The phase 3 PROfound trial led to the recent approval of the PARP inhibitor olaparib for men with metastatic castration-resistant prostate cancer and mutations in homologous recombination repair ...genes. We raise methodological concerns about the trial, including: a suboptimal control arm, problematic use of crossover, use of radiographic progression-free survival as the primary endpoint, and ambiguous benefit for patients with mutations in homologous recombination repair genes other than BRCA1, BRCA2, and ATM.
In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality ...from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.
The randomized clinical trial (RCT) in oncology has evolved since its widespread adoption in the 1970s. In recent years, concerns have emerged regarding the use of putative surrogate end points, such ...as progression-free survival (PFS), and marginal effect sizes.
To describe contemporary trends in oncology RCTs and compare these findings with earlier eras of RCT design and output.
Retrospective cohort study of systemic therapy RCTs in breast, colorectal, and non-small cell lung cancer published in 7 major journals between 2010 and 2020. This strategy replicates prior work and allows for comparison of trends with RCTs published between 1995 to 2004 and 2005 to 2009.
Data on RCT design, funding, results, and reporting were extracted from the published RCT report. Findings from the current period (2010-2020) were compared with data from RCTs published from 1995 to 2004 and 2005 to 2009. Descriptive and bivariate statistics were used to analyze temporal trends.
The cohort included 298 RCTs (132 44% breast, 111 37% non-small cell lung cancer, 55 19% colorectal cancer). Experimental treatment included molecular inhibitor (171 of 298 57%), cytotoxic (83 of 298 28%), hormone (15 of 298 5%), and immune (24 of 298 8%) therapies. Sixty-nine percent (206 of 298) of RCTs were of palliative intent. The most common primary end point is now PFS; this has increased substantially over time (from 0% 0 of 167 to 18% 25 of 137 to 42% 125 of 298; P < .001). Of 298 RCTs, 265 (89%) are now funded by industry (previously 95 of 167 57% and 107 of 137 78%; P < .001). Fifty-eight percent (173 of 298) of trials met their primary end point. Among positive trials, median improvement in overall survival and PFS was 3.4 and 2.9 months, respectively. More than one-third (117 of 298 39%) of reports used a professional medical writer; this increased substantially during the study period (from 3 of 27 11% in 2010 to 12 of 18 67% in 2020; P < .001).
This cohort study suggests that contemporary oncology RCTs now largely measure putative surrogate end points and are almost exclusively funded by the pharmaceutical industry. The increasing role of medical writers warrants attention. To demonstrate that new cancer treatments are high value, the oncology community needs to consider the extent to which study end points and target effect size provide meaningful benefit to patients.
Medical journal publishing has changed dramatically over the past decade. The shift from print to electronic distribution altered the industry’s economic model. This was followed by open access ...mandates from funding organizations and the subsequent imposition of article processing charges on authors. The medical publishing industry is large and while there is variation across journals, it is overall highly profitable. As journals have moved to digital dissemination, advertising revenues decreased and publishers shifted some of the losses onto authors by way of article processing charges. The number of open access journals has increased substantially in recent years. The open access model presents an equity paradox; while it liberates scientific knowledge for the consumer, it presents barriers to those who produce research. This emerging “pay-to-publish” system offers advantages to authors who work in countries and at institutes with more resources. Finally, the medical publishing industry represents an unusual business model; the people who provide both the content and the external peer review receive no payment from the publisher, who generates revenue from the content. The very unusual economic model of this industry makes it vulnerable to disruptive change. The economic model of medical publishing is rapidly evolving and this will lead to disruption of the industry. These changes will accelerate dissemination of science and may lead to a shift away from lower-impact journals towards pre-print servers.
Abstract Background More than half of the patients undergoing resection for colorectal cancer liver metastases develop recurrent hepatic disease. We report management and outcomes of patients ...undergoing repeat hepatectomy in routine practice. Methods All cases of repeat hepatectomy for colorectal cancer liver metastases from 2002 to 2009 in the Canadian Province of Ontario were identified using the population-based Ontario Cancer Registry and linked treatment records. Results Of 1,310 patients who underwent resection of CRLM, 78 (6.0%) underwent a repeat liver resection. Mean age was 56 years and the median time between resections was 19 months. Compared with the first resection, second resections were associated with fewer lesions (2.7 vs 1.5; P = .001) and fewer major resections (58% vs 31%; P = .024). The size of largest lesion, positive margin rate, length of hospital stay, and 90-day mortality were similar. Unadjusted 5-year overall survival from the time of second resection was 45% (95% confidence interval = 32% to 59%) and cancer-specific survival was 47% (95% confidence interval = 30% to 64%). Conclusions Repeat liver resections for metastatic CRC involve fewer lesions and less extensive surgery and a substantial proportion of patients achieve long-term survival.
The WHO Essential Medicines List (EML) identifies priority medicines that are most important to public health. Over time, the EML has included an increasing number of cancer medicines. We aimed to ...investigate whether the cancer medicines in the EML are aligned with the priority medicines of frontline oncologists worldwide, and the extent to which these medicines are accessible in routine clinical practice.
This international, cross-sectional survey was developed by investigators from a range of clinical practice settings across low-income to high-income countries, including members of the WHO Essential Medicines Cancer Working Group. A 28-question electronic survey was developed and disseminated to a global network of oncologists in 89 countries and regions by use of a hierarchical snowball method; each primary contact distributed the survey through their national and regional oncology associations or personal networks. The survey was open from Oct 15 to Dec 7, 2020. Fully qualified physicians who prescribe systemic anticancer therapy to adults were eligible to participate in the survey. The primary question asked respondents to select the ten cancer medicines that would provide the greatest public health benefit to their country; subsequent questions explored availability and cost of cancer medicines. Descriptive statistics were used to compare access to medicines between low-income and lower-middle-income countries, upper-middle-income countries, and high-income countries.
87 country-level contacts and two regional networks were invited to participate in the survey; 46 (52%) accepted the invitation and distributed the survey. 1697 respondents opened the survey link; 423 were excluded as they did not answer the primary study question and 326 were excluded because of ineligibility. 948 eligible oncologists from 82 countries completed the survey (165 17% in low-income and lower-middle-income countries, 165 17% in upper-middle-income countries, and 618 65% in high-income countries). The most commonly selected medicines were doxorubicin (by 499 53% of 948 respondents), cisplatin (by 470 50%), paclitaxel (by 423 45%), pembrolizumab (by 414 44%), trastuzumab (by 402 42%), carboplatin (by 390 41%), and 5-fluorouracil (by 386 41%). Of the 20 most frequently selected high-priority cancer medicines, 19 (95%) are currently on the WHO EML; 12 (60%) were cytotoxic agents and 13 (65%) were granted US Food and Drug Administration regulatory approval before 2000. The proportion of respondents indicating universal availability of each top 20 medication was 9–54% in low-income and lower-middle-income countries, 13–90% in upper-middle-income countries, and 68–94% in high-income countries. The risk of catastrophic expenditure (spending >40% of total consumption net of spending on food) was more common in low-income and lower-middle-income countries, with 13–68% of respondents indicating a substantial risk of catastrophic expenditures for each of the top 20 medications in lower-middle-income countries versus 2–41% of respondents in upper-middle-income countries and 0–9% in high-income countries.
These data demonstrate major barriers in access to core cancer medicines worldwide. These findings challenge the feasibility of adding additional expensive cancer medicines to the EML. There is an urgent need for global and country-level policy action to ensure patients with cancer globally have access to high priority medicines.
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The scheme has the potential to revolutionise health care in India by substantially reducing financial constraints to accessing care and providing the economic drive to improve quality of care. The ...problem of overdiagnosis, overinvestigation, and overtreatment can be addressed by linking reimbursement to adherence to established evidence-based guidelines and the Choosing Wisely India recommendations—both from India's National Cancer Grid.3 Without evidence-based guidelines, feasible quality indicators, and mandatory data collection and reporting, public money could be seen as free money, which could further contribute to inappropriate, excessive, and unnecessary care. India needs to revisit and revise its national cancer control programme with a focus on better overall care, not just access to new technologies.4 Ayushman Bharat offers an important opportunity—and responsibility—to improve care meaningfully for patients across the health system. saiko3p/Shutterstock.com We declare no competing interests.
Health-care systems in sub-Saharan Africa are considered to be new markets for pharmaceutical companies. This perception is particularly relevant within oncology, as the pharmaceutical industry has ...changed strategic priorities in the past 10 years to focus on cancer. Since the 1930s, pharmaceutical companies have used advertisements, sample drugs, gifts, paid speaking engagements, advisory boards, and trips to conferences to influence clinical practice and policy. A large amount of literature describes the commonness of these practices and their effects on the behaviour of doctors. However, these data come almost exclusively from high-income countries. Industry–doctor relationships are increasingly common in sub-Saharan Africa and other low-income and middle-income countries. Although there are undoubtedly risks of industry engagement in low-income and middle-income countries, many programmes with educational, research, and clinical value would not occur in these countries without industry support. Thus, what is known about these relationships in high-income countries will not necessarily apply in low-income and middle-income countries. There is a need for widespread discussion about industry–oncologist interactions across the African continent and context-specific data to understand the potential risks and benefits of these relationships.
This study aims to explore gender-related differences in persistent opioid use following an acute pain episode and evaluate potential explanatory variables.
This retrospective population-based study ...using administrative databases included all opioid-naïve patients in Ontario with renal colic between 2013 and 2017. The primary outcome was to assess any association between persistent opioid use at 3-6 months by gender. Key confounding covariates and explanatory variables examined included both care- and patient-related factors, specifically past evidence of mental health diagnoses.
The dataset of 64,240 males and 37,656 females demonstrated that 8.7% of males and 9.6% of females had evidence of persistent opioid use 3-6 months after presentation (OR 1.11, 95% CI 1.05, 1.17). Females had a higher incidence of mental health services utilization 44.5% vs 29.6% (p<0.001) and were more likely to be on a provincial disability program 5.1% vs 3.8% (p<0.001). Age, income quintile, mental health diagnoses and dose of opioid prescribed were associated with the primary outcome in both genders. On adjusted analysis for multiple confounding and explanatory variables, females were still more likely than males to demonstrate persistent opioid use (OR 1.07, 95% CI 1.01, 1.13) with even more pronounced associations at 1-2 years.
After controlling for key covariates, females are at slightly higher risk of demonstrating long term opioid use following an episode of renal colic. Evidence of prior mental health service utilization and acute colic care did not appear to significantly explain these observations.
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