Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy report by the radiation therapy oncology group

Abstract

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.

Alternating chemotherapy and accelerated split-course irradiation in locally advanced nonsmall cell lung carcinoma

“…The overall median survival and the 2-year survival were similar to those previously published by several teams 26,28,34,35 that studied combined local irradiation and systemic chemotherapy in the treatment of inoperable NSCLC. Our approach resulted in a high response rate and prolonged survival of 21% at 5 years.…”

Radiation Therapy Potentiates Effective Oncolytic Viral Therapy in the Treatment of Lung Cancer

“…NV1066 infection was carried out at multiplicities of infection (MOI: number of viral plaque forming units per tumor cell) of 0.1, 0.2, 0.3, 0.4 or 0.5 in a total volume of 100 μl of medium. Combination therapy was performed using serial dilutions of RT (2,4,6,8, and 10 Gy) and NV1066 (MOI 0.1, 0.2, 0.3, 0.4 and 0.5) in a 1:20 ratio for both cell lines. These ratios were determined by estimating the LD 50 for each therapy in initial experiments and by using these doses to determine the ratio of combination therapy.…”

“…After preliminary experiments, the following sequence targeting from codon 635 was chosen for further experiments: 5-GUCAAUUUGCAGAUGGCCATTUGGCCAUCUGCAAAUUGACTT-3. A549 and H1299 cells were plated at a concentration of 5x10 4 per well in 24 well plates twelve hours prior to transfection in appropriate medium without antibiotics. Standard siRNA transfection protocol as described before was used(24).…”

Continuous hyperfractionated accelerated radiotherapy – Escalated dose (CHART-ED): A phase I study

“…Bronchoscopic re-evaluation after radical thoracic RT has demonstrated persistent tumour in 85% of cases 3 . Successful local control has been found to correlate with improved survival , 4 .…”