scholarly journals Immune-Related Pneumonitis Was Decreased by Addition of Chemotherapy with PD-1/L1 Inhibitors: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials (RCTs)

2022 ◽  
Vol 29 (1) ◽  
pp. 267-282
Author(s):  
Yi-Xiu Long ◽  
Yue Sun ◽  
Rui-Zhi Liu ◽  
Ming-Yi Zhang ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Lower Risk ◽  
Meta Analysis ◽  
Treatment Method ◽  
Immunosuppressive Agent ◽  
Solid Cancer ◽  
Cancer Type ◽  
Cancer Types ◽  
Grade 3 ◽  
Nsclc Patients ◽  
Inhibitor Treatment

Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP’s risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP’s risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.42; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.

scholarly journals The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592098054
Author(s):  
Huilin Xu ◽  
Ximing Xu ◽  
Wei Ge ◽  
Jinju Lei ◽  
Dedong Cao
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Good Survival ◽  
Solid Cancer ◽  
Cancer Type ◽  
Early Effect ◽  
Overall Response

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs. Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly. Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46). Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

scholarly journals Chemotherapy for Late-Stage Cancer Patients: Meta-Analysis of Complete Response Rates

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 232 ◽  
Author(s):  
Martin L. Ashdown ◽  
Andrew P. Robinson ◽  
Steven L. Yatomi-Clarke ◽  
M. Luisa Ashdown ◽  
Andrew Allison ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Late Stage ◽  
Meta Analysis ◽  
Complete Response ◽  
Drug Regimen ◽  
Cancer Type ◽  
Late Stage Cancer ◽  
Pubmed Database ◽  
Wide Range ◽  
Cancer Types

Complete response (CR) rates reported for cytotoxic chemotherapy for late-stage cancer patients are generally low, with few exceptions, regardless of the solid cancer type or drug regimen. We investigated CR rates reported in the literature for clinical trials using chemotherapy alone, across a wide range of tumour types and chemotherapeutic regimens, to determine an overall CR rate for late-stage cancers. A total of 141 reports were located using the PubMed database. A meta-analysis was performed of reported CR from 68 chemotherapy trials (total 2732 patients) using standard agents across late-stage solid cancers—a binomial model with random effects was adopted. Mean CR rates were compared for different cancer types, and for chemotherapeutic agents with different mechanisms of action, using a logistic regression. Our results showed that the CR rates for chemotherapy treatment of late-stage cancer were generally low at 7.4%, regardless of the cancer type or drug regimen used. We found no evidence that CR rates differed between different chemotherapy drug types, but amongst different cancer types small CR differences were evident, although none exceeded a mean CR rate of 11%. This remarkable concordance of CR rates regardless of cancer or therapy type remains currently unexplained, and motivates further investigation.

Assessment of ethnic difference in the incidence of thrombocytopenia induced by trastuzumab emtansine (T-DM1): A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15096-e15096
Author(s):  
Jingyi Zhang ◽  
Yaning Yang ◽  
Ru Chen ◽  
Shanshan Chen ◽  
Jiayu Wang ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Data Extraction ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Single Agent ◽  
Cancer Type ◽  
Trastuzumab Emtansine ◽  
Cancer Disease ◽  
Asian Patients ◽  
Grade 3

e15096 Background: Trastuzumab emtansine (T-DM1) has been proved its value and efficacy in advanced metastatic cancer disease as well as in the adjuvant setting. However, there is an increasing concern in T-DM1-induced thrombocytopenia (TCP), which also showed difference of incidence in races. This meta-analysis, combining available data from all single-agent T-DM1 studies to date, aimed to evaluate the incidence of treatment-related thrombocytopenia of T-DM1 and the differences between Asian and non-Asian patients. Methods: We conducted a systematic search of the relevant published clinical studies of T-DM1 that reported safety profile including thrombocytopenia, from 1980 to March of 2020 using PubMed, Embase, and the Cochrane database. Screening and data extraction were conducted by two independent reviewers. Pooled-effect estimates calculated with fixed-effects or random-effects model were expressed as incidence with 95% CIs. Results: A total of 29 studies involving 6188 patients were included. The incidence of all-grade thrombocytopenia in Asian patients was 0.39 (95%CI 0.11-0.67) and 0.29 (95%CI 0.23-0.35) in non-Asian patients. And the incidence of the grade 3 or higher thrombocytopenia in Asians was 0.20 (95%CI 0.10-0.29), in non-Asians was 0.02 (95%CI 0.01-0.03). Gastrointestinal cancer type and the dose of 2.4 mg/kg Q3W T-DM1 treatment were both associated with the higher incidence of grade 3 or higher thrombocytopenia. Conclusions: Asian patients have the higher risk of thrombocytopenia induced by T-DM1. Clinicians should have an awareness of careful observation in platelet counts when patients receive T-DM1 therapy.

scholarly journals The association of FOXP3 gene polymorphisms with cancer susceptibility: a comprehensive systemic review and meta-analysis

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Yan Chen ◽  
Xiaoxue Qi ◽  
Ce Bian ◽  
Chen Ling ◽  
Tao Yi ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Chinese Population ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Systemic Review ◽  
Cancer Type ◽  
Case Control Studies ◽  
Foxp3 Gene ◽  
Cancer Types ◽  
Risk Of Cancer

Abstract The role of forkhead box P3 (FOXP3) protein in tumorigenesis has long been controversial and existing data on the association between FOXP3 gene polymorphisms and cancer susceptibility were inconsistent. Here, we conducted a meta-analysis to better clarify the relationship. A comprehensive search of studies published from July 2008 to June 2018 was conducted. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were performed using the Revman 5.2 software. A total of 12 articles with 19 case–control studies and 10389 participants were included. Three FOXP3 polymorphisms and six cancer types were evaluated. While no significant results were observed in overall and breast cancer groups for rs3761548 (A/C) polymorphisms, the pooled data showed an elevated risk of cancer in variant AA genotypes and A allele for Chinese population (AA vs. AC+CC: OR = 1.61, 95% CI = 1.09, 2.39; AA vs. CC: OR = 1.74, 95% CI = 1.05, 2.89; A vs. C: OR = 1.34, 95% CI = 1.00, 1.78). Neither the overall group analyses nor the subgroup analyses stratified by cancer type and ethnicity proposed any significant association of rs2280883 (C/T) and rs3761549 (T/C) polymorphisms with cancer susceptibility. This meta-analysis suggested that FOXP3 rs3761548 (A/C) polymorphisms were associated with increased cancer risk in Chinese population while rs2280883 (C/T) and rs3761549 (T/C) polymorphisms were not. More large-sample researches with diverse ethnicities and cancer types are needed to draw a concrete conclusion.

scholarly journals The Significance of SIX1 as a Prognostic Biomarker for Survival Outcome in Various Cancer Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Guang Zhu ◽  
Ying Liu ◽  
Lei Zhao ◽  
Zhenhua Lin ◽  
Yingshi Piao
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Cancer Patients ◽  
Human Cancer ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Cancer Type ◽  
Free Survival ◽  
Cancer Types ◽  
Disease Free

Sine Oculis Homeobox Homolog 1 (SIX1) is reported to promote cancer initiation and progression in many preclinical models and is demonstrated in human cancer tissues. However, the correlation between SIX1 and cancer patients’ prognosis has not yet been systematically evaluated. Therefore, we performed a systematic review and meta-analysis in various human cancer types and extracted some data from TCGA datasets for further verification and perfection. We constructed 27 studies and estimated the association between SIX1 expression in various cancer patients’ overall survival and verified with TCGA datasets. Twenty-seven studies with 4899 patients are include in the analysis of overall, and disease-free survival, most of them were retrospective. The pooled hazard ratios (HRs) for overall and disease-free survival in high SIX1 expression patients were 1.54 (95% CI: 1.32-1.80, P&lt;0.00001) and 1.83 (95% CI: 1.31-2.55, P=0.0004) respectively. On subgroup analysis classified in cancer type, high SIX1 expression was associated with poor overall survival in patients with hepatocellular carcinoma (HR 1.50; 95% CI: 1.17-1.93, P =0.001), breast cancer (HR 1.31; 95% CI: 1.10-1.55, P =0.002) and esophageal squamous cell carcinoma (HR 1.89; 95% CI: 1.42-2.52, P&lt;0.0001). Next, we utilized TCGA online datasets, and the consistent results were verified in various cancer types. SIX1 expression indicated its potential to serve as a cancer biomarker and deliver prognostic information in various cancer patients. More works still need to improve the understandings of SIX1 expression and prognosis in different cancer types.

scholarly journals The Relationship Between Fears of Cancer Recurrence and Patient Gender: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuan Pang ◽  
Gerry Humphris
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Cancer Recurrence ◽  
Fear Of Cancer Recurrence ◽  
Cancer Type ◽  
Publication Type ◽  
Cancer Types ◽  
Meta Regression ◽  
Fear Of Cancer ◽  
The Relationship

Background: A significant concern for patients treated for cancer is fear of cancer recurrence (FCR). Although a common experience, some patients report high levels of FCR that are difficult to manage and result in over vigilant checking and high use of health services. There has been speculation about the relationship of FCR with gender with mixed reports from several systematic reviews.Aims: To determine the association of FCR with gender in previous reported studies and investigate the strength of this relationship with various moderators including year of publication, type of cancer and measurement attributes of self-reported FCR instruments.Methods: A systematic review was conducted with searches of the literature from the MEDLINE, PubMed, Embase, and PsycINFO databases following PRISMA guidelines. All the included papers were divided into two groups, namely: “pure” that comprise only of patients with cancer types that both men and women can contract and “mixed” that report on patients with a variety of cancer types. The association between gender and FCR level was assessed by meta-analysis. A meta-regression was performed to investigate the moderating effects of factors including: the year of publication, cancer type, mean age of the sample and the length of the FCR scale measurement. This review was registered with PROSPERO, ID: CRD42020184812.Results: Finally, 29 studies were included. The N size of pooled participants was 33,339. The meta-analysis showed females to have an overall higher level of FCR than males (ES = 0.30; 95% CI, 0.23, 0.36). The meta-regression of moderating or control variables found little, if any, systematic variation in effect-sizes.Conclusion: This systematic review has clarified a potentially confused pattern of previous results in understanding the relationship between gender and FCR. Women report higher levels of FCR than men and this feature is one that clinicians and researchers can factor into their practice and future studies. The effect size is moderate, hence there is ample variation in FCR level, independent of gender, that requires further investigation.

Chemoradiation-induced pneumonitis in patients with unresectable stage III non-small cell lung cancer: A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20532-e20532
Author(s):  
Christine Pierce ◽  
Yuting Kuang ◽  
Hsiu-Ching Chang ◽  
Arianna Nevo ◽  
Anne Deitz ◽  
...  
Keyword(s):  
Observational Studies ◽  
Meta Analysis ◽  
Stage Iii ◽  
Baseline Risk ◽  
Small Cell Lung ◽  
Unresectable Stage ◽  
Immune Mediated ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Nsclc Patients

e20532 Background: Recent clinical trials have shown positive results for therapies combining concurrent chemoradiation therapy (cCRT) and checkpoint immunotherapy in unresectable non-small cell lung cancer (NSCLC). cCRT is associated with an increased risk of pneumonitis, a severe and life-threatening inflammation of the lungs. To further inform clinical decision-making and support the evaluation of new therapies combining immunotherapies with cCRT, it is important to understand the baseline risk of pneumonitis associated with cCRT alone. The objective of this study was to quantify the incidence of cCRT-induced grade 3−5 pneumonitis (immune-mediated and radiation pneumonitis) in unresectable stage III NSCLC patients. Methods: A systematic literature review and meta-analysis were performed in accordance with PRISMA guidelines. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to April 24, 2020. Chemotherapies of interest were cisplatin, pemetrexed, etoposide, carboplatin, and paclitaxel. Randomized controlled trials (RCTs), observational studies, and non-randomized trials were included. Bayesian meta-analysis using a binomial model random effects model was conducted with SAS 9.4. Results: Among 1,889 records identified from the search, 17 studies (6 RCTs, 8 observational studies, 3 single-arm trials) met inclusion criteria. Eleven studies were included in the meta-analysis (5 RCTs, 6 observational studies; 1,788 patients). All studies specified radiation-related pneumonitis (RP), although this is clinically indistinguishable from immune-mediated pneumonitis. Patient populations were comparable across studies; the most common chemotherapies were paclitaxel + carboplatin (n = 6) and pemetrexed + cisplatin (n = 5), and radiation doses ranged from 60–74 Gy. There was variation across studies in intervention, outcome reporting, and follow-up (median range: 12–73 months), but this variation was considered acceptable based on sensitivity analyses. The estimated pooled incidence of grade 3−5 RP in cCRT-treated unresectable stage III NSCLC patients was 3.62% [95% confidence interval (CI): 1.65−6.21] in RCTs and 5.98% [95% CI: 2.26−12.91] in observational studies. The pooled incidence of fatal (grade 5) RP was 0.37% [95% CI: 0−2.78] in RCTs and 1.73% [95% CI: 0.53−4.33] in observational studies. Conclusions: This study estimates that 3.62–5.98% of patients with unresectable stage III NSCLC develop grade 3−5 RP when treated with cCRT, with incidence varying by study design. Estimates of RP incidence were higher in the real-world setting compared to RCTs. These results can be used to contextualize the baseline risk of cCRT-induced pneumonitis in unresectable stage III NSCLC to better understand the adverse event of pneumonitis associated with novel immunotherapy treatments indicated for concomitant use with this modality.

scholarly journals Investigating Multi-cancer Biomarkers and Their Cross-predictability in the Expression Profiles of Multiple Cancer Types

2009 ◽  
Vol 4 ◽  
pp. BMI.S930 ◽  
Author(s):  
George C. Tseng ◽  
Chunrong Cheng ◽  
Yan Ping Yu ◽  
Joel Nelson ◽  
George Michalopoulos ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Meta Analysis ◽  
Organ Donor ◽  
Cancer Biomarkers ◽  
Data Sets ◽  
Cancer Type ◽  
Whole Genome ◽  
Multiple Cancer ◽  
Cancer Data ◽  
Cancer Types

Microarray technology has been widely applied to the analysis of many malignancies, however, integrative analyses across multiple studies are rarely investigated. In this study we performed a meta-analysis on the expression profiles of four published studies analyzing organ donor, benign tissues adjacent to tumor and tumor tissues from liver, prostate, lung and bladder samples. We identified 99 distinct multi-cancer biomarkers in the comparison of all three tissues in liver and prostate and 44 in the comparison of normal versus tumor in liver, prostate and lung. The bladder samples appeared to have a different list of biomarkers from the other three cancer types. The identified multi-cancer biomarkers achieved high accuracy similar to using whole genome in the within-cancer-type prediction. They also performed superior than the one using whole genome in inter-cancer-type prediction. To test the validity of the multi-cancer biomarkers, 23 independent prostate cancer samples were evaluated and 96% accuracy was achieved in inter-study prediction from the original prostate, liver and lung cancer data sets respectively. The result suggests that the compact lists of multi-cancer biomarkers are important in cancer development and represent the common signatures of malignancies of multiple cancer types. Pathway analysis revealed important tumorogenesis functional categories.

Mutation burden as a biomarker of response to immune checkpoint therapy in nine solid cancers.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 35-35 ◽  
Author(s):  
Shridar Ganesan ◽  
Gyan Bhanot ◽  
Janice M. Mehnert ◽  
Ann W. Silk ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Immune Checkpoint ◽  
Solid Cancer ◽  
Cancer Type ◽  
Her2 Breast Cancer ◽  
Mutation Burden ◽  
Gene Expression Signatures ◽  
Cancer Types

35 Background: A high mutation burden a biomarker of response to immune checkpoint therapy in melanoma, non-small cell lung cancer, and colorectal cancer. It is unknown whether mutation burden is predictive of response in other cancer types, and whether it is identifiable using available clinical assays. Methods: Using data for 10,745 tumors from 33 solid cancer types in TCGA, we looked for a mutation burden threshold (iCAM) in each cancer type associated with gene expression signatures of a blocked immune response of robust CD8+T cell response and up-regulation of immune checkpoint genes. Results: A unique iCAM threshold was identified in nine cancers: melanoma and lung, colon, endometrial, and gastric adenocarcinoma; serous ovarian, bladder urothelial, cervical, and ER+ HER2− breast cancer. iCAM thresholds applied to published clinical data for patients treated with immune checkpoint therapy showed that iCAM+ patients had significantly better response. iCAM+ tumors can be identified from clinical-grade NGS assays with high accuracy . In a prospective melanoma cohort of patients treated with anti- PD-1 patients with iCAM+ tumors had significantly better objective response rates, progression free survival, and overall survival compared patients to iCAM− tumors. Pattern of somatic mutations were different in iCAM+ and iCAM− tumors, suggesting different mechanism of carcinogenesis in iCAM+ versus iCAM− tumors. Higher fractions of leukocytes were NK (Natural Killer) cells and macrophages were M1 polarized, and a lower fraction of T cells were regulatory T cells in iCAM+ tumors compared to iCAM− tumors. Over 75% of the genes significantly up-regulated in iCAM+ tumors in every cancer types were in the immune response pathway, confirming immune response to be the main differentiator in iCAM+ veruss iCAM− tumors. Conclusions: In nine cancer types, a clinically useful mutation burden threshold (iCAM) associated with gene expression signatures of blocked immune response can identify likely responders to immune checkpoint therapy, and iCAM status is identifiable using currently available clinical NGS assays.

External validation of two predictive scores of chemotherapy toxicities among older patients with solid cancer, from ELCAPA prospective cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12050-12050
Author(s):  
Maxime Frelaut ◽  
Philippe Caillet ◽  
Stephane Culine ◽  
Elena Paillaud ◽  
Christophe Tournigand ◽  
...  
Keyword(s):  
High Risk ◽  
Prospective Cohort ◽  
Older Patients ◽  
Risk Groups ◽  
Low Risk ◽  
Solid Cancer ◽  
Cancer Type ◽  
Severe Toxicity ◽  
Increased Risk ◽  
Grade 3

12050 Background: Severe chemotherapy toxicities are frequent among older patients, and may have a major impact on mortality, comorbidities, and quality of life. Two scores were developed to predict severe toxicities: Chemotherapy Risk Assessment Scale for High-age patients (CRASH) score, and Cancer and Aging Research Group Study (CARG) score. The main objective of the present study was to evaluate the predictive value of both scores on an external cohort. Secondary objective was to identify individual predictive factors of severe chemotherapy toxicities. Methods: The Elderly Cancer Patients (ELCAPA) survey consists in a prospective cohort including patients aged 70 years or older referred for a geriatric assessment (GA) before anticancer treatment, such as chemotherapy for solid cancer. CARG and CRASH score were retrospectively collected. Main endpoint was grade 3/4/5 toxicities for CARG-score, hematologic grade 4/5 and non-hematologic grade 3/4/5 toxicities for CRASH-score. Calibration and discrimination (Area Under ROC Curve, AUC) were evaluated. Results: From July 2010 to March 2017, 248 patients were included. Among them, 150 (61%) experienced severe toxicity as defined in CARG study, and 126 (51%) as defined in CRASH study. There was no increased risk of toxicity in intermediate and high risk groups of CARG-score compared to low risk group (OR = 0.3, IC95% [0.1 – 1.4], p= 0.1; and OR = 0.4, IC95%[0.1 – 1.7], p= 0.2 respectively, AUC-ROC = 0.55). Similarly, there was no more risk of severe toxicities in intermediate low, intermediate high, and high risk groups compared to low risk groups of CRASH combined score (respectively OR = 1, IC95% [0.3 – 3.6], p= 0.99; OR = 1, IC95% [0.3 – 3.4], p= 0.9; OR = 1.5, IC95% [0.3 – 8.1], p= 0.67; AUC-ROC = 0.52). A multivariate predictive model including cancer type, performance status (PS 0 vs. PS 1-2), number of severe comorbidities (Cumulative Illness Rating Scale for Geriatrics, CIRS-G, ≥1 grade 3 or 4 comorbidity), body mass index (BMI > 25 kg/m² protective vs. normal BMI), and Chemotox score (1 vs. 0) had an AUC of 0.78. Conclusions: Neither CARG nor CRASH score was predictive of severe chemotherapy toxicities in the ELCAPA cohort. There is a need to identify new predictors of chemotherapy toxicity in older patients with solid cancers.

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