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Quality of Life Analysis of Patients With Non–Small-Cell Lung Cancer
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Editor's Note
The Importance of Quality of Life Assessment
Charles R. Thomas Jr, MD, PhD
Dose escalation of an antineoplastic modality such as radiotherapy (RT) may result in an increased therapeutic ratio with
the use of effective strategies to mitigate normal tissue toxic
effects. Successful execution of dose escalation using
Related article page 359
external beam RT (EBRT) approaches has yielded unintended outcomes.1,2 While increased disease control and survival are a focus of such strategies to increase the therapeutic
ratio, quality of life (QOL), as measured by appropriate patientrelated outcomes tools, are nearly as important. To that end,
Movsas et al,3 in this issue of JAMA Oncology, document that
an attempt to deliver nearly a quarter higher total dose (74 Gy
vs 60 Gy) of EBRT given concomitantly with a platinumtaxane doublet for locally advanced non–small-cell lung cancer (LA-NSCLC) results in a clinically meaningful decrement
in QOL at 3 months.3
However, the Radiation Therapy Oncology Group 0617
trial is not the definitive treatise regarding the RT dosejamaoncology.com
escalation question for LA-NSCLC. The QOL assessments, as
well as the survival results, likely were influenced by numerous factors that are difficult to control for in a multi-institutional, cooperative group clinical trial setting. 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 RT-based treatment. Moreover, not all
modes of potential RT 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 QOL during treatment.
Movsas and colleagues are to be congratulated for executing
a trial that will help in the design of next-generation QOL
trials for LA-NSCLC.
(Reprinted) JAMA Oncology March 2016 Volume 2, Number 3
Copyright 2016 American Medical Association. All rights reserved.
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367
Research Original Investigation
Quality of Life Analysis of Patients With Non–Small-Cell Lung Cancer
Conflict of Interest Disclosures: None reported.
a randomised, two-by-two factorial phase 3 study.
Lancet Oncol. 2015;16(2):187-199.
REFERENCES
2. Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123
(Radiation Therapy Oncology Group 94-05) phase
III trial of combined-modality therapy for
esophageal cancer: high-dose versus standard-dose
radiation therapy. J Clin Oncol. 2002;20(5):
1167-1174.
1. Bradley JD, Paulus R, Komaki R, et al.
Standard-dose versus high-dose conformal
radiotherapy with concurrent and consolidation
carboplatin plus paclitaxel with or without
cetuximab for patients with stage IIIA or IIIB
non-small-cell lung cancer (RTOG 0617):
3. Movsas B, Hu C, Sloan J, et al. Quality of life
analysis of a radiation dose–escalation study of
patients with non–small-cell lung cancer:
a secondary analysis of the Radiation Therapy
Oncology Group 0617 randomized clinical trial
[published online November 25, 2015]. JAMA Oncol.
doi:10.1001/jamaoncol.2015.3969.
Invited Commentary
Dose Escalation in Stage III Non–Small-Cell Lung Cancer
Patients Agree With the Clinical Results
David Cella, PhD
As we conduct clinical research to continue to “move the dial”
of progress against lung cancer, it has become increasingly important to consider the patient’s perspective alongside that of
more standard efficacy and
safety end points. Besides the
Related article page 359
obvious reason of patient centricity, there are several compelling clinical reasons to do so. In this issue of JAMA Oncology,
the article by Movsas and colleagues1 provides us with more
evidence to illustrate the importance of the patient’s perspective on efficacy and safety in clinical trials, and especially the
importance of studies in advanced disease. The results reaffirm a few principles of quality-of-life measurement in advanced tumor oncology that can now be considered teachable facts, supported by robust results, reproduced in multiple
studies, using various questionnaires. Three such facts are
(1) quality-of-life reports taken at the start of a new therapy for
advanced disease are predictive of survival; (2) clinicianrated toxicity on the Common Terminology Criteria for Adverse Events (CTCAE) grading system underestimates the adverse effects of treatments on patients’ lives; and (3) dose
escalation, whether chemotherapeutic or radiotherapeutic, has
predictable, deleterious effects on quality of life, as reported
on a well-validated lung cancer questionnaire. To frame these
“facts,” I will discuss them in the context of the article by
Movsas et al.1
Despite promising phase 2 trial data in patients with
unresectable stage III non–small-cell lung cancer (NSCLC),
escalating dose of radiation therapy (RT) and adding cetuximab did not lengthen survival when compared with standard dose RT with concurrent and consolidation chemotherapy.2 This article1 presents detail on the quality-of-life
data from the same study.2 The authors1 used the Trial Outcome Index (TOI) from the Functional Assessment of Cancer
Therapy-Lung Cancer Subscale (FACT-LCS) quality-of-life
instrument. The FACT-LCS produces 5 individual subscale
scores and 2 summary scores: one (TOI) to reflect the physical dimension of life quality, and the other (FACT-LCS total
score) to reflect an overall summary of health-related quality
of life. Movsas et al1 chose to administer and focus only on
368
the physical dimension, using the 3 subscales that comprise
the TOI: Physical Well-Being, Functional Well-Being, and
Lung Cancer Symptoms.
Lessons learned:
1. Quality-of-life reports taken at the start of a new therapy
for advanced disease are predictive of survival. As has been
shown in several prior studies,3 across many groups of
patients with advanced disease, baseline patient report of
quality-of-life (TOI score) was associated (P = .046) with
survival time. It has also been shown in several investigations,3 although not apparently analyzed in this investigation, that change in patient report while on therapy is also
predictive of survival, above and beyond the baseline
report. Analysis of both baseline scores and early change in
scores can shed further light on which patients benefits,
and which do not, from therapy in early treatment, perhaps contributing to clinical decision-making after initiation of treatment.
2. Clinician-rated toxic effects on the CTCAE grading system
underestimates the adverse effects of treatments on patients’ lives. On the one hand, Movsas and colleagues1 reported that very few of the clinician-rated adverse events
were worse in the treatment arm receiving the escalated dose
of RT. On the other hand, patient report of symptoms, adverse effects, and functioning, as manifest in the FACTLCS TOI and its components, were significantly and meaningfully worse in the arm receiving the escalating dose.
Significantly more patients in the arm receiving 74-Gy (45%
vs 30%) had clinically meaningful decline in FACT-LCS at 3
months than those receiving 60 Gy (P = .02).
3. Dose escalation, whether chemotherapeutic or radiotherapeutic, has predictable, deleterious effects on quality of life.
Here are some of the most novel and interesting findings by
Movsas et al.1 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. To their credit, these investigators1
studied several patient-reported toxic effects, and they asked
the right questions to answer their questions. Several dosimetric factors were associated with clinically meaning-
JAMA Oncology March 2016 Volume 2, Number 3 (Reprinted)
Copyright 2016 American Medical Association. All rights reserved.
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