Patient-Reported Quality of Life Outcomes Shed Light on Poor Survival in an RTOG Trial Evaluating Increased Radiotherapy Dose for Lung Cancer
ATLANTA— Results of a quality of life (QOL) analysis presented today during a plenary session of the 2013 Annual Meeting of the American Society for Radiation Oncology (ASTRO) show that, at three months after the start of treatment, almost half of patients with stage III non-small cell lung cancer (NSCLC) who received a higher dose of radiotherapy (RT) with chemotherapy reported a clinically meaningful decline in QOL compared with less than a third of those who received a standard dose of radiation with chemotherapy.
In the Radiation Therapy Oncology Group (RTOG) Community Clinical Oncology Program (CCOP)-supported QOL analysis of the RTOG 0617 trial, investigators found, despite few differences in provider-reported toxicities between the study arms, patients on the higher-RT dose arm experienced a greater decline in quality of life. “This speaks to the disconnect that can occur between the provider and patient perspective,” states Benjamin Movsas, M.D., chair of radiation oncology at Henry Ford Hospital in Detroit, and the QOL co-chair for the RTOG 0617 study.
“Provider-reported toxicities, while important, often do not capture the whole story. Analyzing QOL reports coming directly from the patients demonstrated more clearly clinically meaningful differences in how the patients were doing in each of this study’s two arms.”
The primary aim of the phase III randomized trial was to determine whether a higher dose of RT (74 Gy) with chemotherapy versus a standard dose of RT (60 Gy) with chemotherapy improved overall survival. These results, previously presented, revealed inferior patient survival on the higher-dose RT arm. At today’s ASTRO plenary session, the QOL results were presented for the first time, shedding light on the perplexing results of this study.
Of the 357 study participants (out of 419 eligible) who consented to the QOL study component, 88 percent completed a validated lung cancer QOL instrument (Functional Assessment of Cancer Therapy-Trial Outcome Index [FACT-TOI]) that assessed physical well-being (eg, pain level), functional well-being (eg, sleep quality, life enjoyment), and a lung cancer subscale (eg, shortness of breath, cough). “These are fundamental issues that get to the core of what’s going on regarding the patients’ quality of life,” states Dr. Movsas.
Commenting on the finding that baseline QOL also predicted for survival of study participants, Movsas points out, “It’s noteworthy that patients on the higher-dose RT arm had a lower quality of life at 3 months and, unfortunately, this arm also ended up having lower survival. It’s intriguing that, when you add quality of life to the mix of prognostic variables, it becomes a critical and independent predictor of outcome.”
Although the study was not randomized for the RT technique (3-dimensional conformal RT [3D-CRT] or the more sophisticated technique, intensity-modulated RT [IMRT]), IMRT, which was used in almost half (45 percent) of patients, resulted in significantly less QOL decline than 3D-CRT. At 12 months, significantly fewer patients who received IMRT (vs. 3D) reported QOL declines across the areas assessed via the validated FACT-TOI instrument (36 percent vs. 57 percent).
“This lower rate of a clinically meaningful decline in quality of life by using IMRT remained through 1 year of follow-up, suggesting that this was not a transient effect,” explains Movsas. “Although this study was not randomized to compare these RT treatment methods directly, the trial reveals the need to better understand the role of IMRT for patients with lung cancer and the potential benefits of applying more sophisticated radiation techniques.”
With a wealth of data still to be mined, investigators plan to examine how the RT planning dosimetric parameters tie into the demonstrated outcomes and QOL findings. Additional analyses of the connection of translational research markers and molecular factors with the study outcomes are also planned. As Jeffrey Bradley, M.D., from the Washington University in St. Louis, Mo., and the principal investigator for the study, states, “These results highlight the value that quality of life data bring to clinical research for increasing insight into trial results and understanding of the nuances of how treatment impacts patients’ lives.”
Reflecting on the significance of the ASTRO plenary presentation, Deborah W. Bruner, R.N., Ph.D., FAAN, Principal Investigator of the RTOG CCOP Research Base and associate director of outcomes at the Winship Cancer Institute of Emory University in Atlanta states, “We’ve come a long way—from a time when QOL was considered by some to be a ‘soft science’ to the current appreciation by clinicians that obtaining validated QOL information directly from our patients profoundly impacts clinical results. QOL truly tells us the ‘rest of the story’ from the patient perspective.” Movsas anticipates that web-based HIPAA-secure QOL collection methods and greater use of electronic medical records will facilitate practical, user-friendly QOL data collection. “It’s just a matter of time before QOL becomes another critical parameter that we incorporate into our everyday clinical routine.”
“RTOG has long played an active role in advocating for the incorporation of quality of life research in the conduct of cancer clinical trials. It is gratifying to see these kinds of research insights come about as a result of the emphasis placed on patient-reported outcomes in this and other RTOG clinical studies,” says Walter J. Curran, M.D., FACR, RTOG Group Chair and Executive Director of the Winship Cancer Center at Emory University in Atlanta.
The Radiation Therapy Oncology Group (RTOG) is administered by the American College of Radiology (ACR) and located in the ACR Clinical Research Center in Philadelphia, PA. RTOG is a multi-institutional international clinical cooperative group funded primarily by National Cancer Institute grants CA21661, CA32115 and CA37422. RTOG has 40 years of experience in conducting clinical trials and is comprised of over 300 major research institutions in the United States, Canada and internationally.
The group is currently accruing to 40 studies that involve radiation therapy alone or in conjunction with surgery and/or chemotherapeutic drugs or which investigate quality of life issues and their effects on the cancer patient. RTOG is administered by the American College of Radiology (ACR) is a national professional organization serving more than 32,000 radiologists, radiation oncologists, interventional radiologists and medical physicists with programs focusing on the practice of radiology and the delivery of comprehensive health care services. To learn more: www.rtog.org
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