Hypofractionated radiotherapy as definitive treatment of stage I non-small cell lung cancer in older patients.

PURPOSE/OBJECTIVE(S): We report our experience using hypofractionated radiotherapy in older patients. MATERIALS/METHODS: This analysis includes patients aged 60 years and older at our institution with inoperable Stage I (T1/T2 N0 M0) non--small-cell lung cancer that completed a curative course of radiotherapy alone using a hypofractionated schedule. Between 1991 and 2006, 75 such patients were identified with median age of 74 years (range, 60-86). Patient characteristics were as follows: male, 65/75 (86.7%); stage IA (T1N0), 47/75 (62.7%); stage IB (T2N0), 28/75 (37.3%). Patients received a median total dose of 6500 cGy using median daily dose fractions of 250 cGy. The following outcomes were analyzed: local failure free survival (time to local failure or death from any cause), time to distal failure as first event, and overall survival. Toxicities were evaluated using Common Terminology Criteria for Adverse Events v 3.0. RESULTS: The median follow-up was 19.6 months (range: 4.0-128.8 months). Median local failure free survival was 19.6 months (95% confidence interval [CI]: 14.4-28.8 months); and median overall survival was 21.2 months (95% CI: 14.9-29.3 months). Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 22.1% (95% CI: 12.8%-32.9%); the probability of distal failure as the first detected event was 14.5% (95% CI: 7.3%-24.0%); and the probability of death without recording a failure was 48.6% (95% CI: 36.1%-60.1%). Radiation-related toxicity of grade 3 or greater was seen in 3 patients and there were no treatment-related deaths. CONCLUSIONS: Hypofractionated radiotherapy is an effective, safe treatment for older patients with stage I non--small-cell lung cancer.

Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904.

PURPOSE: The optimal treatment for medically inoperable stage I non-small-cell lung cancer (NSCLC) has not been defined. PATIENTS AND METHODS: Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. RESULTS: Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. CONCLUSION: Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted.

Definitive radiation therapy for stage I non-small-cell lung carcinoma: institutional experience with contemporary conformal planning.

PURPOSE: Surgical resection for stage I non-small-cell lung cancer (NSCLC) is not always feasible because of the high likelihood of medical comorbidity in this patient population. We report our experience using conventional and hypofractionated radiation therapy schedules with a conformal approach. PATIENTS AND METHODS: Between 1991 and 2006, 102 patients with medically or otherwise inoperable stage T1/T2 N0 NSCLC were treated with curative radiation therapy alone at our institution. Patients received a median total dose of 6600 cGy, with median daily dose fractions of 250 cGy. The following outcomes were analyzed: local failure-free survival (LFFS; time to local failure or death from any cause), time to local or distal failure or death as first event, and overall survival (OS). Local failure was defined as an increase in size on imaging studies. Toxicities were evaluated using Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: Median follow-up was 20.9 months (range, 4.0-138.9 months). Median LFFS was 21.2 months (95% CI, 17.3-27.2 months), and median OS was 21.3 months (95% CI, 17.9-28.8 months). Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 15.1% (95% CI, 8.5%-23.4%), the probability of distal failure as the first detected event was 18% (95% CI, 10.9%-26.5%), and the probability of death without recording a failure was 51.6% (95% CI, 40.6%-61.5%). No patients experienced grade >or= 4 toxicity, and only 4 patients experienced grade 3 toxicity. CONCLUSION: Conformal radiation therapy is an effective and safe alternative to surgery for selected patients with stage I NSCLC.

Interruptions of once-daily thoracic radiotherapy do not correlate with outcomes in limited stage small cell lung cancer: analysis of CALGB phase III trial 9235.

PURPOSE: Retrospective data suggests prolonging the time to complete thoracic radiotherapy (TRT) may negatively impact tumor control and survival in limited stage small cell lung cancer (LSCLC). We examined the association between TRT duration and outcomes on a prospective phase III study. MATERIAL AND METHODS: This review included 267 patients who received protocol TRT on a phase III CALGB LSCLC study assessing the addition of tamoxifen to standard chemo-radiotherapy. TRT, to a planned dose of 50Gy in 2Gy daily fractions, was initiated with the fourth chemotherapy cycle. TRT interruptions were mandated for hematologic toxicity (granulocytes<1000/mm3 or platelets<75,000/mm3) and esophageal toxicity (dysphagia necessitating intravenous hydration). RESULTS: TRT interruptions > or =3 days occurred in 115 patients (43%), most frequently during the 4th week of TRT, and did not differ between treatment arms. Hematologic toxicity and esophageal toxicity were the most frequent indications for interrupting TRT. Variables including advanced age (>70 years), gender, race, or radiotherapy treatment volume did not predict for TRT interruptions. Overall survival (OS) and local tumor control did not correlate with the administration of TRT interruptions or with TRT duration. CONCLUSION: Toxicity mandated interruptions of conventional dose, once-daily, TRT may not adversely affect outcomes for patients receiving TRT concurrent with chemotherapy (cycle 4) for LSCLC. The implications for accelerated or high dose TRT regimens are not clear.

Radiation oncology research in the cancer and leukemia group B.

Radiation oncology initiatives have been an integral component in the evolution of multidisciplinary research in the Cancer and Leukemia Group B. Although early studies in the Group primarily focused on chemotherapy for hematologic and pediatric malignancies, the Radiation Oncology Committee was established in 1972, reflecting the broadening scope of clinical investigation with an increased emphasis on solid tumor research. A major early contribution of the Radiation Oncology Committee was the recognition of the importance of formalized radiation quality review, which led to the development of the Quality Assurance Review Center. The committee has been instrumental in designing trials, in conjunction with our medical oncology and surgical oncology colleagues, to assess multimodality therapy. The results of many of these studies have had important implications for clinical practice. Recent efforts have explored our major research theme of treatment intensification via radiotherapy dose modulation and novel combinations of radiotherapy with sensitizing agents, with an emphasis on safely implementing advanced technologies in the cooperative group setting.