Population-Based Long-term Cardiac-Specific Mortality Among Patients With Major Gastrointestinal Cancers

Abstract

IMPORTANCE Patients with major gastrointestinal (GI) cancers are at long-term risk for cardiac disease and mortality. OBJECTIVE To investigate the cardiac-specific mortality rate among individuals with major GI cancers and the association of radiation and chemotherapy with survival outcomes in the United States. DESIGN, SETTING, AND PARTICIPANTS This US cohort study included individual patient-level data of men and women older than 18 years with 5 major gastrointestinal cancers, including colorectal, esophageal, gastric, pancreatic, and hepatocellular cancer from 1990 to 2016. Data was extracted from the Surveillance, Epidemiology, and End Results (SEER) national cancer database. Data cleaning and analyses were conducted between November 2020 and March 2021. EXPOSURES Patients received chemotherapy, radiotherapy, or a combination of adjuvant therapy for major GI cancers. MAIN OUTCOMES AND MEASURES The primary outcome was cardiac-specific mortality. Examined factors associated with cardiac mortality included age, sex, race, tumor location, tumor grade, SEER stage, TNM (seventh edition) staging criteria, cancer treatment (ie, the use of radiation, chemotherapy, or surgery), survival months, and cause of death.RESULTS A total of 359 032 patients (mean [SD] age at baseline, 65.1 [12.9] years; 186 921 [52.1%] men) with GI cancers were analyzed, including 313 940 patients (87.4%) with colorectal cancer, 7613 patients (2.1%) with esophageal cancer, 21 048 patients (5.9%) with gastric cancer, 7227 patients (2.0%) with pancreatic cancer, and 9204 patients (2.6%) with hepatocellular cancer. Most cancers were localized except pancreatic cancer, which presented with regional and distant involvement (3680 cancers [50.9%]). Overall, all major gastrointestinal tumors were associated with increased risk of cardiac mortality compared with noncardiac mortality (median survival time: 121 [95% CI, 120-122] months vs 287 [95% CI, 284.44-290] months). Patients with hepatocellular cancer had the lowest cardiac-specific median survival time (98 [95% CI, 90-106] months), followed by pancreatic cancer (105 [95% CI, 98-112] months), esophageal cancer (113 [95% CI, 107-119] months), gastric cancer (113 [95% CI, 110-116] months), and colorectal cancer (122 [95% CI, 121-123] months). At 15 years of follow up, the use of only chemotherapy, only radiation, or radiation and chemotherapy combined was associated with poor survival rates from cardiac causes of death (eg, colorectal: chemotherapy, 0 patients; radiation, 1 patient [1.9%]; radiation and chemotherapy, 3 patients [2.7%]).

Age‐specific cardiovascular disease‐related mortality among patients with major gastrointestinal cancers: A SEER population‐based study

“…A further study reported greater hazards among older patients for predicting post‐cancer CVD‐related morbidities, such as congestive heart failure (CHF) and CVD 32 . Regarding the cardiac mortality among those colorectal cancer patients, the study reported a 1.12‐fold increased risk of CVD for every 1‐year increase in age 15 . In line with these studies, our study also found that middle‐aged (aged 45–59 years) and older (aged ≥60 years) colorectal cancer patients had a higher SHR than young patients (aged ≤44 years) for CVD‐related mortality.…”

“…Among esophageal cancer patients, age was regarded as the most risk factor determining heart death, with those aged ≥80 years being 14.297 times at risk for cardiac‐specific survival compared with those aged <40 years 34 . Furthermore, the risk of cardiac mortality increased 1.08‐fold for every 1‐year increase in age 15 . Similar to these studies, older esophageal cancer patients had a 4.40‐fold higher risk of CVD‐related mortality than those aged ≤44 years.…”

Cardiovascular Mortality among Patients with Pancreatic Cancer: A Population-based Study

“…Ramai et al concluded that patients with pancreatic cancer had a lower cardiac-speci c median survival time of 105 (95%CI:98-112) months compared with noncardiac mortality of 293 (95%CI:271-315) months. Furthermore, these patients had a cardiac-speci c survival rate of 261 (84.6%) patients at 10 years and 9 (2.8%) patients at 15 years compared with an other-cause survival rate of 6793 (98.2%) patients at 10 years and 4712 patients (68.1%) at 15 years in a cohort study of a total of 7227 patients 9 . In a study of 67,694 pancreatic adenocarcinoma patients, Harvitkar et al illustrated that the percentage of heart disease accounted for the total number of all causes of death in the following time frames : less than 1 year (SMR : 3.17; 95% CI: 2.93-3.43), 1-5 years (SMR : 2.00; 95% CI: 1.72-2.32), 5-10 years (SMR : 2.65; 95% CI: 1.84-3.68), and more than 10 years (SMR : 2.05; 95% CI: 0.66-4.78) 10 .…”

“…For example, Hardy et al reported that cardiac dysfunction was signi cantly associated with chemotherapy and radiation therapy use in non-small-cell lung cancer 8 . Similarly, Ramai et al found that the application of chemotherapy, radiation, or both together was associated with poor prognosis from cardiac causes of death after 15 years of follow-up 9 . Despite these nding, there are few reports on cardiovascular disease among pancreatic cancer patients in the literature.…”

Mesenchymal stem cell-derived exosomes for gastrointestinal cancer

“…Gastrointestinal (GI) cancer is one of the most common malignancies in the digestive system, such as the stomach, liver, pancreas, and colorectum[ 1 ]. Based on the latest global epidemiological data, GI cancer accounts for 26% of all kinds of cancers and 35% of cancer patients died from GI cancer with approximately 4.8 million new cases and 3.4 million deaths each year[ 2 , 3 ]. Current therapeutic strategies for GI malignancies mainly include surgery, endoscopy, radiotherapy, chemotherapy, targeted therapy, and immunotherapy[ 4 - 6 ].…”