Simron Singh

Background and Objectives: At diagnosis, the initial staging of well-differentiated neuroendocrine tumors (WD NETs) aids in treatment planning. The somatostatin receptor (SSTR)-PET has been recommended for staging of WD NETs although limited data are available on its impact on non-gastroeneteropancreatic (GEP) NETs. The main purpose of this study was to compare the stage migration after the addition of SSTR-PET to the workup of patients at the initial staging of GEP NETs to those with non-GEP NETs, and its potential impact on patient management. Methods: This prospective study included patients with WD NETs at initial staging. Demographic data, results of conventional and SSTR-PET staging, and SUVmax were recorded. Three panels of experts assessed the potential impact of SSTR-PET to management. Results: There were 482 patients, including 376 with gastroenteropancreatic (GEP) NETs and 106 non-GEP NETs with a median SUVmax of 34.7 [Q1, Q3: 22.8, 59.1]) and 19.0 [Q1, Q3: 7.9, 39.8]), respectively; p < 0.001. The discordant M-stage was recorded in 111/473 patients (23.5%). PET suggested a higher stage in 78/369 GEP NETs (21.1%), including the detection of extrahepatic metastatic disease in 42/114 (36.8%) patients with liver metastases only on CI. For non-GEP NETs, PET suggested a higher stage in 10/104 (9.6%) and CI suggested a higher stage in 15/104 (14.4%), with CI detecting liver metastases more frequently. The potential impact to management for patients with discordant M-stage was scored as moderate to high between 57/101 (56.4%) and 79/101 (78.2%) of patients. Conclusions: One in five patients are upstaged following SSTR-PET, more frequently with GEP NETs than others. SSTR-PET identifies extrahepatic metastatic disease in >1/3 of patients with presumed liver-only metastases on CI. Stage migration following SSTR-PET may result in frequent moderate or significant management change.

We undertook a retrospective study to compare the quality of care delivered to a cohort of newly diagnosed adults with colon, rectal or anal cancer during the early phase of COVID-19 (02/20–12/20) relative to the same period in the year prior (the comparator cohort), and examine the impact of the pandemic on 2-year disease progression and all-cause mortality. We observed poorer performance on a number of quality measures, such as approximately three times as many patients in the COVID-19 cohort experienced 30-day post-surgical readmission (10.5% vs. 3.6%; SD:0.27). Despite these differences, we observed no statistically significant adjusted associations between COVID-19 and time to either all-cause mortality (HR: 0.88, 95% CI: 0.61–1.27, p = 0.50) or disease progression (HR: 1.16, 95% CI: 0.82–1.64, p = 0.41). However, there was a substantial reduction in new patient consults during the early phase of COVID-19 (12.2% decrease), which appeared to disproportionally impact patients who traditionally experience sociodemographic disparities in access to care, given that the COVID-19 cohort skewed younger and there were fewer patients from neighborhoods with the highest Housing and Dwelling, ands Age and Labour Force marginalization quintiles. Future work is needed to understand the more downstream effects of COVID-19 related changes on cancer care to inform planning for future disruptions in care.

Background: The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG). Methods: SORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator’s choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events. Discussion: This is the first trial investigating the efficacy of CAM2029 versus SoC SRL therapy using a head-to-head, superiority trial design. It is expected to be the first trial to investigate the efficacy of increased dosing frequency of a high-exposure SRL. A BIRC will limit bias and measurement variability and ensure high-quality efficacy data. Additionally, inclusion of patients with well-differentiated Grade 3 NET may elucidate treatment strategies for this rarely investigated patient population. Trial registration: ClinicalTrials.gov NCT05050942. Registered on 21st September 2021.

Background: Patients with advanced neuroendocrine tumors (NETs) have multiple treatment options. Ideally, treatment decisions are shared between physician and patient; however, previous studies suggest that oncologists and patients place different value on treatment attributes such as adverse event (AE) rates. High-quality information on NET patient treatment preferences may facilitate patient-centered decision making by helping clinicians understand patient priorities. Methods: This study used 2 discrete choice experiments (DCE) to elicit preferences of NET patients regarding advanced midgut and pancreatic NET (pNET) treatments. The DCEs used the “potentially all pairwise rankings of all possible alternatives” (PAPRIKA) method. The primary objective was to determine relative utility rankings for treatment attributes, including progression-free survival (PFS), treatment modality, and AE rates. Ranking of attribute profiles matching specific treatments was also determined. Levels for treatment attributes were obtained from randomized clinical trial data of NET treatments. Results: One hundred and 10 participants completed the midgut NET DCE, and 132 completed the pNET DCE. Longer PFS was the highest ranked treatment attribute in 64.5% of participants in the midgut NET DCE, and in 59% in the pNET DCE. Approximately, 40% of participants in both scenarios prioritized lower AE rates or less invasive treatment modalities over PFS. Ranking of treatment profiles in the midgut NET scenario identified 60.9% of participants favoring peptide receptor radionuclide therapy (PRRT), and 30.0% somatostatin analogue dose escalation. Conclusion: NET patients have heterogeneous priorities when choosing between treatment options based on the results of 2 independent DCEs. These results highlight the importance of shared decision making for NET patients.

In many jurisdictions, cancer patients were prioritized for COVID-19 vaccination because of increased risk of infection and death. To understand sociodemographic disparities that affected timely receipt of COVID-19 vaccination among cancer patients, we undertook a population-based study in Ontario, Canada. Patients older than 18 years and diagnosed with cancer January 2010 to September 2020 were identified using administrative data; vaccination administration was captured between approval (December 2020) up to February 2022. Factors associated with time to vaccination were evaluated using multivariable Cox proportional hazards regression. The cohort consisted of 356 535 patients, the majority of whom had solid tumor cancers (85.9%) and were not on active treatment (74.1%); 86.8% had received at least 2 doses. The rate of vaccination was 25% lower in recent (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.72 to 0.76) and nonrecent immigrants (HR = 0.80, 95% CI = 0.79 to 0.81). A greater proportion of unvaccinated patients were from neighborhoods with a high concentration of new immigrants or self-reported members of racialized groups (26.0% vs 21.3%, standardized difference = 0.111, P < .001), residential instability (27.1% vs 23.0%, standardized difference = 0.094, P < .001), or material deprivation (22.1% vs 16.8%, standardized difference = 0.134, P < .001) and low socioeconomic status (20.9% vs 16.0%, standardized difference = 0.041, P < .001). The rate of vaccination was 20% lower in patients from neighborhoods with the lowest socioeconomic status (HR = 0.82, 95% CI = 0.81 to 0.84) and highest material deprivation (HR = 0.80, 95% CI = 0.78 to 0.81) relative to those in more advantaged neighborhoods. Despite funding of vaccines and prioritization of high-risk populations, marginalized patients were less likely to be vaccinated. Differences are likely due to the interplay between systemic barriers to access and cultural or social influences affecting uptake.

Due to the ramping down of cancer surgery in early pandemic, many newly diagnosed patients received other treatments first. We aimed to quantify the pandemic-related shift in rate of surgery following chemotherapy. This is a retrospective population-based cohort study involving adults diagnosed with cancer between 3 January 2016 and 7 November 2020 in Ontario, Canada who received chemotherapy as first treatment within 6-months of diagnosis. Competing-risks regression models with interaction effects were used to quantify the association between COVID-19 period (receiving a cancer diagnosis before or on/after 15 March 2020) and receipt of surgical reSection 9-months after first chemotherapy. Among 51,653 patients, 8.5% (n = 19,558) of them ultimately underwent surgery 9-months after chemotherapy initiation. Receipt of surgery was higher during the pandemic than before (sHR 1.07, 95% CI 1.02–1.13). Material deprivation was independently associated with lower receipt of surgery (least vs. most deprived quintile: sHR 1.11, 95% CI 1.04–1.17), but did not change with the pandemic. The surgical rate increase was most pronounced for breast cancer (sHR 1.13, 95% CI 1.06–1.20). These pandemic-related shifts in cancer treatment requires further evaluations to understand the long-term consequences. Persistent material deprivation-related inequity in cancer surgical access needs to be addressed.

Emergency department (ED) use is a concern for surgery patients, physicians and health administrators particularly during a pandemic. The objective of this study was to assess the impact of the pandemic on ED use following cancer-directed surgeries. This is a retrospective cohort study of patients undergoing cancer-directed surgeries comparing ED use from 7 January 2018 to 14 March 2020 (pre-pandemic) and 15 March 2020 to 27 June 2020 (pandemic) in Ontario, Canada. Logistic regression models were used to (1) determine the association between pandemic vs. pre-pandemic periods and the odds of an ED visit within 30 days after discharge from hospital for surgery and (2) to assess the odds of an ED visit being of high acuity (level 1 and 2 as per the Canadian Triage and Acuity Scale). Of our cohort of 499,008 cancer-directed surgeries, 468,879 occurred during the pre-pandemic period and 30,129 occurred during the pandemic period. Even though there was a substantial decrease in the general population ED rates, after covariate adjustment, there was no significant decrease in ED use among surgical patients (OR 1.002, 95% CI 0.957–1.048). However, the adjusted odds of an ED visit being of high acuity was 23% higher among surgeries occurring during the pandemic (OR 1.23, 95% CI 1.14–1.33). Although ED visits in the general population decreased substantially during the pandemic, the rate of ED visits did not decrease among those receiving cancer-directed surgery. Moreover, those presenting in the ED post-operatively during the pandemic had significantly higher levels of acuity.