Luther W. Brady

Principles and practice of radiation oncology , Principles and practice of radiation oncology , کتابخانه دیجیتال جندی شاپور اهواز

This report details the patterns of tumor recurrence in two prospective randomized studies involving 551 patients with histologically proven unresectable or medically inoperable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Patients were treated according to two protocols, depending on the stage of the tumor: (1) Patients with T1, 2, 3-NO, 1, 2 tumors were randomized to four different regimens: 4000 cGy split course (2000 cGy in five fractions, per 1 week, 2 weeks rest and additional 2000 cGy in five fractions, per 1 week) or 4000, 5000, or 6000 cGy continuous courses, five fractions per week. (2) Patients with T4, any N or N3, any T stage tumors were randomized to be treated with 3000 cGy tumor dose (TD), ten fractions in 2 weeks, 4000 cGy split course (described above), or 4000 cGy continuous course. In the patients with less advanced tumors (Study 1) the intrathoracic failure rate within the irradiated volume was 48% with 4000 cGy continuous, 38% with 4000 cGy split course or 5000 cGy continuous, and 27% for patients receiving 6000 cGy continuous course. The failure rate in the nonirradiated lung ranged from 25% to 30% in the various groups. Patients with adenocarcinoma or large cell undifferentiated carcinoma had better intrathoracic tumor control (35%) than those with squamous cell carcinoma (20%). The incidence of distant metastases was 75% to 80% in all histologic groups. Distant metastases appeared sooner after therapy in the patients with adenocarcinoma or large cell undifferentiated carcinoma. The initial failure rate in the brain was 7% in patients with squamous cell carcinoma, 19% with adenocarcinoma, and 13% in patients with large cell carcinoma. The ultimate incidence of brain metastases was 16% in squamous cell carcinoma, and 30% for adenocarcinoma or large cell undifferentiated carcinoma. Higher doses of irradiation will be necessary in order to improve the intrathoracic tumor control. Clinical trials by the Radiation Therapy Oncology Group, some of them involving multiple daily fractionation, are in progress. Furthermore, because of the high incidence of distant metastases, effective systemic cytotoxic agents are critically needed to improve survival of lung cancer patients. The high frequency of brain metastases suggests that, as in small cell carcinoma of the lung, elective irradiation of the brain may be necessary, if not to improve survival to enhance the quality of life of patients with adenocarcinoma and large cell carcinoma.

Preliminary analysis is presented of a prospective randomized study involving 365 patients with histologically proven unresectable non-oat-cell carcinoma of the lung treated with definitive radiotherapy. The patients were randomized to one of four treatment regimens: 4000 rad split course (2000 rad in five fractions one week, two weeks rest, and an additional 2000 rad in five fractions in one week) or 4000, 5000, or 6000-rad continuous courses in five fractions per week. Ninety to 100 patients were accessioned to each group. The one-year survival rate is 50% and the two-year survival rate, 25%. The patients treated with the split course have the lowest survival rate (10% at two years) in comparison with the other groups (range = 20–25%). The complete and partial local regression of tumor was 49% in patients treated with 4000 rad and 55% in the groups treated with 5000 and 6000 rad. For patients who achieved complete regression of the tumor following irradiation, the two-year survival rate is 40%, in contrast to 20% for those with partial regression, and no survivors among the patients with stable or progressive disease. The incidence of intrathoracic recurrence was 33% for patients treated with 6000 rad, 39% for those receiving 5000 rad, and 44–49% for those treated with a 4000-rad split or continuous course. At present, the data strongly suggest that patients treated with 5000 or 6000 rad have a better response, tumor control, and survival rate than those receiving lower doses. However, additional followup of patients at risk in each group will be necessary before a final conclusion is drawn. Patients with high performance status (Kornofsky index higher than 70), or with tumors in earlier stages (T1N2 or T3N0) have a two-year survival rate of approximately 40%, in comparison with 20% for other patients. The various irradiation regimens have been well tolerated, with complications being slightly higher in the 4000-rad split course group (10 severe and 2 life-threatening) and in the 6000-rad continuous course group (9 severe and 4 life-threatening). The most frequent complications have been pneumonitis, pulmonary fibrosis, and dysphagia due to transient esophagitis. Further investigation will be necessary before the optimal management of patients with bronchogenic carcinoma by irradiation is established.

An analysis of intrathoracic tumor control was carried out in 378 patients with histologically proven unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy, randomized to one of four treatment regimens: 4000 rad split course (2000 rad in five fractions in one week, two weeks rest and additional 2000 rad in five fractions in one week) or 4000, 5000 or 6000 rad continuous courses, five fractions per week. Between 85 and 101 patients are analyzed in each treatment group. The complete plus partial response was 46–51% in the 4000 rad groups in contrast to 61–66% in the 5000 to 6000 rad groups (P = 0.008). The overall two year survival rate was 10–11% for the patients treated with 4000 rad split or continuous course, and 19% in the patients treated with 5000 to 6000 rad. The complete response in patients with tumors 3 cm or less in diameter was 16% when treated with 4000 rad in contrast to 20–31% in those treated with 5000–6000 rad. In the patients with lesions from 4 to 6 cm in diameter, complete and partial tumor regression was 48% in the 4000 rad group, 67% with 5000 rad, and 71% with 6000 rad. These differences are statistically significant (P = 0.033). Intrathoracic recurrences were correlated with the dose of irradiation given: 52% with 4000 rad, 41% with 5000 rad, and 30% with 6000 rad (P = 0.006). An analysis of protocol compliance was carried out in 301 patients with available data, irradiated at the primary site according to protocol instruction (none or minor variation). Median survival for patients treated to the ipsilateral or contralateral hilar lymph nodes according to the protocol varied from 46–50 weeks in contrast to 20–30 weeks for those with major protocol variations in nodal irradiation. Variations in ipsilateral and contralateral nodal irradiation correlated with significant reductions in tumor control (P = 0.02 and P = 0.009, respectively). In addition to patient and tumor characteristics, the technical factors of irradiation are critical parameters that affect tumor control and survival in patients with non-oat cell bronchogenic carcinoma. Strict quality assurance criteria in radiotherapy are necessary to achieve optimal treatment results and a careful program to evaluate techniques of irradiation and protocol compliance should be maintained in cooperative group studies in order to enhance the validity of clinical trials.