Does Sarcopenia Affect Outcome in Patients with Non-Small-Cell Lung Cancer Harboring EGFR Mutations?

Rossi, Sabrina; Noia, Vincenzo Di; Tonetti, Lorenzo; Strippoli, Antonia; Basso, Michele; Schinzari, Giovanni; Cassano, Alessandra; Leone, Alessandro; Barone, Carlo; D’Argento, Ettore

doi:10.2217/fon-2017-0499

Cited by 31 publications

(33 citation statements)

References 25 publications

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“…Since 1980, weight loss, low lean body mass, and BMI have been well known factors associated with poor prognosis in lung cancer patients, affecting patient responsiveness, tolerance to oncologic therapy, survival, and quality of life . However, our analysis showed no correlation between low SMM, the main component of weight loss, and OS, in contrast with the results of previous studies that examined a population of lung cancer patients, despite different biological and histological characteristics between samples. Similarly, changes in SMI at different time points were not predictive of outcome.…”

Section: Discussioncontrasting

confidence: 99%

“…Similarly Rossi et al . showed that baseline sarcopenia was associated with longer OS, even if it did not affect the response to gefitinib treatment, in EGFR mutated NSCLC patients …”

Section: Discussionmentioning

confidence: 99%

“…8 Similarly Rossi et al showed that baseline sarcopenia was associated with longer OS, even if it did not affect the response to gefitinib treatment, in EGFR mutated NSCLC patients. 41 The discrepancies in these findings are difficult to explain, however, it is possible that in studies investigating the association between survival and muscle mass, SMI was dichotomized according to survival-related thresholds of the analysis samples, which were likely different among the studies, and this may to some extent have overestimated the effect. 3,13 In addition, the prognostic weight of sarcopenia seems to particularly affect obese patients, who accounted for only 16% of our cohort.…”

Section: Discussionmentioning

confidence: 99%

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Single‐institution study of correlations between skeletal muscle mass, its density, and clinical outcomes in non‐small cell lung cancer patients treated with first‐line chemotherapy

et al. 2018

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BackgroundSarcopenia and muscle tissue degradation are hallmarks of the majority of chronic diseases, including non‐small cell lung cancer (NSCLC). A computed tomography scan could be an easy modality to estimate the skeletal muscle mass through cross‐sectional image analysis at the level of the third lumbar vertebra.MethodsBaseline skeletal muscle mass (SMM) was evaluated through the skeletal muscle index (SMI), together with skeletal muscle radiodensity (SMD), in NSCLC patients undergoing first‐line chemotherapy to evaluate correlations with safety and clinical outcomes. When SMIs at different time points were available, further comparison was made between patients with worse and improved SMIs.ResultsAmong 81 stage IV NSCLC patients, 28 had low SMM and 23 had low SMD. There were no significant differences in univariate analysis of progression‐free survival (PFS) between patients with baseline low and non‐low SMM (P = 0.06388) or between patients with low and non‐low SMD (P = 0.9126). Baseline low SMM, however, proved a significant predictor of shorter PFS in multivariate analysis (hazard ratio 0.54, 95% confidence interval 0.31–0.93; P = 0.0278), but not low SMD. There were no differences in overall survival (OS) between patients with baseline low and non‐low SMM or low and non‐low SMD. No differences in PFS and OS between evaluable patients with worse or improved SMI were found. A significant difference in hematological toxicities between patients with baseline low and non‐low SMM (P = 0.0358) was observed.ConclusionsLow SMM is predictive of shorter PFS, while consecutive changes in muscular mass do not seem to be a predictor of PFS or OS. The role of muscle radiodensity remains a matter of debate.

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Section: Discussioncontrasting

confidence: 99%

“…Similarly Rossi et al . showed that baseline sarcopenia was associated with longer OS, even if it did not affect the response to gefitinib treatment, in EGFR mutated NSCLC patients …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Single‐institution study of correlations between skeletal muscle mass, its density, and clinical outcomes in non‐small cell lung cancer patients treated with first‐line chemotherapy

et al. 2018

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“…On the other hand, there was only one study that had investigated the association of sarcopenia with molecular-targeted therapy for advanced NSCLC. The Italian study failed to detect sarcopenia as a significant prognostic factor of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), gefitinib [10]. Regarding cancer immunotherapy, little has been known about association of sarcopenia with immunecheckpoint inhibitors (ICI).…”

Section: Introductionmentioning

confidence: 99%

Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer

Minami¹,

Ihara²,

Tanaka³

et al. 2020

World J Oncol

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Background: This study aimed to investigate the association of computed tomography (CT)-assessed sarcopenia and visceral adiposity with efficacy and prognosis of immune-checkpoint inhibitor (ICI) therapy for pretreated non-small cell lung cancer (NSCLC). Methods: We retrospectively collected 74 patients with pretreated NSCLC who had initiated programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor monotherapy between December 2015 and November 2018 at our hospital. As CT-assessed pretreatment markers, we used psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), visceral-tosubcutaneous ratio (VSR) and visceral fat area (VFA) at lumbar vertebra L3 level. We divided 74 patients into high and low groups according to each Japanese sex-specific cutoff value. Using Kaplan-Meier curves and log-rank tests, we compared overall survival (OS) and progression-free survival (PFS). Adjusted by serum albumin, neutrophil-to-lymphocyte ratio, performance status and driver mutations, multivariate Cox proportional hazard analyses evaluated various variables as independent prognostic factors of OS and PFS. Results: We could not find significant difference in response rate (RR) and disease control rate (DCR) between low and high groups according to any factors. The OS of patients with body mass index (BMI) < 18.5 was significantly shorter than that of patients with BMI ≥ 18.5 (median 3.3 vs. 15.8 months, P < 0.01), while there was no significant difference in OS and PFS according to PMI, IMAC, VSR and VFA. Multivariate analyses detected no significant prognostic factor in OS and PFS, except for low IMAC (hazard ratio 0.43, 95% confidence interval 0.18-0.998, P = 0.0496) as a favorable prognostic factor of longer OS. Conclusions: Neither PMI nor VSR, VFA might be a significant prognostic factor of PFS and OS of ICI monotherapy for pretreated NSCLC. According to our multivariate analyses, IMAC was a significant prognostic factor of OS, but not of PFS. Thus, neither sarcopenia nor visceral adiposity may be associated with the efficacy of ICI therapy.

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“…and follow-up in lung cancer patients and offers an elegant way to simultaneously assess sarcopenia by calculating the skeletal muscle mass index (5,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

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confidence: 99%

Sarcopenia as Prognostic Factor in Lung Cancer Patients: A Systematic Review and Meta-analysis

et al. 2019

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Background/Aim: Sarcopenia describes the loss of skeletal muscle mass. While this condition is associated with a high mortality in cancer patients, its influence on survival is still underestimated. Patients and Methods: A systematic review for articles was performed using the PubMed database, Cochrane Library, Biomed Central, Science Direct and by manual search. We used data of overall survival in sarcopenic patients for assessing the death risk. We extracted hazard ratio estimates from univariate and multivariate Cox proportional hazards models for meta-analysis. Results: A total of 15 studies were eligible for meta-analysis including a total of 2,521 lung cancer patients. Univariate meta-analysis revealed a twofold increased death risk in sarcopenic patients; multivariate meta-analysis yielded a significant, threefold elevated risk of death. This higher mortality is independent of tumour stage. Conclusion: Muscle loss is an independent risk factor for increased death risk in lung cancer patients independent of cancer stage. This argues for implementing screening for sarcopenia into cancer care. Sarcopenia describes the age-related loss of muscle mass and strength starting during the fourth to fifth decade of life. It is defined as a muscle mass of at least two standard deviations below the mean muscle mass found in young healthy adults (1-3). While often reported in the elderly, loss of muscle mass does also manifest in patients suffering from a chronical disease like congestive heart failure, chronical obstructive pulmonary disease, chronical renal failure or cancer. Muscle loss has a relevant impact on survival, especially in the latter group. The prevalence of sarcopenia in cancer patients depends on cancer entity, which is why a prevalence of 16% is described in breast cancer patients, whereas 71% of lung cancer patients under palliative therapy suffer from sarcopenia (4-6). Muscle wasting is an unfavourable prognostic factor for cancer specific survival of rectum, liver, oesophagus, stomach or kidney cancer patients (1, 7). If muscle mass is maintained or increased, patients show a longer overall survival (5). Sarcopenia may be caused by several different factors; cancer, chemotherapy or locoregional impairment caused by surgery or radiation therapy, comorbidities, malnutrition or physical inactivity (8). Sarcopenia itself is also a risk factor for an increase in chemotoxicity and a decrease in therapy response (1). Physical activity prevents muscle wasting; a small pilot study showed that smartphones are a good tool to implement personalized physical activity programs and to increase physical activity of patients (9, 10). Sarcopenia is assessed by using Dual-energy X-ray absorptiometry scan (DEXA), bioelectrical impedance analysis (BIA) or computed tomography (2). Especially computed tomography is used routinely for investigations 4603 This article is freely accessible online.

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Does Sarcopenia Affect Outcome in Patients with Non-Small-Cell Lung Cancer Harboring EGFR Mutations?

Abstract: Early recognition of sarcopenia is beneficial for prevention of cancer cachexia and detection of patients at potential risk of serious adverse events. Gefitinib dosage should be reduced and modulated in sarcopenic patients.

Cited by 31 publications

References 25 publications

Single‐institution study of correlations between skeletal muscle mass, its density, and clinical outcomes in non‐small cell lung cancer patients treated with first‐line chemotherapy

Single‐institution study of correlations between skeletal muscle mass, its density, and clinical outcomes in non‐small cell lung cancer patients treated with first‐line chemotherapy

Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer

Sarcopenia as Prognostic Factor in Lung Cancer Patients: A Systematic Review and Meta-analysis

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