Association of Sarcopenia with and Efficacy of Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer

Nishioka, Naoya; Uchino, Junichi; Hirai, Soichi; Katayama, Yuki; Yoshimura, Akihiro; Okura, Naoko; Tanimura, Keiko; Harita, Sachi; Imabayashi, Tatsuya; Chihara, Yusuke; Tamiya, Nanako; Kaneko, Yoshiko; Takayama, K.

doi:10.3390/jcm8040450

Cited by 82 publications

(102 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, Nishioka and colleagues evaluated the change in muscle mass over time in 38 NSCLC patients receiving PD-1 Inhibitors 11 . Even if not significant, they found a higher change rate (decrease in muscle mass) among patients with poorer PS (p = 0.056) 11 .…”

Section: Overallmentioning

confidence: 82%

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

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: Overallmentioning

confidence: 82%

“…In a preliminary report, we found that sarcopenic non-small cell lung cancer (NSCLC) patients receiving nivolumab had shorter progression free survival (PFS) and overall survival (OS) 9 . Moreover, other two retrospective studies found a significant association between sarcopenia, shorter PFS and worse objective response rate (ORR) 10,11 .…”

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…In addition, a lower BMI is associated with increased mortality risk [21][22][23][24]. Our previous clinical study demonstrated that NSCLC patients with sarcopenia exhibit a significantly shorter median PFS following ICI treatment compared to that of non-sarcopenia patients [25]. Given these observations, a poor ECOG-PS and a low BMI at the time of ICI treatment intervention may be useful for predicting non-responders to initial ICI treatment, as well as ICI rechallenge treatment among patients with NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer

Katayama

Shimamoto

Yamada

et al. 2019

JCM

Self Cite

View full text Add to dashboard Cite

Little is known regarding the effectiveness and tolerability of immune checkpoint inhibitor (ICI) rechallenge after disease progression following initial ICI treatments. To identify eligible patients for ICI rechallenge, we retrospectively analyzed the relationship between clinical profiles and the effect of ICI rechallenge in patients with non-small cell lung cancer (NSCLC). We enrolled 35 NSCLC patients at six different institutions who were retreated with ICIs after discontinued initial ICI treatments due to disease progression. Cox proportional hazards models were used to assess the impact of clinical profiles on overall survival (OS) and progression-free survival (PFS). Median PFS and OS were 81 d (95% confidence interval, CI, 41–112 d) and 225 d (95% CI 106–361 d), respectively. The objective response rate was 2.9%, and the disease control rate was 42.9%. Multivariate analysis demonstrated that Eastern Cooperative Oncology Group Performance Score (ECOG-PS) ≥ 2 (hazard ratio, HR, 2.38; 95% CI 1.03–5.52; p = 0.043) and body mass index (BMI) > 20 (HR 0.43, 95% CI 0.19–0.95, p = 0.036) were significantly associated with PFS of ICI rechallenge. Our observations suggest that poor ECOG-PS and low BMI at intervention with ICI rechallenge may be negative predictors for ICI rechallenge treatment in patients with NSCLC.

show abstract

“…[13][14][15] Recently, the psoas muscle index (PMI), which indicates the degree of skeletal muscle atrophy, has attracted attention for the purpose of assessing the severity of cancer-induced sarcopenia. 13,16 Thus, various indicators reflecting cancer severity affecting the general condition or sarcopenia have been identified, whereas their significance has continued to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Sarcopenia as a Predictor of Survival Among Patients With Organ Metastatic Cervical Cancer

et al. 2020

View full text Add to dashboard Cite

Background: This study was conducted to investigate the prognostic significance of sarcopenia in patients with organ metastatic cervical cancer. Methods: Accordingly, the data of 40 patients with organ metastatic cervical cancer treated at our institute from December 2004 to December 2017 were retrospectively analyzed. The correlation between clinicopathological characteristics and survival was then evaluated using univariate and multivariate analyses. Psoas muscle index (PMI), calculated from the psoas muscle area at the L3 vertebral-body level using computed tomography images obtained for pretreatment evaluation, was adopted as an index of sarcopenia. Results: The median follow-up period was 14 months (range, 1-91 months). Kaplan-Meier analysis showed a 3-and 5-year overall survival (OS) rate of 46.1% and 35.8% for all patients, respectively. Receiver operating characteristic curve maximizing the area under the curve showed that the optimal PMI for predicting 1-year survival was 3.72 cm 2 /m 2. Patients with a PMI > 3.72 cm 2 /m 2 had significantly better OS than those with a PMI ≤ 3.72 cm 2 /m 2 (P = .046). Multivariate analysis revealed that only PMI was significantly associated with OS in patients with organ metastatic cervical cancer. Furthermore, patients with a PMI > 3.72 cm 2 /m 2 who underwent concurrent chemoradiotherapy (CCRT) had a longer OS than those receiving other therapies (P < .001). Conclusions: High PMI was determined to be a favorable prognostic factor for patients with organ metastatic cervical cancer. Moreover, patients with organ metastatic cervical cancer who have a PMI > 3.72 cm 2 /m 2 may benefit from CCRT as an initial treatment.

show abstract

Association of Sarcopenia with and Efficacy of Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer

Cited by 82 publications

References 36 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

Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer

Sarcopenia as a Predictor of Survival Among Patients With Organ Metastatic Cervical Cancer

Contact Info

Product

Resources

About