Conditional immune toxicity rate in patients with metastatic renal and urothelial cancer treated with immune checkpoint inhibitors

BackgroundImmune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). Although the incidence and prevalence of irAEs have been well characterized in the literature, less is known about the cumulative incidence rate of irAEs. We studied the cumulative incidence of irAEs, defined as the probability of irAE occurrence over time and the risk factors for irAE development in metastatic urothelial carcinoma (mUC) and renal cell carcinoma (mRCC) patients treated with ICIs.MethodsWe identified a cohort of patients who received ICIs for mUC and mRCC. irAEs were classified using Common Terminology Criteria for Adverse Event (CTCAE) V.5.0 guidelines. The monthly incidence of irAEs over time was reported after landmark duration of therapy. Cumulative incidence of irAEs was calculated to evaluate the time to the first occurrence of an irAE accounting for the competing risk of death. Prognostic factors for irAE were assessed using the Fine and Gray method.ResultsA total of 470 patients were treated with ICIs between July 2013 and October 2018 (mUC: 199 (42.3%); mRCC: 271 (57.7%)). 341 (72.6%) patients received monotherapy, 86 (18.3%) received ICIs in combination with targeted therapies, and 43 (9.2%) received dual ICI therapy. Overall, 186 patients (39.5%) experienced an irAE at any time point. Common irAEs included hypothyroidism (n=42, 22.6%), rush and pruritus (n=36, 19.4%), diarrhea/colitis (n=35, 18.8%), transaminitis (n=32, 17.2%), and pneumonitis (n=14, 7.5%). Monthly incidence rates decreased over time; however, 17 of 109 (15.6%, 95% CI: 9.4% to 23.8%) experienced their first irAE at least 1 year after treatment initiation. No differences in cumulative incidence were observed based on cancer type, agent, or irAE grade. On multivariable analysis, combined ICI therapy with another ICI or with targeted therapy (p<0.001), first-line ICI therapy (p=0.011), and PD-1 inhibitor therapy (p=0.007) were all significantly associated with irAE development.ConclusionsThis study quantitates the incidence of developing irAEs due to ICI conditioned on time elapsed without irAE development. Although the monthly incidence of irAEs decreased over time on therapy, patients can still develop delayed irAEs beyond ICI discontinuation, and thus, continuous vigilant monitoring is warranted.

Download Full-text

Conditional immune adverse event rate in urothelial and renal cell carcinoma patients treated with immune checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.481 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 481-481

Author(s):

Pier Vitale Nuzzo ◽

Gregory Russell Pond ◽

Sarah Abou Alaiwi ◽

Amin Nassar ◽

Ronan Flippot ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Immune Checkpoint ◽

Renal Cell ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Multivariable Analysis ◽

Adverse Event Rate ◽

Risk Of Death ◽

Over Time

481 Background: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). While the incidence and prevalence of irAEs have been well characterized in the literature, much less is known about the cumulative incidence (CI) rate of irAEs. We sought to evaluate the CI of irAEs in metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC) patients (pts) treated with ICIs. Methods: We identified a cohort of mUC and mRCC pts who received ICIs at DFCI. irAEs were classified using CTCAE v.5.0 guidelines. The CI rate was a defined measure that accounted for elapsed time since treatment initiation and estimated the risk of irAE development conditioned on time elapsed without experiencing an irAE, accounting for the competing risk of death. Incidence and CI of irAEs at each monthly landmark time was calculated. Prognostic factors of irAE were assessed using the Fine and Gray method. Results: A total of 470 pts was treated with ICIs between July 2013 and October 2018 [mUC: 199 (42.3%); mRCC: 271 (57.7%)]. 341 (72.6%) pts received ICI monotherapy, 86 (18.3%) received ICIs in combination with targeted therapies, and 43 (9.2%) received a combination of two ICIs. Overall, 186 pts (39.5%) experienced any irAE at any time point. Common irAEs included hypothyroidism (n=42 [22.6%]), skin (n=36 [19.4%]), colitis (n=35 [18.8%]), transaminitis (n=32 [17.2%]), and pneumonitis (n=14 [7.5%]). The risk of developing an irAE over time was as follows: 33.5% if no irAE within the 1st month(mo), 27.3% if no irAE in 3mo, 18.8% if no irAE in 6mo, and 16.4% if no irAE by 12mo. No difference was observed in CI based on type of cancer (mUC vs mRCC) or agent (PD1 vs. PD-L1). Multivariable analysis showed that ICI combined with ICI or other agents vs. ICI monotherapy (p<0.001), firstline therapy (p=0.013) and PD-1 vs. PD-L1 inhibitors (p=0.008) were statistically correlated with the development of irAEs. Conclusions: This study quantitates the incidence of developing irAEs with ICI conditioned on time elapsed without irAE development. Although the incidence of irAEs decreased over time on therapy, irAEs require continuous vigilant monitoring because of the long tail in its incidence.

Download Full-text

Immune-Related Adverse Events (irAE) in Cancer Immune Checkpoint Inhibitors (ICI) and Survival Outcomes Correlation: To Rechallenge or Not?

Cancers ◽

10.3390/cancers13050989 ◽

2021 ◽

Vol 13 (5) ◽

pp. 989

Author(s):

Heidar J. Albandar ◽

Jacob Fuqua ◽

Jasim M. Albandar ◽

Salahuddin Safi ◽

Samuel A. Merrill ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Survival Outcomes ◽

Limited Data ◽

Risk Of Death ◽

Survival Difference ◽

Histopathologic Diagnosis ◽

Cancer Types

Introduction: There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. Methods: We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011–2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. Results: Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. Conclusions: Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.

Download Full-text

TERT promoter mutation as a prognostic marker in patients with advanced urothelial carcinoma treated with immune checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.476 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 476-476

Author(s):

Ivan de Kouchkovsky ◽

Li Zhang ◽

Errol Philip ◽

Francis Wright ◽

Daniel Myung Kim ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Genomic Profiling ◽

Clinical Variables ◽

Tert Promoter ◽

Visceral Metastases

476 Background: Reliable predictive markers are lacking in patients (pts) with locally advanced or metastatic urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICI). We sought to determine whether specific genomic alterations could be used to predict overall survival (OS) in this patient population. Methods: We undertook a retrospective cohort study of pts with aUC who received ICI and underwent genomic profiling by next-generation sequencing (NGS). All patients underwent NGS using commercially available platforms (e.g. Foundation Medicine, Strata, Invitae), or testing on the CLIA-certified institutional panel UCSF500. Associations between the 20 most frequently altered genes and OS were first examined by Cox regression. Genes with a p <0.1 on univariate analysis and relevant clinical variables were then included in a multivariable analysis. Results: We identified 78 pts treated with ICI for aUC with available genomic profiling results. Median age at ICI initiation was 71; the majority of patients had visceral metastases (70.5%), ECOG performance status ≤1 (62.8%) and received ICI in the post-platinum setting (52.6%). Objective response rate in this cohort was 35.9%, median progression free survival was 4.0 months (95% CI 2.6-10.5) and median OS was 17.5 months (95% CI 14.1-NR) from ICI start. The most commonly altered genes were the TERT promoter (TERTp) (61%), TP53 (52%), RB1 (31%), CDKN2A(29%) and CDKN2B (27%). On univariable analysis there was a trend towards longer OS in pts with TERTp mutations (HR 0.53, 95% CI 0.27-1.06, p = 0.07), and shorter OS in pts with CDKN2B mutations (HR 1.91, 95% CI 0.98-3.73, p = 0.06). Both mutations were included in a multivariable analysis. After adjusting for known prognostic variables (ECOG PS, visceral metastases, albumin, hemoglobin, body mass index [BMI], neutrophil to lymphocyte ratio [NLR], and histology), the presence of a TERTp mutation was significantly associated with improved OS (HR 0.30, 95% CI 0.10-0.93, p = 0.04; Table). Conclusions: The presence of a TERTp mutation was an independent predictor of improved OS in a cohort of aUC pts treated with ICI. Other common mutations and clinical variables were not associated with OS on a multivariable analysis. These findings are hypothesis-generating and prospective validation is needed. [Table: see text]

Download Full-text

Efficacy and immune-related adverse event associations in avelumab-treated patients

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001427 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001427

Author(s):

Karen Kelly ◽

Juliane Manitz ◽

Manish R Patel ◽

Sandra P D’Angelo ◽

Andrea B Apolo ◽

...

Keyword(s):

Solid Tumor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cox Model ◽

Safety Data ◽

Time Dependent ◽

Risk Of Death ◽

Link Type ◽

Event Order

BackgroundAdverse events (AEs) of special interest that arise during treatment with immune checkpoint inhibitors, including immune-related AEs (irAEs), have been reported to be associated with improved clinical outcomes. We analyzed patients treated with avelumab from the JAVELIN Solid Tumor and Merkel 200 trials, examining the association between AEs and efficacy while adjusting for confounding factors such as treatment duration and event order.MethodsWe analyzed efficacy and safety data from 1783 patients treated with the programmed death ligand 1 inhibitor avelumab who were enrolled in expansion cohorts of the JAVELIN Solid Tumor and Merkel 200 trials. To analyze the association between irAEs and efficacy with regard to survival, we used a time-dependent Cox model with time-varying indicators for irAEs, as well as multistate models that accounted for competing risks and time inhomogeneity.Results295 patients (16.5%) experienced irAEs and 454 patients (25.5%) experienced infusion-related reactions. There was a reduced risk of death in patients who experienced irAEs compared with those who did not (HR 0.71, 95% CI 0.59 to 0.85) using the time-dependent Cox model. The multistate model did not suggest that the occurrence of irAEs could predict response; however, it predicted a higher chance of irAEs occurring after a response. No association was observed between response and infusion-related reactions.ConclusionsPatients who experience irAEs showed improved survival. Although irAEs are not predictors for response to immune checkpoint inhibitors, increased vigilance for irAEs is needed after treatment with avelumab.Trial registration numbersNCT01772004 and NCT02155647.

Download Full-text

Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy

Rheumatology ◽

10.1093/rheumatology/kez297 ◽

2019 ◽

Vol 58 (Supplement_7) ◽

pp. vii40-vii48 ◽

Cited By ~ 9

Author(s):

Noha Abdel-Wahab ◽

Maria E Suarez-Almazor

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Incidence Rates ◽

Cancer Therapies ◽

True Incidence ◽

Immune System Activation ◽

Treatment Paradigm ◽

Checkpoint Inhibitor Therapy ◽

Prospective Longitudinal

Abstract Immune checkpoint inhibitors have advanced the treatment paradigm of various cancers, achieving remarkable survival benefits. However, a myriad of immune-related adverse events (irAE) has been recognized in almost every organ system, presumably because of persistent immune system activation. Rheumatic symptoms such as arthralgia or myalgia are very common. More specific irAE are increasingly being reported. The most frequent ones are inflammatory arthritis, polymyalgia-like syndromes, myositis and sicca manifestations. These rheumatic irAE can develop in ∼5–10% of patients treated with immune checkpoint inhibitors, although true incidence rates cannot be estimated given the lack of prospective cohort studies, and likely underreporting of rheumatic irAE in oncology trials. In this review, we will provide a summary of the epidemiologic data reported for these rheumatic irAE, until more robust prospective longitudinal studies become available to further define the true incidence rate of rheumatic irAE in patients receiving these novel cancer therapies.

Download Full-text

PD-L1 expression of high grade glial tumors at diagnosis and change of expression status at recurrence.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.2035 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 2035-2035 ◽

Cited By ~ 1

Author(s):

Basak Oyan ◽

Seyma Eren ◽

Ozlem Sonmez ◽

Ferda Ozkan ◽

Kaan Yaltırak ◽

...

Keyword(s):

Tumor Cells ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

High Grade ◽

Cross Sectional ◽

Glial Tumors ◽

The Impact ◽

Expression Status ◽

Over Time

2035 Background: PD-L1 expression status is the main predictive factor for response to immune checkpoint inhibitors. PD-L1 status may change over time with the impact of therapies. The aim of this study is to determine if PD-L1 expression status changes in recurrent gliomas after chemoradiotherapy. Methods: Thirty eight patients with recurrent high grade gliomas who had surgical excision at least two times were included in this retrospective cross-sectional study. Nine patients were excluded because of the lack of appropriate pathology slides for pathologic evaluation. PD-L1 expression of 29 patients was evaluated by an expert pathologist with immunohistochemical methods. PD-L1 positivity was defined as expression in ≥1% of tumor cells. Change in PD-L1 expression status was defined as an absolute 5% difference between two resections. Results: Of the 29 patients, 15 patients (51.7%) had PD-L1 expression in ≥1% of tumor cells and 7 patients (24.1%) had PD-L1 expression in ≥10% of tumor cells. Tumor PD-L1 expression (defined as expression in ≥1% of tumor cells) was positive in 15 (51.7%) of 29 patients at diagnosis and at the time of recurrence. The PD-L1 status did not change in 17 patients (58.6%). 8 patients had PD-L1 negative tumors both at diagnosis and at recurrence, while 9 patients had PD-L1 positive tumors both at diagnosis and at recurrence. In 6 patients (20.7%) a negative-to-positive switch and in 6 patients (20.7%) a positive to negative switch were seen. Tumor PD-L1 expression increased in 7 of 29 patients (24.1%) and decreased in 9 of 29 patients (31.1%). PD-L1 expression remained stable in 13 of 29 patients (34.4%). The change in PD-L1 status over time was not statistically significant. Conclusions: More than 50% of high grade glial tumors express PD-L1 at diagnosis, so these tumors are good candidates for immune checkpoint inhibitors. The expression status changes in more than 40% of high grade glial tumors at recurrence, so immune responsiveness of glial tumors can be modified by treatments like chemotherapy and radiotherapy.

Download Full-text

Host metabolic factors and prognosis in patients treated with immune checkpoint inhibitors for advanced malignancies.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14162 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14162-e14162

Author(s):

Federica Biello ◽

Marco Audisio ◽

Silvia Genestroni ◽

Gloria Borra ◽

Francesca D'Avanzo ◽

...

Keyword(s):

Clinical Outcome ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Fold Increase ◽

Advanced Melanoma ◽

Host Metabolism ◽

Increase In Risk

e14162 Background: It is well established that an altered host metabolism has an impact on cancer outcome, possibly mediated by several mechanisms, including hyperglicaemia, hyperinsulinemia and presence of chronic inflammation. The aim of our analysis was to evaluate the correlation between host metabolism and clinical outcome in patients with advanced melanoma, kidney and non-small cell lung cancer (NSCLC), treated with immune checkpoint inhibitors (anti-CTLA4, anti PD1 and anti PDL1). Methods: The relationship between presence of type 2 diabetes mellitus (DMII) at baseline and outcome was assessed in 187 patients treated with immune checkpoint inhibitors in two cancer centers. Progression Free Survival (PFS) and Overall Survival (OS) were calculated by Kaplan-Meier estimation; multivariate Cox analysis was performed according to age, gender, BMI (normal < 25 kg/m2, overweight 25-30 kg/m2, obese > 30 kg/m2), type of cancer and line of treatment. Results: One-hundred-sixty-eight patients were available for our analysis. Twenty-eight patients (17%) were diabetic at baseline. Median age was 65 (range 25-80); 83 patients were males (49%); 82 (48%) had advanced melanoma, 83 (49%) NSCLC and 3 (3%) kidney cancer. One-hundred-two (60%) patients had BMI < 25, 51 (30%) were overweight and 16 (10%) were obese. The first line of treatment was immunotherapy in 83 (49%) patients. By univariable analysis median PFS was 4.2 months in non diabetics vs 6.4 in diabetics patients (HR 0.95; 95%CI 0.58-1.58); median OS was 6.17 and 9.1 months, respectively (HR 1.00; 95%CI 0.58-1.75). At multivariable analysis, taking into account DMII, BMI, sex, age, line of treatment and type of cancer, we found that BMI ≤25 was associated with a two fold increase in risk of progression (PD) or death (p = 0.005), whereas patients who received immunotherapy as second or subsequent line had a two fold increase in risk of PD or death (p = 0.003). Conclusions: The results of our analysis show that in patients with advanced cancer treated with immune checkpoint inhibitors, the presence of DMII does not adversely affect the clinical outcome. Conversely, lower BMI was associated with a significantly worse PFS and OS, independently from type of cancer, age and gender. As expected, patients who received immunotherapy in later lines of treatment had a significantly shorter survival.

Download Full-text

Risk factors for myocarditis associated with immune checkpoint inhibitors using real-world clinical data.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15100 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15100-e15100 ◽

Cited By ~ 1

Author(s):

Prantesh Jain ◽

Jahir Gutierrez Bugarin ◽

Avirup Guha ◽

Chhavi Jain ◽

Tingke Shen ◽

...

Keyword(s):

Risk Factors ◽

Liver Disease ◽

Cancer Patients ◽

Real World ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cox Proportional Hazards ◽

Cancer Type ◽

Real World Data

e15100 Background: Immune checkpoint inhibitors (ICIs) can cause unique, high-grade immune-related adverse events. Although rare, ICI related myocarditis has the highest fatality rate (~50%). Cardiovascular monitoring is not routinely performed in patients on ICI treatment, thus risk factors remain unknown. Characterizing rare but fatal cardiac toxicities requires integration of real-world data. Methods: U.S claims data (IBM MarketScan) of over 30 million commercially insured individuals was leveraged to identify 2,687,301 cancer patients between 2011-2018. Patients ≥18 years of age treated with ICIs (targeting CTLA4 (ipilimumab) and/or the PD1 (nivolumab, pembrolizumab)/PDL1 (atezolizumab, avelumab, durvalumab) alone or in combination with ICI and/or chemotherapy were identified and followed until disenrollment. Myocarditis, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics and Cox proportional hazards regression. Results: 16,541 ICI treated cancer patients were included (median age 60; 58% male). Myocarditis was identified in 252 (1.5%) patients, majority (90%) ≥50 years old (median 63) with 12,040 person-years of follow up. 62% received anti-PD1 monotherapy, 12% anti-CTLA4, and 15% received combination treatment with other ICIs and/or chemotherapy. Most common cancer types were lung (48%), melanoma (25%), and renal cancer (14%). Cumulative incidence of myocarditis at 1 year was 2.06%; 95% CI (1.78-2.37), median onset of 80.5 days, 42% occurring within 60 days of treatment. By univariate analyses, age, cancer type, diabetes (DM), hypertension (HTN), kidney, liver disease, atrial fibrillation (AF) were related to myocarditis. Risk was lower in patients who received anti-CTLA4 monotherapy (HR: 0.490; 95% CI: 0.26-0.92; p = 0.0251). On multivariable regression analyses only age, cancer type (renal, lung cancer), comorbidities DM and liver disease were significantly associated with myocarditis (Table). Conclusions: This is the largest real-world longitudinal study for ICI associated myocarditis showing higher than reported incidence and identifiable risk factors. [Table: see text]

Download Full-text

Case Report: Cardiac Toxicity Associated With Immune Checkpoint Inhibitors

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.727445 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ru Chen ◽

Ling Peng ◽

Zhihua Qiu ◽

Yan Wang ◽

Fen Wei ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Troponin I ◽

Systemic Corticosteroid ◽

Checkpoint Inhibitors ◽

Cardiac Conduction ◽

Fulminant Myocarditis ◽

Cancer Type ◽

Life Threatening ◽

The Subject

Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancer. Along with the development of ICIs, immune-related adverse effects (irAEs) have been the subject of wide attention. The cardiac irAE, a rare but potentially fatal and fulminant effect, have been reported recently. This article retrospectively reviewed 10 cases from our hospital with cardiac irAEs, with severity ranging from asymptomatic troponin-I elevations to cardiac conduction abnormalities and even fulminant myocarditis. In our series, all the cases were solid tumors and lung cancer was the most frequent cancer type (4,40%). In total, three (30.0%) patients experienced more than one type of life-threatening complication. A systemic corticosteroid was given to nine patients (90.0%). The majority of cases (7, 70%) were performed at an initial dose of 1–2 mg/kg/day. Two (20.0%) patients were admitted to ICU, three (30.0%) patients were put on mechanical ventilation, two (20.0%) patients received the plasma exchange therapy, and one patient was implanted with a pacemaker. Two (20.0%) of the patients succumbed and died, with a median duration of 7.5 days (IQR5.0–10.0) from diagnosis of cardiac irAE to death. Based on these results, we recommend that clinicians be alert to cardiac irAEs, including performing cardiovascular examinations before ICI treatment to accurately diagnose suspected myocarditis, enabling immediate initiation of immunosuppressive therapy to improve prognosis.

Download Full-text

The Incidence of Cancer Associated Thrombosis is Increasing Over Time

Blood Advances ◽

10.1182/bloodadvances.2021005590 ◽

2021 ◽

Author(s):

Anjlee Mahajan ◽

Ann Brunson ◽

Oyebimpe Adesina ◽

Theresa HM Keegan ◽

Ted Wun

Keyword(s):

Risk Factors ◽

Cumulative Incidence ◽

Temporal Trends ◽

Individual Risk ◽

Cancer Type ◽

Tumor Type ◽

Risk Of Death ◽

Breast And Prostate Cancer ◽

Cancer Associated Thrombosis ◽

Over Time

Cancer associated thrombosis (CAT) is an important cause of morbidity and mortality for patients with malignancy and varies by primary cancer type, stage and therapy. We aimed to characterize the incidence, risk factors, temporal trends and the effect on mortality of CAT. The California Cancer Registry was linked to the statewide hospitalization database to identify individuals with the 13 most common malignancies diagnosed 2005 -2017 and determine the 6 and 12-month cumulative incidence of CAT by venous thromboembolism (VTE) location, tumor type and stage after adjusting for competing risk of death. Cox proportional hazard regression models were used to determine risk factors associated with CAT and the effect of CAT on all-cause mortality. 942,019 patients with cancer were identified; 62,003 (6.6%) had an incident diagnosis of CAT. Patients with pancreatic, brain, ovarian, and lung cancer had the highest and patients with breast and prostate cancer had the lowest 12-month cumulative incidence of CAT. For most malignancies, men, those with metastatic disease and more co-morbidities, and African-Americans (vs. non-Hispanic Whites) were at highest risk for CAT. Patients diagnosed with cancer 2014-2017 had higher risk of CAT compared to those diagnosed 2005-2007. CAT was associated with increased overall mortality for all malignancies (HR ranges 1.89 - 4.79). The incidence of CAT increased over time and was driven by an increase in PE±DVT. CAT incidence varies based on tumor type and stage, and on individual risk factors including gender, race/ethnicity, and co-morbidities. For all tumor types CAT is associated with an increased mortality.

Download Full-text