Involvement of low- and middle-income countries in randomized controlled trial publications in oncology

Background: We describe trends in participation by investigators from low- and middle-income countries (LMCs) in publications describing oncology randomized control trials (RCTs) over a decade. Methods: We used Medline to identify RCTs published in English from 1998 to 2008 evaluating treatment in lung, breast, colorectal, stomach and liver cancers. Data on author affiliations, authorship roles, trial characteristics, funding and interventions were extracted from each article. Countries were stratified as low-, middle- or high-income using World Bank data. Interventions were categorized as requiring basic, limited, enhanced or maximal resources as per the Breast Health Global Initiative classification. Logistic regression was used to identify factors associated with authorship by investigators from LMCs. Results: 454 publications were identified. Proportion of articles with at least one LMC author increased over time from 20% in 1998 to 29% in 2008 (p = 0.01), but almost all LMC authors were from middle-income countries. Proportion of articles with at least one LMC author was higher among articles that explicitly reported recruitment in at least one LMC vs those that did not (76% vs 13%). Among 87 articles (19%) that involved authors from LMCs, 17% had LMC authors as first or corresponding authors, and 67% evaluated interventions requiring enhanced or maximal resources. Factors associated with LMC authorship included industry funding (OR = 3.54, p = 0.0001), placebo comparator arm (OR = 2.57, p = 0.02) and palliative intent treatment (OR = 4.00, p = 0.0003). Conclusion: An increasing number of publications describing oncology RCTs involve authors from LMC countries but primarily in non-leadership roles in industry-funded trials

E-mail communication practices and preferences among patients and providers in a large comprehensive cancer center

Purpose: Little is known about how electronic mail (e-mail) is currently used in oncology practice to facilitate patient care. The objective of our study was to understand the current e-mail practices and preferences of patients and physicians in a large comprehensive cancer center. Methods: Separate cross-sectional surveys were administered to patients and physicians (staff physicians and clinical fellows) at the Princess Margaret Cancer Centre. Logistic regression was used to identify factors associated with current e-mail use. Record review was performed to assess the impact of e-mail communication on care. Results: The survey was completed by 833 patients. E-mail contact with a member of the health care team was reported by 41% of respondents. The team members contacted included administrative assistants (52%), nurses (45%), specialist physicians (36%), and family physicians (18%). Patient factors associated with a higher likelihood of e-mail contact with the health care team included younger age, higher education, higher income, enrollment in a clinical trial, and receipt of multiple treatments. Eighty percent of physicians (n = 63 of 79) reported previous contact with a patient via e-mail. Physician factors associated with a greater likelihood of e-mail contact with patients included older age, more senior clinical position, and higher patient volume. Nine hundred sixty-two patient records were reviewed, with e-mail correspondence documented in only 9% of cases. Conclusion: E-mail is commonly used for patient care but is poorly documented. The use of e-mail in this setting can be developed with appropriate guidance; however, there may be concerns about widening the gap between certain groups of patients. </jats:sec

Lessons Learned: It Takes a Village to Understand Inter-Sectoral Care Using Administrative Data across Jurisdictions

Cancer care is complex and exists within the broader healthcare system. The CanIMPACT team sought to enhance primary cancer care capacity and improve integration between primary and cancer specialist care, focusing on breast cancer. In Canada, all medically-necessary healthcare is publicly funded but overseen at the provincial/territorial level. The CanIMPACT Administrative Health Data Group’s (AHDG) role was to describe inter-sectoral care across five Canadian provinces: British Columbia, Alberta, Manitoba, Ontario and Nova Scotia. This paper describes the process used and challenges faced in creating four parallel administrative health datasets. We present the content of those datasets and population characteristics. We provide guidance for future research based on ‘lessons learned’. The AHDG conducted population-based comparisons of care for breast cancer patients diagnosed from 2007-2011. We created parallel provincial datasets using knowledge from data inventories, our previous work, and ongoing bi-weekly conference calls. Common dataset creation plans (DCPs) ensured data comparability and documentation of data differences. In general, the process had to be flexible and iterative as our understanding of the data and needs of the broader team evolved. Inter-sectoral data inconsistencies that we had to address occurred due to differences in: 1) healthcare systems, 2) data sources, 3) data elements and 4) variable definitions. Our parallel provincial datasets describe the breast cancer diagnostic, treatment and survivorship phases and address ten research objectives. Breast cancer patient demographics reflect inter-provincial general population differences. Across provinces, disease characteristics are similar but underlying health status and use of healthcare services differ. Describing healthcare across Canadian jurisdictions assesses whether our provincial healthcare systems are delivering similar high quality, timely, accessible care to all of our citizens. We have provided a description of our experience in trying to achieve this goal and include a list of ‘lessons learned’ and a study process checklist for future use

A Randomized Study of Lenvatinib 18 mg vs 24 mg in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer

Background: Lenvatinib is a multikinase inhibitor approved to treat radioiodine-refractory differentiated thyroid cancer (RR-DTC) at a starting dose of 24 mg/day. This study explored, in a double-blinded fashion, whether a starting dose of 18 mg/day would provide comparable efficacy with reduced toxicity. Methods: Patients with RR-DTC were randomized to lenvatinib 24 mg/day or 18 mg/day. The primary efficacy endpoint was objective response rate as of week 24 (ORRwk24); the odds ratio noninferiority margin was 0.4. The primary safety endpoint was frequency of grade ≥3 treatment-emergent adverse events (TEAEs) as of week 24. Tumors were assessed using RECIST v1.1. TEAEs were monitored and recorded. Results: The ORRwk24 was 57.3% (95% CI 46.1, 68.5) in the lenvatinib 24-mg arm and 40.3% (95% CI 29.3, 51.2) in the lenvatinib 18-mg arm, with an odds ratio (18/24 mg) of 0.50 (95% CI 0.26, 0.96). As of week 24, the rates of TEAEs grade ≥3 were 61.3% in the lenvatinib 24-mg arm and 57.1% in the lenvatinib 18-mg arm, a difference of -4.2% (95% CI -19.8, 11.4). Conclusion: A starting dose of lenvatinib 18 mg/day did not demonstrate noninferiority compared to a starting dose of 24 mg/day as assessed by ORRwk24 in patients with RR-DTC. The results represent a clinically meaningful difference in ORRwk24. The safety profile was comparable, with no clinically relevant difference between arms. These results support the continued use of the approved starting dose of lenvatinib 24 mg/day in patients with RR-DTC and adjusting the dose as necessary. Trial registration: ClinicalTrials.gov NCT02702388

Phase II Efficacy and Pharmacogenomic Study of Selumetinib (AZD6244; ARRY-142886) in Iodine-131 Refractory Papillary Thyroid Carcinoma with or without Follicular Elements

A multicenter, open-label, phase II trial was conducted to evaluate the efficacy, safety, and tolerability of selumetinib in iodine-refractory papillary thyroid cancer (IRPTC)

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown