Switch to generic formulation of temozolomide results in statistically significant increase in grade 3 and 4 bone marrow toxicity in glioma patients in the province of Alberta.

Background: Temozolomide (TMZ) is an oral, systemic chemotherapy used chiefly for treating high-grade glioma. Due to the rising costs of systemic chemotherapy, many jurisdictions have replaced brand name with generic formulations. The aim of this study was to determine whether or not there was difference in the incidence of grade 3 or 4 bone marrow toxicity and median overall survival in patients treated with brand name versus generic TMZ in the province of Alberta, Canada. The province suspended the use of generic TMZ based on preliminary data pointing to excess toxicity. Methods: This multicenter, retrospective study included data from patients with newly diagnosed high-grade glioma that received treatment with TMZ in Alberta. Multivariate logistic regression analysis was performed to determine the association between grade 3 or 4 toxicity to generic versus brand name TMZ exposure, ECOG score, and age. Kaplan-Meier survival estimates and log-rank testing were used to determine differences in overall survival between the brand name and generic TMZ cohorts, as well as the cytopenic versus non-cytopenic patients. Furthermore, a screening analysis for grade 3 or 4 bone marrow toxicity was conducted on all de novo glioma patients treated with brand name TMZ after Alberta preemptively stopped generic TMZ. Results: Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15% and 19% of patients treated with generic TMZ (n = 156) as compared to 3% and 5% of patients (n = 100) treated with brand name TMZ-treated patients; P= .003 and .001. A trend toward increased median overall survival in glioblastoma patients treated with generic TMZ (13.7 months) versus brand name (15.8 months, P = .178.) was also observed through meeting statistical significance. Based on these results, the province stopped the use of generic TMZ and reverted to the Merck TMZ. An initial review of all new glioma patients (n = 89) treated with Merck TMZ since the province stopped the generic drug demonstrated 3.4% and 10.1% grade 3 or 4 neutropenia, respectively. Conclusions: The statistically significant difference in toxicity profile has prompted the province of Alberta to replace generic TMZ with brand name TMZ in high-grade glioma patients pending more detailed analysis. Our study provides evidence supporting the importance of conducting prospective studies on long-term safety for generic chemotherapies.

Remission of Ectopic Cushing Syndrome Secondary to Medullary Thyroid Cancer With Vandetanib and Selpercatinib.

Medullary thyroid cancer (MTC) is a neuroendocrine tumor associated with activating mutations of the rearranged during transfection (RET) proto-oncogene. These tumors may rarely secrete adrenocorticotropin or corticotropin-releasing hormone, resulting in a paraneoplastic ectopic Cushing syndrome (ECS). Paraneoplastic ECS carries a high risk of mortality, and management is difficult due to the lack of response to antiadrenal therapies. We report on a 37-year-old man who was diagnosed with metastatic MTC and reported symptoms of cortisol excess with laboratory testing in keeping with ECS. He began treatment with vandetanib, a multitargeted tyrosine kinase inhibitor, which resulted in decreased tumor burden as well as clinical and biochemical resolution of ECS. Due to progressive structural disease 10 months later, he was switched to the selective RET inhibitor selpercatinib, which was followed by a rapid reduction of cortisol nearing the threshold of adrenal insufficiency. Tumor markers were also improved, and repeat imaging showed decreased tumor burden. Our case highlights the efficacy of tyrosine kinase inhibitors in the management of paraneoplastic ECS. Selective RET inhibitors may emerge as preferred targeted treatment options due to better efficacy and toxicity profiles compared to multitargeted inhibitors. Clinicians should monitor for adrenal insufficiency with the use of selective RET inhibitors.

Changes in the outcomes of patients with anaplastic thyroid carcinoma over the past two decades.

OBJECTIVE: To assess the changes in survival outcomes among patients with anaplastic thyroid carcinoma in the US over the past two decades. METHODS: Surveillance, Epidemiology, and End Results (SEER) database research data were reviewed, and patients with anaplastic thyroid carcinoma, who were diagnosed from 2004 to 2020 were evaluated. Kaplan-Meier survival estimates were conducted to examine differences in overall survival between three year-of-diagnosis groups (2004 to 2010; 2011 to 2016; and 2017 to 2020). Multivariable Cox regression analysis was then performed to explore the factors affecting overall survival. RESULTS: A total of 1804 patients with anaplastic thyroid carcinoma were included. Using Kaplan-Meier survival estimates, overall survival was better among patients diagnosed from 2017 to 2020 versus those diagnosed at earlier periods (P < 0.001). One-year survival estimates were 25% among patients diagnosed from 2017 to 2020 versus 15% for patients diagnosed from 2011 to 2016, and 19%, for patients diagnosed from 2004 to 2010. Using the multivariable Cox regression model, an earlier year of diagnosis was associated with worse overall survival compared to the diagnosis year 2017 to 2020 (HR for diagnosis 2004 to 2010 versus diagnosis 2017 to 2020: 1.170; 95% CI: 1.029 to 1.331, and HR for diagnosis 2011 to 2016 versus diagnosis 2017 to 2020: 1.251; 95% CI: 1.103 to 1.419). CONCLUSIONS: While anaplastic thyroid carcinoma remains a deadly cancer, survival seems to be improving for the last few years compared to earlier years. There is still additional work to be done to improve the outcomes of those patients.

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.

Geographic Disparities in Access to Cancer Clinical Trials in Canada.

OBJECTIVE: This study aims to evaluate geographic disparities in access to cancer clinical trials across Canada. METHODS: Cancer clinical trial data recorded within the clinicaltrials.gov and reporting the conduct of any of these trials in Canada, 2005 to 2023 were reviewed. Frequency analyses of the number of clinical trials that were registered on clinicaltrials.gov for Canada, individual Canadian provinces, main Canadian urban centers, and different cancer types, according to the funding source (industry versus non-industry), as well as according to different periods (using 3-y intervals) were conducted. Moreover, a comparison of cancer clinical trials per 10,000 persons was done between Canada and the United States. RESULTS: The number of cancer clinical trials per 10,000 individuals (according to the 2021 census) in each province/territory varied between 6.79 (New Brunswick) to 0 (the 3 territories). The number of cancer clinical trials in relation to 1000 projected cancer cases for some of the common tumor types in Canada was then reviewed. The highest number was for lymphoma clinical trials (32.85), whereas the lowest number was for bladder cancer clinical trials (7.06). Most of the trials have industry funding (69%). Using 3-year intervals, the highest number of cancer clinical trials was observed from 2014 to 2016 (778 trials), and the lowest number was observed from 2020 to 2022 (633 trials). CONCLUSIONS: Access to clinical trials in Canada is not equitably distributed, with geographical and primary tumor site disparities. Moreover, access to cancer clinical trials has been negatively impacted during the time of the COVID-19 pandemic.

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.

Challenges in Diagnosis and Treatment of Pancreatic Exocrine Insufficiency among Patients with Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to effective anticancer treatments, gravely influence their quality of life, and decrease their overall survival. Pancreatic exocrine insufficiency (PEI) is defined as impaired digestion due to inadequate secretion of pancreatic enzymes and is a common cause of malnutrition in PDAC. This review first summarizes the existing literature around malnutrition in PDAC, with a particular focus on PEI and its management with pancreatic enzyme replacement therapy (PERT). Second, we summarize existing guidelines and recommendations for the management of PEI among patients with PDAC. Lastly, we highlight potential gaps of knowledge of PEI among healthcare providers resulting in underdiagnosis and treatment, which may have implications for the quality of life and overall survival of PDAC patients.

Impact of Patient Characteristics on the Outcomes of Patients with Gastrointestinal Cancers Treated with Immune Checkpoint Inhibitors.

Gastrointestinal (GI) cancers are a group of malignancies that globally account for a significant portion of cancer incidence and cancer-related death. Survival outcomes for esophageal, gastric, pancreatic, and hepatobiliary cancers remain poor, but new treatment paradigms are emerging with the advent of immune checkpoint inhibitor (ICI) therapy. This review characterizes patient-related prognostic factors that influence the response to ICI therapy. We performed an analysis of the landmark randomized clinical trials in esophageal, gastric, colorectal, hepatocellular, pancreatic, and biliary tract cancers in terms of patient demographic factors. A literature review of smaller retrospective studies investigating patient-related factors was completed. The immunological bases for these associations were further explored. The key predictive factors identified include age, sex, performance status, geography, body mass index, sarcopenia, gut microbiome, various biochemical factors, and disease distribution.

Impact of Time From Diagnosis to Treatment Start on the Outcomes of Patients With Nonmetastatic Anal Squamous Cell Carcinoma.

OBJECTIVE: To assess the impact of time from diagnosis to treatment on the survival outcomes of patients with nonmetastatic anal squamous cell carcinoma, controlling for other clinicopathological features. METHODS: Surveillance, Epidemiology, and End Results research plus database was accessed, and patients with nonmetastatic anal squamous cell carcinoma were reviewed. Factors associated with longer time to treatment were evaluated through multivariable logistic regression analysis. Kaplan-Meier survival estimates were used to examine survival differences according to time to treatment (≤2 vs. >2 mo), and multivariable Cox regression analysis was used to examine factors associated with worse overall and cancer-specific survival. RESULTS: A total of 13,032 patients were considered eligible and they were included in this study. The following factors were associated with longer time to treatment (>2 mo): male sex (odds ratio [OR]: 1.503; 95% CI, 1.292 to 1.749), and non-White race (OR for Black vs. White patients: 1.846; 95% CI, 1.488 to 2.290; OR for American Indian vs. White patients: 2.414; 95% CI, 1.197 to 4.872; OR for Asian-Pacific Islanders vs. White patients: 2.182; 95% CI, 1.440 to 3.309). Using Kaplan-Meier survival estimates, longer time to treatment was associated with worse overall survival (median OS for >2 mo=109 mo; for ≤2 mo=164 mo P <0.0001). Using multivariable Cox regression analysis, the following factors were associated with worse overall survival: older age (hazard ratio [HR]: 1.037; 95% CI, 1.034 to 1.039), male sex (HR: 1.650; 95% CI, 1.548 to 1.758), Black race (HR: 1.341; 95% CI, 1.210 to 1.487), advanced stage (HR for regional vs. localized stage: 1.596; 95% CI, 1.500 to 1.698), and longer time to treatment (HR: 1.385; 95% CI, 1.222 to 1.571). CONCLUSIONS: Time from diagnosis to treatment longer than 2 months is associated with worse survival outcomes among patients with nonmetastatic anal squamous cell carcinoma.

Patterns of cigarette smoking and alcohol drinking among Canadian adults with cancer in a contemporary national cohort.

OBJECTIVE: To evaluate the patterns of cigarette smoking and alcohol drinking among Canadian adults with cancer in a contemporary national cohort. METHODS: Canadian Community Health Survey (CCHS) annual surveys (2007-2016) were accessed, and cancer patients (identified by the question: Do you have cancer?) with complete information regarding smoking and alcohol drinking were included in the current analysis. Multivariable logistic regression analyses were conducted to evaluate factors associated with current smoking and alcohol drinking habits. RESULTS: A total of 15,168 adult patients with cancer with complete information about smoking history and alcohol drinking in the past 12 months were included in the current analysis. Fifteen percent of patients were current smokers at the time of survey completion, and 3.2% exceed national limits for alcohol drinking. The following factors were associated with current smoking: younger age (OR: 2.42; 95% CI: 1.54-3.82), common-law partnership (OR versus single status: 2.61; 95% CI: 1.62-4.18), lower income (OR for patients with income <20,000 versus patients with income >80,000: 3.19; 95% CI: 2.26-4.49), poor self-perceived health (OR for excellent versus poor self-perceived health: 0.52; 95% CI: 0.33-0.83), poor self-perceived mental health (OR for excellent versus poor self-perceived mental health: 0.47; 95% CI: 0.29-0.78), heavy alcohol drinking (OR for no heavy alcohol drinking versus heavy alcohol drinking: 0.41; 95% CI: 0.29-0.58), and illicit drug use (OR: 2.42; 95% CI: 1.96-2.98). The following factors are associated with alcohol drinking beyond recommended levels: male sex (OR: 1.59; 95% CI: 1.18-2.14), heavy smoking status (OR for non-smokers versus heavy smokers: 0.30; 95% CI: 0.19-0.48), and illicit drug use (OR: 2.71; 95% CI: 1.96-3.74). CONCLUSIONS: Current smoking and alcohol drinking are not uncommon among Canadian adults with cancer. Further efforts focusing on smoking cessation and alcohol moderation are needed. IMPLICATIONS FOR CANCER SURVIVORS: Coordinated national and provincial efforts are needed to address cigarette smoking and heavy alcohol drinking among individuals with history of cancer.

Exploring the Relationship between Obesity, Metabolic Syndrome and Neuroendocrine Neoplasms.

Obesity is a major burden for modern medicine, with many links to negative health outcomes, including the increased incidence of certain cancer types. Interestingly, some studies have supported the concept of an "Obesity Paradox", where some cancer patients living with obesity have been shown to have a better prognosis than non-obese patients. Neuroendocrine neoplasms (NENs) are malignancies originating from neuroendocrine cells, in some cases retaining important functional properties with consequences for metabolism and nutritional status. In this review, we summarize the existing evidence demonstrating that obesity is both a risk factor for developing NENs as well as a good prognostic factor. We further identify the limitations of existing studies and further avenues of research that will be necessary to optimize the metabolic and nutritional status of patients living with NENs to ensure improved outcomes.

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

OBJECTIVES: The aim of this study was to assess incidence and outcomes of neuroendocrine neoplasms (NENs) arising from primary sites other than digestive organs, lung, or thymic gland. METHODS: Surveillance, Epidemiology, and End Results database (1975-2016) was accessed, and cases of NENs arising from primary sites other than digestive organs, lung, or thymic gland were reviewed. Overall and cancer-specific survival outcomes for NENs arising from different organs compared with small intestinal NENs were evaluated. RESULTS: A total of 4405 patients were included in the study. Compared with small intestinal NENs, some NENs arising from uncommon sites in the current study have worse cancer-specific survival (hazard ratio [HR] for genitourinary vs small intestinal NENs, 1.80; 95% confidence interval [CI], 1.44-2.25; HR for gynecological vs small intestinal NENs, 1.88; 95% CI, 1.52-2.33). When the analysis was limited for patients with distant stage only, small intestinal NENs have better outcomes compared with genitourinary and gynecological NENs (HR for genitourinary NENs with distant stage vs small intestinal NENs with distant stage, 1.38; 95% CI, 1.01-1.88; HR for gynecological NENs with distant stage vs small intestinal NENs with distant stage, 2.02; 95% CI, 1.54-2.66). CONCLUSIONS: Compared with small intestinal NENs, NENs arising from uncommon sites (such as genitourinary, gynecological) have worse survival outcomes.

Impact of perioperative chemotherapy on survival outcomes among patients with metastatic colorectal cancer to the liver.

Aim: Compare overall survival (OS) between adjuvant and neoadjuvant chemotherapy and analyze the effect of chemotherapy on OS. Materials & methods: National Cancer Database was queried for patients diagnosed with metastatic colorectal adenocarcinoma with isolated liver metastases between 2004 and 2016. We evaluated the OS and chemotherapy effect using Kaplan-Meier estimates and multivariable cox regression analyses. Results: Total 6883 patients with metastatic colorectal cancer and liver metastases were included, of which 6042 patients were treated with surgery and chemotherapy and 841 patients were treated with surgery only. Patients who received neoadjuvant chemotherapy had better OS compared with patients who received adjuvant chemotherapy. Conclusion: Patients with colorectal cancer with isolated liver metastases who were treated with neoadjuvant chemotherapy had better OS compared with adjuvant chemotherapy.

The role of surgery in small differentiated thyroid cancer.

INTRODUCTION: The incidence of small, differentiated thyroid cancer (DTC) cases has been increasing in the United States and the world mainly due to incidental detection because of widespread use of diagnostic modalities. While the option of active surveillance instead of surgical resection is getting more popular, there is still an open discussion about the best approach in these cases. MATERIALS AND METHODS: The National Cancer Database was queried for patients diagnosed with non-metastatic small T1/N0 DTC between 2004 and 2016, who have known surgical status and Charlson comorbidity index of two or less. We evaluated the overall survival (OS) based on the surgery status using Kaplan-Meier estimates and multivariable cox regression analyses. RESULTS: A total of 98,501 patients with non-metastatic small DTC were included, within which 96,612 (98.1%) were treated with surgery, and 1889 (1.9%) were not treated with surgery or other ablative modalities. We found that patients who were treated with surgery had better OS compared to patients who were not treated with surgery (mean OS 171 months vs 134.1 months, P < 0.001, median OS was not reached). This difference was still statistically significant even after we used propensity score matching for age, gender, race, Charlson-Deyo score, tumor size, and histology. On multivariate analysis, surgery was associated with better OS (HR 0.218; 95% CI: 0.196-0.244; P < 0.001). Same trend was found in subgroup analysis when we split the cohort according to tumor size (<1 and ≥1 cm), histology (follicular, papillary and Hurthle cell carcinoma), and age (<55 years vs ≥55 years). CONCLUSION: Patients with non-metastatic small DTC who were treated with surgery had significant improvement in OS compared to patients who were not treated with surgery. Notwithstanding the limitations of the current analysis, these results call for caution prior to recommending routine surveillance for all patients with small DTC.

A Real-World Study of the Incidence and Outcomes of Early-Onset Well-differentiated Neuroendocrine Neoplasms.

OBJECTIVE: The objective of this study was to evaluate the incidence and outcomes of adults with early-onset (20 to 34 y) diagnosis of well-differentiated neuroendocrine neoplasms. METHODS: Surveillance, Epidemiology, and End Results (SEER)-18 database was accessed, and patients with well-differentiated lung or digestive tract neuroendocrine neoplasms diagnosed 2000 to 2018 were reviewed. Annual percent changes (APCs) were calculated for the 3 disease subsites (foregut, midgut, and hindgut) stratified by age group. Kaplan-Meier survival estimates/log-rank testing were used to examine differences in overall survival between the 3 age groups. Multivariable Cox regression analyses were used to evaluate factors affecting overall and cancer-specific survivals. RESULTS: Throughout the study period, patients with early-onset disease (20 to 34 y) have experienced the greatest APC (20 to 34 y: 9.7; 35 to 49 y: 5.4; ≥50 y: 4.1). When APCs were stratified by disease subsite, this difference in APCs appears to be driven by midgut tumors (20 to 34 y: 19.2; 35 to 49: 8.4; ≥50 y: 3.8). Using multivariable Cox regression modeling, the following variables were associated with a higher risk of all-cause death (worse overall survival): male sex (hazard ratio [HR] 1.27; 95% confidence interval [CI]: 1.22-1.31), African American race (HR vs. white race: 1.20; 95% CI: 1.15-1.26), nonhindgut primary (HR foregut vs. hindgut primary: 2.02; 95% CI: 1.91-2.13; HR midgut vs. hindgut primary: 2.09; 95% CI: 1.95-2.24), distant disease (HR vs. regional disease: 2.06; 95% CI: 1.96-2.18), no surgery to the primary (HR: 2.34; 95% CI: 2.24-2.46), and older age (HR: 5.80; 95% CI: 4.87-6.91). CONCLUSION: Cases of early-onset well-differentiated neuroendocrine neoplasms have disproportionately increased over the past 2 decades (compared with other age groups), and this appears to have been driven mainly by midgut tumors.

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.

Changes in Survival Outcomes of Patients With Neuroendocrine Neoplasms Over the Past 15 Years: A Real-World Study.

BACKGROUND: The past 2 decades have observed a number of advances in therapeutic approaches to patients with neuroendocrine neoplasms (NENs). This study aims to assess whether survival outcomes have changed among patients with NENs over the past 15 years, in a real-world, population-based study. MATERIALS AND METHODS: We accessed administrative databases within the province of Alberta, Canada, and we reviewed patients with invasive NENs diagnosed 2004 to 2019. Patients were classified according to the year of diagnosis into 3 groups: 2004 to 2008; 2009 to 2013; and 2014 to 2019. Kaplan-Meier survival estimates were used to compare overall survival (OS) according to different baseline characteristics (including the year of diagnosis). Multivariable Cox regression modeling was used to examine factors associated with the risk of death in this cohort. RESULTS: We included a total of 3431 patients in the study cohort. Using multivariable Cox regression analysis, the following factors were associated with worse survival: older age at diagnosis (hazard ratio [HR]: 3.45; 95% CI [confidence interval]: 2.74-4.35), male sex (HR: 1.38; 95% CI: 1.21-1.56), lung primary site (HR for lung vs. appendicular primary: 1.39; 95% CI: 1.01-1.92), Stage 4 disease (HR: 2.80; 95% CI: 2.38-3.30), South zone of the province (HR for South zone vs. Calgary zone: 1.85; 95% CI: 1.49-2.30), and higher comorbidity index (HR for ≥3 vs. 0: 2.66; 95% CI: 2.19-3.24). Although Kaplan-Meier method showed significant difference in OS according to diagnosis period, multivariable regression model showed that the period of diagnosis did not appear to impact OS (HR for diagnosis period 2004 to 2009 vs. 2014 to 2019: 1.04; 95% CI: 0.89-1.22). CONCLUSIONS: Over the study period (2004 to 2019), patients diagnosed during later periods did not appear to experience better OS compared with patients diagnosed at an earlier time.

Sex-based differences in the outcomes of patients with lung carcinoids.

Objective: To assess the impact of sex on the outcomes of patients with well-differentiated lung neuroendocrine neoplasms in a real-world setting. Methods: The Surveillance, Epidemiology and End Results Research Plus database (2000-2018) was accessed, and patients with a diagnosis of typical or atypical carcinoid of the lung were reviewed. Trends in age-standardized rates (per 100,000) of the incidence of lung carcinoid tumors were reviewed among male and female patients as well as the overall population, and annual percent change (APC) was determined for the three groups. Multivariate Cox regression analysis was then used to assess the factors associated with overall and cancer-specific survival. Results: Among all patients, APC (2000-2018) for lung carcinoid diagnosis was 2.9 (95% CI: 2.4-3.5). Among male patients, APC (2000-2018) for lung carcinoid diagnosis was 1.8 (95% CI: 1.2-2.5). By contrast, among female patients, APC (2000-2018) for lung carcinoid diagnosis was 3.4 (95% CI: 2.8-4.1). Based on Kaplan-Meier survival estimates, female sex was associated with better overall survival compared with male sex (p < 0.001). Based on multivariate Cox regression analysis, the following factors were associated with worse cancer-specific survival: older age (hazard ratio [HR]: 1.036; 95% CI: 1.031-1.041), atypical carcinoid histology (HR: 3.10; 95% CI: 2.71-3.56), stage (distant vs localized stage HR: 4.05; 95% CI: 3.48-4.71), sex (male vs female sex HR: 1.76; 95% CI: 1.56-1.99) and no surgical treatment (HR: 3.77; 95% CI: 3.22-4.42). Conclusion: Female patients with lung carcinoid tumors have better overall survival compared with male patients, particularly among patients with typical carcinoid tumors.