Clinical impact of skeletal muscle area in patients with non-small cell lung cancer treated with anti-PD-1 inhibitors

Takada, Kazuki; Yoneshima, Yasuto; Tanaka, Kentaro; Shimokawa, Mototsugu; Wakasu, Sho; Takamori, Shinkichi; Toyokawa, Gouji; Oba, Taro; Osoegawa, Atsushi; Tagawa, Tetsuzo; Oda, Yoshinao; Nakanishi, Yoichi; Mori, Masaki

doi:10.1007/s00432-020-03146-5

Cited by 45 publications

(68 citation statements)

References 51 publications

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“…This detrimental effect of SAR/hNLR has been widely investigated in patients with other solid tumors treated with ICB. Increased levels of interleukin-6 or transforming growth factor-b related to skeletal muscle atrophy contributed to poor treatment response in malignant melanoma, non-small cell lung cancer, and urothelial cancer treated with ICB (24,27,28). In our analysis, RT was significantly associated with improved outcomes in patients with SAR/hNLR or MSS/EBV-negative tumors.…”

Section: Discussionmentioning

confidence: 65%

Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody

Kim

Lim

et al. 2021

Front. Immunol.

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BackgroundWe explored the combined effects of sarcopenia (SAR) and radiotherapy (RT) on outcomes in patients with advanced gastric cancer (AGC) treated with immune-checkpoint blockade (ICB).MethodsAmong 185 patients with AGC treated with ICB, we defined SAR as skeletal muscle index <49 cm2/m2 for men and <31 cm2/m2 for women; 93 patients met criteria. We defined high neutrophil-to-lymphocyte ratio (hNLR) as NLR≥3. Palliative RT was performed in 37 patients (20%) before ICB.ResultsWe frequently observed hNLR in patients with SAR (53% vs. 35%, p = 0.02). The median overall survival (OS) for the entire cohort was 5 months. Stratification by risk factors of SAR or hNLR revealed a significant difference in median OS (0 [N = 60] vs. 1 [N = 76] vs. 2 [N = 49]: 7.6 vs. 6.4 vs. 2.2 months, p < 0.001). Patients with microsatellite instability-high (MSI-H, N = 19) or Epstein-Barr virus (EBV)-positive tumors (N = 13) showed favorable outcomes compared to those with microsatellite stable (MSS, N = 142) tumors (median OS, not reached vs. 16.8 vs. 3.8 months, respectively). The benefit of RT was evident in patients with both SAR and hNLR (median OS, 3.1 vs. 1.3 months, p = 0.02) and MSS/EBV-negative tumor (median OS, 6.5 vs. 3.5 months, p = 0.03), but outcomes after RT in MSI-H tumor were not significantly different. In multivariable analysis, SAR/hNLR, molecular subtypes, and a history of RT were associated with OS (all p < 0.05).ConclusionsWe demonstrated the negative predictive value of SAR/hNLR on outcomes after ICB for AGC, and the history of RT could overcome the negative impact of SAR/hNLR and the MSS/EBV-negative subtype.

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Section: Discussionmentioning

confidence: 65%

Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody

Kim

Lim

et al. 2021

Front. Immunol.

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“…In our study, weight loss failed to be included in the nomograms by LASSO Cox regression analysis, whereas skeletal muscle change was identified as a prognostic factor in the final model. Low SMI at baseline or dynamic skeletal muscle alteration during treatment, as a determinant of survival, has got attention in previous studies (29)(30)(31). Low SMI presenting at baseline failed to be a prognostic factor in our patients, whereas skeletal muscle change before the initiation of the treatment significantly impaired prognosis independent of other wellestablished clinical prognostic indicators.…”

Section: Discussionmentioning

confidence: 53%

Novel Nutrition-Based Nomograms to Assess the Outcomes of Lung Cancer Patients Treated With Anlotinib or Apatinib

et al. 2021

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BackgroundPrevious studies have indicated that the changes in body composition during treatment are prognostic in lung cancer. The question which follows is it may be too late to identify vulnerable patients after treatment and to improve outcomes for these patients. In our study, we sought to explore the alterations of body composition and weight before the outset of the antiangiogenic treatment and its role in predicting clinical response and outcomes.MethodsIn this retrospective study, 122 patients with advanced lung cancer treated with anlotinib or apatinib were analyzed. The changes in weight and body composition including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) for 3 months before the outset of antiangiogenic treatment and other clinical characteristics were evaluated with LASSO Cox regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomograms was validated internally by using bootstrap method with 1,000 resamples models and was assessed by the concordance index (C-index), calibration plots, decision curve analysis (DCA).ResultsThe median progression-free survival (PFS) and overall survival (OS) were 128 (95% CI 103.2–152.8) days and 292 (95% CI 270.9–313.1) days. Eastern Cooperative Oncology Group performance status (ECOG PS), brain metastases, the Glasgow Prognostic Score (GPS), clinical response, therapeutic regimen, and ΔL1SMI per 90 days were significantly associated with PFS, while ECOG PS, GPS, clinical response, therapeutic regimen, ΔL1SMI per 90 days were identified for OS. The C-index for the nomograms of PFS and OS were 0.763 and 0.748, respectively. The calibration curves indicated excellent agreement between the predicted and actual survival outcomes of 3- and 4-month PFS and 7- and 8-month OS. DCA showed the considerable value of the model.ConclusionNomograms were developed from clinical features and nutritional indicators to predict the probability of achieving 3-month and 4-month PFS and 7-month and 8-month OS with antiangiogenic therapy for advanced lung cancer. Dynamic changes in body composition before the initiation of treatment contributed to early detection of poor outcome.

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“…The first was considering the effect of adipose tissue and obesity on survival in patients treated with ICI; while the other approach used skeletal muscle indices as a surrogate for sarcopenia. The feasibility of using such indicators to understand the interconnection was convenient given the simple methodology used to obtain these variables and soon led to several observational and comparative retrospective studies that are summarized in Table 3 (31,39,52,(105)(106)(107)(108)(109)(110)(111)(112)(113). The findings from retrospective studies seem to be consistent with a trend towards improved PFS and OS in patients with NSCLC treated with PD-1/PD-L1 inhibitors and have been verified with meta-analyses (79,114).…”

Section: Immune Checkpoint Inhibitors Body Composition and Outcomes In Non-small Cell Lung Cancermentioning

confidence: 84%

Obesity, Sarcopenia, and Outcomes in Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors

et al. 2020

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Body composition refers to the proportional content of body fat mass and lean body mass that can lead to a continuum of different phenotypes ranging from cachectic/sarcopenic state to obesity. The heterogenetic phenotypes of body composition can contribute to formation of some cancer types and can sometimes lead to disparate outcomes. Both of these extremes of the spectrum exist in patients with non-small cell lung carcinoma (NSCLC). The discovery of new pathways that drive tumorigenesis contributing to cancer progression and resistance have expanded our understanding of cancer biology leading to development of new targeted therapies including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) that have changed the landscape of NSCLC treatment. However, in the new era of precision medicine, the impact of body composition phenotypes on treatment outcomes and survival is now being elucidated. In this review, we will discuss the emerging evidence of a link between body composition and outcomes in patients with NSCLC treated with TKI and ICI. We will also discuss suggested mechanisms by which body composition can impact tumor behavior and anti-tumor immunological response.

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Clinical impact of skeletal muscle area in patients with non-small cell lung cancer treated with anti-PD-1 inhibitors

Cited by 45 publications

References 51 publications

Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody

Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody

Novel Nutrition-Based Nomograms to Assess the Outcomes of Lung Cancer Patients Treated With Anlotinib or Apatinib

Obesity, Sarcopenia, and Outcomes in Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors

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