 44%) compared to patients clinically negative. Free of metastasis rates are increased in Stage T-3,4 (C) pathologic negative patients compared to imaging negative patients (75% vs 60%). A comparison of clinical positive versus clinical negative patients shows no difference in survival, NED survival or rate of metastasis, while a similar comparison of pathologic positive versus pathologic negative shows significant difference for all three endpoints (survival: Stage T-2 (B) 84% vs 61%, Stage T-3,4 (C) 82% vs 66%, NED survival: Stage T-2 (B) 72% vs 32%, Stage T-3,4 (C) 64% vs 32%; free of metastasis: Stage T-2 (B) 82% vs 64%, Stage T-3,4 (C) 75% vs 44%). The clinical determination of nodal status, therefore, has no prognostic value in contrast to pathologic determination and should not be used for stratifying patients in clinical trials. The CT scans often used to evaluate nodal status are more useful if delayed until they can be done as part of the treatment planning process where the CT has value. When imaging tests suggest positive lymph nodes in prostate cancer patients, the imaging finding is confirmed by biopsy.

Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small-cell lung cancer (LA-NSCLC): identification of five groups with different survival.

PURPOSE: Survival of patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) is predicted by the stage of the disease and other characteristics. This analysis was undertaken to identify these characteristics in a large cooperative group patient population, as well as to define subgroups of the population with differing outcomes. PATIENTS AND METHODS: Analysis included 1,999 patients treated in 9 RTOG trials between 1983 and 1994 with thoracic irradiation (RT) with (n = 355) or without chemotherapy (CT). RESULTS: In univariate analysis, the following characteristics were significantly associated with an improved survival: use of CT, CT delivered without major deviation, abnormal pulmonary function tests, normal hemoglobin, protein, LDH and BUN, presence of dyspnea, hemoptysis, cough or hoarseness, uninvolved lymph nodes, T1 or T2 stage, no malignant pleural effusion (PE), weight loss of < 8%, Karnofsky performance status (KPS) of at least 90, adenocarcinoma histology, female gender, and age less than 70 years. Recursive partitioning analysis (RPA) was subsequently applied to identify 5 patient subgroups with significantly different median survival times (MST): Group I, KPS of > or = 90, who received chemotherapy (MST 16.2 months); Group II, KPS of > or = 90, who received no CT, but had no PE (MST 11.9 months); Group III, KPS < 90, younger than 70 years, with non-large cell histology (MST 9.6 months); Group IV, KPS > or = 90, but with PE, or KPS < 90, younger than 70 years, and with large cell histology, or older than 70 years, but without PE (MST 5.6-6.4 months); Group V, older than 70, with PE (MST 2.9 months). CONCLUSION: Cisplatinum-based CT improves survival, for excellent prognosis of LA-NSCLC patients, over RT alone. The presence of a malignant pleural effusion is a major negative prognostic factor for survival. The identification of RPA prognostic groups among patients with LA-NSCLC provides prognostic information and may serve as a basis of stratification in future trials.

Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG phase III study for A2 and B prostate carcinoma.

Radiation Therapy Oncology Group (RTOG) protocol 7706 was a randomized Phase III study designed to test the value of elective (prophylactic) pelvic irradiation in addition to prostatic irradiation in patients with carcinoma of the prostate with no clinical evidence of tumor extension through the capsule. Eligible patients were those who had clinical Stage T1bNOMO (A2) or T2NOMO (B), who did not have curative surgery, and who had no evidence of lymph node metastases. Assessment of the regional lymphatics was mandatory but, at the discretion of the investigator, lymphangiography (LAG) or staging lymphadenectomy (SL) could be used. A total of 445 eligible and analyzable patients were entered in the study between 1978 and 1983 when the study was closed. The median follow-up was 7 years; minimum follow-up was 5 years. There were no significant differences in survival or local control whether treatment was administered to the prostate or to the prostate and pelvic lymph nodes. The nodal status for 117 (26%) patients was assessed by staging lymphadenectomy (SL) whereas for 328 (74%) patients it was assessed by lymphangiography (LAG). Pretreatment characteristics felt to have impact on survival were evaluated and found to be free of serious imbalance between the staging lymphadenectomy and lymphangiography groups. Compared to the lymphangiography group, the staging lymphadenectomy group showed better overall survival (87% to 76% at 5 years, p = .02), better disease-free survival (76% to 63% at 5 years, p = .008) and better metastases-free survival (88% to 82% at 5 years, p = .04). There was no difference between the groups in local control. The lymphangiography evaluation of pelvic nodes was clearly inferior for demonstration of the absence of pelvic node metastasis as reflected by reduced survival and increased metastasis.

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.