Publications by authors named "Bishal Gyawali"

168 Publications

Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer.

JCO Glob Oncol 2022 Jan;8:e2100153

Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Purpose: Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues.

Methods: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed.

Results: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively.

Conclusion: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.
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http://dx.doi.org/10.1200/GO.21.00153DOI Listing
January 2022

Radiographic progression-free survival in the ACIS trial for prostate cancer.

Lancet Oncol 2022 Jan;23(1):e4

Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia.

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http://dx.doi.org/10.1016/S1470-2045(21)00719-1DOI Listing
January 2022

Knowledge, attitude, preventive practices and utilization of cervical cancer screening among women in Nepal: a community-based cross-sectional study.

Eur J Cancer Prev 2022 Jan;31(1):73-81

Center for Global Health, Department of Public Health, Aarhus University, Denmark.

Background: Cervical cancer continues to be a global public health concern and a leading cause of cancer deaths among Nepalese women. In spite of the availability of screening and treatment services in Nepal, the utilization of screening has been low. This study investigated knowledge, attitude, preventive practices and utilization of cervical cancer screening among women in a semi-urban area of Pokhara Metropolitan City of Nepal.

Methods: A community-based cross-sectional survey was carried out among 729 women 30-60 years of age, between April and June 2019. Participants were selected by systematic random sampling, and a door-to-door home visit was conducted for data collection. A pretested interviewer-administered Nepali questionnaire was used to collect information on sociodemographic variables, knowledge, attitude and preventive practices regarding cervical cancer screening.

Results: The mean age of the participants was 45.9 years (SD ±7.7); the majority were married (86.7%). Among the participants, 44.9% were ever screened for cervical cancer. However, only 10.4% of participants received timely repeated screening for cervical cancer. The median knowledge score achieved by participants was 2.0 [interquartile range (IQR) 1-4] on a scale of maximum score 36, the median attitude score was 31.0 (IQR 29-32) on a scale of 40 and the median preventive practice score was 3.0 (IQR 3-4) on a scale of five.

Conclusion: This study showed low knowledge and low utilization of cervical cancer screening among women in Nepal. We recommend a community-based educational intervention to educate and empower women to increase knowledge and utilization of cervical cancer screening.
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http://dx.doi.org/10.1097/CEJ.0000000000000670DOI Listing
January 2022

Healthcare delivery for non-communicable diseases among breast cancer survivors in Sri Lanka: Is there a missed opportunity?

Ecancermedicalscience 2021 12;15:1301. Epub 2021 Oct 12.

Sri Lanka Cancer Research Group, Colombo 10230, Sri Lanka.

Purpose: Breast cancer is the most common cancer globally as well as in Sri Lanka. Improvements in cancer care have allowed patients to live to an older age. With advancing age, incidence of non-communicable diseases (NCDs) increases. Cancer diagnoses tend to take attention away from the treatment of other comorbidities, given its importance. The objective of this study was to describe healthcare delivery for NCDs among female breast cancer survivors treated at the National Cancer Institute of Sri Lanka (NCISL) and identify opportunities to optimise non-cancer medical care in this cohort.

Methods: A total of 420 women were identified from the breast cancer database at the NCISL, who were 50-80 years at the time of their breast cancer diagnosis, were within 12-24 months from the date of diagnosis, had completed their active cancer treatment and were in complete remission. Of this population, 228 (54%) women who had documented NCDs at the time of diagnosis were identified and were followed-up via telephone to collect details regarding existing comorbidities and the screening and development of new comorbidities.

Results: At the time of cancer diagnosis, 216/228 (95%) of patients had hypertension, 104/228 (46%) had type 2 diabetes and 17/228 (8%) had ischaemic heart disease (IHD). The prevalence of other comorbidities was very low. During the post diagnosis period, 11 patients developed type 2 diabetes, while 2 developed IHD. Osteoporosis screening using dual-energy X-ray absorptiometry scanning was very low at diagnosis 21/228 (9%) but improved in post cancer treatment follow-up 112/228 (49%, p < 0.001). Only 95/228 (42%) were screened for other cancers.

Conclusions: Hypertension was the most prevalent comorbidity while type 2 diabetes and dyslipidaemia were the most common diagnoses post-treatment. In these patients, screening for osteoporosis and other cancers remains very low, emphasising a missed opportunity.
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http://dx.doi.org/10.3332/ecancer.2021.1301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580723PMC
October 2021

Real-world Use of and Spending on New Oral Targeted Cancer Drugs in the US, 2011-2018.

JAMA Intern Med 2021 12;181(12):1596-1604

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.

Importance: Launch prices of new cancer drugs in the US have substantially increased in recent years despite growing concerns about the quantity and quality of evidence supporting their approval by the US Food and Drug Administration (FDA).

Objective: To assess the use of and spending on new oral targeted cancer drugs among US residents with employer-sponsored insurance between 2011 and 2018, stratified by the strength of available evidence of benefit.

Design, Setting, And Participants: In this cross-sectional study, dispensing claims for oral targeted cancer drugs first approved by the FDA between January 1, 2011, and December 31, 2018, were analyzed. The number of patients with drugs dispensed and the total payment for all claims were aggregated by calendar year, and these outcomes were arrayed according to evidence underlying FDA approvals, including pivotal study design (availability of randomized clinical trials) and overall survival (OS) benefit, as documented in drug labels. This study was conducted from July 17, 2019, to July 23, 2021.

Main Outcomes And Measures: Annual and cumulative numbers of patients who had dispensing events, and annual and cumulative sums of payment for eligible drugs.

Results: Of 37 348 patients who had at least 1 of the 44 new oral targeted drugs dispensed between 2011 and 2018, 21 324 were men (57.1%); mean (SD) age was 64.1 (13.1) years. Most individuals (36 246 [97.0%]) received drugs for which evidence from randomized clinical trials existed; however, a growing share of patients received drugs without documented OS benefit during the study period: from 12.7% in 2011 to 58.8% in 2018. Cumulative spending on all sample drugs totaled $3.5 billion by the end of 2018, of which 96.8% was spent on drugs that were approved based on a pivotal randomized clinical trial. Cumulative spending on drugs without documented OS benefit ($1.8 billion [51.6%]) surpassed that on drugs with documented OS benefit ($1.7 billion [48.4%]) by the end of 2018.

Conclusions And Relevance: The findings of this cross-sectional study suggest that drugs used for treatment of cancer without documented OS benefits are adopted in the health system and account for substantial spending.
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http://dx.doi.org/10.1001/jamainternmed.2021.5983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524355PMC
December 2021

Trends in drug revenue among major pharmaceutical companies: A 2010-2019 cohort study.

Cancer 2022 Jan 6;128(2):311-316. Epub 2021 Oct 6.

Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, Canada.

Background: Over the past 2 decades there has been a substantial increase in the number of new cancer medicines; this has been accompanied by a dramatic rise in drug costs. It is unknown how these trends impact the revenue of the pharmaceutical sector.

Methods: Retrospective cohort study to characterize temporal trends of revenue generated from cancer medicines as a proportion of total drug revenue among 10 large pharmaceutical companies from 2010 to 2019. Itemized product-sales data publicly available through company websites or annual filings were used to identify annual drug revenue. Revenue data were adjusted for inflation and converted to 2019 US dollars.

Results: During the study period, cumulative annual revenue generated from cancer drugs increased by 70%: from $55.8 billion to $95.1 billion, while cumulative revenue from nononcology drugs decreased 18%: from $342.2 billion to $281.5 billion. The proportion of total drug revenue generated from oncology drugs increased substantially over the study period: from 14% in 2010 to 25% in 2019 (τ = 1.0, P < .001).

Conclusions: Among 10 of the world's largest pharmaceutical companies, revenues generated from the sale of cancer drugs have increased by 70% over the past decade, while revenues from other medicines have decreased by 18%. Revenues from cancer drugs now account for one-quarter of the net revenues from these companies. Further work is needed to understand if this increase in sales revenue reflects industry profit, and to what extent increased spending has translated into improvements in patient and population outcomes.
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http://dx.doi.org/10.1002/cncr.33934DOI Listing
January 2022

Utilization of imaging for active surveillance in testicular cancer: Is real-world practice concordant with guidelines?

Can Urol Assoc J 2021 Sep 24. Epub 2021 Sep 24.

Division of Cancer Care and Epidemiology, Queen's Cancer Research Institute, Kingston, ON, Canada.

Introduction: Imaging is an integral component of active surveillance following orchiectomy for stage 1 non-seminoma (NSGCT) and seminoma germ cell tumors. In this population-based study, we describe use of imaging among patients with early-stage testicular cancer and evaluate whether they are concordant with guideline recommendations.

Methods: This is a population-based, retrospective cohort study to describe utilization of imaging among all patients with early-stage testicular cancer treated with active surveillance in the Canadian province of Ontario. The Ontario Cancer Registry was linked to electronic records of treatment to identify use of chest and abdomen/pelvis imaging. Data from 2000--2010 were included with followup for up to five years for patients with non-seminoma and 10 years for patients with seminoma. The key outcome of interest was the frequency of imaging at temporal milestones following orchiectomy. Compared to the most contemporaneous guidelines in Ontario, any discordant frequency of imaging was defined as underutilization or overutilization. Substantial under- or overutilization was defined as >1 imaging test less/more than what was recommended during a 12-month period.

Results: The study population included 569 patients with NSGCT (median age 28) and 1107 with seminoma (median age 37). Among patients with NSGCT, adherence with body imaging was low in years 1-3 of surveillance (range 26-37%, predominantly underuse) and higher in years 4-5 (63-67%, predominantly overuse). Adherence with chest imaging was even lower (range 11-34% during years 1-5). Among patients with seminoma, adherence with abdominal and chest imaging was relatively stable and comparable throughout the 10-year followup period (range 23-47% abdomen and 28-47% chest). Multivariable analysis confirmed that underutilization of imaging was more common in recent years. NSGCT histology was associated with underutilization in years 1-2 but overutilization in years 3-5.

Conclusions: In routine clinical practice, patients with testicular cancer commonly receive imaging discordant to the protocol for active surveillance, with a substantial proportion receiving both under- and overutilization at various times during surveillance followup.
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http://dx.doi.org/10.5489/cuaj.7246DOI Listing
September 2021

Access to cancer medicines deemed essential by oncologists in 82 countries: an international, cross-sectional survey.

Lancet Oncol 2021 10 21;22(10):1367-1377. Epub 2021 Sep 21.

Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, ON, Canada; Departments of Oncology, Queen's University, Kingston, ON, Canada; Public Health Sciences, Queen's University, Kingston, ON, Canada. Electronic address:

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

Funding: None.
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http://dx.doi.org/10.1016/S1470-2045(21)00463-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476341PMC
October 2021

Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study.

BMJ 2021 09 8;374:n1959. Epub 2021 Sep 8.

Program On Regulation, Therapeutics And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Objectives: To investigate the regulatory handling of cancer drugs that were granted accelerated approval by the US Food and Drug Administration (FDA) but failed to improve the primary endpoint in post-approval trials and to evaluate the extent to which negative post-approval trials changed the recommendations in treatment guidelines.

Design: Retrospective observational study.

Setting: FDA and National Comprehensive Cancer Network (NCCN) reports.

Included Drugs: Cancer drugs that received accelerated approval from the FDA and had negative post-approval trials.

Main Outcome Measures: Regulatory outcomes, including withdrawal, conversion to regular approval, and no action.

Results: 18 indications for 10 cancer drugs that received accelerated approval but failed to improve the primary endpoint in post-approval trials were identified. Of these, 11 (61%) were voluntarily withdrawn by the manufacturer and one (bevacizumab for breast cancer) was revoked by the FDA. Of the 11 withdrawals, six occurred in 2021 alone. The remaining six (33%) indications remain on the label. The NCCN guidelines provide a high level of endorsement (category 1 endorsement for one and category 2A endorsement for seven) for accelerated approval drugs that have failed post-approval trials, sometimes even after the approval has been withdrawn or revoked.

Conclusion: Cancer drug indications that received accelerated approval often remained on formal FDA approved drug labelling and continued to be recommended in clinical guidelines several years after statutorily required post-approval trials showed no improvement in the primary efficacy endpoint. Clinical guidelines should better align with the results of post-approval trials of cancer drugs that received accelerated approval.
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http://dx.doi.org/10.1136/bmj.n1959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424519PMC
September 2021

A systematic review and meta-analysis of non-adherence to anti-diabetic medication: Evidence from low- and middle-income countries.

Int J Clin Pract 2021 Nov 23;75(11):e14717. Epub 2021 Aug 23.

Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Background: Non-adherence to anti-diabetic medication is an important cause of uncontrolled blood glucose that leads to complications of diabetes. However, there is a lack of evidence on the burden of and factors associated with non-adherence to anti-diabetic medication among individuals living with diabetes in low-and middle-income countries (LMICs).

Objectives: This systematic literature review and meta-analytic synthesis aims to estimate non-adherence to anti-diabetic medication reported among individuals in LMICs and explores factors affecting non-adherence.

Methods: We systematically searched MEDLINE and Embase to identify studies investigating non-adherence to anti-diabetic medications published from January 2000 to May 2020. Two authors carried out study selection, screening, and data extraction independently. Cross-sectional studies that had been conducted among individuals with diabetes in LMICs were eligible for the selection process. Critical appraisal of the included studies was carried out using the Newcastle Ottawa Scale. Meta-analysis was carried out using Stata 14.2. Random effects model was used to compute the pooled proportion at a 95% confidence interval (CI).

Results: Forty-three studies met the inclusion criteria, of which 13 studies were used in meta-analysis. The pooled proportion of non-adherence to anti-diabetic medications using the eight-item Morisky Medication Adherence Scale (MMAS-8) was 43.4% (95% CI: 17.5-69.4; P < 0.001) and 29.1% (95% CI: 19.8-38.4; P < 0.001) when using the cut-off at 80 or 90%. The pooled proportion of non-adherence was 29.5% (95% CI: 25.5-33.5; P = .098) when using the four-item Morisky Medication Adherence Scale (MMAS-4). Using the World Health Organization (WHO) five dimensions of medication adherence framework, the factors contributing to non-adherence were varied, including disease factors, therapy-related factors, healthcare system factor, patient-centred factors, and socio-economic factors.

Conclusions: Non-adherence to anti-diabetic medication remains an ongoing challenge in LMICs and several factors operating at different levels were cited as reasons. Comprehensive intervention strategies are urgently needed to address these factors in effectively tackling medication non-adherence in LMICs.
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http://dx.doi.org/10.1111/ijcp.14717DOI Listing
November 2021

Do Editorialists With Industry-Related Conflicts of Interest Write Unduly Favorable Editorials for Cancer Drugs in Top Journals?

J Natl Compr Canc Netw 2021 07 29. Epub 2021 Jul 29.

Department of Oncology.

Background: Editorials accompanying the publication of trials in major oncology journals can have a substantial influence on clinical practice. We describe the prevalence of financial conflicts of interest (FCOIs) of authors writing such editorials and the extent to which FCOIs may shape the interpretation of clinical trials.

Methods: We examined editorials published in 2018 alongside trial reports in the top 5 journals that publish cancer drug trials (New England Journal of Medicine, Lancet, Lancet Oncology, JAMA Oncology, and Journal of Clinical Oncology). An editorial was considered to have an FCOI if at least one of the editorialists had any disclosed FCOI. An FCOI with the same company whose drug was being discussed in the editorial was classified as a direct FCOI. Editorials were reviewed for their content and classified as being unduly favorable (defined as the presence of a positive spin without discussion of limitations) or not. Association of an FCOI and a direct FCOI with writing an unduly favorable editorial was assessed.

Results: Of the 90 editorials assessed, 74% (n=67) were classified as having an FCOI with the pharmaceutical industry, and 39% (n=35) had an FCOI with the same company whose product was being discussed in the editorial (direct FCOI). Editorials were classified as being unduly favorable toward the study drug in 12% (8 of 67) and 13% (3 of 23) (P=1.0) of those with and without FCOIs, respectively; corresponding rates with and without direct FCOI were 23% (8 of 35) and 5% (3 of 55), respectively (P=.009).

Conclusions: Editorials in top oncology journals were frequently authored by experts with FCOIs, including direct FCOIs. Authoring an unduly favorable editorial for a new cancer drug was significantly associated with the author having a direct FCOI with the same company. These findings support the call for journals to ensure that authors of editorials have no direct FCOIs.
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http://dx.doi.org/10.6004/jnccn.2021.7016DOI Listing
July 2021

Text Messaging in Cancer-Supportive Care: A Systematic Review.

Cancers (Basel) 2021 Jul 15;13(14). Epub 2021 Jul 15.

Department of Public Health Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.

The global cancer disease burden is substantial, resulting in increased economic and clinical strain on our healthcare systems. A proposed solution is text-based communication, which can be used for cancer-supportive care. We conducted a systematic review to synthesize and describe the use of text-based communications for cancer-supportive care. Our population of interest included adult patients with cancer. A total of 18 studies were included in the review: 9 RCTs and 9 non-randomized interventional/observational studies. Patients were largely satisfied with text-based communication during their cancer care. Compared to controls, results for other outcomes including symptoms and quality of life were largely mixed; however, no harms were observed. Furthermore, positive outcomes were seen for specific interventions, such as text message medication reminders. These findings should be considered with caution due to the considerable heterogeneity observed between studies regarding their design and reported outcomes and the high risk of bias associated with 6/18 studies. Overall, this review suggests that text-based communication may be a complementary tool for cancer-supportive care; however, more research is needed to examine the feasibility of implementation and use.
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http://dx.doi.org/10.3390/cancers13143542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307703PMC
July 2021

Oncology training programmes for general practitioners: a scoping review.

Ecancermedicalscience 2021 3;15:1241. Epub 2021 Jun 3.

Department of Oncology, Queen's University, 76 Stuart Street, Kingston, ON K7L 2V6, Canada.

Introduction: Due to the increasing global burden of cancer and the shortage of trained medical oncologists, training General Practitioners (GPs) in Oncology (known as GPOs) has been proposed as a means to potentially ease some burden on medical oncologists with heavy workloads, especially in low-and-middle-income countries (LMICs), by task-sharing and task-shifting. We undertook a scoping review to identify and characterise the existing training programmes and curricula for GPOs globally.

Design: We searched three major electronic databases: EMBASE, Medline/PubMed and Education Source for articles that described a medical oncology training programme for GPs. All study types were eligible in this review. We followed a two-stage standardised screening process using two independent reviewers to evaluate the eligibility of the articles.

Results: Five peer-reviewed articles were included in our review and grey literature scans identified an additional seven GPO training programmes for a total of 12 programmes and their curricula. All of the included studies were from high-income countries. The duration of programmes varied from comprehensive programmes structured over 2 years ( = 2) to shorter duration medical oncology training activities ( = 2), a short, 1.5-day workshop and a 10-hour course. In the grey literature, GPO training programme durations ranged from 2 weeks to 13 months. A mixture of delivery methods was employed including didactic lectures and clinical rotations.

Conclusion: This scoping review identified a small number of heterogeneous studies and grey literature sources that described and/or evaluated medical oncology training programmes for GPs. The information synthesised here can be used to foster the collaboration needed for the continued development of GPO programmes that could help address the problem of lack of workforce to meet the rising burden of cancer, especially in LMICs.
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http://dx.doi.org/10.3332/ecancer.2021.1241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241444PMC
June 2021

Fulfilling the Mandate of the US Food and Drug Administration's Accelerated Approval Pathway: The Need for Reforms.

JAMA Intern Med 2021 10;181(10):1275-1276

Program On Regulation, Therapeutics and Law (PORTAL), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamainternmed.2021.4604DOI Listing
October 2021

Atezolizumab in Metastatic Triple-Negative Breast Cancer-No Contradiction in the Eyes of a Dispassionate Observer.

JAMA Oncol 2021 Sep;7(9):1285-1286

Departments of Oncology and Public Health Sciences, Queen's University, Kingston, Ontario, Canada.

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http://dx.doi.org/10.1001/jamaoncol.2021.1966DOI Listing
September 2021

Differences in cancer incidence and pattern between urban and rural Nepal: one-year experience from two population-based cancer registries.

Ecancermedicalscience 2021 11;15:1229. Epub 2021 May 11.

Nepal Health Research Council, RamshahPath, Kathmandu 44600, Nepal.

Variations in cancer incidence, mortality and pattern exist in rural and urban areas. Understanding these differences helps in developing targeted cancer prevention and control strategies. However, no previous studies have explored the differences in cancer demographics between the rural and urban areas of Nepal. The data of Kathmandu Valley (urban area) Population-Based Cancer Registry (PBCR) and Rukum (rural area) PBCR were analysed to identify the differences in cancer pattern in rural and urban areas. The age-adjusted incidence rate (AAR) in Kathmandu was higher than that in Rukum (1.6 times among males and 1.9 times among females). The top two leading sites in males were lungs and stomach in both the regions; however, the rates were higher in Kathmandu. The incidence rate for cancer of the urinary bladder among males in Kathmandu was particularly higher - 4.4 times that of Rukum. In females, the leading site of cancer in Kathmandu was breast, which was eight times higher compared to Rukum, whereas the incidence rate of cervix cancer in Kathmandu is 30% less than in Rukum. The incidence of tobacco-related cancer was found to be higher in Kathmandu compared to Rukum. These findings reveal the need for different policy priorities for cancer control in the urban versus rural regions of Nepal, based on the different demographics of cancer in the two areas. Similar studies from other regions of Nepal are needed to develop a targeted cancer control strategy.
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http://dx.doi.org/10.3332/ecancer.2021.1229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183641PMC
May 2021

Health System Preparedness for COVID-19 and Its Impacts on Frontline Health-Care Workers in Nepal: A Qualitative Study Among Frontline Health-Care Workers and Policy-Makers.

Disaster Med Public Health Prep 2021 Jun 18:1-9. Epub 2021 Jun 18.

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.

Background: Rapidly growing coronavirus disease 2019 (COVID-19) pandemic has brought unprecedented challenges to the health system in Nepal. The main objective of this study was to explore the health system preparedness for COVID-19 and its impacts on frontline health-care workers in Nepal.

Methods: Semi-structured interviews were conducted among 32 health-care workers who were involved in clinical care of COVID-19 patients and four policy-makers who were responsible for COVID-19 control and management at central and provincial level. Interviews were conducted through telephone or Internet-based tools such as Zoom and Skype. All interviews were audio-recorded, transcribed into English, and coded using inductive and deductive approaches.

Results: Both health-care workers and policy-makers reported failure to initiate pre-emptive control measures at the early stages of the outbreak as the pivot in pandemic control. Although several measures were rolled out when cases started to appear, the overall health system preparedness was low. The poor governance, and coordination between three tiers of government was compounded by the inadequate personal protective equipment for health-care workers, insufficient isolation beds for patients, and poor engagement of the private sector. Frontline health-care workers experienced various degrees of stigma because of their profession and yet were able to maintain their motivation to continue serving patients.

Conclusion: Preparedness for COVID-19 was affected by the poor coordination between three tiers of governance. Specifically, the lack of human resources, inadequate logistic chain management and laboratory facilities for testing COVID-19 appeared to have jeopardized the health system preparedness and escalated the pandemic in Nepal. Despite the poor preparedness, and health and safety concerns, health-care workers maintained their motivation. There is an urgent need for an effective coordination mechanism between various tiers of health structure (including private sector) in addition to incentivizing the health-care workers for the current and future pandemics.
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http://dx.doi.org/10.1017/dmp.2021.204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376855PMC
June 2021

Assessing population diversity in phase III trials of cancer drugs supporting Food and Drug Administration approval in solid tumors.

Int J Cancer 2021 10 5;149(7):1455-1462. Epub 2021 Jul 5.

Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey.

Our study aimed to assess inequities in the clinical trial participation for the selected patient groups. We searched the Food and Drug Administration (FDA) database and extracted phase-III clinical trial data from MEDLINE for each approved drug by the FDA between January 1, 2006, and June 30, 2020. We analyzed the inclusion/exclusion criteria, participation according to gender, ethnic group, performance score, the positivity of HBV and HCV, and HIV, having comorbidities and brain metastasis. We compared the findings with that of the general population by retrieving data from the Surveillance, Epidemiology and End Results (SEER) database. We identified 142 phase III pivotal oncology trials that enrolled 105 397 patients. The proportion of female patients in trials was lower than their relative prevalence in the general population from SEER region (36% vs 49.6%, P < .001). The rates of black patients included were lower than their relative prevalence from SEER region (2.1% vs 9.8%, P < .001). 1.3% and 0.8% of patients had HBV and HCV infections, respectively. The patients' numbers with organ dysfunction were not established due to insufficient data from clinical trials. 1.6% of all patients had controlled brain metastasis. Black patients, women and patients with brain metastasis or with HBV and HCV were underrepresented. Our study underscores the importance of expanding the inclusion/exclusion criteria of pivotal oncology trials to be more representative of patients seen in clinical practice.
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http://dx.doi.org/10.1002/ijc.33708DOI Listing
October 2021

Risk and Benefit for Targeted Therapy Agents in Pediatric Phase II Trials in Oncology: A Systematic Review with a Meta-Analysis.

Target Oncol 2021 07 10;16(4):415-424. Epub 2021 Jun 10.

Research Ethics in Medicine Study Group (REMEDY), Department of Philosophy and Bioethics, Jagiellonian University Medical College, ul. Kopernika 40, 31-501, Kraków, Poland.

Background: For research with human participants to be ethical, risk must be in a favorable balance with potential benefits. Little is known about the risk/benefit ratio for pediatric cancer phase II trials testing targeted therapies.

Objective: Our aim was to conduct a systematic review of preliminary efficacy and safety profiles of phase II targeted therapy clinical trials in pediatric oncology.

Methods: Our protocol was prospectively registered in PROSPERO (CRD42020146491). We searched EMBASE and PubMed for phase II pediatric cancer trials testing targeted agents. We included solid and hematological malignancy studies published between 1 January, 2015 and 27 February, 2020. We measured risk using drug-related grade 3 or higher adverse events, and benefit by response rates. When possible, data were meta-analyzed. All statistical tests were two-sided.

Results: We identified 34 clinical trials (1202 patients) that met our eligibility criteria. The pooled overall response rate was 24.4% (95% confidence interval [CI] 14.5-34.2) and was lower in solid tumors, 6.4% (95% CI 3.2-9.6), compared with hematological malignancies, 55.1% (95% CI 35.9-74.3); p < 0.001. The overall fatal drug-related (grade 5) adverse event rate was 1.6% (95% CI 0.6-2.5), and the average drug-related grade 3/4 adverse event rate per person was 0.66 (95% CI 0.55-0.78).

Conclusions: We provide an estimate for the risks and benefits of participation in pediatric phase II cancer trials. These data may be used as an empirical basis for informed communication about benefits and burdens in pediatric oncology research.
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http://dx.doi.org/10.1007/s11523-021-00822-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266705PMC
July 2021

Reviewing the Reviewers: Potential Financial Conflicts of Interest in Editorial Boards of Surgery Journals.

Ann Surg 2021 Jun 2. Epub 2021 Jun 2.

Department of Surgery, University of Toronto, Toronto, Canada Department of Oncology, Queen's University, Kingston, Canada Department of Surgery, Queen's University, Kingston, Canada.

Objective: To assess the prevalence, magnitude, and disclosure status of industry funding in editorial boards of surgery journals.

Summary Of Background Data: Financial conflicts of interest (COI) can bias research. While authors seeking to publish in peer-reviewed surgery journals are required to provide COI disclosures, editorial board members' COI disclosures are generally not disclosed to readers.

Methods: We present a cross-sectional analysis of industry funding to editorial board members of high-impact surgery journals. We reviewed top US-based surgery journals by impact factor to determine the presence of financial COI in members of each journal's editorial board. The prevalence and magnitude of COI was determined using 2018 industry reported payments found in the CMS Open Payments database. Journal websites were also reviewed looking for the presence of editorial board disclosure statements.

Results: A total of 1,002 names of editorial board members from the top 10 high-impact American surgery journals were identified. Of 688 individual physicians based in the USA, 452 (65.7%) were found to have received industry payments in 2018, totaling $21,916,503 with a median funding amount per physician of $1,253 (IQR $156 - $10,769). Funding levels varied by surgical specialty and journal. Editorial board disclosure information was found in only 3.3% of physicians.

Conclusions: Industry funding to editorial board members of high impact surgery journals is prevalent and underreported. Mechanisms of disclosure for COI are needed at the editorial board level to provide readers full transparency. This would acknowledge this COI of editorial board members, and thereby attempt to potentially further reduce the risk of bias in editorial decisions.
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http://dx.doi.org/10.1097/SLA.0000000000004929DOI Listing
June 2021

Integrating New Effectiveness Data Into US Food and Drug Administration-Approved Drug Labeling.

JAMA Intern Med 2021 07;181(7):897-898

Program On Regulation, Therapeutics, And Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamainternmed.2021.1994DOI Listing
July 2021

An Arm and a Leg: The Rising Cost of Cancer Drugs and Impact on Access.

Am Soc Clin Oncol Educ Book 2021 Mar;41:1-12

Department of Oncology, Queen's University, Kingston, Ontario, Canada.

Increasing cancer drug prices present global challenges to treatment access and cancer outcomes. Substantial variability exists in drug pricing across countries. In countries without universal health care, patients are responsible for treatment costs. Low- or middle-income countries are heavily impacted, with limited patient access to novel cancer treatments. Financial toxicity is seen across cancer types, countries, and health care systems. Those at highest risk include younger patients, new immigrants, visible minority groups, and those without private health coverage. Currently, cancer drug pricing does not correlate with value or clinical benefit. Value-based pricing of oncology drugs may incentivize development of higher-value medicines and eliminate excess spending on drugs that yield little benefit. Generics and biosimilars in oncology can also improve affordability and patient access, offering dramatic reductions in drug spending while maintaining patient benefit. Oncologists can promote value-based care by following evidence-based clinical guidelines that avoid low-value treatments. Researchers can also engage in value-based research that critically explores optimal cancer drug dosing, schedules, and treatment duration and defines patient populations most likely to benefit (e.g., through biomarker selection). Cancer Groundshot proposes that we improve outcomes for today's patients with cancer, including broader global access for high-value treatments, promotion of affordable cancer control strategies, and reduction of cancer morbidity and mortality through low-cost prevention and screening initiatives. Moving forward, major oncology societies recommend promoting uniform global access to essential cancer medicines and avoiding financial harm for patients as key principles in addressing the affordability of cancer drugs.
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http://dx.doi.org/10.1200/EDBK_100028DOI Listing
March 2021

Assessing the benefit of cancer drugs approved by the European Medicines Agency using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale over time.

Eur J Cancer 2021 06 29;150:203-210. Epub 2021 Apr 29.

Evaluative Clinical Sciences, Odette Cancer Centre Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Canadian Centre for Applied Research in Cancer Control, Toronto, Ontario, Canada. Electronic address:

Background: Increasingly, cancer drugs are being approved based on surrogate measurements of efficacy. Clinically meaningful data, such as overall survival (OS) and quality of life, are often only presented in subsequent publications. We examined if the clinical benefit of cancer drugs, as measured by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), improves post-European Medicines Agency (EMA) approval as more data emerges.

Methods: Cancer drug indications approved by the EMA from January 2006 to December 2016 were reviewed and trials cited for efficacy were identified. Primary and subsequent publications (up to December 2019) of scorable trials were included. Changes in benefit over time were measured using ESMO-MCBS thresholds for non-curative (≥4 for substantial, =3 for intermediate and ≤2 for low benefit) and curative intent (A or B for major benefit) scoring.

Results: Fifty-five non-curative and two curative intent trials were included. At approval, 29.1% of non-curative trials were substantial, 45.5% intermediate and 25.5% low benefit. For curative intent trials, one displayed major benefit and one displayed no major benefit. We identified 82 subsequent publications for reassessment. A change in ESMO-MCBS classification was seen in 34.5% of non-curative trials (11 raised and 8 lowered). At 3-year reassessment, 36.4% of non-curative trials were substantial, 34.5% intermediate and 29.1% low benefit. Both curative trials showed no major benefit at reassessment.

Conclusion: As over a third of trials changed classification, in either direction, reassessing the ESMO-MCBS score of approved cancer drugs may help to inform patients and ensure ongoing relevance of regulatory and reimbursement decisions.
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http://dx.doi.org/10.1016/j.ejca.2021.03.044DOI Listing
June 2021

Cancer, Clinical Trials, and Canada: Our Contribution to Worldwide Randomized Controlled Trials.

Curr Oncol 2021 04 13;28(2):1518-1527. Epub 2021 Apr 13.

Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, ON K7L 3N6, Canada.

Canada has a long tradition of leading practice-changing clinical trials in oncology. Here, we describe methodology, results, and interpretation of oncology RCTs with Canadian involvement compared to RCTs from other high-income countries (HICs). A literature search identified all RCTs evaluating anti-cancer therapies published 2014-2017. RCTs were classified based on the country affiliation of first authors. The study cohort included 636 HIC-led RCTs; 155 (24%) had Canadian authors. Three-quarters (112/155, 72%) of Canadian RCTs were conducted in the palliative setting, compared to two thirds (299/481, 62%) of RCTs from other HICs ( = 0.022). Canadian RCTs were more likely than those from other HICs to be supported by industry (85% vs. 69%, < 0.001). The proportion of positive Canadian trials that met the ESMO-MCBS threshold for substantial clinical benefit was comparable to RCTs without Canadian authors (29% vs. 32%, = 0.137). Thirteen percent (20/155) of all Canadian trials were affiliated with the Canadian Cancer Trials Group (CCTG). Canada plays a meaningful role in the global cancer research ecosystem but is overly reliant on industry support. The very low proportion of trials that identify a new treatment with substantial clinical benefit is worrisome. A renewed investment in cancer clinical trials is needed in Canada.
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http://dx.doi.org/10.3390/curroncol28020143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167552PMC
April 2021

Risk-Stratifying Treatment Strategies for Febrile Neutropenia-Tools, Tools Everywhere, and Not a Single One That Works?

JCO Oncol Pract 2021 Nov 29;17(11):651-654. Epub 2021 Apr 29.

Department of Oncology, Queen's University, Kingston, ON, Canada.

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http://dx.doi.org/10.1200/OP.21.00148DOI Listing
November 2021

Can locally developed me-too drugs aid price negotiation? An example of cancer therapies from China.

Semin Oncol 2021 Apr 6;48(2):141-144. Epub 2021 Apr 6.

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.

Rapid growth in pharmaceutical expenditures and high prices have greatly hampered access to medicines, especially targeted anticancer medicines. Confronted with such difficulties, the Chinese government has put more effort into supporting local research and development of cancer medicines, resulting in locally developed me-too drugs. Since 2016, the government has implemented a central reimbursement-linked drug price negotiation policy aimed at reducing the prices of expensive medicines. Locally developed me-too drugs marketed at lower prices may inject price competition and help negotiate reduced prices of similar internationally-developed products. As an example, we selected 3 tyrosine kinase inhibitors (TKIs) developed for the therapy of advanced non-small cell lung cancer harboring mutations in the epidermal growth factor receptor (EGFR). Descriptive analysis was applied to data from the Chinese Medical Economic Information database to describe the impact on the price and utilization of three TKIs after the introduction of icotinib, a locally developed me-too TKI and two national negotiations regarding the price of EGFR-TKIs in China. After two national negotiations, the daily costs of all three EGFR-TKIs were reduced to around $30. From the first quarter of 2013 to the second quarter of 2016, the market share of the purchasing volume of icotinib, China's locally developed TKI, increased from 13% to 40%, while the market shares of two internationally developed TKIs decreased from 35% to 15% and from 52% to 45%, for erlotinib and gefitinib, respectively. The prices of EGFR-TKIs decreased and China's locally developed TKI accounted for a considerable proportion of market share. Locally developed me-too drugs aid price negotiation by injecting price competition and helping negotiate reduced prices of similar internationally-developed products. Through efforts to develop me-too drugs, combined with national drug price negotiation and reimbursement policies, developing countries might improve access to more affordable targeted cancer therapies.
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http://dx.doi.org/10.1053/j.seminoncol.2021.03.001DOI Listing
April 2021

Financial Toxicity Among Patients with Prostate, Bladder, and Kidney Cancer: A Systematic Review and Call to Action.

Eur Urol Oncol 2021 Jun 2;4(3):396-404. Epub 2021 Apr 2.

Vanderbilt University Medical Center, Nashville, TN.

Context: Financial toxicity (FT) refers to the detrimental effects of financial strain caused by a cancer diagnosis on the well-being of patients and their families. It is highly prevalent among cancer patients and has been associated with inferior clinical outcomes.

Objective: To summarize the literature regarding FT among patients with prostate, bladder, and kidney cancer, and to propose a framework for future FT investigations.

Evidence Acquisition: Primary manuscripts and abstracts reporting FT as a primary or secondary outcome or a covariate in patients with prostate, bladder, or kidney cancer, published before May 2020, were retrieved using the PubMed, Scopus, Embase, CINAHL, and Cochrane databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Of 629 titles identified, 19, ten, and two studies met the inclusion criteria for prostate, bladder, and kidney cancer, respectively, and were included (24 unique articles).

Evidence Synthesis: Significant heterogeneity was observed in covariates, methodology, and measure of FT. Factors commonly associated with FT included younger age at diagnosis, black race, low socioeconomic status, low education attainment, and rurality. FT was commonly associated with lower quality of life and nonadherence. FT was common among patients in countries with universal health coverage as well as those without, although the nature of these costs differed.

Conclusions: Despite paucity of literature, it is suggested that FT is common among patients with prostate and bladder cancer, and remains uncharacterized in kidney cancer patients. Future work will benefit from the incorporation of a formal FT framework, utilization of validated FT instruments to characterize FT consistently, and inclusion of FT measures in outcomes reported by patients with genitourinary cancers.

Patient Summary: Financial toxicity affects many prostate, bladder, and kidney cancer patients; however, this toxicity is understudied. It is associated with decreased quality of life and lower medication and treatment adherence.
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http://dx.doi.org/10.1016/j.euo.2021.02.007DOI Listing
June 2021

Epidemiologic Pattern of Cancer in Kathmandu Valley, Nepal: Findings of Population-Based Cancer Registry, 2018.

JCO Glob Oncol 2021 03;7:443-452

Radiation Oncology, Nepal Health Research Council (NHRC), Ramshahpath, Kathmandu, Nepal.

Purpose: Although cancer is an important and growing public health issue in Nepal, the country lacked any population-based cancer registry (PBCR) until 2018. In this study, we describe the establishment of the PBCR for the first time in Nepal and use the registry data to understand incidence, mortality, and patterns of cancer in the Kathmandu Valley (consisting of Kathmandu, Lalitpur, and Bhaktapur districts), which comprises 10.5% of the estimated 29 million population of Nepal in 2018.

Materials And Methods: The PBCR collects information from facilities and communities through the active process. The facilities include cancer or general hospitals, pathology laboratories, hospice, and Ayurvedic centers. In the communities, the field enumerators or female community health volunteers collected the data from the households. In addition, the Social Security and Nursing Division under the Department of Health Services, which provides subsidy for cancer treatment of underprivileged patients, was another major source of data. The collected data were verified for residence, accuracy, and completeness and then entered and analyzed using CanReg5 software.

Results: In the Kathmandu Valley, the PBCR registered 2,156 new cancer cases with overall age-adjusted incidence rate for all cancers of 95.7 per 100,000 population (95.3 for males and 98.1 for females). The age-adjusted mortality rate for males was 36.3 (n = 365) and for females 27.0 (n = 305) per 100,000 population. We found that the commonest cancers in males were lung and stomach, whereas in females, they were breast and lung cancer. Gallbladder cancer was among the top five common cancers in both sex.

Conclusion: These findings provide a milestone to understand the cancer burden in the country for the first time using the PBCR and will be helpful to develop and prioritize cancer control strategies.
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http://dx.doi.org/10.1200/GO.20.00574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081507PMC
March 2021

FDA approval standards for anticancer agents - lessons from two recent approvals in breast cancer.

Nat Rev Clin Oncol 2021 07;18(7):397-398

Program on Regulation, Therapeutics and Law (PORTAL), Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

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http://dx.doi.org/10.1038/s41571-021-00504-1DOI Listing
July 2021
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