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The rapid implementation of precision medicine tools in diagnosing and treating breast cancer (BC) has widened the potential therapeutic options for patients. The applications of gene sequencing, including next-generation gene sequencing (NGS), have led to numerous questions on how to validate, implement, interpret, prioritize and operationalize precision medicine tools to deliver meaningful and impactful interventions. Limited benefit has been portended with earlier experiences of NGS-driven treatment, in BC. However, the development and use of frameworks of clinical actionability of genomic alterations, for example, detected with NGS, has resulted in better patient selection, and potentially higher therapeutic value. The European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) is a framework that includes five tiers of clinical actionability, with tier 1 reserved for approved drugs with demonstrated benefits for targetable genomic alterations. The re-analysis of clinical studies by grouping the genomic alterations and matched drugs with ESCAT, in high vs lower tiers has demonstrated a significant benefit portended by high tiers alterations, with the availability of efficacious treatments. As a result, frameworks for actionability, like ESCAT, should be fundamental in developing and implementing NGS-driven, and broadly, precision medicine research and treatments., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

There is a growing global debate over barriers affecting the timely access to innovative anticancer therapies. Access to medicines is often traced back to the issue of costs: however, more commonly, the distance between valuable innovative treatments and the actual treatment of patients is far beyond the mere problem of financial barriers. A comprehensive approach to understand, assess to medicines should be pursued, to dissect the determinants and formulate solutions for all patients. In this chapter, we discuss drivers of access to innovation for patients with breast cancer, based on a case study of access to HER2-diagnositcs and therapeutics yielding a global landscape analysis, based on the efforts and expertise of the global collaborative group "ONCOLLEGE"., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The growing national economic burden linked to cancer spending is certainly impacted by an aging population, yet it finds its greatest obstacle in the ever-increasing costs for diagnostics, therapies, and hospital care, putting a strain on patients' finances of the family and the health system. Even in a universal healthcare system like the Italian one, where much of the difficult decisions on healthcare spending are in the hands of government technicians, and shaped by political will, patients contribute to cancer costs out of their own pockets to a much greater extent than is perceived from common sense. The sustainability of the cancer care system cannot ignore the meticulous control of public spending, which is fundamental and essential for societies that aim to keep the standards of care extremely high and continuously improve access and reduce inequalities in cancer care. Clinical trials, healthcare professionals and patients are best placed to evaluate the costs and benefits of treatment choices and are among the most financially affected by such decisions. Can scientific journals in the sector have their contribution for improvement? How can journals potentially close this gap and inform doctors, taxpayers, and the general population? To address this problem effectively, attention needs to be paid to two fundamental issues: one is high-quality science, and another is the ability to inform decision-making.

The selection of cancer medicines for national procurement requires deliberate evaluation of population benefit, budget impact, sustainability, and health system capacity. However, this process is complicated by numerous challenges, including the large volume and rapid pace of newly developed therapies offering marginal gains at prohibitively high prices. The WHO Model List of Essential Medicines (EML) and Model List of Essential Medicines for Children (EMLc) have undergone a series of evidence-based updates to ensure recommended cancer medicines offer meaningful clinical benefit. This Health Policy paper describes how cancer medicines are listed on the EML and EMLc, including two updated WHO processes: (1) the formation of the Cancer Medicines Working Group, and (2) additional selection principles for recommending cancer medicines, including a minimum overall survival benefit of 4-6 months with improvement to quality of life compared with standard treatment. These updates, along with proposals to include formal price considerations, additional selection criteria, and multisectoral collaboration (eg, voluntary licensing) promote procurement of high-value essential cancer medicines on national formularies in the context of supporting sustainable health systems to achieve universal health coverage., Competing Interests: Declaration of interests BG declares consulting fees from Vivio Health in matters unrelated to this manuscript. EGEdV declares research support from Amgen, Genentech, Roche, CytomX, G1 Therapeutics, Bayer, Synthon, Servier, Regeneron, Crescendo Biologics, GE Healthcare, and AstraZeneca; and consulting fees from National Surgical Adjuvant Breast and Bowel Project, Daiichi Sankyo, and Crescendo Biologics, in matters unrelated to this manuscript. All other authors declare no competing interests., (Copyright © 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Purpose of Review: Longitudinal evaluation of circulating tumour DNA (ctDNA) represents a promising tool for monitoring tumour evolution. In patients with breast cancer, ctDNA dynamics for the assessment of molecular residual disease (MRD) and resistances may, respectively, help clinicians in treatment modulation of adjuvant treatments, and in anticipating resistance to ongoing treatments and switch treatments before clinical progression, to improve disease control. Anyway, the introduction of this dynamic biomarker into clinical practice requires the demonstration of analytical validity, clinical validity and clinical utility., Recent Findings: In early breast cancer setting, several observational studies demonstrated the clinical validity of MRD monitoring through ctDNA in identifying patients at a higher risk of relapse, but many clinical trials evaluating the clinical utility are still ongoing, and few data resulted in inconclusive results.Instead, ctDNA dynamics for intercepting resistance have not been fully evaluated in terms of clinical validity, because monitoring schedules of most observational studies are not intensive. The only trial assessing their clinical utility (PADA-1) demonstrated a benefit in terms of progression-free survival, portraying a new landscape for clinical trials in this space., Summary: Rigorous clinical trials with adequate assays and patient-relevant endpoints are paramount to demonstrate the clinical utility of ctDNA dynamics and eventually increase clinical outcomes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Triple-negative breast cancer (TNBC) has been conventionally associated with poor prognosis, as a result of limited therapeutic options. In the early setting, prognosis is informed by clinical-pathological factors; for patients receiving neoadjuvant treatments, pathological complete response (pCR) is the strongest factor. In this review, we mapped the landscape of clinical trials in the postneoadjuvant space, and identified three patterns of clinical trial design., Recent Findings: For patients at higher risk, effective postneoadjuvant treatments are of paramount importance to address a high clinical need. Postneoadjuvant risk-adapted treatments have demonstrated to improve survival in patients at high of recurrence., Summary: Patients at high risk have indication for adjuvant treatment intensification, informed by baseline clinical, pathological or molecular factors (type 1 approach), on the presence, extent and molecular characteristics of the residual disease at the time of surgery (type 2) or on risk factors assessed in the postsurgical setting (type 3), for example, circulating tumour DNA. Most of the past trials were based on type 2 approaches, for example, with capecitabine and Olaparib. Few trials were based on a type 1 approach, notably pembrolizumab for early TNBC. The clinical validity of type 3 approaches is under investigation in several ongoing trials., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The WHO essential medicines list (EML) guides selection of drugs for national formularies. Here, we evaluate which medicines are considered highest priority by Indian oncologists and the extent to which they are available in routine practice., Methods: This is a secondary analysis of an electronic survey developed by the WHO EML Cancer Medicine Working Group. The survey was distributed globally using a hierarchical snowball method to physicians who prescribe systemic anticancer therapy. The survey captured the 10 medicines oncologists considered highest priority for population health and their availability in routine practice., Results: The global study cohort included 948 respondents from 82 countries; 98 were from India and 67 were from other low- and middle-income countries. Compared with other low- and middle-income countries, the Indian cohort was more likely to be medical oncologist (70% v 31%, P < .001) and work exclusively in the private health system (52% v 17%, P < .001). 14/20 most commonly selected medicines were conventional cytotoxic drugs. Universal access to these medicines was reported by a minority of oncologists; risks of significant out-of-pocket expenditures for each medicine were reported by 19%-58% of oncologists. Risk of catastrophic expenditure was reported by 58%-67% of oncologists for rituximab and trastuzumab. Risks of financial toxicity were substantially higher within the private health system compared with the public system., Conclusion: Most high-priority cancer medicines identified by Indian oncologists are generic chemotherapy agents that provide substantial improvements in survival and are already included in WHO EML. Access to these treatments remains limited by major financial burdens experienced by patients. This is particularly acute within the private health system. Strategies are urgently needed to ensure that high-quality cancer care is affordable and accessible to all patients in India.

Purpose: Access to essential cancer medicines is a major determinant of childhood cancer outcomes globally. The degree to which pediatric oncologists deem medicines listed on WHO's Model List of Essential Medicines for Children (EMLc) essential is unknown, as is the extent to which such medicines are accessible on the front lines of clinical care., Methods: An electronic survey developed was distributed through the International Society of Pediatric Oncology mailing list to members from 87 countries. Respondents were asked to select 10 cancer medicines that would provide the greatest benefit to patients in their context; subsequent questions explored medicine availability and cost. Descriptive and bivariate statistics compared access to medicines between low- and lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs)., Results: Among 159 respondents from 44 countries, 43 (27%) were from LMICs, 79 (50%) from UMICs, and 37 (23%) from HICs. The top five medicines were methotrexate (75%), vincristine (74%), doxorubicin (74%), cyclophosphamide (69%), and cytarabine (65%). Of the priority medicines identified, 87% (27 of 31) are represented on the 2021 EMLc and 77% (24 of 31) were common to the lists generated by LMIC, UMIC, and HIC respondents. The proportion of respondents indicating universal availability for each of the top medicines ranged from 9% to 46% for LMIC, 25% to 89% for UMIC, and 67% to 100% for HIC. Risk of catastrophic expenditure was more common in LMIC (8%-20%), compared with UMIC (0%-28%) and HIC (0%)., Conclusion: Most medicines that oncologists deem essential for childhood cancer treatment are currently included on the EMLc. Barriers remain in access to these medicines, characterized by gaps in availability and risks of catastrophic expenditure for families that are most pronounced in low-income settings but evident across all income contexts., Competing Interests: Scott C. HowardConsulting or Advisory Role: Sanofi, BTG, ServierSpeakers' Bureau: Sanofi, Jazz Pharmaceuticals Dorothy LombeThis author is a member of the Journal of Global Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript. Bishal GyawaliThis author is a member of the Journal of Global Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Vivio Health Felipe RoitbergHonoraria: Boehringer Ingelheim, AstraZeneca, Oncologia BrasilConsulting or Advisory Role: MSD OncologyResearch Funding: Roche (Inst), Boehringer Ingelheim (Inst), MSD (Inst), Bayer (Inst), AstraZeneca (Inst), Takeda (Inst) Elisabeth G. E. De VriesConsulting or Advisory Role: Daiichi Sankyo (Inst), NSABP Foundation (Inst), Crescendo Biologics (Inst)Research Funding: Amgen (Inst), Synthon (Inst), CytomX Therapeutics (Inst), Regeneron (Inst), G1 Therapeutics (Inst), Bayer (Inst), Roche (Inst), Genentech (Inst), Servier (Inst), Crescendo Biologics (Inst)Uncompensated Relationships: ESMO (Inst)Uncompensated Relationships: World Health Organization (Inst)Uncompensated Relationships: RECIST (Inst) Richard SullivanThis author is a member of the Journal of Global Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Honoraria: PfizerConsulting or Advisory Role: Pfizer (Inst)No other potential conflicts of interest were reported.

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., Competing Interests: Cynthia Villarreal-GarzaConsulting or Advisory Role: Roche, Novartis, Pfizer, LillySpeakers' Bureau: Roche, Myriad Genetics, NovartisResearch Funding: AstraZeneca (Inst), Roche (Inst)Travel, Accommodations, Expenses: Roche, MSD Oncology, Pfizer Bhawna SirohiHonoraria: Roche Pharma AG, EisaiConsulting or Advisory Role: Sanofi (Inst), Merck Serono (Inst)Research Funding: Dr Reddy's (Inst), Roche (Inst), Novartis (Inst)Patents, Royalties, Other Intellectual Property: Elsevier Book on Modern GI Oncology, Harper Collins—book on cancer Noam F. PondeEmployment: IQVIA Mariana BrandãoSpeakers' Bureau: Roche/GenentechResearch Funding: Pfizer (Inst), Roche/Genentech (Inst), AstraZeneca (Inst) Hatem A. Azim JrEmployment: Innate Pharma, Pierre FabreStock and Other Ownership Interests: Innate PharmaHonoraria: NovartisConsulting or Advisory Role: DiaacurateTravel, Accommodations, Expenses: Novartis Ivana Bozovic-SpasojevicHonoraria: Roche, Novartis, PfizerResearch Funding: Roche (Inst) Andrew OdhiamboHonoraria: Novartis, AstraZeneca, RocheConsulting or Advisory Role: AstraZenecaTravel, Accommodations, Expenses: AstraZeneca, Janssen, Beacon Medicare, Merck Radu VidraConsulting or Advisory Role: Sandoz, Accord Healthcare, ServierSpeakers' Bureau: Lilly, Servier, Roche, Bristol Myers Squibb/Medarex, Pfizer, Egis Pharmaceuticals, SandozResearch Funding: Bristol Myers Squibb/Medarex, Amgen, MSD, RocheTravel, Accommodations, Expenses: Amgen Hampig Raphael KourieHonoraria: Pfizer, Amgen, Roche, Novartis, AstraZeneca, JanssenConsulting or Advisory Role: AstraZenecaResearch Funding: Merck Serono (Inst) Mehmet Akif OzturkHonoraria: Pfizer, AstellasTravel, Accommodations, Expenses: Pfizer Csongor György LengyelEmployment: Bristol Myers Squibb Karina Perez SacardoConsulting or Advisory Role: Eurofarma Narjust DumaConsulting or Advisory Role: AstraZeneca, Pfizer, NeoGenomics Laboratories, Janssen, Boehringer Ingelheim, Bristol Myers Squibb/MedarexSpeakers' Bureau: MJH Life Sciences Bishal GyawaliConsulting or Advisory Role: Vivio Health Marco TagliamentoTravel, Accommodations, Expenses: Roche, Bristol Myers Squibb, AstraZeneca, TakedaOther Relationship: Novartis, Amgen Matteo LambertiniConsulting or Advisory Role: Roche, Novartis, Lilly, AstraZenecaSpeakers' Bureau: Theramex, Takeda, Roche, Lilly, Novartis, Pfizer, SandozNo other potential conflicts of interest were reported.

Very recently, emerging evidence demonstrated that laterality might be an independent prognostic factor in patients with advanced ovarian cancer (OC). Based on preliminary provocative observations, our study aimed to investigate the prognostic impact of sidedness in a large cohort of women with OC. Survival was estimated based on Kaplan-Meier method and survival curves were compared using Log-rank test. Cox proportional-hazards model was used to study the association between survival and covariates. A total of 10,177 women with OC were included. Mean age at diagnosis was 59.58 years (±13.5); 36.7% OC right-sided, 36.9% were left- sided, and 26.4% had bilateral OC. The median overall survival (OS) for the entire population was 77 months, with the lowest median OS observed in bilateral OC (median OS: 34 months). The prognostic value of OC sidedness was not confirmed at the univariable analysis (HR = 0.958; 95% CI: 0.888-1.033, p = 0.268). However, women with bilateral OC has a 45% higher risk of death as compared with unilateral diagnosis (HR = 1.453; 95% CI: 1.410-1.497; p< 0.001). The independent prognostic value was further confirmed on multivarible analysis after adjusting for covariates including age, marital status, histological type, CA-125 at diagnosis, grade, stage, chemotherapy and surgery (HR = 1.087; 95% CI: 1.043-1.136, p = 0.02). However, the ultimate prognostic significance appeared less prominent, with bilateral OC conferring a relative increase of 8.7% of mortality. Our real-world study demonstrated that impact of tumor sidedness has no prognostic implication (right vs left OC) but bilateral OCs might be marginally more prognostically unfavorable. Prospective validation might be warranted, to confirm the prognostic significance of OC sidedness, including for the presence of key genetic alterations and lymph nodes asymmetry, to better stratify patients with OC and predict outcomes according to tumor sidedness at diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Despite advances in supportive care, cancer-related symptoms tend to be persistent regardless of cancer type, stage of disease, or treatment received. There is an increasing prescription for complementary and alternative medicines, such as medical cannabis (MC). Knowledge and attitudes of Italian medical oncologists and palliative care physicians toward medical cannabis in cancer care remain unknown., Methods: We conducted a cross-sectional study to investigate the knowledge and attitude toward MC prescription among cancer care professionals in Italy. All invited participants received an email with the electronic questionnaire accessible through a direct link., Results: Among the 2616 members who received the invitation, 475 replied to the questionnaire and were considered for the survey analysis. The most prescribed formulations among those available in Italy were cannabis FM2. The most frequent clinical indications for the use of MC were pain, gastrointestinal, and mood disorders. Only 9 responders reported MC-related side effects like anxiety insomnia and muscle spasms. The question regarding the normative references for MC prescription and use in Italy had conflicting results: only 14% indicated the exact legislative reference., Conclusion: Our study highlights a significant discrepancy between personal attitudes, prescription levels, and actual knowledge on MC. This represent a critical issue that should be systemically faced, building educational programs and national guidelines that sublimate personal physicians' beliefs and predispositions, resulting in a robust science-based MC practice. Only through coordinated interventions on science and health policy of MC, there will be success of safety and efficacy, ensuring the best knowledge for the best outcomes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In some countries, breast cancer age-standardised mortality rates have decreased by 2-4% per year since the 1990s, but others have yet to achieve this outcome. In this study, we aimed to characterise the associations between national health system characteristics and breast cancer age-standardised mortality rate, and the degree of breast cancer downstaging correlating with national age-standardised mortality rate reductions., Methods: In this population-based study, national age-standardised mortality rate estimates for women aged 69 years or younger obtained from GLOBOCAN 2020 were correlated with a broad panel of standardised national health system data as reported in the WHO Cancer Country Profiles 2020. These health system characteristics include health expenditure, the Universal Health Coverage Service Coverage Index (UHC Index), dedicated funding for early detection programmes, breast cancer early detection guidelines, referral systems, cancer plans, number of dedicated public and private cancer centres per 10 000 patients with cancer, and pathology services. We tested for differences between continuous variables using the non-parametric Kruskal-Wallis test, and for categorical variables using the Pearson χ 2 test. Simple and multiple linear regression analyses were fitted to identify associations between health system characteristics and age-standardised breast cancer mortality rates. Data on TNM stage at diagnosis were obtained from national or subnational cancer registries, supplemented by a literature review of PubMed from 2010 to 2020. Mortality trends from 1950 to 2016 were assessed using the WHO Cancer Mortality Database. The threshold for significance was set at a p value of 0·05 or less., Findings: 148 countries had complete health system data. The following variables were significantly higher in high-income countries than in low-income countries in unadjusted analyses: health expenditure (p=0·0002), UHC Index (p<0·0001), dedicated funding for early detection programmes (p=0·0020), breast cancer early detection guidelines (p<0·0001), breast cancer referral systems (p=0·0030), national cancer plans (p=0·014), cervical cancer early detection programmes (p=0·0010), number of dedicated public (p<0·0001) and private (p=0·027) cancer centres per 10 000 patients with cancer, and pathology services (p<0·0001). In adjusted multivariable regression analyses in 141 countries, two health system characteristics were significantly associated with lower age-standardised mortality rates: higher UHC Index levels (β=-0·12, 95% CI -0·16 to -0·08) and increasing numbers of public cancer centres (β=-0·23, -0·36 to -0·10). These findings indicate that each unit increase in the UHC Index was associated with a 0·12-unit decline in age-standardised mortality rates, and each additional public cancer centre per 10 000 patients with cancer was associated with a 0·23-unit decline in age-standardised mortality rate. Among 35 countries with available breast cancer TNM staging data, all 20 that achieved sustained mean reductions in age-standardised mortality rate of 2% or more per year for at least 3 consecutive years since 1990 had at least 60% of patients with invasive breast cancer presenting as stage I or II disease. Some countries achieved this reduction without most women having access to population-based mammographic screening., Interpretation: Countries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes., Funding: None., Competing Interests: Declaration of interests GC reports consulting fees or honoraria from Bristol Myers Squibb, AstraZeneca, Daichii Sankyo, Novartis, Lilly, Pfizer, Seagen, and Ellipsis, and also reports participation on data safety monitoring or advisory boards for Roche and AstraZeneca. All other authors declare no competing interests., (Copyright © 2021 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology., Material and Methods: The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts., Results: The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology., Conclusions: As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients., Competing Interests: Declaration of Competing Interest There are no conflicts of interest reported., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2021 UICC.)

Background: Breast cancer (BC) is a leading cause of morbidity, mortality, and disability for women worldwide. There is substantial variation in treatment outcomes, which is function of multiple variables, including access to treatment. Treatment standards can promote quality and improve survival; thus, their development should be a priority for the cancer-control planning., Methods: We extracted the guidelines for the treatment of BC from a systematic review of the literature. We evaluated the development process, the methodology, and the recommendations formulated and surveyed the country resource stratification. Metrics of health-system capacity were selected to study the guidelines context appropriateness., Results: We analyzed 49 distinct guidelines for BC, mostly in English language (n = 23), developed in upper-middle and high-income countries of the European and American regions (n = 39). A resource-stratified approach was identified in a quarter of the guidelines (n = 11), mostly from resource-constrained settings. Only one-half of the guidelines reached a gender balance of the authorship, and 10.2% were based on a multidisciplinary steering committee. A number of efforts and solutions of resource adaptations were recognized, mostly in low- and middle-income countries. Overall, the national guidelines appeared not sensitive enough of the local health-system capacity in formulating recommendations, with possible exception for the radiation therapy availability., Conclusion: This global landscape of treatment standards for BC demonstrates that the majority is not context appropriate. Research on the formulation of cancer treatment standards is highly warranted, along with novel platforms for developing and disseminating resource-appropriate guidance., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Mutations in the epidermal growth factor receptor ( EGFR ) gene are commonly observed in non-small cell lung cancer (NSCLC), particularly in adenocarcinoma histology. The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion reported in Asian populations than Caucasian populations. There is a lack of data on these mutations in north Africa., Methods: Tumor specimens from Moroccan patients with NSCLC were collected from five pathology laboratories between November 2010 and December 2017 to determine frequency and types of EGFR mutations. Tumors were tested in a reference center for EGFR by polymerase chain reaction and sequencing of exons 18, 19, 20, and 21., Results: A total of 334 patients were enrolled: 242 (72.5%) males and 92 females (27.5%). A total of 56.9% had a history of smoking. EGFR testing of the 334 lung adenocarcinoma samples demonstrated a wild-type EGFR in 261 (78.1%) and mutated EGFR in 73 (21.9%). Mutations were mainly detected in the exon 19 deletion (65.8%), followed by exon 21 L858 (17.8%) and other exon 21 codon mutations (5.5%) and exon 18 (6.8%), whereas primary mutations of exon 20 were less frequent (4.1%). In patients with advanced NSCLC, the detection of EGFR mutation was independently associated with sex (41.3% female vs 14.5% male; p < 0.001) and smoking status (34.8% nonsmokers vs 12.9% active smokers; p < 0.001). The mean age was significantly different between the two groups ( p = 0.041)., Conclusion: Our findings confirm the genetic heterogeneity of NSCLC worldwide, reporting frequency of EGFR mutations in Moroccan patients with NSCLC between those of Asian and Caucasian populations.

Background: Several authors claimed that the Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) needs a prolonged learning curve, and outcomes during this phase could be suboptimal., Objective: To verify the safety and outcomes of RS-RARP performed by young surgeons during the learning curve., Design, Setting, and Participants: We conducted a retrospective analysis of the pre-, intra-, and postoperative features of all the patients who underwent RS-RARP from 2013 to 2017. We divided our patients into two groups: patients operated by two experienced surgeons (ESs) with >100 procedures and patients operated on by five younger surgeons in the learning curve (LCSs). LCSs had no previous experience in radical prostatectomy, and the very first RS-RARP procedures of each LCS case are included in the analysis., Outcome Measurements and Statistical Analysis: Perioperative, oncological, and functional data were analyzed. Short-term oncological results were reported as positive surgical margins (PSMs) and 1-yr disease-free survival. Complications were graded according to the Clavien-Dindo system. Potency was defined as erections sufficient for intercourse; continence was defined as no pad or one safety liner. A propensity score-matching analysis was used to adjust the difference in baseline preoperative parameters between the groups., Results and Limitations: We obtained two homogeneous groups of 256 patients each. After the matching, preoperative variables were similar in the two groups. The mean console time was longer for younger surgeons (98 vs 122 min, p < 0.001). Postoperative course, complications, and functional results were similar in the two groups; the final pathological analysis showed a worse T stage in the ES group (p = 0.017). PSMs and 1-yr disease-free survival did not differ between the groups., Conclusions: RS-RARP can be safely performed by inexperienced surgeons who have received adequate training., Patient Summary: Surgeons in the learning curve can perform Retzius-sparing robot-assisted radical prostatectomy safely, with similar early oncological results and functional outcomes., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Limited access to prevention, screening, timely diagnosis, affordable and effective treatment is the main driver of disparities in cancer care. The high costs represent a common barrier for the affordable access to biological agents. The only biological agent included in the World Health Organization list of essential medicines for the management of breast cancer is trastuzumab, and its biosimilars., Methods: We reviewed the pivotal trials for approved trastuzumab biosimilars and searched the proposed biosimilars under investigation in clinical trials, then mapped them against metrics of national epidemiology and health system capacity., Results: Thirteen clinical trials were extracted. Across 40 countries and 825 research facilities, more than three- fourth enrolling centers were located in low- and middle- income countries (n = 633) Correlation analysis suggested that the research and drug development of biosimilars was prioritized in settings where weaker health systems can result in poorer cancer- related outcomes and higher out of pocket expenses (range of r: -0,37; + 0.53; all p-values <0.05). Eleven countries had no biosimilars approved at the time of the analysis: in these countries, the drug development of biosimilars was more represented., Conclusion: The drug development of biosimilars occurs significantly in low- and middle- income countries. Our correlative findings must be interpreted cautiously, to understand if the biosimilar drug development is congruent with the national health priorities of cancer control. Health, societal and economic impacts on populations should be accounted, as relevant metrics for clinical trial implementations., Policy Summary: The implementation of cancer research should be developed under the national cancer control priorities, to ensure consistency across the evidence- informed relevant national policies, thus result in a population health impact. Biosimilars drug development can drive tangible population health benefits by accelerating the uptake of more sustainable health interventions and shaping more efficient regulatory environments., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Cervical cancer is controllable through appropriate interventions such as vaccination, screening, treatment, early diagnosis and palliative care. The greatest burden of cervical cancer lies in low-income countries (LIC) where most of these services are missing or developed asymmetrically. Indeed, it is important to have not just an expansion, but a symmetric and concordant development of each service. Therefore, policies of countries should be aligned to provide concordant services and achieve the best outcomes with available resources. This is called 'policy cohesion' and for the first time in literature we will analyse cervical cancer policy coherence in all the 194 WHO member states., Methods: The study is based on the 2017 WHO Non-Communicable Disease Country Capacity Surveys (NCD CCS). Although the survey covers multiple non-communicable diseases, in this report we will only discuss those results pertaining to cervical cancer, analysing the cervical cancer policy cohesion of 194 WHO member states, divided by WHO region and World Bank income group., Results: Human papilloma virus vaccination exists in 53% of countries. 76% of countries offer cervical screening: among these countries, treatment, early diagnosis guidelines and palliative care are missing in 13%, 13% and 40%, respectively. In the African region, this discord is even more profound: 32%, 17% and 60%, respectively., Conclusion: Especially in those settings where resources are limited, early detection guidelines, treatment and palliative care should be implemented along with secondary prevention strategies. Symmetric development of concordant cervical cancer services maximises cervical cancer control efficacy., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

The global preparedness and response to the rapid escalation to severe acute respiratory syndrome coronavirus (SARS-CoV)-2-related disease (COVID-19) to a pandemic proportion has demanded the formulation of a reliable, useful and evidence-based mechanism for health services prioritisation, to achieve the highest quality standards of care to all patients. The prioritisation of high value cancer interventions must be embedded in the agenda for the pandemic response, ensuring that no inconsistency or discrepancy emerge in the health planning processes.The aim of this work is to organise health interventions for breast cancer management and research in a tiered framework (high, medium, low value), formulating a scheme of prioritisation per clinical cogency and intrinsic value or magnitude of benefit. The public health tools and schemes for priority setting in oncology have been used as models, aspiring to capture clinical urgency, value in healthcare, community goals and fairness, while respecting the principles of benevolence, non-maleficence, autonomy and justice.We discuss the priority health interventions across the cancer continuum, giving a perspective on the role and meaning to maintain some services (undeferrable) while temporarily abrogate some others (deferrable). Considerations for implementation and the essential link to pre-existing health services, especially primary healthcare, are addressed, outlining a framework for the development of effective and functional services, such as telemedicine.The discussion covers the theme of health systems strategising, and why oncology care, in particular breast cancer care, should be maintained in parallel to pandemic control measures, providing a pragmatic clinical model within the broader context of public healthcare schemes., Competing Interests: Competing interests: GC has received honoraria from Pfizer, Novartis, Eli Lilly, Roche; fees for expert testimony and medical education from Pfizer and has participated in advisory boards for Pfizer, Roche, Eli Lilly, Novartis, Seattle Genetics, Celltrion. SD reports grants, institutional fees from Roche/Genentech, Pfizer, Puma, AstraZeneca, Novartis, Amgen, Sanofi, Eli Lilly, MSD, BMS, Daichi and non-financial support from Roche/Genentech, Pfizer, AstraZeneca. SDC has received fees for medical education from Novartis and Pierre-Fabre and is the recipient of the IG 20774 of Fondazione AIRC. MG reports personal fees/travel support from Amgen, AstraZeneca, Celgene, Eli Lilly, Invectys, Pfizer, Novartis, Puma, Nanostring, Roche, Medison, LifeBrain, all outside the submitted work; an immediate family member is employed by Sandoz. PP is medical advisor of Sordina IORT Technologies. ES has received honoraria from Amgen, AstraZeneca, Clinigen, Egis, Eli Lilly, Genomic Health, Novartis, Pfizer, Pierre-Fabre, Roche, Sandoz, TLC Biopharmaceuticals and travel support from Amgen, AstraZeneca, Egis, Novartis, Pfizer, Roche. FC has consultancy role for Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seattle Genetics, Teva. EdA honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen and Zodiac; travel grants from Roche/GNE and GSK/Novartis; research grant to the institution from Roche/GNE, AstraZeneca, GSK/Novartis and Servier. CC declares consultancy/advisory role/speaker's bureau: Pfizer, Eli Lilly, Roche, Novartis. SP-S discloses honoraria, consultancy and speaker’s bureau: Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, Nanostring., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

This review article is an overview of the session at the European Society for Medical Oncology (ESMO) Asia 2018 Congress entitled: 'Cancer medicines in Asia and Asia-Pacific: What is available, and is it effective enough?'. The article provides an overview of the session speakers' views on the impact that the lack of accessibility and availability of medicines has on patient outcomes in the treatment of breast cancer, colorectal cancer and lung cancer, responsible for more than one-third of cancer deaths in the Asian region. It also lists the various global policy initiatives that ESMO supports to promote the best cancer care in the Asian and Asia-Pacific region. The review presents extrapolated data from the 'ESMO International Consortium Study on the availability, out-of-pocket costs and accessibility of antineoplastic medicines in countries outside of Europe', which reveals several disparities among Asian countries, across the different income levels. In low- and middle-income countries, some barriers to the accessibility of anticancer medicines include the lack of government reimbursement, budget allocation for healthcare and quality-assured generic and biosimilar medicines, as well as shortages and patent rights. Throughout the article, the session presenters provide their views on strategies that can be considered to overcome these barriers., Competing Interests: Competing interests: AE has received research support from AstraZeneca, Pfizer, Celltrion, Novartis, none in relation to this publication.

Background: Robot-assisted laparoscopic radical prostatectomy (RARP) has become the main surgical option for localized prostate cancer. We recently developed a new approach for RARP, passing through the pouch of Douglas and avoiding all the Retzius structures involved in continence and potency preservation., Objective: To report the functional and oncologic results of our first 200 patients operated on using this new approach., Design, Setting, and Participants: This was a prospective, noncontrolled case series including the first 200 consecutive patients undergoing this kind of surgery (January the 1st, 2010 to December the 31st, 2011)., Surgical Procedure: Retzius-sparing RARP., Outcome Measurements and Statistical Analysis: All perioperative, oncologic, and functional data were prospectively recorded. Potency was defined as an International Index of Erectile Function-5 questionnaire score >17; continence was defined as use of no pad or of one safety liner. Oncologic results were reported as positive surgical margins (PSM) and 1-yr biochemical disease-free survival (1y-bDFS). Recurrence was defined as a repeated prostate-specific antigen >0.2 ng/ml. Complications were graded according to the Clavien-Dindo system. The first 100 patients (group 1) were compared with the second 100 (group 2) to evaluate the learning curve effects., Results and Limitations: The median patient age was 65 yr. Comparing the two groups, transfusions were needed in 8% versus 4% of cases in groups 1 and 2, respectively (p=0.02). There was one Clavien-Dindo grade 3b in group 1 versus one grade 3a complication in group 2. In patients with pT2 disease, PSMs were recorded in 22.4% of those in group 1 versus 10.1% in group 2 (p=0.045). 1y-bDFS was 89% in group 1 versus 92% in group 2. For groups 1 and 2, respectively, immediate continence was reached in 92% versus 90% of patients, and the 1-yr continence rate was 96% versus 96%. Considering the 77 potent patients aged <65 yr who underwent bilateral intrafascial nerve-sparing surgery, 40.4% of those in group 1 versus 40% of those in group 2 reached their first intercourse within 1 mo; at 1 yr of follow-up, these figures had increased to 81% versus 71%, respectively (p=0.162). The main limitation of this study is its noncontrolled nature., Conclusions: We demonstrated Retzius-sparing RARP to be oncologically safe and to result in high early continence and potency rates. Long-term, prospective, comparative, and possibly randomized studies are needed., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)