Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States.

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients

Developments in Checkpoint Inhibitor Therapy for the Management of Deficient Mismatch Repair (dMMR) Rectal Cancer.

Deficient mismatch repair (dMMR)/microsatellite instability-high (MSIH) colorectal cancer is resistant to conventional chemotherapy but responds to immune checkpoint inhibition (ICI). We review the standard of care in locally advanced dMMR rectal cancer with a focus on ICI. We also present a case report to highlight the treatment complexities and unique challenges of this novel treatment approach. ICI can lead to immune related adverse events (irAEs), resulting in early treatment discontinuation as well as new challenges to surveillance and surgical management. Overall, neoadjuvant ICI can lead to robust treatment responses, but its impact on durable response and organ preservation requires further study

Case Report of Cirrhosis following Yttrium-90 Radioembolization for Pancreatic Neuroendocrine Liver Metastases

Background: Management options for pancreatic neuroendocrine tumors (pNETs) metastatic to the liver include surgical, ablative, cytotoxic, and radioisotope approaches. One potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 (90Y) microspheres. 90Y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver. It appears to be well tolerated; however, there is no randomized controlled trial reporting long-term toxicities. Previous retrospective reports have described biliary damage as a potential complication of therapy with 90Y and chemoembolization; however, the long-term sequelae of 90Y treatment are poorly understood. Case Presentation: We present the case of a 65-year-old Caucasian woman who suffered biliary damage following 90Y administration for metastatic pNETs and subsequently developed cirrhosis. Given the timeline of her various treatments and the lack of any other identifiable etiology for her cirrhosis, we believe this to be a potential long-term complication of 90Y therapy. Conclusion: This case provides pathologic confirmation of cirrhosis as a potential long-term sequela of 90Y treatment. This long-term risk needs to be considered when sequencing therapy for patients with neuroendocrine tumors who have a good prognosis. There are now several other systemic and ablative treatment options available to these patients, and long-term complications must be considered during treatment

Changes in Carcinoid Syndrome Symptoms Among Patients Receiving Telotristat Ethyl in US Clinical Practice: Findings from the TELEPRO-II Real-World Study.

Background: Inadequately controlled symptoms incur a substantial burden on patients with neuroendocrine tumors and carcinoid syndrome (CS). The effectiveness of telotristat ethyl (TE) with a somatostatin analog for uncontrolled CS diarrhea has been demonstrated in clinical trials and observational studies. TELEPRO-II was a prospective observational study evaluating TE\u27s effectiveness in clinical practice over the first 3 months of treatment. Methods: Patients initiating TE in 2018 participated in an optional nurse support program reporting CS symptoms during interviews at baseline and 1, 2, and 3 months after TE initiation. Eligible patients received TE for ≥3 months and reported symptom burden at baseline and ≥1 follow-up visit within the first 3 months. Daily bowel movement (BM) frequency and flushing episodes were reported as events/episodes per day. Stool consistency, nausea severity, urgency severity, and abdominal pain were reported on a severity scale (1-10). Symptom changes were evaluated using paired-sample Results: A total of 684/1603 (43%) patients were eligible for analysis. At baseline, patients reported a mean of 6.3 BM/day, nausea severity of 8.4/10 and stool urgency of 8.2/10. Significant improvements in all CS symptoms were observed after 3 months of TE. Mean daily BMs were reduced 64% after 3 months of TE (mean reduction [SD], -3.99 [3.8]; P Conclusion: Patients treated with TE in a real-world setting experienced significant, clinically meaningful improvements in CS symptoms

Supportive Management of Patients with Advanced Pheochromocytomas and Paragangliomas Receiving PRRT.

Peptide receptor radionuclide therapy (PRRT) is used to treat patients with advanced malignant pheochromocytomas (PCCs) and paragangliomas (PGLs). Patients are at risk of a PRRT-induced catecholamine crisis, and standard guidelines regarding the prevention and management of infusion reactions are lacking. In this case series, the institutional experience of five sequential patients with metastatic PCCs and PGLs receiving PRRT on an outpatient basis is described, of which four had symptomatic tumors and three had a high burden of disease. All patients with symptomatic tumors were treated with preventive management prior to the initiation of PRRT, and no infusion reactions or catecholamine crises were documented. PRRT may be delivered safely on an outpatient basis for patients with metastatic PCCs and PGLs with the involvement of an interdisciplinary team

Treatment dependent improvements in survival of stage 2/3 rectal cancer patients treated with trimodality therapy between 2006-2016, an NCDB analysis.

Research Funding: None Background:Trimodality therapy (TT) with chemo/radiation (C/RT), chemotherapy and total mesorectal excision (TME) surgery remains the standard for patients with stage 2/3 rectal cancer. Use of pre-operative (pre-op) C/RT is an important Commission on Cancer (CoC) quality benchmark but has not previously been shown to improve overall survival when compared to post-op C/RT. The objective of this study was to document the impact on survival of peri-op C/RT in stage 2/3 rectal cancer in a broad population.Methods:The National Cancer Database was used to identify all patients diagnosed with stage 2/3 rectal cancer from 2006-16. Included patients received true TT and were classified into groups A, Total Neoadjuvant Therapy (TNT) with pre-op C/RT + pre-op multi-agent (MA) chemotherapy (CT); group B, pre-op C/RT+ post-op single-agent CT; group C, pre-op C/RT + post-op MA CT; and group D, post-op C/RT and MA CT. Cox multivariate survival analysis were performed including demographics, peri-op C/RT, surgery type, stage, lymph node count, year of diagnosis and facility type: academic (Acad), Comprehensive (Comp)/Community (Comm), Integrated (Integ) and unknown (Unkn).Results:Of 110,372 stage 2/3 patients, 32,467 received TT (mean age 58, 61% male) and were included. Of these, 8883 (27%, group A) received TNT, 5967 (18%) were in group B, 12,928 (40%) in group C, while 4,689 (14%) were in group D. A reduction in use of post-operative C/RT (group D) was observed between 2006 (28%) and 2016 (8%), p \u3c .001, accompanied by a reciprocal increase in patients receiving pre-op C/RT and post-op MA CT (Group C) between 2006 and 2016 (24 to 45%, respectively, p\u3c0.001). Increasing use of pre-op C/RT led to a migration to lower pathologic stages 0/1/2/3 from 0.60/10/31/57% in 2006, to 2.8/22/29/45% in 2016, respectively (p \u3c .001), while clinical stage 2/3 distribution remained unchanged. Receipt of pre-operative C/RT (Groups A/B/C) was associated with improved survival compared to post-op C/RT (group D) (table).Conclusions:Between 2006-2016 the proportion of patients with stage 2/3 rectal cancer treated with post-op C/RT declined dramatically and in 2016 accounted for 8% of all patients treated with TT. Multivariate analysis documented superior overall survival among patients treated with pre-operative C/RT, justifying the introduction of the CoC quality benchmark