Quality of Life Analysis of a Radiation Dose–Escalation Study of Patients With Non–Small-Cell Lung Cancer

Abstract

Importance A recent randomized radiation dose escalation trial in unresectable stage III NSCLC showed a lower survival in the high-dose arm (74Gy vs. 60Gy) with concurrent chemotherapy. Quality of life (QOL), an important secondary endpoint, is presented here. Objective The primary QOL hypothesis predicted a clinically meaningful decline (CMD) in QOL via the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) in the high-dose RT-arm at 3 months. Design RTOG 0617 was a randomized phase III study (conducted from Nov 2007 to Nov 2011) in stage III NSCLC using a 2×2 factorial design and stratified by histology, PET staging, performance status and radiation technique (3D-conformal RT [3DCRT] vs. intensity-modulated radiation [IMRT]). Setting 185 institutions in the USA and Canada. Participants Of 424 eligible stage III NSCLC patients randomized, 360 (85%) consented to QOL, of whom 313 (88%) completed baseline QOL assessments. Intervention for Clinical Trials 74Gy vs. 60Gy with concurrent and consolidation carboplatin/paclitaxel +/− cetuximab. Main Outcomes and Measures QOL was collected prospectively via FACT-Trial Outcome Index (FACT-TOI), equaling Physical-Well-Being (PWB) + Functional-Well-Being (FWB) + Lung Cancer Subscale (LCS). Data are presented at baseline & 3 and 12 months via minimal clinically meaningful changes of >=2 points for PWB, FWB or LCS or >=5 points for TOI. Results Patient demographics and baseline QOL scores were comparable between the 74Gy and 60Gy arms. Two-hundred-nineteen (72%) of living patients who completed QOL at baseline did so at 3 months and 137 (57%) of living patients did so at 12 months. Significantly more patients on 74Gy arm had clinically meaningful decline in FACT-LCS at 3 months than on the 60Gy arm (45% vs. 30%, p=0.02). At 12 months, fewer patients who received IMRT (vs 3DCRT) had clinically meaningful decline in FACT-LCS (21% vs 46%, p=0.003). Baseline FACT-TOI was associated with overall survival in multivariate analysis. Conclusions and Relevance Despite few differences in provider-reported toxicity between arms, QOL analysis demonstrated a clinically meaningful decline in QOL on the 74Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival. Study registered with ClinicalTrials.gov, number NCT00533949.

Results of a Single Institution Experience with Dose-Escalated Chemoradiation for Locally Advanced Unresectable Non-Small Cell Lung Cancer

“…In addition, there was an increased likelihood of completing adjuvant chemotherapy (2, 9). We found that IMRT use was greater for IIIB patients, likely due to the requirement for coverage of supraclavicular and contralateral mediastinal disease, while achieving acceptable V 20 volumes (mean, 30%) and attempting to still reduce lung toxicity.…”

Heart dosimetric analysis of three types of cardiac toxicity in patients treated on dose-escalation trials for Stage III non-small-cell lung cancer

“…The importance of minimizing cardiac radiation exposure is increasingly recognized and secondary analyses of RTOG 0617 showed reduced toxicities and improved quality of life with the use of IMRT. 44,45 Given the importance of tumor control, coverage of gross disease should be given the highest priority. However, guidelines are needed to help clinicians balance the competing priorities of minimizing dose to heart, lung and esophagus.…”

Results of a Single-Institution Experience With Dose-Escalated Chemoradiation for Locally Advanced Unresectable Non-Small Cell Lung Cancer

“…In addition, there was an increased likelihood of completing adjuvant chemotherapy (2,9). We found that IMRT use was greater for IIIB patients, likely due to the requirement for coverage of supraclavicular and contralateral mediastinal disease, while achieving acceptable V20 volumes (mean, 30%) and attempting to still reduce lung toxicity.…”

“…In a secondary analysis of the data in RTOG 0617, the high-dose arm was associated with a lower patient reported QOL at 3 months, and baseline pretreatment QOL was predictive of survival (9). IMRT use was associated with a less deterioration of QOL compared to patients receiving 3D-CRT.…”

“…The 74-Gy arm showed no benefit and was associated with a survival detriment. Both arms had the same LRC, distant metastasis rate and measured toxicity; however, further analysis showed that the use of IMRT was associated with better patient reported quality of life, and also that improved baseline pretreatment QOL was predictive of survival (9). Other parameters influencing survival included low heart dose, low esophageal morbidity, and smaller planning target volume (PTV).…”