Early Weight Loss during Chemoradiotherapy Has a Detrimental Impact on Outcome in NSCLC

Sanders, Karin J. C.; Hendriks, Lizza; Troost, Esther G.C.; Bootsma, Gerben; Houben, Ruud; Schols, A.M.W.J.; Dingemans, Anne‐Marie C.

doi:10.1016/j.jtho.2016.02.013

Cited by 42 publications

(34 citation statements)

References 20 publications

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“…Firstly, the findings support the observation made previously by Martin et al 12 that survival significantly worsens with increasing weight loss grade and are consistent with several other publications showing that patients with involuntary weight loss have a poor prognosis. 4,18,19 Looking at weight loss grades 1 and 2 individually, survival did worsen compared with that at weight loss grade 0. However, the difference did not reach Adjusted for age, sex, and cancer type and stage.…”

Section: Discussionmentioning

confidence: 98%

The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis

Vagnildhaug

Blum

Wilcock

et al. 2017

J cachexia sarcopenia muscle

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BackgroundA body mass index (BMI) adjusted weight loss grading system (WLGS) is related to survival in patients with cancer. The aim of this study was to examine the applicability of the WLGS by confirming its prognostic validity, evaluating its relationship to cachexia domains, and exploring its ability to predict cachexia progression.MethodsAn international, prospective observational study of patients with incurable cancer was conducted. For each patient, weight loss grade was scored 0–4. Weight loss grade 0 represents a high BMI with limited weight loss, progressing through to weight loss grade 4 representing low BMI and a high degree of weight loss. Survival analyses were used to confirm prognostic validity. Analyses of variance were used to evaluate the relationship between the WLGS and cachexia domains [anorexia, dietary intake, Karnofsky performance status (KPS), and physical and emotional functioning]. Cox regression was used to evaluate if the addition of cachexia domains to the WLGS improved prognostic accuracy. Predictive ability of cachexia progression was assessed by estimating proportion of patients progressing to a more advanced weight loss grade.ResultsOne thousand four hundred six patients were analysed (median age 66 years; 50% female, 63% KPS ≤ 70). The overall effect of the WLGS on survival was significant as expressed by change in −2 log likelihood (P < 0.001) and persisted after adjustment for age, sex, and cancer type and stage (P < 0.001). Median survival decreased across the weight loss grades ranging from 407 days (95% CI 312–502)—weight loss grade 0 to 119 days (95% CI 93–145)—weight loss grade 4. All cachexia domains significantly deteriorated with increasing weight loss grade, and deterioration was greatest for dietary intake, with a difference corresponding to 0.87 standard deviations between weight loss grades 0 and 4. The addition of KPS, anorexia, and physical and emotional functioning improved the prognostic accuracy of the WLGS. Likelihood of cachexia progression was greater in patients with weight loss grade 2 (39%) than that with weight loss grade 0 (19%) or 1 (22%).ConclusionsThe WLGS is related to survival, cachexia domains, and the likelihood of progression. Adding certain cachexia domains to the WLGS improves prognostic accuracy.

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Section: Discussionmentioning

confidence: 98%

The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis

Vagnildhaug

Blum

Wilcock

et al. 2017

J cachexia sarcopenia muscle

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“…This was initially described in stage 3 patients receiving cCRT who lost weight between the first and last day of treatment with inferior OS and PFS in patients whose body mass index reduced by 0.5kg/m2 over this time [47]. Early weight loss (5% loss between the start and third week of radiotherapy) is also associated with a significantly poorer OS [48]. In this study all patients were weight-stable prior to the commencement of cCRT and received weekly dietetic support.…”

Section: Clinical Response Heterogeneitymentioning

confidence: 95%

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

et al. 2018

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The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected.

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“…Interstitial lung abnormalities, as well as severe chronic obstructive pulmonary disease (COPD), are associated with high all-cause mortality [115, 116], and a higher risk of toxicity after CRT [117, 118]. Other patient factors, including weight loss during the first three weeks of CRT may also profoundly affect survival [119]. An improved understanding of what drives poor outcomes in patients with factors like large tumors and co-morbid illness is needed.…”

Section: Introductionmentioning

confidence: 99%

A critical review of recent developments in radiotherapy for non-small cell lung cancer

Baker¹,

et al. 2016

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Lung cancer is the leading cause of cancer mortality, and radiotherapy plays a key role in both curative and palliative treatments for this disease. Recent advances include stereotactic ablative radiotherapy (SABR), which is now established as a curative-intent treatment option for patients with peripheral early-stage NSCLC who are medically inoperable, or at high risk for surgical complications. Improved delivery techniques have facilitated studies evaluating the role of SABR in oligometastatic NSCLC, and encouraged the use of high-technology radiotherapy in some palliative settings. Although outcomes in locally advanced NSCLC remain disappointing for many patients, future progress may come about from an improved understanding of disease biology and the development of radiotherapy approaches that further reduce normal tissue irradiation. At the moment, the benefits, if any, of radiotherapy technologies such as proton beam therapy remain unproven. This paper provides a critical review of selected aspects of modern radiotherapy for lung cancer, highlights the current limitations in our understanding and treatment approaches, and discuss future treatment strategies for NSCLC.

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Early Weight Loss during Chemoradiotherapy Has a Detrimental Impact on Outcome in NSCLC

Abstract: Early weight loss in patients with non-small cell lung cancer was found to be associated with worse prognosis. These data warrant further investigation into the efficacy of tailored intervention to prevent early weight loss.

Cited by 42 publications

References 20 publications

The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis

The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

A critical review of recent developments in radiotherapy for non-small cell lung cancer

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