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

Cortellini, Alessio; Palumbo, Pierpaolo; Porzio, Giampiero; Verna, Lucilla; Giordano, Aldo Victor; Masciocchi, Carlo; Parisi, Alessandro; Cannita, Katia; Ficorella, Corrado; Bozzetti, Federico

doi:10.1111/1759-7714.12870

Cited by 40 publications

(53 citation statements)

References 44 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given to the emerging association between BMI, patients sex and clinical outcomes of cancer patients receiving immunotherapy 13,14 , we did not used the already available sex-specific, BMI-incorporated, cut offs values for SMI and muscle attenuation 15 , which were established before the advent of immune checkpoint inhibitors. On the other hand, several correlations between sex 16 , BMI 3,17 and skeletal muscle are already known. Moreover, SMI and BMI are inevitably related, because they are both computed with the squared height as denominator.…”

Section: Methodsmentioning

confidence: 99%

“…Low www.nature.com/scientificreports www.nature.com/scientificreports/ The SMD can be used to provide a qualitative, rather than quantitative (as the SMI), estimation of skeletal muscle composition; it asses distribution of adipose tissue (myosteatosis), muscle atrophy/wasting caused by or associated with inactivity, denervation, and chronic diseases 24 . The role of SMD as a predictive and prognostic parameter still remains uncertain in cancer patients, compared to other chronic disorders, but surely retain its importance in identifying more frail patients, with body composition alterations 1,3 .…”

Section: Overallmentioning

confidence: 99%

“…In cancer patients, the skeletal muscle index (SMI) is widely used as surrogate of the body muscle mass (and sarcopenia), and is often evaluated through cross-sectional image analysis from CT (computed tomography) scans 1 . The SMI, together with the skeletal muscle radiodensity (SMD), which is used to quantify muscle degradation and myosteatosis, have already revealed to be prognostic and predictive parameters in cancer patients 1,3 .…”

mentioning

confidence: 99%

See 2 more Smart Citations

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Cortellini

Bozzetti

Palumbo

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/−25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 [95% CI: 1.05-2.61]; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 [95% CI: 1.31-3.64]; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 [1.31-3.67]; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.Sarcopenia is the condition of loss of muscle mass, with decreased muscle power, and it is one of the hallmarks of cancer, which negatively affects the most of clinical outcomes such as toxicities and survival 1 . The interactions must recognize also the lack of other adiposity metrics, such as the waist circumference, the waist-to-height ratio, and the body fat percentage. Moreover, the CT imaging analysis was limited by the data availability; indeed, the acquisition protocol was planned according to the presence of previous examination. conclusionOur finding of a significant shorter OS for low-SMI patients treated with PD-1/PD-L1 checkpoint inhibitors, suggests that sarcopenia might have a prognostic role, rather than predictive. However, to properly weighing our results, we must consider the significant association between poorer PS and low-SMI. Without making conclusive considerations, we can assume that after the advent of ICIs, we should give back further relevance to baseline nut...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Overallmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Cortellini

Bozzetti

Palumbo

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…For advanced NSCLC, in addition to conventional cytotoxic chemotherapy, new molecular targeted drugs and cancer immunotherapy have revolutionized treatment. Sarcopenia is still controversial as a prognostic factor of cytotoxic chemotherapy for patients with advanced NSCLC [6][7][8][9]. Skeletal muscle index (SMI), but not skeletal muscle radiodensity (SMD), was a significant prognostic factor in an Italian study [9].…”

Section: Introductionmentioning

confidence: 97%

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

View full text Add to dashboard Cite

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.

show abstract

“…Herein, we present a preliminary analysis performed on NSCLC patients in the above‐mentioned cohort with available CT scans at the start of second‐line treatment with single agent nivolumab.…”

Section: Introductionmentioning

confidence: 99%

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

et al. 2019

Self Cite

View full text Add to dashboard Cite

Sarcopenia represents one of the hallmarks of all chronic disease, including non‐small cell lung cancer (NSCLC). A computed tomography scan is an easy modality to estimate the skeletal muscle mass through cross‐sectional image analysis at the level of the third lumbar vertebra (L3). Baseline skeletal muscle mass (SMM) was evaluated using gender‐specific cutoffs for skeletal muscle index in NSCLC patients administered immunotherapy with nivolumab to evaluate its possible correlations with clinical outcomes. From April 2015 to August 2018, 23 stage IV NSCLC patients were eligible for image analysis. Nine patients (39.1%) had low SMM. Among patients with baseline low and non‐low SMM, median progression free survival was 3.1 and 3.8 months, respectively (P = 0.0560), while median overall survival was 4.1 and 13 months, respectively (P = 0.2866). This hypothesis‐generating preliminary report offers the opportunity to speculate about the negative influence of sarcopenia on immune response. In our opinion, nutritional status could affect the clinical outcomes of immunotherapy, even if we cannot make definitive conclusions here. Further studies on the topic are required.

show abstract

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

Cited by 40 publications

References 44 publications

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

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

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

Contact Info

Product

Resources

About