Cardiovascular Risk in Cancer Patients Treated with Immune Checkpoint Inhibitors: Challenges and Future Directions.

Cardiovascular disease is the leading cause of non-cancer related mortality and morbidity among people living with or cured from cancer. Immune checkpoint inhibitors (ICIs) are systemic anti-cancer therapies that have revolutionised the treatment of numerous cancers, even achieving durable long-term responses among patients with metastatic disease. However, the pro-inflammatory effects of ICIs have been postulated to increase the risk of atherosclerotic cardiovascular disease (ASCVD) in cancer survivorship. Standard modifiable cardiovascular risk factors can further contribute to ASCVD risk during cancer survivorship but are not routinely screened and are often untreated in patients with cancer. With the expanding use of ICIs leading to improved cancer survivorship, cardiovascular risk identification and prevention will be paramount in the care of patients with cancer. This review highlights the practical challenges associated with ASCVD prevention among the growing number of patients treated with ICIs for cancer, including balancing competing mortality risks from cancer and ASCVD, the lack of ICI-specific cardiovascular risk stratification tools, potential interactions between cardiovascular and oncological therapies, and barriers to implementation of cardiovascular screening and prevention within existing healthcare systems.

Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

An association between Dasatinib, elevated left atrial pressure and pleural effusion.

BACKGROUND: Tyrosine kinase inhibitors (TKI), such as Dasatinib, are effective in the treatment of chronic myeloid leukemia (CML) but associated with development of pleural effusions (PE). The relationship between haemodynamic parameters identified on transthoracic echocardiogram (TTE) such as elevated estimated left atrial pressure (LAP), and PE development is unknown. This study aims to describe associations between Dasatinib, elevated LAP and PE. METHODS: This was a retrospective study of 71 CML patients who underwent TTE during treatment with various TKIs. Descriptive analysis was performed to identify associations between TKI use, PE and elevated LAP on TTE. Multivariate logistic regression was performed to identify predictors of elevated LAP. RESULTS: There were 36 patients treated with Dasatinib, 15 Nilotinib, and 20 Imatinib. Those treated with Dasatinib had higher rates of elevated LAP (44% vs 7% Nilotinib vs 10% Imatinib, p < 0.01) and PE (39% vs 7% vs 0%, p < 0.01). In the 15 patients who developed PE, 14 (93%) patients were treated with Dasatinib. Patients with PE had higher rates of elevated LAP (67% vs 16%, p < 0.01). Nineteen (26.8%) patients in the entire cohort had elevated LAP. After multivariate adjustment, Dasatinib (OR 33.50, 95% CI = 4.99-224.73, p < 0.01) and age (OR 1.12, 95% CI = 1.04-1.20, p < 0.01) were associated with elevated LAP. CONCLUSIONS: Among patients with CML, there was an association between Dasatinib use, PE and elevated LAP on TTE. These findings are hypothesis generating and further studies are required to evaluate the utility of elevated LAP on TTE as a novel marker for prediction and surveillance of PE.

Association Between Smoking and Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease of the upper airway. The impact of smoking on CRS has not been clearly established. We aim to clarify the association between first-hand cigarette smoking and the prevalence and prognoses of CRS. REVIEW METHODS: PubMed, Embase, SCOPUS, and Cochrane Library were searched from inception until May 15, 2022. Three blinded reviewers selected relevant studies, extracted data, and evaluated study bias following a PROSPERO-registered protocol (CRD42022345585). We used random-effects meta-analyses to pool the prevalence of smoking in CRS, association between smoking status and CRS, and association of smoking with quality of life (QOL) before and after functional endoscopic sinus surgery (FESS). We also performed descriptive analyses of olfactory function, CT scores, and endoscopy scores before and after FESS. RESULTS: We included 23 cross-sectional studies, 19 cohort studies, two case-control studies, and one prospective clinical trial. The pooled prevalence of ever-smokers was 40% (95% CI = 0.30-0.51) and 33% (95% CI = 0.25-0.43) in patients with and without CRS. Compared to never-smokers, active smokers and past smokers had 1.35 (95% CI = 1.18-1.55) and 1.23 (95% CI = 1.17-1.29) higher odds of having CRS. Among patients with CRS, non-smokers reported higher initial QOL than smokers (standardized mean difference [SMD] = 0.23, 95% CI = 0.11-0.35), although post-FESS QOL was similar (SMD = 0.10, 95% CI = -0.30-0.51). Descriptive analysis found no significant correlations between smoking and post-FESS olfactory function and endoscopy scores. CONCLUSIONS: Cigarette smoking is associated with higher prevalence and odds of CRS. Clinicians should be aware that smoking predisposes to CRS, but does not negatively impact the rhinologic outcomes of FESS. Laryngoscope, 134:2513-2524, 2024.

Atherosclerotic Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective therapies for numerous cancers, but have been associated with atherosclerotic cardiovascular disease (ASCVD). This study aimed to identify predictors for ASCVD events among cancer patients treated with ICIs and the cardiovascular risk factor (CVRF) control of those who developed ASCVD. METHOD: A single-centre retrospective study of 366 cancer patients who received ICIs from 2018 to 2020 was performed. Demographic, baseline CVRF, cancer history, and ICI regimen data were obtained from medical records. The primary end point of ASCVD events was defined as myocardial infarction, coronary revascularisation, ischaemic stroke, or acute limb ischaemia. Cox proportional multivariable modelling and competing risks analysis were performed to assess ASCVD predictors. Descriptive analysis was performed to describe CVRF management among those who developed ASCVD events. RESULTS: Over a median follow-up of 3.4 years (2.8-4.3), 26 patients (7.1%) experienced 27 ASCVD events (seven myocardial infarction, one coronary revascularisation, 13 ischaemic stroke, and six acute limb ischaemia events). There were 226 (61.8%) cancer-related deaths and no cardiac deaths. History of ASCVD before ICI initiation was independently associated with ASCVD events on traditional Cox modelling (hazard ratio [HR] 4.00; 95% confidence interval [CI] 1.79-8.91; p<0.01) and competing risks analysis (HR 4.23; 95% CI 1.87-9.60; p<0.01). A total of 17 patients developed ASCVD events after ICI cessation (median 1.4 years). Among those with ASCVD events, 12 had prior ASCVD, 16 had hypertension, nine had hypercholesterolaemia, and four had diabetes, and nine were actively smoking. Variable prescription of cardiovascular preventative therapies was noted. CONCLUSIONS: History of ASCVD was associated with subsequent ASCVD events among patients treated with ICIs, which could occur even after active treatment was stopped. Identification and aggressive management of modifiable CVRFs should be considered throughout cancer survivorship in patients who received ICI treatment.

Cardiovascular Effects of GnRH Antagonists Compared With Agonists in Prostate Cancer: A Systematic Review.

Background: Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest gonadotropin-releasing hormone (GnRH) antagonists may be associated with fewer adverse cardiovascular outcomes compared with GnRH agonists. Objectives: This study sought to determine whether GnRH antagonists were associated with fewer major adverse cardiovascular events compared with GnRH agonists. Methods: Electronic databases were searched for all prospective, randomized trials comparing GnRH antagonists with agonists. The primary outcome was a major adverse cardiovascular event as defined by the following standardized Medical Dictionary for Regulatory Activities terms: "myocardial infarction," "central nervous system hemorrhages and cerebrovascular conditions," and all-cause mortality. Bayesian meta-analysis models with random effects were fitted. Results: A total of 11 eligible studies of a maximum duration of 3 to 36 months (median = 12 months) enrolling 4,248 participants were included. Only 1 trial used a blinded, adjudicated event process, whereas potential bias persisted in all trials given their open-label design. A total of 152 patients with primary outcome events were observed, 76 of 2,655 (2.9%) in GnRH antagonist-treated participants and 76 of 1,593 (4.8%) in agonist-treated individuals. Compared with GnRH agonists, the pooled OR of GnRH antagonists for the primary endpoint was 0.57 (95% credible interval: 0.37-0.86) and 0.58 (95% credible interval: 0.32-1.08) for all-cause death. Conclusions: Despite the addition of the largest, dedicated cardiovascular outcome trial, the volume and quality of available data to definitively answer this question remain suboptimal. Notwithstanding these limitations, the available data suggest that GnRH antagonists are associated with fewer cardiovascular events, and possibly mortality, compared with GnRH agonists.

Perceptions and Attitudes of Patients and Health Care Stakeholders on Implementing a Telehealth Service for Preoperative Evaluation: A Qualitative Analysis.

Background: Studies suggest that preoperative evaluation can be effectively conducted through telehealth. As the COVID-19 pandemic has accelerated digital transformation, we hypothesize that a new telehealth model of care may be feasibly implemented for preoperative evaluation at our institution. This qualitative study seeks to evaluate the attitudes and perception of elective surgery patients and health care providers toward telehealth conducted for preanesthesia evaluation. Methods: At a tertiary women's hospital in Asia, health care providers and elective surgery patients were recruited by convenience and snowball sampling to undergo one-on-one semistructured interviews regarding a new telehealth model of care for preanesthesia evaluation, under-pinned by the Normalization Process Theory. Data were analyzed, coded, and consolidated into themes using the framework analysis method by a team of four researchers from diverse backgrounds. Results: Twenty-five interviews were conducted among 10 patients and 15 health care participants. Ninety-five codes were identified, consolidated into four themes that connect to guide the implementation of a new telehealth pathway for preoperative care, mapped to the Normalization Process Theory. The themes pertain to advantages of telehealth workflow (coherence), requisites for new telehealth workflow (coherence, collective action), barriers to implementation (cognitive participation, collective action), and enablers of implementation (cognitive participation, collective action). All participants were receptive to telehealth, but health care participants expressed concern about the impact of additional tasks on current clinical workload. Training in videoconferencing was deemed essential by both patients and health care providers. Conclusions: The study has provided insights into levels of coherence and cognitive participation among patients and health care providers. The telehealth workflow should be redesigned, considering systems' constraints and stakeholders' needs. Greater buy-in is needed to gain health care providers' commitment for collective action. Clinicaltrials.gov identifier: NCT05781789.

Inter-software and inter-scan variability in measurement of epicardial adipose tissue: a three-way comparison of a research-specific, a freeware and a coronary application software platform.

OBJECTIVES: Epicardial adipose tissue (EAT) is a proposed marker of cardiovascular risk; however, clinical application may be limited by variability in post-processing software platforms. We assessed inter-vendor agreement of EAT volume (EATv) and attenuation on both contrast-enhanced (CE) and non-contrast CT (NCT) using a standard coronary CT reporting software (Vitrea), an EAT research-specific software (QFAT) and a freeware imaging software (OsiriX). METHODS: Seventy-six consecutive patients undergoing simultaneous CE and NCT had complete volumetric EAT measurement. Between-software, within-software NCT vs. CE, and inter- and intra-observer agreement were evaluated with analysis by ANOVA (with post hoc adjustment), Bland-Altman with 95% levels of agreement (LoA) and intraclass correlation coefficient (ICC). RESULTS: Mean EATv (freeware 53 ± 31 mL vs. research 93 ± 43 mL vs. coronary 157 ± 64 mL) and attenuation (freeware - 72 ± 25 HU vs. research - 75 ± 3 HU vs. coronary - 61 ± 10 HU) were significantly different between all vendors (ANOVA p < 0.001). EATv was consistently higher in NCT vs. CE for all software packages, with most reproducibility found in research software (bias 26 mL, 95% LoA: 2 to 56 mL), compared to freeware (bias 11 mL 95% LoA: - 46 mL to 69 mL) and coronary software (bias 10 mL 95% LoA: - 127 to 147 mL). Research software had more comparable NCT vs. CE attenuation (- 75 vs. - 72 HU) compared to freeware (- 72 vs. - 57 HU) and coronary (- 61 vs. - 39 HU). Excellent inter-observer agreement was seen with research (ICC 0.98) compared to freeware (ICC 0.73) and coronary software (ICC 0.75) with narrow LoA on Bland-Altman analysis. CONCLUSION: There are significant inter-vendor differences in EAT assessment. Our study suggests that research-specific software has better agreement and reproducibility compared to freeware or coronary software platforms. KEY POINTS: • There are significant differences between EAT volume and attenuation values between software platforms, regardless of scan type. • Non-contrast scans routinely have higher mean EAT volume and attenuation; however, this finding is only consistently seen with research-specific software. • Of the three analyzed packages, research-specific software demonstrates the highest reproducibility, agreement, and reliability for both inter-scan and inter-observer agreement.

Blood pressure surveillance in cancer patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) are cancer therapies that have been associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood pressure (BP) measurements are routinely performed during day oncology center visits for administration of ICI therapy but are often not assessed temporally to screen and monitor hypertension, which could independently increase the risk of ASCVD in cancer survivorship. This study reports the feasibility of using serial BP measurements from routine visits to day oncology center to diagnose and monitor hypertension control in cancer patients receiving ICIs.

Cardiovascular risk factor reporting in immune checkpoint inhibitor trials: A systematic review.

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of numerous cancers but are associated with increased risk of myocardial infarction. The prevalence of traditional cardiovascular risk factors (CVRF) in patients treated with ICIs is unknown. This study sought to describe the frequency of reporting of CVRFs among landmark ICI trials. METHODS: A systematic review of all phase 2 or 3 cancer trials employing ICIs that led to United States Food and Drug Administration approval was conducted. RESULTS: Of the 69 identified trials, only one study reported baseline rates of hypertension, diabetes mellitus, and dyslipidemia. Smoking history was reported in 27 studies (39 %) and three (4 %) reported body mass index. No study reported history of previous cardiovascular disease, although 17 (25 %), six (9 %), and 21 (30 %) studies excluded patients with recent myocardial infarction, revascularization and heart failure respectively. Similarly low rates of cardiovascular risk factor reporting were observed in studies employing concurrent vascular endothelial growth factor inhibitors and recruiting (neo)adjuvant cohorts. CONCLUSION: The prevalence of CVRFs is poorly described in ICI trials despite increasingly reported risks of myocardial infarction. A systematic approach to collecting and reporting CVRFs should be considered in future trials and real world populations.

An Unusual Pathologic Ulna Fracture Induced by Intraosseous Tumoral Calcium Pyrophosphate Dihydrate Crystal Deposition Disease.

In this case report, we describe a novel occurrence of tumoral calcium pyrophosphate dihydrate crystal deposition disease (TCPPDCD) in a 76-year-old man that presented as an unusual, intraosseous, metadiaphyseal lesion of a long bone causing a pathologic fracture. A routine intralesional biopsy was performed, demonstrating granular deposits composed of polarizing, overlapping rhomboid crystals consistent with TCPPDCD. With limited numbers of reported cases of TCPPDCD, and the atypical intraosseous origin seen in this case, it is paramount to thoroughly evaluate all cases of TCPPDCD to clearly differentiate key findings that are essential in diagnosing and managing TCPPDCD.

Breast arterial calcification and epicardial adipose tissue volume, but not density are independently associated with cardiovascular risk.

BACKGROUND: Mammographically detected breast arterial calcification (BAC) has been proposed as surrogate marker for coronary artery disease (CAD) in women. Epicardial adipose tissue (EAT) and peri-coronary adipose tissue (PCAT) are inflammatory fat depots linked to atherogenesis. BAC has demonstrated association with inflammation, therefore we aimed to determine the association between BAC, EAT and PCAT. METHODS: Single-centre, retrospective, cross-sectional study of women with digital mammography and coronary computed tomography angiography (CCTA). EAT and PCAT were quantitively assessed using semi-automated software. Patient demographics and cardiovascular risk factors were obtained from medical records and mammograms reviewed for BAC. Pre-test cardiovascular risk was determined with CAD Consortium Score. Chi-square, t-test and Mann-Whitney U tests were used to assess between group differences. Multivariable linear and logistic regression modelling was conducted to adjust for confounders. RESULTS: Among 153 patients (age 61, SD 11) included in this study, BAC was present in 37 (24%) patients. BAC-positive patients had higher EAT volume (EATv) (110.2 mL, SD 41 mL vs 94.4 mL, SD 41 mL, p = 0.02) but this association was not significant after adjusting for cardiovascular risk factors (p = 0.26). BAC did not associate with EAT density or PCAT. BAC and EATv were strongly associated with cardiovascular risk and CAD independent of each other: CV risk (BAC OR 7.55 (3.26-18.49), p < 0.001, EATv OR 1.02 (1.01-1.03), p < 0.001), CAD presence (BAC OR 4.26 (1.39-13), p = 0.01; EATv OR 1.01 (1.0-1.03), p = 0.04). CONCLUSION: BAC and EATv are independent predictors of CV risk and CAD, but don't independently associate with each other, the relationship confounded by shared cardiovascular risk factors. BAC doesn't appear to associate with adipose tissue density and its presence may be cumulative result of long-term exposure to CV risk factors.

Immune Checkpoint Inhibitor Therapy in Oncology: Current Uses and Future Directions: JACC: CardioOncology State-of-the-Art Review.

Immune checkpoint inhibitors (ICIs) are a major class of immuno-oncology therapeutics that have significantly improved the prognosis of various cancers, both in (neo)adjuvant and metastatic settings. Unlike other conventional therapies, ICIs elicit antitumor effects by enhancing host immune systems to eliminate cancer cells. There are 3 approved ICI classes by the U.S. Food and Drug Administration: inhibitors targeting cytotoxic T lymphocyte associated antigen 4, programmed death 1/programmed death-ligand 1, and lymphocyte-activation gene 3, with many more in development. ICIs are commonly associated with distinct toxicities, known as immune-related adverse events, which can arise during treatment or less frequently be of late onset, usually relating to excessive activation of the immune system. Acute cardiovascular immune-related adverse events such as myocarditis are rare; however, data suggesting chronic cardiovascular sequelae are emerging. This review presents the current landscape of ICIs in oncology, with a focus on important aspects relevant to cardiology.

Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring.

A standardised method for cardiovascular risk stratification in chronic myeloid leukaemia patients treated with tyrosine kinase inhibitors is lacking. We report an algorithm for risk stratification applicable to all patients commencing tyrosine kinase inhibitor therapy based on age, prior cardiovascular disease and Framingham Risk Score, incorporating coronary artery calcium scoring in patients at intermediate Framingham Risk Score risk. Of 88 patients retrospectively studied, major adverse cardiovascular event rates in our study-defined low-, intermediate- and high-risk categories were 0%, 10% and 19% respectively. Of nine patients down-classified from intermediate to low risk on the basis of coronary artery calcium scoring, none went on to experience a major adverse cardiovascular event.

DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells.

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance.

Predictors of acute hospital mortality and length of stay in patients with new-onset atrial fibrillation: a first-hand experience from a medical emergency team response provider.

BACKGROUND: Atrial fibrillation (AF) occurs frequently following cardiothoracic surgery and treatment decisions are informed by evidence-based clinical guidelines. Outside this setting there are few data to guide clinical management. AIM: To describe the characteristics, management and outcomes of hospitalised adult patients with new-onset AF. METHODS: The medical emergency team (MET) database was utilised to identify patients who had a 'MET call' activated for tachycardia between 2015 and 2016. Patients with sinus tachycardia, pre-existing AF/atrial flutter or other known tachyarrhythmia were excluded. Primary outcomes were length of hospital stay and in-hospital mortality. RESULTS: New-onset AF was identified in 137 patients: 68 medically managed; 38 non-cardiothoracic post-operative; and 31 cardiothoracic post-operative. Mean age was 74 ± 11.6 years and 72 (53%) were male. Of 79 patients who underwent echocardiography, 80% had left atrial dilatation and 14% had reduced left ventricular ejection fraction (LVEF). Mean length of stay (LOS) was 12 days and in-hospital mortality rate was 11%. On multivariable analysis, the odds of death during acute hospitalisation was 7.4 times higher in patients with heart failure with reduced LVEF (odds ratio 7.4, 95% confidence interval (CI) 1.23-44.8, P = 0.028). Length of acute hospital stay increased by 36% if the duration of AF was longer than 48 h (beta coefficient 0.36, 95% CI -0.015 to 0.74, P = 0.059). CONCLUSION: Left ventricular systolic dysfunction in hospitalised patients with new-onset AF is associated with increased all-cause mortality whereas lower serum potassium levels are associated with an increased LOS. A prospective study is planned to compare outcomes based on in-hospital treatment strategies.

The roles of circular RNAs in human development and diseases.

For many years, circular ribonucleic acids (circRNAs) have been counted as aberrant splicing by-products. Advanced bioinformatics analysis and deep sequencing techniques have allowed researchers to discover more interesting facts about circRNAs. Intriguing evidence has shed light on the functions of circRNAs in many tissues. Furthermore, emerging reports showed that circRNAs are found abundantly in saliva and blood samples, suggesting that circRNAs are potential clinical biomarkers for human embryonic development, diseases progression and prognosis, in addition to its role in organogenesis and pathogenesis. The implementation of circRNAs in human developmental stages and diseases would be a tremendous discovery in the science and medical field. Therefore, circRNAs have been studied for its biological function as well as its implication in various human diseases. The aim of this review is to highlight the importance of circRNAs in cardiac, respiratory, nervous, endocrine and digestive systems. In addition, the role and impact of circRNAs in, cardiogenesis, neurogenesis and cancer have been discussed.

Real-World Effect of Maintenance and Intermittent Chemotherapy on Survival in Metastatic Colorectal Cancer.

BACKGROUND: With improved survival and longer duration of treatment, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent (IC) or maintenance chemotherapy (MC), but the effect of these treatment modifications on real-world outcomes is unclear. PATIENTS AND METHODS: Using a population-based cohort of mCRC patients who received combination chemotherapy, we aimed to describe the use of IC/MC and their effect on overall survival (OS). RESULTS: Among 617 patients, 120 (19%) had periods of IC, 67 (11%) had periods of MC, and 53 (9%) had periods of both. Most (85.5%) modifications occurred in the first-line setting. The receipt of IC (median OS [mOS], 37 vs. 21 months; P < .0001) or MC (mOS, 36 vs. 24 months; P = .0015) was associated with improved mOS compared with continuous combination therapy. In multivariate analysis adjusting for age, sex, and regimen used at the time of treatment modification, IC (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.42-0.65; P < .0001), MC (HR, 0.71; 95% CI, 0.58-0.88; P = .002), and the combination (HR, 0.45; 95% CI, 0.33-0.63; P < .0001) were all associated with improved mOS. Among patients receiving MC, individuals with (HR, 0.69; 95% CI, 0.53-0.90; P = .005) and without (HR, 0.74; 95% CI, 0.55-1.00; P = .048) re-escalation to their original cytotoxic regimen had improved mOS compared with continuous therapy. The use of IC was associated with an improved OS compared with MC (HR, 0.65; 95% CI, 0.47-0.90; P = .009). CONCLUSION: In patients with mCRC, IC and MC are reasonable options to maintain quality of life and do not appear to negatively affect OS in carefully selected patients.