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Introduction: This phase I/II trial was designed to determine the maximally tolerated dose of thoracic radiotherapy as part of a combined modality approach. This report includes the long-term outcomes of patients treated on this study. The phase II portion was never completed, as RTOG-0617 opened before it was concluded., Methods: In this study, the maximally tolerated dose was defined as 74 Gy of radiation in 37 fractions. Twenty-five patients with unresectable NSCLC were treated with 2-Gy daily fractions and concurrent weekly carboplatin and paclitaxel. Of these patients, 20 had stage III disease and five had stage I or II disease., Results: Patients were followed until death or for a minimum of 5 years in the case of survivors. The median and 5-year survivals were 42.5 months and 20% for all patients, 52.9 months and 40% in patients with stages I or II disease, and 39.8 months and 15% in patients with stage III disease., Conclusions: The median survival of the stage III patients was quite favorable. We believe that this may have been due to a robust central review program of radiotherapy plans before treatment, ensuring compliance with protocol guidelines along with very low exposure of the heart to radiotherapy. Further improvements in 5-year survival will likely require research on both systemic therapy and thoracic radiotherapy. Potential therapeutic modalities that may aid in these efforts include immunotherapy, targeted therapy, improved imaging, adaptive radiotherapy, simultaneous integrated boost techniques, novel dose fractionation regimens, and charged particle therapy., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: The objective of this study was to assess the value of combined-modality therapy in elderly patients by comparing the differences in outcome between patients who received radiotherapy (RT) alone and patients who received RT plus chemotherapy for stage III nonsmall cell lung cancer (NSCLC)., Methods: The North Central Cancer Treatment Group performed 2 recent Phase III trials for stage III NSCLC. The first trial, NCCTG 90-24-51, included 3 arms: once-daily RT (QDRT) alone, twice-daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, NCCTG 94-24-52, included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients aged >/=65 years (elderly) who participated in those trials were included in this analysis., Results: Of the 166 elderly patients who were included in this analysis, 37 patients received RT alone, and 129 patients received concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5 months and 5.4% for the RT alone group compared with 13.7 months and 14.7% for the RT plus chemotherapy group (log-rank P = .05). Patients who received RT plus chemotherapy experienced significantly greater severe toxicity (grade >/=3) compared with patients who received RT alone (89.9% vs 32.4%; P < 0.01)., Conclusions: Elderly patients who participated in these trials appeared to gain a survival advantage from RT and chemotherapy compared with RT alone. As is the case with younger patients, this benefit came at the cost of additional toxicity.

Purpose: This trial was performed to determine the maximum tolerated dose (MTD) of radiation that can be administered with carboplatin and paclitaxel., Methods and Materials: This trial included 15 patients with unresectable non-small-cell lung cancer. Paclitaxel (50 mg/m2) and carboplatin (area under the curve=2) were given weekly during radiation therapy (RT). The RT included 2 Gy daily to an initial dose of 70 Gy, and the dose was increased in 4 Gy increments until determining the MTD. The MTD was defined as the highest safely tolerated dose where at most 1 patient of 6 experienced dose-limiting toxicity (DLT) with the next higher dose having at least 2 of 6 patients experiencing DLT. Three-dimensional treatment planning techniques were used without prophylactic nodal RT., Results: Two patients were not evaluable because they did not receive therapy according to the protocol. No DLTs occurred in the 3 patients who received 70 Gy, 1 DLT occurred in the 6 patients who received 74 Gy, and 2 DLTs occurred in the 4 patients who received 78 Gy. The DLTs included Grade 3 pneumonitis (n=2) and Grade 4 pneumonitis (n=1). There have been 3 deaths during follow-up ranging from 14 to 38 months (median, 28 months)., Conclusions: The MTD of the RT was 74 Gy with weekly carboplatin and paclitaxel. The Phase II portion of this trial is currently under way. The goal is to improve local control and survival with higher doses of RT delivered with this combined modality approach.

Background: A Phase III trial was conducted by the North Central Cancer Treatment Group to determine whether chemotherapy (etoposide and cisplatin) plus either twice-daily radiotherapy (BIDRT) or once-daily radiotherapy (QDRT) resulted in a better outcome for patients with limited-stage small cell lung carcinoma (LD-SCLC). No difference in survival was identified between the two arms. The current analysis examined the relation between age and outcome for patients treated during this trial., Methods: The current study included 263 patients with LD-SCLC and an Eastern Cooperative Oncology Group performance status of < or = 2 who were randomized to receive QDRT or split-course BIDRT. The outcomes of the 209 (79%) younger patients (age < 70 years old) were compared with the 54 (21%) elderly patients (age > or = 70 years old)., Results: Elderly patients presented with significantly greater weight loss and poorer performance status. The 2-year and 5-year survival rates were 48% and 22% for younger patients compared with 33% and 17% for older patients (P = 0.14). One specific toxicity (i.e., Grade > or = 4 pneumonitis [according to National Cancer Institute Common Toxicity Criteria]) occurred in 0% of those patients age < 70 years compared with 6% of older patients (P = 0.008). Grade 5 toxicity occurred in 1 of 209 (0.5%) patients age < 70 years compared with 3 of 54 (5.6%) older patients (P = 0.03)., Conclusions: Despite having more weight loss, poorer performance status, increased pulmonary toxicity, and more deaths due to treatment, survival was not found to be significantly worse in older individuals. Fit elderly patients with LD-SCLC can receive combined-modality therapy with the expectation of relatively favorable long-term survival. Future research should focus on ways to decrease toxicity especially in the elderly.

Purpose: The North Central Cancer Treatment Group performed a phase III trial to determine whether chemotherapy plus either bid radiation therapy (RT) or daily (qd) RT resulted in a better outcome for patients with stage III non-small-cell lung cancer (NSCLC). No difference in survival was identified between the two arms. This secondary analysis was performed to examine the relationship between patient age and outcome., Patients and Methods: Two hundred forty-six patients were randomized to receive etoposide plus cisplatin and either RT qd or split-course RT bid. This retrospective study compared the outcomes of patients aged >/=70 years ("elderly patients") with those of younger individuals. Of the 244 assessable patients, 63 (26%) were elderly, and 181 (74%) were younger individuals., Results: The 2-year and 5-year survival rates were 39% and 18%, respectively, in patients younger than 70 years, compared with 36% and 13%, respectively, in elderly patients (P =.4). Grade 4+ toxicity occurred in 62% of patients younger than 70 years compared with 81% of elderly patients (P =.007). Grade 4+ hematologic toxicity occurred in 56% of patients younger than 70 years, compared with 78% of elderly patients (P =.003). Grade 4+ pneumonitis occurred in 1% of those younger than 70 years, compared with 6% of elderly patients (P =.02)., Conclusion: Toxicity, especially myelosuppression and pneumonitis, was more pronounced in the elderly patients receiving combined-modality therapy for locally advanced NSCLC. Despite increased toxicity, elderly patients have survival rates equivalent to younger individuals. Therefore, fit, elderly patients with locally advanced NSCLC should be encouraged to receive combined-modality therapy, preferably on clinical trials with cautious, judicious monitoring. Future studies should explore ways to decrease toxicity of therapy in elderly patients.

There is limited research of smoking cessation following diagnosis of lung cancer. This prospective study assessed cigarette smoking behavior among 226 patients (142 males, 84 females) prior to, at the time of, and after the diagnosis of unresectable stage IIIA/IIIB non-small cell lung cancer and entry into a phase III trial examining combined thoracic radiation therapy and chemotherapy. Their mean +/-S.D. age was 62.7+/-9.4 years and 95.6% were Caucasian. Of 215 patients with a history of cigarette smoking, 69% (148/215) stopped smoking prior to entry in the trial, 9% (20/215) stopped smoking at some point during the course of the trial, 11% (24/215) continued smoking throughout the trial, 7% (16/215) were smoking at baseline but did not report subsequent smoking status, and smoking status at study entry was missing for the remaining patients. The majority of lung cancer patients were able to stop smoking. A notable subset of patients continued smoking despite diagnosis of lung cancer, enrollment in a clinical trial, treatment-related toxicity, and encouragement from clinicians to stop smoking. Smoking cessation interventions are needed for lung cancer patients who continue to smoke., (Copyright 2002 John Wiley & Sons, Ltd.)

Purpose: This Phase III study was performed to determine whether chemotherapy plus b.i.d. or q.d. radiotherapy (RT) resulted in superior survival for patients with Stage III non-small-cell lung cancer (NSCLC)., Methods and Materials: Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of

Background: The current study was conducted to determine whether the addition of interferon-alpha (IFN-alpha) to treatment with radiation therapy and carmustine (BCNU) improves time to disease progression or overall survival in patients with high-grade glioma., Methods: Patients with anaplastic astrocytoma, anaplastic oligoastrocytoma, glioblastoma multiforme, or gliosarcoma received radiation therapy plus BCNU as initial therapy. Subsequently, patients without tumor progression at the completion of radiation therapy were stratified by age, extent of surgery, tumor grade and histology, Eastern Cooperative Oncology Group performance status, and treating institution, and then were randomly assigned to receive either BCNU alone (200 mg/m(2) on Day 1) or BCNU (150 mg/m(2) on Day 3) plus IFN--alpha (12 million U/m(2) on Days 1-3, Weeks 1, 3, and 5) every 7 weeks for a maximum of 6 cycles., Results: Of the 383 patients enrolled in the study, 275 eligible patients were randomized. There was no significant difference with regard to time to disease progression or overall survival between the two groups. Patients receiving IFN-alpha experienced more fever, chills, myalgias, and neurocortical symptoms including somnolence, confusion, and exacerbation of neurologic deficits. Cox multivariate regression models confirmed known favorable prognostic variables including younger age, Grade 3 tumor (according to World Health Organization criteria), and greater extent of surgery. Cox and classification and regression tree analysis models also demonstrated that a normal baseline Folstein mini-mental status examination (MMSE) score was associated with better prognosis., Conclusions: IFN-alpha does not appear to improve time to disease progression or overall survival in patients with high-grade glioma and appears to add significantly to toxicity. The baseline MMSE score may serve as an independent prognostic factor and warrants further investigation., (Copyright 2001 American Cancer Society.)

Object: It is standard practice for the oncological follow-up of patients with brain tumors (especially in the setting of clinical trials) to include neurological examination and neuroradiological studies such as computerized tomography (CT) or magnetic resonance (MR) imaging in addition to evaluation of the patients' symptomatology and performance score. The validity of this practice and its impact on the welfare of patients with high-grade gliomas has not been adequately assessed. The purpose of this study is to provide such an assessment., Methods: The authors studied 231 similarly treated patients who were participating in three prospective North Central Cancer Treatment Group or Mayo Clinic trials who developed progressive disease during follow up. According to the protocol, the symptom status, performance score, results of neurological examination, and CT or MR status were recorded prospectively in each patient at each evaluation (every 6-8 weeks). At progression, 177 (77%) of 231 patients experienced worsening of their baseline symptoms or they developed new ones. In the remaining 54 asymptomatic patients (23%), neuroradiological imaging revealed the progression. Asymptomatic progression was more likely to be detected on MR imaging compared with CT studies (p < 0.01). In no asymptomatic patient was progression detected on neurological examination alone. The median survival time after tumor recurrence was 13.3 weeks in symptomatic patients compared with 41.7 weeks in the asymptomatic group (p < 0.0001). Asymptomatic patients were more aggressively treated, with surgery (p < 0.0001) and second-line chemotherapy (p < 0.0002). Multivariate analysis of survival time following first progression by using both classification and regression trees and Cox models showed that treatment at recurrence was the most important prognostic variable., Conclusions: Symptoms are the most frequent indicators of progression in patients with high-grade gliomas (77%). All asymptomatic progressions were detected on neuroradiological studies; MR imaging was more likely than CT scanning to reveal asymptomatic recurrences. Survival after disease progression was significantly longer in asymptomatic patients and could be related both to treatment following progression and to other favorable prognostic factors such as performance score.

Purpose: We herein report updated survival and toxicity data on the entire cohort of 53 eligible patients treated on North Central Cancer Treatment Group (NCCTG) protocol 86-72-52, which is now closed., Methods and Materials: An initial report was published in this journal in 1995. No substantive changes in the conclusions of that report were identified in this analysis. Median survival was 9.6 months for the entire cohort; median survival for the 20 patients who completed the prescribed protocol treatment was 20.7 months. The hematologic and non-hematologic toxicity distributions are virtually the same as those reported in the original paper., Results: Results are given for the entire group and for subsets defined by age < or = 60 versus > 60 years, and < 70 versus > or = 70 years of age., Conclusions: No significant differences were observed in any of the outcome variables by age group. There was, however, a nonsignificant suggestion of poorer outcome in those who were > 60 years of age.

Background: A three-arm Phase III randomized trial was performed to compare response rates, time to local or distant progression, and survival for patients with unresectable (Stage IIIA or IIIB) nonsmall cell lung carcinoma treated with standard fractionated thoracic radiotherapy (SFTRT) versus accelerated hyperfractionated thoracic radiotherapy (AHTRT) with or without combination etoposide and cisplatin chemotherapy., Methods: This trial was initiated in 1992 by the North Central Cancer Treatment Group. Patients with Stage IIIA or IIIB nonsmall cell lung carcinoma were eligible. They were randomly assigned to either SFTRT (6000 centigray [cGy] in 30 fractions) or AHTRT (150 cGy twice daily to a total dose of 6000 cGy, with a 2-week break after the initial 3000 cGy); the AHTRT was given alone or with concomitant cisplatin (30 mg/m2, Days 1-3 and 28-30) and etoposide (100 mg/m2, Days 1-3 and 28-30)., Results: A total of 110 patients were entered on study. Eleven patients were declared ineligible or off study on the day of study entry. This analysis was confined to the 99 eligible patients. This article reports mature follow-up, because more than 80% of the patients have died. The median follow-up of living patients was 2.5 years. There were suggestions of improvement in the rates of freedom from local recurrence and survival for patients treated with AHTRT (with or without chemotherapy) as opposed to SFTRT (P = 0.06 and P = 0.10, respectively). The improvement in survival associated with AHTRT (with or without chemotherapy) was statistically significant for the subgroup of patients with nonsquamous cell carcinoma after adjustment for other potentially confounding factors (P = 0.02). No differences in freedom from systemic progression or survival were found in a comparison of AHTRT with chemotherapy and AHTRT without chemotherapy., Conclusions: These results suggest that treatment of Stage IIIA or IIIB nonsmall cell lung carcinoma with AHTRT with or without chemotherapy may improve freedom from local progression and survival as compared with SFTRT, especially for patients with nonsquamous cell carcinoma. The statistical powers to detect the observed differences in median time to local progression and survival were approximately 55% and 35%, respectively. Therefore, further investigation comparing SFTRT with AHTRT is warranted.

Purpose: To determine whether a sucralfate oral solution can prevent/alleviate radiation-induced esophagitis., Patients and Methods: Patients included on this clinical trial were beginning thoracic radiation therapy to the mediastinum. Following stratification, they were randomized, in a double-blind manner, to receive a sucralfate solution or an identical-appearing placebo solution. Esophagitis was measured by physicians who used standard criteria and also by patients who used short questionnaires completed weekly during the course of the trial., Results: A total of 97 assessable patients were entered onto this clinical trial. During the first 2 weeks of the study, two placebo patients (4%) stopped their study medication, compared with 20 sucralfate patients (40%). This was related to substantially increased incidences of gastrointestinal toxicity (58% of sucralfate patients v 14% of placebo patients; P > .0001). There was no substantial benefit from the sucralfate in terms of esophagitis scores., Conclusion: This oral sucralfate solution does not appear to inhibit radiation-induced esophagitis and is associated with disagreeable gastrointestinal side effects in this patient population.

Objective: To compare the survival of patients with medically inoperable or unresectable stage III non-small cell lung cancer treated with thoracic radiotherapy alone or in combination with chemotherapy., Design: Randomized, prospective phase III trial., Setting: Multi-institutional cooperative oncology group., Patients: A total of 121 patients were enrolled in the study, of whom 7 (5.8%) were ineligible. All patients were ambulatory and had measurable or evaluable disease. Before they were randomized, patients were stratified by ECOG performance score, histologic type, maximum tumor diameter, and NCCTG institution., Interventions: Radiotherapy consisted of a total of 5000 cGy in 5 weeks with a 1000 cGy boost in 5 fractions to a small tumor field. Combined modality therapy was MACC which is intravenous methotrexate, intravenous doxorubicin, intravenous cyclophosphamide, and oral lomustine (CCNU), on day 1 and 28. Chemotherapy was followed by identical thoracic radiotherapy 4 weeks after the second cycle of chemotherapy. Four weeks after thoracic radiotherapy was completed, patients received another two cycles of identical chemotherapy. Patients who had progression of disease after chest irradiation only were treated with MACC chemotherapy., Main Results: Major clinical responses were observed in 31 of 56 (55%; 95% Cl, 42% to 68%) patients treated with combination therapy and 37 of 58 (64%; Cl, 51% to 76%) treated with radiation only (P greater than 0.2). The median time to progression was 192 days with radiotherapy only compared with 199 days for combined modality therapy (P greater than 0.2). The median survival time was 313 days compared with 317 days, respectively (P greater than 0.2). The 1-, 2-, and 5-year survival rates after thoracic radiation only were 45% (Cl, 32% to 58%), 16% (Cl, 6% to 25%), and 7%. With chemoradiotherapy, the survival rates were 46% (Cl, 33% to 60%), 21% (Cl, 11% to 32%), and 5%, respectively. Myelosuppression was significantly greater for the combined modality therapy arm (P = 0.002)., Conclusion: Chemotherapy with MACC, in combination with thoracic radiotherapy, did not result in significant survival advantage compared with radiation alone (P greater than 0.2) in patients with medically inoperable or unresectable stage III non-small cell lung cancer.