Patterns of emergency department visits before diagnosis with digestive neuroendocrine neoplasms.

OBJECTIVE: To evaluate the patterns of emergency department visits before diagnosis with digestive neuroendocrine neoplasms (NENs). METHODS: Linked administrative databases from the province of Alberta, Canada, were examined, and patients diagnosed with digestive NENs from 2004 to 2019 were reviewed. Incidents of emergency department visits in the 3 months before histological diagnosis were reviewed. Multivariable logistic regression analyses were used to examine factors associated with at least one emergency department (ED) visit as well as factors associated with more than one ED visit. The impact of pre-diagnosis ED visits on overall survival was further assessed in a multivariable Cox regression model, which included (in addition to ED visits), age at diagnosis, sex, histology, Charlson comorbidity index, and stage. RESULTS: A total of 2120 patients were considered eligible for the study, and they were included in the analysis (including 1041 patients (49.1%) with at least one ED visit in the 3 months before diagnosis). The following factors were associated with a higher likelihood of an ED visit prior to diagnosis: younger age (OR with increasing age: 0.983; 95% CI: 0.977-0.989), higher comorbidity index (OR: 1.332; 95% CI: 1.215-1.460), female sex (OR: 1.292; 95% CI: 1.084-1.540), and stage IV (OR: 1.515; 95% CI: 1.106-2.075). Likewise, the following factors were associated with more than one ED visit within 3 months before diagnosis: younger age (OR with increasing age: 0.985; 95% CI: 0.979-0.992), higher comorbidity index (OR: 1.280; 95% CI: 1.167-1.405), and female sex (OR: 1.516; 95% CI: 1.230-1.868). Using multivariable Cox regression modeling, the following factors were associated with worse overall survival (higher risk of death): older age (HR: 1.050; 95% CI: 1.043-1.056), higher comorbidity index (HR: 1.280; 95% CI: 1.209-1.356), stage IV (HR: 3.163; 95% CI: 2.562-3.905), neuroendocrine carcinoma histology (HR: 1.645; 95% CI: 1.350-2.003), pre-diagnosis ED visit (HR: 1.784; 95% CI: 1.529-2.083). CONCLUSION: Almost one-half of patients with NENs visit the ED within 3 months before diagnosis. ED visits were associated with younger age, female sex, advanced disease, and higher comorbidity. Moreover, pre-diagnosis ED visit(s) were associated with worse overall survival in the current cohort.

Increasing access to palliative care for patients with advanced cancer of African and Latin American descent: a patient-oriented community-based study protocol.

BACKGROUND: Cancer disparities are a major public health concern in Canada, affecting racialized communities of Latin American and African descent, among others. This is evident in lower screening rates, lower access to curative, and palliative-intent treatments, higher rates of late cancer diagnoses and lower survival rates than the general Canadian population. We will develop an Access to Palliative Care Strategy informed by health equity and patient-oriented research principles to accelerate care improvements for patients with advanced cancer of African and Latin American descent. METHODS: This is a community-based participatory research study that will take place in two Canadian provinces. Patients and community members representatives have been engaged as partners in the planning and design of the study. We have formed a patient advisory council (PAC) with patient partners to guide the development of the Access to Palliative Care Strategy for people of African and Latin American descent. We will engage100 participants consisting of advanced cancer patients, families, and community members of African and Latin American descent, and health care providers. We will conduct in-depth interviews to delineate participants' experiences of access to palliative care. We will explore the intersections of race, gender, socioeconomic status, language barriers, and other social categorizations to elucidate their role in diverse access experiences. These findings will inform the development of an action plan to increase access to palliative care that is tailored to our study population. We will then organize conversation series to examine together with community partners and healthcare providers the appropriateness, effectiveness, risks, requirements, and convenience of the strategy. At the end of the study, we will hold knowledge exchange gatherings to share findings with the community. DISCUSSION: This study will improve our understanding of how patients with advanced cancer from racialized communities in Canada access palliative care. Elements to address gaps in access to palliative care and reduce inequities in these communities will be identified. Based on the study findings a strategy to increase access to palliative care for this population will be developed. This study will inform ways to improve access to palliative care for racialized communities in other parts of Canada and globally.

Impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma-a real-world, population-based study.

OBJECTIVE: To assess the impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma in a real-world setting. METHODS: The Surveillance, Epidemiology, and End Results Research Plus database was accessed, and patients with resected non-metastatic adrenocortical carcinoma diagnosed 2010-2015 were reviewed. Kaplan-Meier estimates and log-rank testing were used to examine the impact of postoperative radiotherapy on overall and cancer-specific survival. Multivariable Cox regression analysis was used to explore factors associated with overall and cancer-specific survival. RESULTS: A total of 294 patients were included in the final analysis, including 60 patients (20.4%) who received postoperative radiotherapy. Using Kaplan-Meier estimates, individuals who received postoperative radiotherapy have better overall survival (P = 0.002). Multivariable cox regression analysis showed that the following factors were associated with worse overall survival: older age (HR: 1.01; 95% CI: 1.00-1.03), male sex (HR for female sex versus male sex: 0.61; 95% CI: 0.43-0.85), and non-receipt of postoperative radiation therapy (HR: 2.29; 95% CI: 1.38-3.77). Systemic therapy was not associated with differences in overall survival (HR: 0.77; 95% CI: 0.54-1.10). Likewise, the following factors were associated with worse cancer-specific survival: male sex (HR for female sex versus male sex: 0.60; 95% CI: 0.41-0.88), non-receipt of postoperative radiation therapy (HR: 2.17; 95% CI: 1.27-3.70), and receipt of perioperative systemic therapy (HR: 0.67; 95% CI: 0.45-0.99). CONCLUSION: Postoperative radiotherapy following resection of adrenocortical carcinoma is associated with better overall and cancer-specific survival.

Cisplatin-Based versus Carboplatin-Based Chemotherapy for Extrapulmonary Neuroendocrine Carcinomas: A Real-World Study.

OBJECTIVE: This study aimed to assess the survival differences between cisplatin/etoposide versus carboplatin/etoposide chemotherapy regimens in the management of patients with extrapulmonary neuroendocrine carcinomas (NECs). METHODS: Administrative cancer care databases in the province of Alberta, Canada, were reviewed, and patients with extrapulmonary NECs (including those with small cell and large cell neuroendocrine carcinomas) who were treated with either cisplatin/etoposide or carboplatin/etoposide, 2004-2019, were reviewed. Kaplan-Meier survival estimates were used to compare the survival outcomes according to the type of platinum agent, and multivariable Cox regression analysis was used to assess the impact of the type of platinum agent on overall survival outcomes. RESULTS: A total of 263 eligible patients were included in this analysis. These include 176 patients who received cisplatin/etoposide and 87 patients who received carboplatin/etoposide. Using Kaplan-Meier survival estimates, patients treated with cisplatin had better overall survival compared to patients treated with carboplatin (p = 0.005). Multivariable Cox regression analysis suggested that the following factors were associated with worse overall survival: higher Charlson comorbidity index (HR: 1.17; 95% CI: 1.05-1.30), gastrointestinal primary site (HR: 1.55; 95% CI: 1.12-2.14), stage IV disease (HR: 1.75; 95% CI: 1.28-2.38), and use of carboplatin (HR: 1.40; 95% CI: 1.02-1.92). CONCLUSIONS: The current study suggested that cisplatin/etoposide might be associated with better overall survival compared to carboplatin/etoposide among patients with extrapulmonary NECs. It is unclear if this is related to differences in inherent responsiveness to the 2 platinum agents or due to differences in comorbidity burden between the 2 treatment groups.

Socioeconomic disparities in the prevalence of comorbid chronic conditions among Canadian adults with cancer.

OBJECTIVE: To evaluate the prevalence of comorbid chronic conditions among Canadian adults with cancer and the impact of socioeconomic background on the distribution of these conditions. METHODS: Canadian Community Health Survey (CCHS) 2017-2018 dataset was accessed and individuals with complete information about cancer history were reviewed. The prevalence of the following 10 chronic conditions was reviewed: asthma, chronic obstructive pulmonary disease, arthritis, hypertension, hypercholesterolemia/hyperlipidemia, heart disease, stroke, diabetes, mood disorder, and anxiety disorder. Stratification of the prevalence was done according to age, sex, and racial subgroups. Multivariable logistic regression analysis was done to evaluate the association between sociodemographic characteristics and having multiple comorbid conditions. RESULTS: A total of 104,362 participants were included in the current study (including 10,782 participants with a history of cancer; and 93,580 participants without a history of cancer). Among all age, sex, and race strata, participants with a history of cancer were more likely to have multiple chronic conditions (p < 0.05 for all comparisons). The most common three individual comorbid conditions among participants with cancer were arthritis (40.2%), hypertension (36.1%), and hypercholesterolemia (25.2%); while the most common cancer-comorbidity triad among participants with cancer was cancer/arthritis/hypertension (17.7%). In a multivariable logistic regression analysis among participants with cancer, the following sociodemographic factors were associated with having multiple comorbid conditions: older age (OR for age 80+ versus age 18-20 years: 8.32; 95% CI: 5.17-13.39), indigenous racial group (OR: 1.94; 95% CI: 1.43-2.63) and lower income (OR for income ≥80,000 Canadian dollars (CAD) versus income: ≤20,000 CAD: 0.29; 95% CI: 0.23-0.37). CONCLUSION: History of cancer is associated with a higher probability of many comorbid conditions. This excess comorbidity burden seems to be unequally shouldered by individuals in the lower socioeconomic stratum as well as minority populations.

Cyclin-dependent Kinases 4/6 Inhibitors in Neuroendocrine Neoplasms: from Bench to Bedside.

PURPOSE OF REVIEW: Cyclin-dependent kinases (CDKs) are key regulators that play an important role in cell division. Palbociclib, ribociclib and abemaciclib showed significant antitumor activity in several malignancies and, recently, also a myeloprotective effect for trilaciclib when added to chemotherapy. The purpose of this review is to highlight the current evidence for CDK4/6 inhibitors in neuroendocrine neoplasms (NENs). RECENT FINDINGS: Preclinical results showed a promising antitumor activity of CDK4/6 inhibitors in neuroendocrine tumors (NETs), but so far, the very few small clinical trials did not show a strong impact on progression free survival (PFS) and objective response in NETs. Meanwhile, the CDK4/6 inhibitor trilaciclib revealed significant effects in reducing chemotherapy-induced myelosuppression in small cell lung cancer (SCLC). Up to date, CDK4/6 inhibitors are still considered investigational in NETs as antitumor agents, whereas trilaciclib can be used in the routine clinical practice in extensive stage SCLC patients for reducing myelotoxicity of standard chemotherapy.

Pregnancy and perinatal outcomes following exposure to antineoplastic agents around pregnancy within the US FDA Adverse Event Reporting System.

Objective: To review pregnancy and perinatal outcomes associated with exposure to antineoplastic drugs around pregnancy as reported within the US FDA Adverse Event Reporting System (FAERS). Methods: The FAERS database was accessed and reports of exposure to antineoplastic drugs before/during pregnancy 2000-2020 were reviewed. An analysis of the frequency of different adverse pregnancy outcomes and perinatal outcomes was conducted for all agents as well as for specific categories of antineoplastic agents. Results: A total of 5312 reports of pregnancy exposure to antineoplastic drugs within the FAERS database were found to be eligible and were included in the current study. The most frequent adverse pregnancy outcomes included premature delivery (21.8%) and abortion (11.9%). The most frequent adverse perinatal outcomes included congenital malformations (15.9%) and fetal/neonatal death (12.9%). Conclusions: Within the limitations of the study (especially the lack of an accurate denominator), premature delivery, abortion, fetal/neonatal death and congenital malformations seemed to be the main risks associated with pregnancy exposure to antineoplastic drugs.

The current study sought to review the reports of the exposure of pregnant women to anticancer medications in the US FDA Adverse Event Reporting System database. It suggested that premature delivery, abortion and congenital malformations are possible following these exposures.

Patterns of colorectal cancer diagnosis among younger adults in a real-world, population-based cohort.

Aims: To review the patterns of early-onset (<50 years old) colorectal cancer (CRC) in Alberta across the past 15 years among different socioeconomic and demographic patient subgroups. Methods: This is a retrospective, population-based study based on Alberta administrative databases. Income level was identified via income information from the 2006 Canadian census. Patients with colorectal adenocarcinoma diagnosed 2004-2018 were included. Frequency analyses were used to examine the percentage of early-onset CRC cases among different subgroups over the period studied. Multivariable logistic regression analysis was used to examine factors associated with the development of early-onset CRC. Results: A total of 24,912 patients were included, of whom 2096 (8.4%) were diagnosed at age <50 years and 22,816 (91.6%) at age ≥50 years. The percentage of patients diagnosed at age <50 years increased over time (10.2% in 2018 vs 7.9% in 2004; p < 0.003). Higher income was associated with younger age at diagnosis of CRC (odds ratio [OR] for quartile 1 vs quartile 4: 0.54; 95% CI: 0.47-0.62). Other factors associated with younger age at diagnosis included female sex (OR for male vs female: 0.85; 95% CI: 0.78-0.94), distal CRC (OR: 1.66; 95% CI: 1.50-1.84) and North zone (OR for South zone vs North zone: 0.74; 95% CI: 0.60-0.92). Conclusion: The proportion of patients (out of the overall CRC population) with early-onset CRC, increased in Alberta throughout the study duration (particularly left-sided CRC). There is a need to reassess the current age limits for CRC screening in Canada in view of these findings.

Lay abstract In this study, we found that the percentage of younger individuals with colorectal cancer has increased in Alberta, particularly for cancers arising from the rectum and left side of the colon. Reassessment of the recommended age to start colorectal cancer screening in Canada is needed.

Dietary Supplements Use among Adults with Cancer in the United States: A Population-Based Study.

To assess the patterns of use of dietary supplements among cancer survivors in the United States in a population-based setting. National Health and Nutrition Examination Survey (NHANES) datasets (1999-2016) were accessed, and adult respondents (≥ 20 years old) with a known status of cancer diagnosis and a known status of dietary supplements intake were included. Multivariable logistic regression analysis was then used to assess factors associated with dietary supplements intake. Moreover, and to evaluate the impact of dietary supplements on overall survival among respondents with cancer, multivariable Cox regression analysis was conducted. A total of 49,387 respondents were included in the current analysis, including a total of 4,575 respondents with cancer. Among respondents with cancer, 3,024 (66.1%) respondents have reported the use of dietary supplements; while 1,551 (33.9%) did not report the use of dietary supplements. Using multivariable logistic regression analysis, factors associated with the use of dietary supplements included older age (OR: 1.028; 95% CI: 1.027-1.030); white race (OR for black race vs. white race: 0.67; 95% CI: 0.63-0.72); female gender (OR for males vs. females: 0.56; 95% CI: 0.53-0.59), higher income (OR: 1.13; 95% CI: 1.11-1.14), higher educational level (0.59; 95% CI: 0.56-0.63), better self-reported health (OR: 1.36; 95% CI: 1.17-1.58), health insurance (OR: 1.35; 95% CI: 1.27-1.44), and history of cancer (OR: 1.20; 95% CI: 1.10-1.31). Using multivariable Cox regression analysis and within the subgroup of respondents with a history of cancer, the use of dietary supplements was not found to be associated with a difference in overall survival (HR: 1.13; 95% CI: 0.98-1.30). Dietary supplement use has increased in the past two decades among individuals with cancer in the United States, and this increase seems to be driven mainly by an increase in the use of vitamins. The use of dietary supplements was not associated with any improvement in overall survival for respondents with cancer in the current study cohort.

A Real-World, Population-Based Study for the Incidence and Outcomes of Neuroendocrine Neoplasms of Unknown Primary.

OBJECTIVE: The aim of the study was to provide a real-world, population-based assessment of the incidence and outcomes of neuroendocrine neoplasms (NENs) of unknown primary. METHODS: Surveillance, Epidemiology, and End Results registry was accessed, and cases with NENs of unknown primary were reviewed. Rates of NENs diagnosis 1975-2017 according to primary tumor site were also reviewed. Survival outcomes of patients with NENs of unknown primary compared to metastatic NENs with known primary were determined through Kaplan-Meier estimates and multivariable Cox regression analysis. Overall and cancer-specific survival analyses were stratified by primary site and histology (neuroendocrine tumor vs. neuroendocrine carcinoma). RESULTS: A total of 3,550 cases (7%) were diagnosed with NENs of unknown primary within the study duration. The annual percent change for NENs of unknown primary was 3.4 (95% CI: 2.6-4.2). Within the cohort of metastatic neuroendocrine tumor patients (carcinoid tumor histology), the following factors were associated with a lower risk of death; younger age (HR: 0.477; 95% CI: 0.443-0.513), female sex (HR: 0.922; 95% CI: 0.860-0.989), and small intestinal primary (HR for unknown primary vs. small intestinal primary: 1.532; 95% CI: 1.408-1.668). Within the cohort of metastatic neuroendocrine carcinoma, the following factors were associated with a lower risk of death in this cohort; younger age (HR: 0.646; 95% CI: 0.612-0.681), female sex (HR: 0.843; 95% CI: 0.801-0.888), and small intestinal primary (HR for unknown primary vs. small intestinal primary: 2.961; 95% CI: 2.586-3.391). CONCLUSIONS: The diagnosis of NENs of unknown primary has increased across the past 4 decades. Outcomes of individuals with metastatic small intestinal NENs seem to be better than those with metastatic NENs of unknown primary (for both carcinoid tumors and neuroendocrine carcinomas).

Patterns and Trends of Cancer Screening in Canada: Results From a Contemporary National Survey.

BACKGROUND: The aim of this study was to assess the patterns and trends of colorectal, breast, and cervical cancer screening within a contemporary cohort of Canadian adults. METHODS: Canadian Community Health Survey datasets (2007-2016) were accessed and 3 cohorts were defined: (1) a colorectal cancer (CRC) screening cohort, defined as men and women aged 50 to 74 years with complete information about CRC screening tests and their timing; (2) a breast cancer screening cohort, defined as women aged 40 to 74 years with complete information about mammography and its timing; and (3) a cervical cancer screening cohort, defined as women aged 25 to 69 years with complete information about the Papanicolaou (Pap) test and its timing. Multivariable logistic regression analysis was then performed to evaluate factors associated with not having timely screening tests at the time of survey completion. RESULTS: A total of 99,820 participants were considered eligible for the CRC screening cohort, 59,724 for the breast cancer screening cohort, and 46,767 for the cervical cancer screening cohort. Among eligible participants, 43% did not have timely recommended screening tests for CRC, 35% did not have timely mammography (this number decreased to 26% when limiting the eligible group to ages 50-74 years), and 25% did not have a timely Pap test. Lower income was associated with not having a timely recommended screening tests for all 3 cohorts (odds ratios [95% CI]: 1.86 [1.76-1.97], 1.89 [1.76-2.04], and 1.96 [1.79-2.14], respectively). Likewise, persons self-identifying as a visible minority were less likely to have timely recommended screening tests in all 3 cohorts (odds ratios for White race vs visible minority [95% CI]: 0.87 [0.83-0.92], 0.85 [0.80-0.91], and 0.66 [0.61-0.70], respectively). CONCLUSIONS: More than one-third of eligible individuals are missing timely screening tests for CRC. Moreover, at least one-quarter of eligible women are missing their recommended breast and cervical cancer screening tests. More efforts from federal and provincial health authorities are needed to deal with socioeconomic disparities in access to cancer screening.

Racial Background and Health Behaviors Among Adults With Cancer in Canada: Results of a National Survey.

BACKGROUND: This study was an assessment of the impact of racial background on health behaviors among Canadian adults with a concurrent or past history of a cancer diagnosis. METHODS: The Canadian Community Health Survey datasets (2015-2018) were accessed, and adults (age ≥18 years) with cancer were reviewed. Information about the racial background, socioeconomic status, and different health behaviors was reviewed. Multivariable logistic regression analyses for factors associated with different health behaviors were conducted. RESULTS: A total of 20,514 participants with a history of cancer were considered eligible and were included in the analysis. Compared with individuals who self-identified as White, those who self-identified as indigenous were less likely to have received an influenza vaccination in the past year (odds ratio [OR], 1.253; 95% CI, 1.084-1.448), less likely to have drunk alcohol in the past 12 months (OR, 0.641; 95% CI, 0.546-0.752), more likely to be current smokers (OR, 2.245; 95% CI, 1.917-2.630), and more likely to have used recreational drugs in the past 12 years (OR, 1.488; 95% CI, 1.076-2.057). Compared with individuals who self-identified as White, those who self-identified as non-White and nonindigenous were less likely to have received an influenza vaccination in the past year (OR, 1.207; 95% CI, 1.035-1.408), less likely to have drunk alcohol in the past 12 months (OR, 0.557; 95% CI, 0.463-0.671), and less likely to be current smokers (OR, 0.605; 95% CI, 0.476-0.769). CONCLUSIONS: Within the Canadian context, there is a considerable variability in the health behaviors of adults with cancer according to their racial background. There is a need to tailor the survivorship care planning of patients with cancer based on socioeconomic context.

The impact of gender and HPV status on anal squamous cell carcinoma survival.

BACKGROUND: Anal cancer is a rare entity and the effect of gender and HPV status on survival is controversial. We aimed to evaluate the difference in overall survival (OS) according to gender and analyzed the effect of HPV status on OS. PATIENTS AND METHODS: The National Cancer Database (NCDB) was queried for patients with anal squamous cell carcinoma between 2004 and 2016. We evaluated the OS based on gender and HPV status using Kaplan-Meier estimates and we used multivariate Cox regression analyses to evaluate factors associated with overall survival. RESULTS: A total of 6133 patients with known HPV status were included for analysis. In the non-metastatic group, male gender was associated with worse OS (HR 1.50, 95% CI 1.32-1.70; P<0.001) whereas HPV status did not affect the OS (HR 1.08, 95% CI 0.96-1.22; P=0.213). In the metastatic group, there was no difference in OS based on gender (HR 1.29, 95% CI 0.91-1.82; P=0.148), whereas HPV-negative status was associated with worse OS (HR 1.52, 95% CI 1.09-2.12; P=0.014). CONCLUSION: Females had better OS only in non-metastatic anal squamous cell carcinoma (ASCC). HPV-negative status was associated with worse OS only in metastatic ASCC.

Hospitalizations among early-stage colon cancer patients receiving adjuvant chemotherapy: a real-world study.

OBJECTIVE: To assess the patterns of hospitalizations among early-stage colon cancer patients receiving adjuvant chemotherapy and to identify high-risk groups that may benefit from more careful monitoring in a real-world, population-based context. METHODS: This is a population-based study using linked administrative databases from the province of Alberta, Canada. Any events of hospitalization among patients with non-metastatic colon cancer undergoing upfront surgery followed by adjuvant chemotherapy were reviewed. Multivariable logistic regression analysis was used to examine factors associated with risk of hospitalization, and the impact of hospitalization on overall survival was assessed through Kaplan-Meier estimates and Multivariable Cox regression analysis. RESULTS: A total of 2257 patients were considered eligible and were included in the current analysis, including 483 patients (21.4%) who were hospitalized within 6 months of the start of adjuvant chemotherapy, and 1774 patients (78.6%) who were not. The following factors were associated with a higher hospitalization risk: older age (OR: 1.02; 95% CI 1.01-1.03), higher comorbidity (OR: 1.48; 95% CI 1.31-1.67), women (OR for men versus women: 0.79; 95% CI 0.64-0.98), living in the North zone (OR for Edmonton zone versus North zone: 0.60; 95% CI 0.42-0.87), and CAPOX chemotherapy (OR for CAPOX versus FOLFOX: 1.50; 95% CI 1.12-2.00). Patients with a history of hospitalization during adjuvant chemotherapy had a worse overall survival compared to patients who were not hospitalized (P < 0.001). CONCLUSION: In this study, one out of five colon cancer patients were hospitalized during adjuvant chemotherapy. Older individuals, women, those with higher comorbidity, and those receiving adjuvant CAPOX were more likely to be hospitalized.

Real-world patterns of chemotherapy administration and attrition among patients with metastatic colorectal cancer.

OBJECTIVE: To assess the real-world patterns of systemic treatment attrition rates among patients with metastatic colorectal cancer. METHODS: Databases based from the provincial cancer registry and electronic medical records in Alberta were accessed, and cases with a de novo diagnosis of metastatic colorectal cancer with no history of other primary cancers (2004-2017) were reviewed. Rates of chemotherapy administration in first and subsequent lines of treatment were assessed. Multivariable logistic regression analysis for factors associated with non-administration of chemotherapy was evaluated. The impact of administration of all three chemotherapy agents (fluoropyrimidines, oxaliplatin, and irinotecan) across the course of treatment was assessed through multivariable Cox regression analysis with time-dependent covariates. RESULTS: A total of 4179 patients with metastatic colorectal cancer were included in the current study. This includes 1988 patients receiving at least one cycle of chemotherapy and 2191 patients who did not receive any chemotherapy. The following factors were associated with a higher probability of no chemotherapy use: older age (OR 1.064; 95% CI 1.057-1.070), higher Charlson comorbidity index (OR 1.444; 95% CI 1.342-1.554), female sex (OR for male sex versus female sex 0.763; 95% CI 0.660-0.881), rural residence (OR for residence in zone 2 (Calgary) versus zone 5 (North zone) 0.346; 95% CI 0.272-0.440), proximal tumor location (OR 1.255; 95% CI 1.083-1.454), and earlier year at diagnosis (OR (continuous) 0.895; 95% CI 0.879-0.911). Within the cohort of patients who received at least one cycle of chemotherapy, 42.5% received one line of chemotherapy only, and 30.5% received two lines of chemotherapy. The use of all three chemotherapy drugs was associated with better overall survival (HR 3.305; 95% CI 2.755-3.965) and colorectal cancer-specific survival (HR 3.367; 95% CI 2.753-4.117). CONCLUSIONS: A considerable proportion of metastatic colorectal cancer patients who received active chemotherapy in this population-based study received only one line of therapy. This highlights the significance of choosing effective treatments in the first-line treatment as the attrition rate is high. Furthermore, the use of all three chemotherapy agents across the course of treatment was associated with better outcomes.

Outcomes of non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms treated with surgery: a real-world population-based study.

OBJECTIVE: To assess the outcomes of non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) treated with radical surgery. METHODS: Surveillance, Epidemiology, and End Results (SEER) database (1998-2015) was accessed, and patients with non-metastatic poorly differentiated/undifferentiated GEP-NENs were reviewed. Multivariable Cox regression analysis was used to evaluate factors affecting overall survival (OS) and cancer-specific survival (CSS). Patients treated with radical surgery were matched to those who did not undergo surgery through propensity score matching and Kaplan-Meier survival estimates were used to evaluate the impact of surgery in the post-propensity cohort. RESULTS: A total of 1517 patients were included. Within multivariable Cox regression models and compared to no surgery, radical surgery was associated with improved OS (HR: 0.41; 95% CI: 0.34-0.50) and CSS (HR: 0.37; 95% CI: 0.29-0.47). A total of 233 patients who underwent no surgery were then matched to 233 patients who underwent radical surgery. Within the post-propensity cohort, radical surgery was associated with improved OS (P < 0.001). CONCLUSIONS: Radical surgery is associated with improved survival outcomes in patients with non-metastatic poorly differentiated GEP-NENs. Further studies are required to better identify the best timing of radical surgery within the context of multimodal management.

Factors associated with fatal coronavirus disease 2019 infections among cancer patients in the US FDA Adverse Event Reporting System database.

Aim: To explore factors affecting coronavirus disease 2019 (COVID-19) mortality among cancer patients based on a pharmacovigilance database. Methods: US FDA Adverse Event Reporting System (FAERS) quarterly data extract files were reviewed for quarters two, three and four of 2020 (i.e., April to December). Patients with an indication related to malignancy and a reported COVID-related reaction were selected. Multivariate logistic regression analysis for factors associated with a fatal outcome was conducted. Results: A total of 2708 patients were included. The following factors were associated with fatal COVID-19 infection: older age (odds ratio [OR]: 1.03; 95% CI: 1.01-1.04), male sex (OR: 1.43; 95% CI: 1.07-1.91), non-US report source (OR: 2.46; 95% CI: 1.93-3.13), hematological malignancy (OR: 1.62; 95% CI: 1.28-2.07), potentially immunosuppressive treatment (OR: 1.83; 95% CI: 1.30-2.58) and diagnosis in quarter two versus quarter four (OR: 1.62; 95% CI: 1.27-2.07). Conclusion: Within FAERS reports, cancer patients who are older, males and receiving immunosuppressive treatment and those with hematological malignancies were at a higher risk of death because of COVID-19 infection.

Lay abstract In this study, individuals with a diagnosis of cancer who were older and males and those receiving immunosuppressive treatment seemed to be at a higher risk of a fatal outcome of coronavirus disease 2019 infection.

Immunotherapy in Neuroendocrine Neoplasms: Where Are We Now?

OPINION STATEMENT: Immune checkpoint inhibitors (ICIs) represent a breakthrough in the management of many hard-to-treat cancers over the past decade with demonstrable improvement in survival outcomes. We reviewed the state of the art of ICIs in neuroendocrine neoplasms (NENs). While ICIs have become part of the standard of care for the management of small cell lung cancer (SCLC), their role is still unclear in the management of extra-pulmonary (EP) poorly differentiated neuroendocrine carcinomas (NECs) as well as in the management of well-differentiated neuroendocrine tumors (NETs). Conflicting results derived from the various studies in NETs and EP NECs therefore for specific settings, such as the lung NETs, or therapeutic regimen, e.g., combo vs single agent, for ICIs benefit. Therefore, at the moment, no ICIs approach is justified for NETs and EP NECs in clinical practice. Future investigations should be designed with the aim to overcome the several limitations of the current trials, e.g., lacking of a central pathology review or heterogeneity of the cohorts, in order to reduce the risk of biases. Future trials combining ICIs with other biological agents are welcome. This review aims to provide a comprehensive overview of the biological rationale and evolving clinical applications of the use of ICIs in the management of NENs (both well-differentiated and poorly differentiated groups).

Risk of arterial and venous thromboembolic events among patients with colorectal carcinoma: a real-world, population-based study.

Objective: To assess real-world patterns of arterial and venous thromboembolism among patients with colorectal carcinoma. Methods: The Alberta provincial cancer registry and other provincial medical records were used to identify patients with colorectal cancer (2004-2018) with no preceding or succeeding cancer diagnosis. The incidence of both arterial and venous thromboembolism in this patient population as well as factors associated with these thromboembolic events were examined through logistic regression analysis. Results: A total of 17,296 patients were found eligible and were included into the current study. We observed that 1564 patients (9%) experienced a thromboembolic event and 15,732 patients (91%) did not. The following factors were associated with any thromboembolic event: male sex (odds ratio [OR]: 1.20; 95% CI: 1.08-1.34), higher comorbidity (OR: 1.36; 95% CI: 1.31-1.41), metastatic disease (OR for nonmetastatic vs metastatic disease: 0.53; 95% CI: 0.47-0.60), living within North zone (OR for Edmonton zone vs North zone: 0.70; 95% CI: 0.59-0.84), treatment with fluoropyrimidines (OR for no fluoropyrimidines vs fluoropyrimidines: 0.53; 95% CI: 0.47-0.60) and treatment with bevacizumab (OR: for no bevacizumab vs bevacizumab: 0.53; 95% CI: 0.47-0.60). Factors associated with venous thromboembolism include, younger age (continuous OR with increasing age: 0.99; 95% CI: 0.98-0.99), higher comorbidity (OR: 1.10; 95% CI: 1.04-1.17), metastatic disease (OR for nonmetastatic disease vs metastatic disease: 0.40; 95% CI: 0.35-0.47), North zone (OR for Edmonton zone vs North zone: 0.70; 95% CI: 0.56-0.86), treatment with fluoropyrimidines (OR for no fluoropyrimidines vs fluoropyrimidines: 0.45; 95% CI: 0.39-0.53) and treatment with bevacizumab (OR for no bevacizumab vs bevacizumab: 0.73; 95% CI: 0.58-0.93). Conclusion: Thromboembolic events are not uncommon among colorectal cancer patients, and the risk is increased with male sex, higher comorbidity, presence of metastatic disease, living within the North zone of the province (where there is limited access to tertiary care centers) and treatment with fluoropyrimidines or bevacizumab.

Lay abstract In this analysis of patients who have been diagnosed of colon and rectal cancers in Alberta, Canada, development of blood clots was not uncommon. Certain patient and treatment risk factors seem to increase the risk of this phenomenon.

Outcomes of Patients With Advanced Gastrointestinal Cancer in Relationship to Opioid Use: Findings From Eight Clinical Trials.

BACKGROUND: This study assessed the patterns of opioid use among patients with advanced gastrointestinal cancers who were included in 8 clinical trials and evaluated the impact of opioid use on survival outcomes of included patients. METHODS: Deidentified datasets from 8 clinical trials evaluating first-line systemic treatment of advanced gastrointestinal cancers were accessed from the Project Data Sphere platform (ClinicalTrial.gov identifiers: NCT01124786, NCT00844649, NCT00290966, NCT00678535, NCT00699374, NCT00272051, NCT00305188, and NCT00384176). These trials evaluated patients with pancreatic carcinoma, gastric carcinoma, hepatocellular carcinoma (HCC), and colorectal carcinoma. Multivariable logistic regression analysis was used to evaluate factors predicting the use of opioids. Kaplan-Meier survival estimates were used to compare survival outcomes in each disease entity among patients who did or did not receive opioid treatment. Multivariable Cox regression analysis was then used to further assess the impact of opioid use on survival outcomes in each disease entity. RESULTS: A total of 3,441 participants were included in the current analysis. The following factors predicted a higher probability of opioid use within logistic regression analysis: younger age at diagnosis (odds ratio [OR], 0.990; 95% CI, 0.984-0.997; P=.004), nonwhite race (OR for white vs nonwhite, 0.749; 95% CI, 0.600-0.933; P=.010), higher ECOG score (OR for 1 vs 0, 1.751; 95% CI, 1.490-2.058; P<.001), and pancreatic primary site (OR for colorectal vs pancreatic, 0.241; 95% CI, 0.198-0.295; P<.001). Use of opioids was consistently associated with worse overall survival (OS) in Kaplan-Meier survival estimates of each disease entity (P=.008 for pancreatic cancer; P<.001 for gastric cancer, HCC, and colorectal cancer). In multivariable Cox regression analysis, opioid use was associated with worse OS among patients with pancreatic cancer (hazard ratio [HR], 1.245; 95% CI, 1.063-1.459; P=.007), gastric cancer (HR, 1.725; 95% CI, 1.403-2.122; P<.001), HCC (HR, 1.841; 95% CI, 1.480-2.290; P<.001), and colorectal cancer (HR, 1.651; 95% CI, 1.380-1.975; P<.001). CONCLUSIONS: Study findings suggest that opioid use is consistently associated with worse OS among patients with different gastrointestinal cancers. Further studies are needed to understand the underlying mechanisms of this observation and its potential implications.