scholarly journals Is there a role for physical activity when treating patients with cancer with immune checkpoint inhibitors? Protocol for a scoping review

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e046052
Author(s):  
Miaoqi Chen ◽  
Ridesh Raj ◽  
Louis Fox ◽  
Charlotte Louise Moss ◽  
Gincy George ◽  
...  
Keyword(s):  
Physical Activity ◽  
Scoping Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Physical Activities ◽  
Biological Mechanisms ◽  
Patients With Cancer ◽  
Oncological Outcomes ◽  
The Impact

IntroductionFor patients with cancer, immune checkpoint inhibitors (ICIs) produce superior long-term responses compared with alternative treatments, although at the cost of manifesting adverse immune-related events. There are many hypotheses of the impacts of physical activities in immunotherapy, but little is known about the oncological outcomes and the underlying mechanisms. This scoping review aims to identify possible physical activity interventions, their efficacy and feasibility and the potential underlying biological mechanisms responsible for their effects.Method and analysisThe Levac methodology framework was used along with guidance from the Joanna Briggs Institute Manual for Evidence Synthesis to inform development of this protocol. Abstracts and titles followed by full-text screening will be performed by two independent reviewers for inclusion. All studies describing the impact of physical activities and exercise interventions on cancer ICIs, with particular focus on oncological outcomes, quality of life or underling biological mechanisms, will be included. After extracting qualitative and quantitative data, they will be evaluated and summarised, respectively. Subsequently, a further consultation step with other scientists and healthcare professionals will be performed.Ethics and disseminationThe research findings will be published through an open-access peer-reviewed journal. The results of this scoping review will be used to inform further studies on physical impacts on immunotherapy. All data included will be from open resources, therefore, no ethical clearances are required.

Age affects the efficacy of immune checkpoint inhibitors in patients with advanced cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2638-2638
Author(s):  
Yongjie Wang ◽  
Ronghua Yang ◽  
Dong Wang ◽  
Donghua Zhao ◽  
Peng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Older Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Sign Test ◽  
Patients With Cancer ◽  
The Impact ◽  
Effect Of Age

2638 Background: Immune checkpoint inhibitors (ICIs), such as programmed death(ligand)1 (PD-(L)1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, have dramatic effects on treatment in patients with various malignancies. High tumor mutation burden (TMB) is predictive of clinical response to ICI in multiple cancer types. Although age-related immune dysfunction might induce difference on the efficacy of ICIs between younger and older patients, the potential effect of age on the efficacy of ICIs remains little known and controversial. Herein, we aimed to analysis the association between age and the efficacy of ICIs based on MSKCC cohort. Methods: We screened out 1661 patients having complete information with advanced cancer, whose tumors underwent next-generation sequencing (NGS) detection and who were treated with at least one dose of ICI in MSKCC cohort. All patients were divided into two groups according to age, the younger group (age ≤50-year old) and the older group (age > 50-year old). We further analyzed the differences in overall survival (OS) and TMB between the two groups. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated via Cox regression model for OS and P-values were calculated via the Wilcoxon sign test for TMB. We analyzed the effect of age on ICI in lung cancer using the same way. Results: In 1661 patients with cancer in our study, 312 (19%) younger and 1349 (81%) older patients were found. The pooled HRs for OS was 1.28 (95% CI: 1.09-1.52) in younger group compared with older group. In 1661 patients with cancer, there was 350 (21%) patients with lung cancer, including 30 (9%) younger and 320 (91%) older patients. The pooled HRs for OS was 1.45 (95% CI: 0.95-2.23) in younger group compared with older group in lung cancer. In addition, TMB in older group was higher than in younger group and significant difference of TMB was found via the Wilcoxon sign test (p = 2.6e-10) between the two groups, especially in lung cancer (p = 1e-4). Conclusions: Our study assessed the impact of age on the efficacy of ICIs using the threshold of 50 years old for the first time and we founded that patients in older group had higher TMB and longer OS than younger group.

scholarly journals COVID-19 and immune checkpoint inhibitors: initial considerations

2020 ◽  
Vol 8 (1) ◽  
pp. e000933 ◽  
Author(s):  
Ryan J Sullivan ◽  
Douglas B Johnson ◽  
Brian I Rini ◽  
Tomas G Neilan ◽  
Christine M Lovly ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Anticancer Therapy ◽  
Therapeutic Implications ◽  
Diagnostic Measures ◽  
Patients With Cancer ◽  
Clinical Community ◽  
The Impact ◽  
Inflammation Of The Lungs

AbstractCOVID-19 infections are characterized by inflammation of the lungs and other organs that ranges from mild and asymptomatic to fulminant and fatal. Patients who are immunocompromised and those with cardiopulmonary comorbidities appear to be particularly afflicted by this illness. During pandemic conditions, many aspects of cancer care have been impacted. One important clinical question is how to manage patients who need anticancer therapy, including immune checkpoint inhibitors (ICIs) during these conditions. Herein, we consider diagnostic and therapeutic implications of using ICI during this unprecedented period of COVID-19 infections. In particular, we consider the impact of ICI on COVID-19 severity, decisions surrounding continuing or interrupting therapy, diagnostic measures in patients with symptoms or manifestations potentially consistent with either COVID-19 or ICI toxicity, and resumption of therapy in infected patients. While more robust data are needed to guide clinicians on management of patients with cancer who may be affected by COVID-19, we hope this commentary provides useful insights for the clinical community.

scholarly journals The Effects of Physical Activity on Cancer Patients Undergoing Treatment with Immune Checkpoint Inhibitors: A Scoping Review

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6364
Author(s):  
Amy L. Shaver ◽  
Swapnil Sharma ◽  
Nikita Nikita ◽  
Daniel S. Lefler ◽  
Atrayee Basu-Mallick ◽  
...  
Keyword(s):  
Physical Activity ◽  
Scoping Review ◽  
Immune Checkpoint ◽  
Clinical Studies ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Human Study ◽  
Cancer Therapies ◽  
Cancer Related Fatigue ◽  
Physical Activity Interventions

Background: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy. Method: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results. Results: In literature published from January 2010 through to August 2021, only one human study and three pre-clinical studies met inclusion criteria. Conclusion: Existing evidence supports that physical activity is associated with decreased treatment-related toxicities such as CRF. However, further investigation is warranted. The dearth of clinical studies illustrates the need for more research to address this question, to guide patients and their providers in the application of appropriate physical activity interventions in those patients undergoing ICI.

RNF43 mutations to predict survival from treatment with immune checkpoint inhibitors and are associated with a high tumor mutation burden in bladder cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16528-e16528
Author(s):  
Liping Li ◽  
Mengmei Yang ◽  
Mengli Huang
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Negative Regulator ◽  
Wilcoxon Test ◽  
Wild Type ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
The Impact

e16528 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have been approved as first-line treatment for cisplatin-ineligible patients and as second-line therapy for patients with metastatic urothelial carcinoma of the bladder. Biomarkers can help select patients who are more likely to response to ICIs. RNF43 is an E3 ubiquitin ligase that acts as a negative regulator of Wnt/β-catenin signaling pathway. In colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs), RNF43 mutations predicted longer overall survival (OS). The impact of RNF43 mutations on the efficiency of ICIs in bladder cancer(BLC) remains to be explored. Methods: We downloaded the mutation and clinical data of 211 BLC patients treated with ICIs from the immunotherapeutic cohort published by Samstein et al. (2019). OS analyses were conducted using Kaplan-Meier curves and log-rank tests. Wilcoxon test was used for the comparison of TMB. We also downloaded a TCGA cohort for prognostic analysis. The correlations between RNF43 and immune infiltrates were analyzed in the TIMER2.0 database. Statistical significance was set at p = 0.05. Results: RNF43 mutations were identified in 4.3%(9/211) and 3%(13/438) BLC patients in the immunotherapeutic and TCGA cohort, respectively. In the immunotherapeutic cohort, patients with RNF43 mutations had significantly longer OS (25 months vs 8 months; p = 0.015) and higher tumor mutation burden(TMB, 42.3 vs 7.9; p = 3.15E-06) than RNF43-wild-type patients. Different from this, no significant difference was found in OS between RNF43-mutant and RNF43-wild-type BLC patients with standard treatment in the TCGA cohort (p = 0.696). These results indicated that RNF43 was not a prognostic factor but a predictive biomarker of survival in BLC treated with ICIs. No difference was observed in subsets of immune cells between RNF43-mutant and the RNF43-wide-type BLC patients, including neutrophils, macrophages, CD8+ T cells, Tregs, B cells and NK cells. Conclusions: RNF43 mutations may be a predictor of survival benefit from ICIs in bladder cancer and correlated with higher TMB. Further studies in other ICI-treated cohorts are needed to confirm these results.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

2021 ◽  
pp. 1-11
Author(s):  
Deniz Can Guven ◽  
Oktay Halit Aktepe ◽  
Melek Seren Aksun ◽  
Taha Koray Sahin ◽  
Gozde Kavgaci ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patients With Cancer ◽  
Early Progression ◽  
Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

scholarly journals Pan-Cancer Analysis Identifies Liver Metastases as Negative Predictive Factor for Immune Checkpoint Inhibitors Treatment Outcome

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Juan Chen ◽  
Aiqun Ren ◽  
Liang Zheng ◽  
En-Dian Zheng ◽  
Tao Jiang
Keyword(s):  
Combination Therapy ◽  
Liver Metastases ◽  
Predictive Factor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Intrinsic Resistance ◽  
The Impact ◽  
Pan Cancer ◽  
Negative Predictive Factor

This study aimed to investigate the predictive value of liver metastases (LM) in patients with various advanced cancers received immune-checkpoint inhibitors (ICIs). First, clinical and survival data from a published cohort of 1,661 patients who received ICIs therapy were downloaded and analyzed. Second, a retrospective review of 182 patients with advanced non-small-cell lung cancer (NSCLC) who received PD-1/PD-L1 monotherapy was identified. Third, a meta-analysis of published trials was performed to explore the impact of LM on the efficacy of anti-PD-1/PD-L1 based therapy in advanced lung cancers. Pan-cancer analysis revealed that patients with LM had significantly shorter overall survival (OS) than those without LM (10 vs. 20 months; P &lt; 0.0001). Subgroup analysis showed that the presence of LM was associated with markedly shorter OS than those without LM in ICI monotherapy group (P &lt; 0.0001), but it did not reach the statistical significance in ICI-based combination therapy (P = 0.0815). In NSCLC, the presence of LM was associated with significantly inferior treatment outcomes in both pan-cancer and real-world cohort. Interestingly, ICI-based monotherapy and combination therapy could simultaneously prolong progression-free survival (PFS) and OS than chemotherapy in patients without LM. However, ICI-based monotherapy could not prolong PFS than chemotherapy in patients with LM while ICI-based combination therapy could dramatically prolong both PFS and OS. Together, these findings suggested that the presence of LM was the negative predictive factor in cancer patients received ICIs monotherapy, especially in NSCLC. ICI-based combination therapy might overcome the intrinsic resistance of LM to ICIs while the optimal combinatorial strategies remain under further investigation.

Metabolic disease and adverse events from immune checkpoint inhibitors

2021 ◽  
Author(s):  
Amanda Leiter ◽  
Emily Carroll ◽  
Sonia De Alwis ◽  
Danielle Brooks ◽  
Jennifer Ben Shimol ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Metabolic Diseases ◽  
Checkpoint Inhibitors ◽  
Normal Weight ◽  
Metabolic Risk ◽  
The Impact ◽  
Metabolic Comorbidities

Objective: Obese and overweight body mass index (BMI) categories have been associated with increased immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors (ICIs); however, the impact of being overweight in conjunction with related metabolic syndrome-associated factors on irAEs have not been investigated. We aimed to evaluate the impact of overweight and obese BMI according to metabolic disease burden on the development of irAEs. Design and Methods: We conducted a retrospective observational study of patients receiving ICIs at a cancer center. Our main study outcome was development of grade 2 (moderate) irAEs. Our main predictor was weight/metabolic disease risk category: (1) normal weight (BMI 18.5-24.9 kg/m2)/low metabolic risk (<2 metabolic diseases [diabetes, dyslipidemia, hypertension] ), (2) normal weight/high metabolic risk (2 metabolic diseases), (3) overweight (BMI 25 kg/m2)/low metabolic risk, and (4) overweight/high metabolic risk. Results: Of 411 patients in our cohort, 374 were eligible for analysis. Overall, 111 (30%) patients developed grade 2 irAEs. In Cox analysis, overweight/low metabolic risk was significantly associated with grade 2 irAEs (hazard ratio [HR]: 2.0, 95% confidence interval [95% CI]: 1.2-3.4) when compared to normal weight/low metabolic risk, while overweight/high metabolic risk (HR: 1.3, 95% CI: 0.7-2.2) and normal weight/high metabolic risk (HR: 1.5, 95% CI: 0.7-3.0) were not. Conclusions: Overweight patients with fewer metabolic comorbidities were at increased risk for irAEs. This study provides an important insight that BMI should be evaluated in the context of associated metabolic comorbidities in assessing risk of irAE development and ICI immune response.

scholarly journals Prognostic Factors and Biomarkers of Responses to Immune Checkpoint Inhibitors in Lung Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4931 ◽  
Author(s):  
Andrea Bianco ◽  
Fabio Perrotta ◽  
Giusi Barra ◽  
Umberto Malapelle ◽  
Danilo Rocco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
T Cell Subsets ◽  
Durable Response ◽  
Lung Cancer Treatment ◽  
The Impact

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

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