The influence of radiation therapy quality control on survival, response and sites of relapse in oat cell carcinoma of the lung. Preliminary report of a Southwest Oncology group study

Abstract

Two hundred and ninety‐eight patients with limited (confined to chest and supraclavicular area, encompassable by a single radiation portal) small cell carcinoma of the lung were entered on Southwest Oncology Group Protocol 7628. Patients were treated with multi‐agent chemotherapy and radiation therapy with or without BCG. Radiation therapy quality control analysis, including dosimetric reconstruction and port film review was introduced after the protocol was activated and was retrospectively applied. Patients who were considered major protocol variations had statistically worse survival (40 weeks versus 60 weeks; P = 0.002), a lesser improvement in response rate after induction chemotherapy (27 versus 48%; P = 0.05) and a higher chest failure rate (77 versus 55%; P = 0.047) than evaluable patients. Five patients relapsed in the brain, all associated with chest failure. Quality control is essential in cooperative group studies.

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

“…In addition to the PCS, there were eight cooperative trial groups represented, based in North America, Europe and Australia. Disease sites were hematologic (13, 17–21), head and neck (3,14–15,23), lung (10–12), breast (2,16) and pancreas (22,24). The central trial question was RT-related in ten trials, and in 11, chemotherapy was to have been delivered to at least half of patients accrued (induction chemotherapy [17,19–21]; induction + adjuvant [10,12]; concurrent [3,13,15]; concurrent + maintenance [22]; and induction + concurrent + adjuvant [24]).…”

“…Nine trials assigned an overall case grade of major deviation which was received by up to 47% of plans. Analysis of the correlation of RT quality with outcomes was controlled for other prognostic factors in approximately half of the protocols (2,3,12,13,15,18, 21–22,24). …”

“…RR with respect to RT quality were evaluated in two trials and no statistical correlation was observed in either, although in one (12), the complete response (CR) rate was higher for those cases with a minor or no deviation (44% [38/85]) as compared to cases scored as a major deviation (39% [16/41]; p=0.68). In RTOG 7301, response rates (55–59%) were comparable between patients with RT plans with a major deviation at the primary site versus those without (11).…”

Radiotherapy quality assurance review for a multi-center randomized trial of locally advanced esophageal cancer: the Japan Clinical Oncology Group (JCOG) trial 0303

“…They also showed that centers that treated only a few patients were the major source of RT quality problems. While many reports have shown that failure to adhere to the treatment protocol degraded the outcomes of clinical trials [7,[16][17][18][19][20][21][22], for the first time they quantified the penalty associated with poor RT and demonstrated a more substantial impact of RT quality on outcomes than any additional effects for new agents. In our study, the numbers enrolled by each institution also adversely affected the number of VU cases.…”

Radiotherapy protocol deviations and clinical outcomes: A meta-analysis of cooperative group clinical trials.

“…These included two lung cancer trials (20,21), three trials for medulloblastoma or supratentorial primitive neuroectodermal tumor (16,22,23), and one trial each for Ewing sarcoma (24), pancreatic cancer (9), and head and neck cancer (10). In all but one trial (10), RT QA reviews were performed in a post hoc fashion.…”