Comparison of prognostic factors and survival among black patients and white patients treated with irradiation for non-small-cell lung cancer.

BACKGROUND: Many studies have reported differences in cancer incidence and survival between populations of Blacks and Whites. A 45% higher death rate from lung cancer for Black men and a survival duration for Black patients with lung cancer that is generally shorter than that for White patients have also been reported. PURPOSE: The purpose of this study was to evaluate whether race affects known prognostic factors for non-small-cell lung cancer in Black versus White patients. This analysis attempts to determine which prognostic factors may contribute to the reported differences in disease outcome. METHODS: We used data from 1565 patients with non-small-cell lung cancer treated in four randomized prospective trials conducted by the Radiation Therapy Oncology Group (RTOG). The data were pooled for a retrospective analysis of survival and prognostic factors by race. RESULTS: Univariate analysis showed significant differences between Blacks and Whites with regard to sex, weight loss, histology, and RTOG T stage (P < .05), but the only clinically significant difference (P < or = .01) was weight loss. Despite these findings, overall survival for Blacks and Whites did not differ significantly (P = .67). Median survival for Blacks and Whites with a Karnofsky performance status (KPS) of 90 or more was 12.1 and 11.3 months, respectively (P = .45). Survival for Blacks and Whites with a KPS of less than 90 was 7.8 and 6.8 months, respectively. Cause of death did not differ between the two races. For both races, KPS, age, sex, weight loss, and RTOG T and N stages were significant prognostic factors for survival (P < .01), but race was not a significant prognostic factor. CONCLUSION: Further studies of the differential in cancer survival for Blacks and Whites may be indicated, but greater impact may be achieved by addressing socioeconomic factors, lifestyle and occupational risk factors, health education, and access to adequate health care.

Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials.

BACKGROUND: Despite notable technical advances in therapy for malignant gliomas during the past decade, improved patient survival has not been clearly documented, suggesting that pretreatment prognostic factors influence outcome more than minor modifications in therapy. Age, performance status, and tumor histopathology have been identified as the pretreatment variables most predictive of survival outcome. However, an analysis of the association of survival with both pretreatment characteristics and treatment-related variables is necessary to assure reliable evaluation of new approaches for treatment of malignant glioma. PURPOSE: This study of malignant glioma patients used a non-parametric statistical technique to examine the associations of both pretreatment patient and tumor characteristics and treatment-related variables with survival duration. This technique was used to identify subgroups with survival rates sufficiently different to create improvements in the design and stratification of clinical trials. METHODS: We used a recursive partitioning technique to analyze survival in 1578 patients entered in three Radiation Therapy Oncology Group malignant glioma trials from 1974 to 1989 that used several radiation therapy (RT) regimens with and without chemotherapy or a radiation sensitizer. This approach creates a regression tree according to prognostic variables that classifies patients into homogeneous subsets by survival. Twenty-six pretreatment characteristics and six treatment-related variables were analyzed. RESULTS: The years). Patients younger than 50 years old were categorized by histology (astrocytomas with anaplastic or atypical foci [AAF] versus glioblastoma multiforme [GBM]) and subsequently by normal or abnormal mental status for AAF patients and by performance status for those with GBM. For patients aged 50 years or older, performance status was the most important variable, with normal or abnormal mental status creating the only significant split in the poorer performance status group. Treatment-related variables produced a subgroup showing significant differences only for better performance status GBM patients over age 50 (by extent of surgery and RT dose). Median survival times were 4.7-58.6 months for the 12 subgroups resulting from this analysis, which ranged in size from 32 to 256 patients. CONCLUSIONS: This approach permits examination of the interaction between prognostic variables not possible with other forms of multivariate analysis. IMPLICATIONS: The recursive partitioning technique can be employed to refine the stratification and design of malignant glioma trials.

Deglycosylation of serum vitamin D3-binding protein leads to immunosuppression in cancer patients.

Serum vitamin D3-binding protein (Gc protein) can be converted by beta-galactosidase of B cells and sialidase of T cells to a potent macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is the precursor of the macrophage activating factor (MAF). Treatment of Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high titered MAF, Gc-MAF. When peripheral blood monocytes/macrophages of 52 patients bearing various types of cancer were incubated with 100 pg/ml of GcMAF, the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of patient plasma Gc protein was found to be severely reduced in about 25% of this patient population. About 45% of the patients had moderately reduced MAF precursor activities. Loss of the precursor activity was found to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase detected in the patient's bloodstream. The source of the enzyme appeared to be cancerous cells. Radiation therapy decreased plasma alpha-N-acetylgalactosaminidase activity with concomitant increase of precursor activity. This implies that radiation therapy decreases the number of cancerous cells capable of secreting alpha-N-acetylgalactosaminidase. Both alpha-N-acetylgalactosaminidase activity and MAF precursor activity of Gc protein in patient bloodstream can serve as diagnostic and prognostic indices.

Survival advantage from higher-dose radiation therapy for clinically localized prostate cancer treated on the Radiation Therapy Oncology Group trials.

PURPOSE: We evaluated the effect of external-beam radiation therapy on disease-specific survival (death from causes related to prostate cancer) and overall survival in men with clinically localized prostate cancer. METHODS: From 1975 to 1992, 1,465 men with clinically localized prostate cancer received radiation therapy on four Radiation Therapy Oncology Group phase III randomized trials and were pooled for this analysis. No one received androgen-deprivation therapy with his initial treatment. All original histology had central pathologic review for grading using the Gleason classification system. Total delivered radiation dose ranged from 60 to 78 Gy (median, 68.4 Gy). The median follow-up time was 8 years. RESULTS: A Cox regression model revealed that Gleason score was an independent predictor of disease-specific survival and overall survival. The 10-year disease-specific survival rates by Gleason score were as follows: score of 2 through 5, 85%; score of 6, 79%; score of 7, 62%; and score of 8 through 10, 43%. Stratifying outcome by this important prognostic factor revealed that higher radiation dose was a significant predictor for improved disease-specific survival and overall survival only for those patients whose cancers had Gleason scores of 8 through 10 (P <.05). After adjusting for clinical T stage, nodal status, and age, treating with a higher radiation dose was associated with a 29% lower relative risk of death from prostate cancer and 27% reduced mortality rate (P <.05). CONCLUSION: These data demonstrate that higher-dose radiation therapy can significantly reduce the risk of dying from prostate cancer in men with clinically localized disease. This survival benefit is restricted to men with poorly differentiated cancers.

Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease.

Thirty-eight patients with advanced, progressive Hodgkin's disease who had relapsed from or who had not responded to treatment with at least two potentially curative combination chemotherapy regimens were entered into this phase 2 study. All patients received 131I antiferritin antibody administered intravenously (IV) at a dose of 30 mCi on day 0 and 20 mCi on day 5. Antibody was derived from rabbit, pig, and monkey species. Objective partial remission of measurable disease was recorded in 40% of patients. Symptomatic response was recorded in 77% of patients. Toxicity was restricted to bone marrow depression with thrombocytopenia greater than leukopenia. These responses are comparable to other reported phase 2 drugs in this patient population and subsequent trials of antibody free of radioactivity and antibody using a beta emitting isotope are being carried out to expand upon these results.

Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413.

PURPOSE: This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%. MATERIALS AND METHODS: Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) < or = 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure; or death for any cause. RESULTS: With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT (P =.022). Patients treated with NCHT experienced a 4-year PFS of 52% versus 49% for AHT (P =.56). When comparing all four arms, there was a progression-free difference among WP RT + NCHT, PO RT + NCHT, WP RT + AHT, and PO RT + AHT (60% v 44% v 49% v 50%, respectively; P =.008). No survival advantage has yet been seen. CONCLUSION: WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%.

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.

A randomized phase III protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with brain metastases (RTOG-7916).

From 1979 through July 1983, 859 patients were enrolled in a Phase III RTOG Protocol (7916) evaluating the role of Misonidazole combined with radiation in the treatment of brain metastasis. Patients were randomized to one of four treatment arms (3.0 Gy x 10 fractions with or without 1 g/m2 of Misonidazole [total 10 g/m2] versus 5.0 Gy x 6 fractions with or without 2 g/m2 of Misonidazole) [total 12 g/m2]. Among the 779 analyzable cases, 63% had a lung primary and 12% had breast. Of the histologic types, 43% were adenocarcinoma and 24% were squamous cell. Seventy-eight percent had a Karnofsky of greater than 70. Of the 779 cases, 773 are dead (99%). Median survival is 3.9 months, with 60% alive at 3 months, 35% at 6 months, and 15% at 1 year. Survival was evaluated by treatment arm, Misonidazole status, and fractionation scheme; none showed any statistical significance. Favorable prognostic factors were assessed (age less than 60, Karnofsky of 70-100, controlled primary and brain metastasis only) in each treatment arm and no difference was found. Brain metastasis was cause of death in 1/3, and 19-33% of patients were retreated. Because up to 1/3 of the patients in this study died secondary to uncontrolled brain metastasis, improvement in local control remains an important goal. Until proven otherwise, the treatment of choice for the majority of patients still remains a conventional palliative course of 3.0 Gy x 10 fractions.

Misonidazole and unconventional radiation in advanced squamous cell carcinoma of the esophagus: a phase II study of the Radiation Therapy Oncology Group.

This is a report on Radiation Therapy Oncology Group (RTOG) Protocol No. 78-32, a Phase I/II prospective study aimed at determining tolerance, tumor response, and survival of squamous cell carcinoma of the esophagus treated with unorthodox fractionation radiotherapy combined with misonidazole. Misonidazole was administered by mouth 4 to 6 hr prior to radiation, at a dose of 1.0 to 1.25 Gm/.m2; blood levels were measured at about 4 hr after intake of the drug and reported in micrograms/ml. Radiotherapy was administered at 4 to 6 hr post-misonidazole dose and given with 400 rad fractions, alternating 2 or 3 times/week, up to 4,800 rad. A total of 43 patients were entered; 26 are evaluable for survival at 1 year post accession. Thirty patients (88%) received the planned radiation course. Twenty-eight patients (78%) received the planned misonidazole dosage. Tumor response, evaluable in 18 patients, showed a complete regression (C.R.) in only 2 patients (11%); and partial response (P.R.) in 6 patients (33%). Eight patients (44%) showed no tumor response to planned therapy. Toxicity was acceptable and in 38 evaluable patients only 4 reported (11%) nausea and vomiting, 7 reported mild paresthesias (18%). The median survival was only five months. In 26 patients evaluable for 1 year survival determination, only 1 survived (3.8%) this period. In view of the poor tumor response and low survival observed, we do not recommend that this particular fractionation regimen with misonidazole be used in a Phase III randomized trial in squamous cell carcinoma of the esophagus.

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.

Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials.

PURPOSE: The influence of tumor site, size, and extent of surgery on the survival of patients with glioblastoma multiforme treated on three consecutive prospectively randomized Radiation Therapy Oncology Group trials employing surgery and irradiation plus or minus chemotherapy was studied. METHODS AND MATERIALS: Six hundred forty-five patients with a diagnosis of glioblastoma multiforme on central pathological review were analyzed for survival with respect to known prognostic factors, that is, age and Karnofsky Performance Status, as well as extent of surgery, site, and size. Surgical treatment consisted of biopsy only in 17%, partial resection in 64%, and total resection in 19%. Tumors were located in frontal lobe in 43%, temporal lobe in 28%, and parietal lobe in 25%. Maximum tumor diameter as determined on computed tomography or magnetic resonance imaging scans was less than 5 cm for 38%, between 5-10 cm for 56% and greater than 10 cm for 6% of patients. The extent of surgical therapy was the same for tumors greater than 5 or greater than 10 cm, whereas total resection was more often performed for tumors less than 5 cm. The extent of surgery did not appear to vary with age or site. RESULTS: Patients undergoing total resection had a median survival of 11.3 months compared to 6.6 months for patients with a biopsy only. A significant difference in median survival was also found for partial resection versus biopsy only treatment (10.4 vs. 6.6 months). There was no difference in survival for the different tumor sizes. Patients with frontal lobe tumors survived longer than those with temporal or parietal lobe lesions (11.4 months, 9.1 months, and 9.6 months, respectively) (p = 0.01). A Cox multivariate model confirmed a significant correlation of age, Karnofsky Performance Status, extent of surgery, and primary site with survival. The best survival rates occurred in patients who had at least three of the following features: < 40 years of age, high Karnofsky Performance Status, frontal tumors, and total resection (17 months median). CONCLUSION: We conclude that biopsy only yields inferior survival to more extensive surgery for patients with glioblastoma multiforme treated with surgery and radiation therapy.

Interruptions of high-dose radiation therapy decrease long-term survival of favorable patients with unresectable non-small cell carcinoma of the lung: analysis of 1244 cases from 3 Radiation Therapy Oncology Group (RTOG) trials.

PURPOSE: To determine if prolonged treatment time adversely affects survival for patients with inoperable non-small cell carcinoma of the lung. METHODS AND MATERIALS: Patients enrolled on three randomized studies (RTOG 8311, 8321, 8403) between 1983-1989 formed the database. Previous analyses found that the addition of thymosin (8321) or prophylactic cranial irradiation (8403) failed to prolong survival: both studies used thoracic irradiation with standard fractionation to 55-60 Gy in 30 fractions. In 8311, patients were treated by hyperfractionated radiation therapy to randomly assigned total doses of 60.0 Gy, 64.8 Gy, 69.6 Gy, 74.4 Gy or 79.2 Gy, 1.2 Gy twice daily, 5 days per week. Patients analyzed received +/- 4% of the assigned total dose and lived > 90 days (to ensure that all patients would have completed treatment). Completion < 5 days beyond protocol specifications was classified as "per protocol." Elapsed treatment time exceeding specifications by 5-9 days was a minor deviation, 10-13 days was a major deviation-acceptable, and > or = 14 days was a major deviation-unacceptable. Absolute survival was the endpoint to evaluate the effect of delays. The log rank statistic was used to test for survival differences in the univariate setting, the Cox regression model was used in the multivariate setting. RESULTS: Of 293 patients treated with standard fractionation, eight (2.7%) had deviations from the specified treatment time (six minor, two major-acceptable). With hyperfractionation, 90 (15%) patients had deviations (40 minor, 21 major-acceptable, 29 major-unacceptable). As the assigned dose increased, the deviation rate increased (9.7% for 60.0 Gy vs. 20.8% for 79.2 Gy). Survivals for hyperfractionation patients with any deviations in treatment time were significantly shorter than those treated "per protocol" (p = 0.16): estimated 2- and 5-years rates were 24% and 10% versus 13% and 3%, respectively. Multivariate analyses showed the delay effect to be entirely in patients treated with 69.6 Gy or higher; there was also dependence upon the patients' prognosis. In patients with favorable prognosis (KPS 90-100, weight loss < or = 5%, no N3), the difference in survival was pronounced (33% and 15% vs. 14% and 0% at 2- and 5-years, respectively). Such differences were not found in patients with unfavorable prognostic factors. CONCLUSIONS: Interruptions delaying completion of planned radiation therapy were more frequent with higher total doses (> or = 69.6 Gy). Favorable patients (high KPS, little weight loss, < N3 nodal metastasis) had markedly adverse effects on long-term survival associated with delays to completion of the planned total dose.

CT characteristics of patients with brain metastases treated in RTOG study 79-16.

The search continues for a favorable subgroup of patients with brain metastases in whom testing of new modalities might show a benefit in overall survival. Complete pre- and post-treatment CT evaluation of the brain was performed in 779 of the 859 patients entered into RTOG protocol 7916, a phase III study of the role of misonidazole combined with radiation therapy in the treatment of brain metastases. Pretreatment scan findings of mass effect, midline shift, massive edema, central necrosis, location of sentinel lesion, and number of lesions were correlated with length of survival for all patients as well as for each treatment group. The only characteristics that showed a statistically significant difference in survival in the overall group were the presence of < or = 3 lesions and the presence of a midline shift. The actual benefit in overall survival, however, was found to be only 3 weeks. The volume of the largest lesion prior to treatment did not correlate well with survival, nor did location of lesions. The time to response, number of responders and absolute decrease in number of lesions were similar for the four treatment arms. Patients who responded to cranial treatment had a significantly prolonged survival over those who did not respond. No CT characteristic evaluated in this study showed value as a clinically relevant prognosticator for patients with brain metastases for the overall group. Patients who fulfilled three of the four favorable clinical characteristics previously described by Diener-West (age < or = 60, KPS > or = 70, primary lesion absent or controlled and brain as sole site of metastasis), were analyzed separately. Those with < or = three lesions had a statistically significantly prolonged survival over those with four or more lesions.

PSA confirmation of cure at 10 years of T1B, T2, N0, M0 prostate cancer patients treated in RTOG protocol 7706 with external beam irradiation.

PURPOSE: This study was done to correlate prostatic specific antigen values with clinical no evidence of disease status for 28 long-term survivors of external beam irradiation from Radiation Therapy Oncology Group Study #77-06, and confirm the clinical observation of cure. METHODS AND MATERIALS: One hundred and four patients in Radiation Therapy Oncology Group 77-06 with T1B T2 N0, M0 with pathologically known negative lymph node status, were previously shown to have a 10 year actuarial outcome equal to radical prostatectomy patients. Of these 104, 28 were 9-13 year survivors with clinically no evidence of disease by physical examination and imaging. RESULTS: Prostatic specific antigen was available or obtained in 17 patients, 15 of the 17 had prostatic specific antigen values of < 3.5 ngm/%, while 11 had values of < 1.5 ngm/%. Depending on which level one selects, 88% or 65% of clinical no evidence of disease 9-13 year survivors have a normal or low prostatic specific antigen. CONCLUSION: Prostatic specific antigen adds to the accuracy of determining clinical long-term cure and shows that 65-88% of patients who are clinical no evidence of disease are "biochemical" cures as well. These correlation percentages are quite similar to the largest contemporary surgical series, and strongly support the concept and fact of cure of prostate cancer with radiation.

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.

Definitive radiotherapy in resectable (stage A2 and B) carcinoma of the prostate--results of a nationwide overview.

To evaluate the efficacy of definitive radiotherapy in a population of patients with carcinoma of the prostate who satisfy the customary selection criteria for radical prostatectomy, a nation-wide search was conducted. The assessed population consists of patients with clinical Stage A2 and B carcinoma of the prostate, negative staging lymphadenectomy, negative bone scan, and normal serum acid phosphatase. The search included patients from Stanford University, Washington University in St. Louis, those participating in the Radiation Therapy Oncology Group and a broad range of radiotherapy practices surveyed by the PCS (Patterns of Care Study). A total of 209 patients satisfying the selection criteria received definitive radiotherapy during the surveyed period. The end-point of analysis was the time to progression (distant metastases). The results of the analysis indicate a very low (less than 10%) probability of progression within the first 5 years after completion of treatment. Contrary to the recent report from the VA Uro-Oncology Group the study demonstrates a comparable outcome in radiotherapeutically and surgically treated patients.

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.

A randomized prospective trial comparing full dose chemotherapy to 131I antiferritin: an RTOG study.

A previously reported Phase I/II multimodality program for non-resectable hepatocellular cancer began with external beam-radiation and chemotherapy, followed by administration of 131I antiferritin-specific radioimmunoglobulin and led to a 48% remission (7% complete remission and 41% partial remission). Survival and response depended on alpha fetoprotein status. AFP+ patients had a median survival of 5 months; AFP- patients had a median survival of 10.5 months. No acute effects occurred relative to treatment with radiolabeled antibody. A randomized prospective study was designed to compare full dose chemotherapy consisting of 60 mg/m2, doxorubicin and 500 mg/m2 of 5-fluorouracil administered every 3 weeks, to 131I antiferritin administration every 8 weeks and allowed for crossover treatment if tumor progression occurred. Overall, radiolabeled antibody administration and full dose chemotherapy led to equivalent partial remission rates (22-30% vs 23-25%) and survival rates compared to chemotherapy (6 month median; AFP+ 5 months; AFP- 10 months). The most important new observations were the response in AFP- patients who, following chemotherapy failure, achieved remission using 131I radiolabeled antibody (7/11) and a subset of patients (7%) who were treated with radiolabeled antibody and converted from non-resectable to resectable status followed by surgical excision.