Higher-dose radiation worsens quality of life among patients with NSCLC

Patients with non–small cell lung cancer assigned a higher radiation dose experienced a clinically meaningful decline in quality of life, according to a secondary analysis of the Radiation Therapy Oncology Group 0617 randomized controlled trial.

Further, baseline quality of life served as an independent prognostic factor for survival, according to the researchers.

The dose-escalation trial assigned patients with unresectable stage III NSCLC to one of four treatment arms that compared high-dose radiation (74 Gy) vs. low-dose (60 Gy) radiation with concurrent and consolidation chemotherapy with or without cetuximab (Erbitux, ImClone). The overall results indicated that survival was lower in the high-dose radiation arm, and the addition of cetuximab did not impact outcomes.

Patient-reported outcomes served as a secondary endpoint of the study. Researchers collected prospective data using the Functional Assessment of Cancer Therapy (FACT)-Trial Outcome Index, which included the physical well-being, functional well-being and Lung Cancer Subscale measures.

Benjamin Movsas, MD, chair of radiation oncology at Henry Ford Hospital in Detroit, and colleagues conducted this secondary analysis to investigate the trial’s primary quality-of-life hypothesis, which predicted a clinically meaningful decline in quality of life at 3 months among patients assigned high-dose radiotherapy.

Among 424 patients randomly assigned on the trial, 85% (n = 360) consented to a quality-of-life evaluation, 88% (n = 313) of whom completed baseline assessments.

Seventy percent of patients (n = 219) with baseline assessments completed the 3-month quality of life assessment.

Although patients in both study arms had comparable baseline quality-of-life scores and demographics, a significantly greater proportion of patients assigned 74-Gy radiation experienced a clinically meaningful quality-of-life decline at 3 months (45% vs. 30%; P = .02).

Twenty-three percent (n = 73) of patients were no longer alive at 12 months; 57% (n = 137) of living patients who completed the baseline assessment also completed a 12-month assessment.

The decline in quality of life at 12 months between the two arms appeared similar for the FACT-Lung Cancer Subscale and for all subscales.

A significantly smaller proportion of patients who received intensity-modulated radiation therapy vs. 3D-conformal radiation therapy experienced a clinically meaningful decline in quality of life measured by the FACT–Lung Cancer Subscale (21% vs. 46%; P = .003).

David Cella

Baseline quality of life served as a predictive factor for improved OS in multivariate analyses. According to the researchers, every 10-point increase in the FACT Trial Outcome Index at baseline corresponded with a 10% decreased risk for death (P = .046).

Movsas and colleagues acknowledged missing data as a study limitation.

“This analysis suggests that improved radiation therapy treatment techniques may enhance the therapeutic window for patients with lung cancer,” Movsas and colleagues wrote. “Despite few differences in clinician-reported toxic effects between dose arms, the patient-reported outcomes demonstrated significantly worse quality of life in the high-dose arm at 3 months, confirming the primary hypothesis.”

In an accompanying editorial, David Cella, PhD, chair of the department of medical social sciences and director of the Institute for Public Health and Medicine Center for Patient-Centered Outcomes at Northwestern University Feinberg School of Medicine, noted that it is important to consider the perspective of patients enrolled in clinical trials, alongside more traditional research endpoints.

“Dose escalation, whether chemotherapeutic or radiotherapeutic, has predictable, deleterious effects on quality of life,” Cella wrote. “Those clinicians planning future studies that include dose escalation can learn from these results, especially with regard to making hypotheses and then measuring and testing them. … Findings like this, linking dose with patient reports of symptoms and functioning, help plan future studies that aim to determine the acceptability of dose escalation and aggressive combined modality treatments.”

In an editor’s note, Charles R. Thomas Jr. MD, PhD, wrote these data are not a definitive assessment of quality of life and radiation dose-escalation.

“Emerging data on molecular signatures that may predict radiosensitivity and/or radioresistance of tumor, as well as normal tissues, may be helpful in future assessment of baseline patient characteristics for those enrolled in prospective, large-scale cancer clinical trials of radiotherapy-based treatment,” Thomas wrote. “Moreover, not all modes of potential radiotherapy delivery and dose escalation are equal. Currently, radiation oncologists see patients on a weekly basis and basically assess symptoms as a ‘snapshot in time.’ This is fraught with recall bias and other factors that contribute to a diminished appreciation of real-time patient-related outcomes, which should ideally be recorded on a continuous 24/7 basis to assess quality of life during treatment.” – by Cameron Kelsall

References:

Cella D. JAMA Oncol. 2015;doi:10.1001/jamaoncol.2015.4683.

Movsas B, et al. JAMA Oncol. 2015;doi:10.1001/jamaoncol.2015.3969.

Thomas CR. JAMA Oncol. 2015;doi:10.1001/jamaoncol.2015.4087.

Disclosure: Bristol-Myers Squibb provided funding for this study. Movsas reports research funding from Philips Inc. and Varian Inc. for projects not related to this study. One other researcher reports institutional grants to the Radiation Therapy Oncology Group during the conduct of this study. The other researchers and Cella report no relevant financial disclosures.