Unfavorable impact of decreased muscle quality on the efficacy of immunotherapy for advanced non‐small cell lung cancer

Nishioka, Naoya; Naito, Tateaki; Notsu, Akifumi; Mori, Keita; Kodama, Hitoshi; Miyawaki, Eriko; Miyawaki, Taichi; Mamesaya, Nobuaki; Kobayashi, Hiroyoshi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Murakami, Haruyasu; Takayama, K.; Takahashi, Toshiaki

doi:10.1002/cam4.3631

Cited by 25 publications

(34 citation statements)

References 42 publications

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“…We excluded duplicate entries and articles written in languages other than English and Japanese and then screened for titles and abstracts. The full texts of the 49 studies selected were then inspected according to the inclusion and exclusion criteria; finally, 26 studies 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 comprising 2501 patients were included in the systematic review. Two studies by Cortellini et al .…”

Section: Resultsmentioning

confidence: 99%

“…The result was similar when any individual study was removed from the analysis. PMI, SMD, and SMI were employed for dichotomization in five, 14,20,21,24,28 four, 15,16,29,31 and seven studies, 16,18,22,23,27,29,31 respectively. The ORs for each procedure showed a tendency for worse response in sarcopenia patients.…”

Section: Objective Response and Sarcopeniamentioning

confidence: 99%

“… 7 In addition, an increasing number of studies are focusing on the impact of sarcopenia on ICI treatment efficacy. 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 However, most previous studies on the topic had a retrospective design and included a small number of patients in whom various methods were employed for the diagnosis of sarcopenia. Therefore, the predictive value of sarcopenia in ICI therapy requires elucidation.…”

Section: Introductionmentioning

confidence: 99%

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Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis

Takenaka

Oya

Takemoto

et al. 2021

J cachexia sarcopenia muscle

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Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice.

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Section: Resultsmentioning

confidence: 99%

Section: Objective Response and Sarcopeniamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis

Takenaka

Oya

Takemoto

et al. 2021

J cachexia sarcopenia muscle

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“…The onset of anorexia/cachexia syndrome may also inhibit immunomodulators activity thus rendering the treatment less useful [71,72]. In a retrospective study of 156 nonsmall-cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors, those with high muscle quality showed higher response rate (35.0 vs. 15.8 %, p < 0.05) and longer PFS (median, 4.5 vs. 2.0 months, p < 0.05) than those with low muscle quality [73]. Another retrospective analysis of over 600 patients with advanced cancer who received immune checkpoint blockade, those with decreased pretreatment BMI and lower PNI had worse response rates (p = 0.0005), disease control rate (p < 0.0001) as well as shorter PFS (p = 0.02 and p = 0.02) and OS (p < 0.001) [69].…”

Section: Nutritional Care During Immunotherapy: Does the Boundless Prairie Have A Fence?mentioning

confidence: 99%

The Clinical Value of Nutritional Care before and during Active Cancer Treatment

Aprile¹,

Basile²,

Giaretta³

et al. 2021

Nutrients

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Malnutrition and muscle wasting are frequently reported in cancer patients, either linked to the tumor itself or caused by oncologic therapies. Understanding the value of nutritional care during cancer treatment remains crucial. In fact, cancer-associated sarcopenia plays a key role in determining higher rates of morbidity, mortality, treatment-induced toxicities, prolonged hospitalizations and reduced adherence to anticancer treatment, worsening quality of life and survival. Planning baseline screening to intercept nutritional troubles earlier, organizing timely reassessments, and providing adequate counselling and dietary support, healthcare professional may positively interfere with this process and improve patients’ overall outcomes during the whole disease course. Several screening tools have been proposed for this purpose. Nutritional Risk Screening (NRS), Mini Nutritional Assessment (MNA), Patient Generated Subjective Global Assessment (PG-SGA) are the most common studied. Interestingly, second-level tools including skeletal muscle index (SMI) and bioelectric impedance analysis (BIA) provide a more precise assessment of body composition, even if they are more complex. However, nutritional assessment is not currently used in clinical practice and procedures must be standardized in order to improve the efficacy of standard chemotherapy, targeted agents or even checkpoint inhibitors that is potentially linked with the patients’ nutritional status. In the present review, we will discuss about malnutrition and the importance of an early nutritional assessment during chemotherapy and treatment with novel checkpoint inhibitors, in order to prevent treatment-induced toxicities and to improve survival outcomes.

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“…Sarcopenia was defined by measuring skeletal muscle mass using CT images. The main characteristics of the included studies are summarized in Table 1 (17,18,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Prognostic Impact of Sarcopenia on Clinical Outcomes in Malignancies Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Wang

Tong

et al. 2021

Front. Oncol.

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BackgroundThe effect of sarcopenia on the clinical outcomes of patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is unclear. The aim of this study was to evaluate the effect and survival of patients with malignancies and sarcopenia receiving ICIs.MethodsWe systematically searched related studies in PubMed, Embase, and Cochrane Library up to March 2021 according to the inclusion and exclusion criteria. Information pertaining to the hazard ratio (HR) corresponding to 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) as determined by univariate and multivariate analyses; the odds ratio (OR) corresponding to the 95% CI of the disease control rate (DCR) and objective response rate (ORR); and immune-related adverse events (irAEs) was collected and analyzed using the RevMan 5.4 software. Study heterogeneity and sensitivity were also assessed.ResultsA total of 19 studies were finalized that included 1763patients with lung, gastrointestinal, and head and neck cancers as well as those with melanoma, renal cell carcinoma, urothelial carcinoma, pancreatic cancer, and soft tissue sarcoma. According to univariate and multivariate analyses, patients with sarcopenia at pre-immunotherapy had poorer PFS and OS than those without. HRs and the corresponding 95% CI of PFS were 1.91(1.55–2.34, p <0.00001) and 1.46 (1.20–1.78, p =0.0001), respectively, and HRs and the corresponding 95% CI of OS were 1.78 (1.47–2.14, p <0.00001) and 1.73 (1.36–2.19, p <0.0001), respectively. Patients with sarcopenia showed poor PFS and OS during treatment. In addition, patients with sarcopenia had worse ORR (OR 0.46, 95% CI 0.28–0.74, p = 0.001) and DCR (OR 0.44, 95% CI 0.31–0.64, p<0.0001); however, the incidence of irAEs of any grade and high-grade in patients with sarcopenia did not increase, OR and the corresponding 95% CI were 0.58(0.30–1.12, p = 0.10) and 0.46(0.19–1.09, p = 0.08). Further, we performed subgroup analysis, skeletal muscle mass index (SMI) and psoas muscle mass index (PMI) stratification. In the SMI group, patients with sarcopenia had poor ORR, DCR, PFS, and OS than those without. In the PMI group, sarcopenia had poor ORR,DCR, and was a poor prognostic factor for PFS and OS according to univariate analysis but had no effect on PFS and OS according to multivariate analysis.ConclusionsPatients with malignancies and sarcopenia at pre-immunotherapy or follow-up visits had poorer clinical outcomes than those without, and sarcopenia was a poor predictive factor of ICI immunotherapy outcomes.

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Unfavorable impact of decreased muscle quality on the efficacy of immunotherapy for advanced non‐small cell lung cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 25 publications

References 42 publications

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis

The Clinical Value of Nutritional Care before and during Active Cancer Treatment

Prognostic Impact of Sarcopenia on Clinical Outcomes in Malignancies Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

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