bims-meluca 2021-05-09 papers

Asian Cardiovasc Thorac Ann. 2021 May 06. 2184923211014002

Preoperative nutritional status is associated with the prognosis for lung cancer.

Ayaka Asakawa, Hironori Ishibashi, Yusuke Matsuyama, Takeo Fujiwara, Masashi Kobayashi, Kenichi Okubo.

BACKGROUND: We investigated whether preoperative nutritional indicators predicted the prognosis for patients with early-stage non-small cell lung cancer.
METHODS: Data for stage I or stage IIA non-small cell lung cancer without lymph node metastasis patients who received anatomical lung resection and were followed-up at least five years after surgery (n = 286) were analyzed. We calculated geriatric nutritional risk index, prognostic nutritional index, controlling nutritional status score, and modified Glasgow prognostic score. Multivariate Cox proportional hazard model adjusting for age, BMI, complication, pathological stage, histology of squamous cell carcinoma, T factor, diffusing capacity for carbon monoxide, surgery and smoking status was fitted to evaluate the association between these nutritional indicators and mortality and recurrence within five years.
RESULTS: After adjusted for covariates other than type of surgery and diffusing capacity for carbon monoxide, controlling nutritional status of ≥3 was significantly associated with mortality (hazard ratio (HR) = 2.68, 95% confidence interval (CI) = 1.02, 7.01). The association remained marginally significant by adjusting for type of surgery and diffusing capacity for carbon monoxide (HR = 2.44, 95% CI = 0.92, 6.45). controlling nutritional status of ≥3 was significantly associated with recurrence (HR = 2.60; 95% CI: 1.20, 5.61) after adjusting for all covariates. Other nutritional indices did not predict the prognosis in multivariate analysis.
CONCLUSION: Preoperative high controlling nutritional status score was marginally and significantly associated with mortality and recurrence of non-small cell lung cancer patients after lung resection.

Keywords: Geriatric nutritional risk index (GNRI); controlling nutritional status (CONUT) score; lung cancer; modified Glasgow prognostic score (mGPS); prognostic nutritional index (PNI)

DOI: https://doi.org/10.1177/02184923211014002

J Cachexia Sarcopenia Muscle. 2021 May 05.

The prognostic value of weight and body composition changes in patients with non-small-cell lung cancer treated with nivolumab.

Juliette H R J Degens, Anne-Marie C Dingemans, Anna C H Willemsen, Hester A Gietema, Daan P Hurkmans, Joachim G Aerts, Lizza E L Hendriks, Annemie M W J Schols.

BACKGROUND: It is not well known to what extent effectiveness of treatment with immune checkpoint inhibitors in stage IV non-small-cell lung cancer (NSCLC) is influenced by weight loss and changes in body composition. Therefore, the goal of this study was to evaluate body composition changes in relation to early weight change and overall survival (OS) in stage IV NSCLC patients treated with second-line nivolumab.
METHODS: All patients with stage IV NSCLC, who were treated with second-line nivolumab between June 2015 and December 2018 at Maastricht University Medical Center, were evaluated. Skeletal muscle mass (SMM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at the first lumbar level on computed tomography images obtained before initiation of nivolumab and at week 6 of treatment. The contribution of changes in body weight (defined as >2% loss), SMM, VAT, and SAT to OS was analysed by Kaplan-Meier method and adjusted for clinical confounders in a Cox regression analysis. The results from the study cohort were validated in another Dutch cohort from Erasmus Medical Center, Rotterdam.
RESULTS: One hundred and six patients were included in the study cohort. Loss of body weight of >2% at week 6 was an independent predictor for poor OS (hazard ratio 2.39, 95% confidence interval 1.51-3.79, P < 0.001) when adjusted for gender, >1 organ with metastasis, pretreatment hypoalbumenaemia, and pretreatment elevated C-reactive protein. The result was confirmed in the validation cohort (N = 62). Loss of SMM as a feature of cancer cachexia did not significantly predict OS in both cohorts. Significant (>2%) weight loss during treatment was reflected by a significant loss of VAT and SAT, while loss of SMM was comparable between weight-stable and weight-losing patients.
CONCLUSIONS: Weight loss, characterized by loss of subcutaneous and visceral adipose tissues, at week 6 of treatment with nivolumab, is a significant poor prognostic factor for survival in patients with Stage IV NSCLC.

Keywords: Body composition changes; Immune checkpoint inhibitors; Metastatic; Non-small-cell lung cancer; Overall survival; Weight changes

DOI: https://doi.org/10.1002/jcsm.12698

J Cell Mol Med. 2021 May 04.

HIF-1α is necessary for activation and tumour-promotion effect of cancer-associated fibroblasts in lung cancer.

Yana Zhang, Yangyang Bian, Yuan Wang, Yuanyuan Wang, Xixi Duan, Yuning Han, Lijing Zhang, Fei Wang, Zhuoyu Gu, Zhihai Qin.

Cancer-associated fibroblasts (CAFs) activation is crucial for the establishment of a tumour promoting microenvironment, but our understanding of CAFs activation is still limited. In this study, we found that hypoxia-inducible factor-1α (HIF-1α) was highly expressed in CAFs of human lung cancer tissues and mouse spontaneous lung tumour. Accordingly, enhancing the expression of HIF-1α in fibroblasts via hypoxia induced the conversion of normal fibroblasts into CAFs. HIF-1α-specific inhibitor or HIF-1α knockout (KO) significantly attenuated CAFs activation, which was manifested by the decreased expression of COL1A2 and α-SMA. In vivo, during tumour formation, the expression of Ki-67 and proliferating cell nuclear antigen (PCNA) in the tumour tissue with HIF-1α KO fibroblasts was significantly lower than that of normal fibroblasts. Moreover, HIF-1α in fibroblasts could activate the NF-κB signalling pathway and enhance a subsequent secretion of CCL5, thus promoting the tumour growth. In conclusion, our results suggest that HIF-1α is essential for the activation and tumour-promotion function of CAFs in lung cancer (LC). And targeting HIF-1α expression on CAFs may be a promising strategy for LC therapy.

Keywords: CAFs; CCL5; HIF-1α; fibroblasts; lung cancer

DOI: https://doi.org/10.1111/jcmm.16556