ESMO expert consensus statements on the screening and management of financial toxicity in patients with cancer.

BACKGROUND: Financial toxicity, defined as both the objective financial burden and subjective financial distress from a cancer diagnosis and its treatment, is a topic of interest in the assessment of the quality of life of patients with cancer and their families. Current evidence implicates financial toxicity in psychosocial, economic and other harms, leading to suboptimal cancer outcomes along the entire trajectory of diagnosis, treatment, supportive care, survivorship and palliation. This paper presents the results of a virtual consensus, based on the evidence base to date, on the screening and management of financial toxicity in patients with and beyond cancer organized by the European Society for Medical Oncology (ESMO) in 2022. METHODS: A Delphi panel of 19 experts from 11 countries was convened taking into account multidisciplinarity, diversity in health system contexts and research relevance. The international panel of experts was divided into four working groups (WGs) to address questions relating to distinct thematic areas: patients with cancer at risk of financial toxicity; management of financial toxicity during the initial phase of treatment at the hospital/ambulatory settings; financial toxicity during the continuing phase and at end of life; and financial risk protection for survivors of cancer, and in cancer recurrence. After comprehensively reviewing the literature, statements were developed by the WGs and then presented to the entire panel for further discussion and amendment, and voting. RESULTS AND DISCUSSION: A total of 25 evidence-informed consensus statements were developed, which answer 13 questions on financial toxicity. They cover evidence summaries, practice recommendations/guiding statements and policy recommendations relevant across health systems. These consensus statements aim to provide a more comprehensive understanding of financial toxicity and guide clinicians globally in mitigating its impact, emphasizing the importance of further research, best practices and guidelines.

Policy strategies for capacity building and scale up of the workforce for comprehensive cancer care: a systematic review.

BACKGROUND: Patients with cancer in low- and middle-income countries experience worse outcomes as a result of the limited capacity of health systems to deliver comprehensive cancer care. The health workforce is a key component of health systems; however, deep gaps exist in the availability and accessibility of cancer care providers. MATERIALS AND METHODS: We carried out a systematic review of the literature evaluating the strategies for capacity building of the cancer workforce. We studied how the policy strategies addressed the availability, accessibility, acceptability, and quality (AAAQ) of the workforce. We used a strategic planning framework (SWOT: strengths, weaknesses, opportunities, threats) to identify actionable areas of capacity building. We contextualized our findings based on the WHO 2030 Global Strategy on Human Resources for Health, evaluating how they can ultimately be framed in a labour market approach and inform strategies to improve the capacity of the workforce (PROSPERO: CRD42020109377). RESULTS: The systematic review of the literature yielded 9617 records, and we selected 45 eligible papers for data extraction. The workforce interventions identified were delivered mostly in the African and American Regions, and in two-thirds of cases, in high-income countries. Many strategies have been shown to increase the number of competent oncology providers. Optimization of the existing workforce through role delegation and digital health interventions was reported as a short- to mid-term solution to optimize cancer care, through quality-oriented, efficiency-improving, and acceptability-enforcing workforce strategies. The increased workload alone was potentially detrimental. The literature on retaining the workforce and reducing brain drain or attrition in underserved areas was commonly limited. CONCLUSIONS: Workforce capacity building is not only a quantitative problem but can also be addressed through quality-oriented, organizational, and managerial solutions of human resources. The delivery of comprehensive, acceptable, and impact-oriented cancer care requires an available, accessible, and competent workforce for comprehensive cancer care. Efficiency-improving strategies may be instrumental for capacity building in resource-constrained settings.

A conceptual framework for cautious escalation of anticancer treatment: How to optimize overall benefit and obviate the need for de-escalation trials.

BACKGROUND: The developmental workflow of the currently performed phase 1, 2 and 3 cancer trial stages lacks essential information required for the determination of the optimal efficacy threshold of new anticancer regimens. Due to this there is a serious risk of overdosing and/or treating for an unnecessary long time, leading to excess toxicity and a higher financial burden for society. But often post-approval de-escalation trials for dose-optimization and treatment de-intensification are not performed due to failing resources and time. Therefore, the developmental workflow needs to be restructured toward cautious systemic cancer treatment escalation, in order to guarantee optimal efficacy and sustainability. METHODS: In this manuscript we discuss opportunities to produce the information needed for cautious escalation, based on models of cancer growth and cancer kill kinetics as well as exploratory biomarkers, for the purpose of designing the optimal phase 3 superiority trial. Subsequently, we compare the sample size needed for a phase 3 superiority trial, followed by a necessary de-escalation trial with the sample size needed for a multi-arm phase 3 trial with intervention arms of differing intensity. All essential items are structured within a Framework for Cautious Escalation (FCE). The discussion uses illustrations from the breast cancer setting, but aims to be applicable for all cancers. RESULTS: The FCE is a promising model of clinical development in oncology to prevent overtreatment and associated issues, especially with regard to the number of repetitive treatment cycles. It will hopefully increase the relevance and success rate of clinical trials, to deliver improved patient-centric outcomes.

Essential cancer medicines: adding feasibility to the magnitude of clinical benefit value chain.

BACKGROUND: Cancer is a global public health problem, requiring efficient health system investments to deliver sustainable impact on population health. Access to medicines is a critical component of health systems, having a crucial role in delivering therapeutic benefits. Since 1977, the World Health Organization (WHO) has published a Model List of Essential Medicines (EML) that includes key health interventions for the prevention and control of conditions of public health relevance. Essential medicines are selected for inclusion in the EML based on the evidence of efficacy, safety, therapeutic value, and the potential to impact population health. With the rapid changes in the therapeutic landscape of cancer treatment with new medicine approvals, there is a critical need to select and prioritise specific cancer interventions based on their intrinsic value. MATERIALS AND METHODS: The European Society for Medical Oncology (ESMO) has developed a decisional methodology based on a threshold with a minimum set of technical specifications and a consensus-based procedure for decisions to select candidate cancer medicines to be submitted to the WHO for consideration for the WHO EML. RESULTS: ESMO recognises the WHO EML as an important reference guide for medicines that all countries should include in their national EMLs. Cancer medicines on the WHO EML are used in the treatment of the majority of cancers, and are recommended in the evidence-based ESMO Clinical Practice Guidelines that medical oncologists use to treat patients. ESMO's submissions to the WHO EML in 2019 and 2021 and their respective outcomes are presented in the manuscript. CONCLUSION: Due to the rising costs associated with newly available therapies, structured, reproducible, and field-tested tools to evaluate the added clinical benefit from these therapies need to be implemented in pre-selecting potential candidate medicines to be included in the WHO EML. ESMO is proud to collaborate closely with WHO on this important global public health initiative.

Management of patients with HER2-positive metastatic breast cancer after trastuzumab deruxtecan failure.

The current treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) has been greatly impacted in the past decade by the introduction of antibody-drug conjugates (ADCs), which represent a relatively novel therapeutic class with the peculiar ability to deliver otherwise overtly toxic chemotherapeutics to tumor sites by exploiting the specificities of monoclonal antibodies. Indeed, drug engineering refinements in ADC design, such as through the introduction of cleavable linkers and hydrophobic payloads, resulted in improved patient outcomes in recent years. Two different ADCs, namely trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have already entered clinical practice for the treatment of HER2-positive ABC. In this scenario, T-DXd has shown to portend better survival outcomes compared to T-DM1, while leaving a large unsought area of unmet medical need upon T-DXd failure. Treatment decision and benefit of cancer drugs following T-DXd still represent an area of clinical controversy, where a preclinical investigation and clinical development should be prioritized. As the pace of innovation is currently accelerating, and with novel ADC formulations advancing in early-phase clinical trials, the whole BC field is changing at an unprecedented rate, with potential broadenings of therapeutic indications. In this review, we present the clinical landscape of HER2-positive advanced BC and discuss our vision on how to tackle T-DXd resistance, providing a perspective on the priority areas of the cancer research in this setting.

ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody-drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from nine different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer; and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This article presents the developed statements, including findings from the expert panel discussions, expert opinion, and a summary of evidence supporting each statement.

ESMO-Magnitude of Clinical Benefit Scale for haematological malignancies (ESMO-MCBS:H) version 1.0.

BACKGROUND: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. METHODS: ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. RESULTS: Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. CONCLUSION: The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies.

Cancer care in transgender and gender-diverse persons: results from two national surveys among providers and health service users by the Italian Association of Medical Oncology.

BACKGROUND: Transgender and gender-diverse (TGD) population represents an underserved group across the cancer care continuum. To assess the perspective of both oncology health care providers (OHPs) and TGD individuals in Italy, we conducted two national surveys: one among 2407 OHPs about their attitudes, knowledge and behavior toward TGD patients, and one among TGD persons about their health needs, experiences and barriers encountered in the use of health services across the cancer continuum. MATERIALS AND METHODS: The surveys were self-compiled web-based computer-aided web interview, conducted in Italy within the 'OncoGender-Promoting Inclusion in Oncology' project, led by the Italian national cancer society [Associazione Italiana di Oncologia Medica (AIOM)]-associated researchers. All members of AIOM were invited by e-mail to participate in the OHP survey. TGD persons were reached through advocacy groups and consumers' panel. The recruitment was completed on a voluntary basis. Survey data were collected and managed using an online platform managed by ELMA Research, an independent pharmaceutical marketing agency. RESULTS: A total of 305 OHPs (13% of AIOM members) and 190 TGD individuals participated in the surveys. Only 19% of OHPs felt competent in providing care to TGD patients and 21% declared not to feel comfortable in treating TGD patients. Seventy-one percent of TGD persons reported that they had never joined any cancer screening program; 32% reported one or more acts of discrimination by health care providers. Seventy-two percent of OHPs recognized the lack of specific education on cancer care for TGD patients and deemed it necessary to receive adequate training. CONCLUSIONS: A general lack of knowledge among OHPs about TGD health issues seems to be the main driver of difficulties in providing assistance and of discriminatory attitudes against TGD individuals. Ultimately, this whole issue generates access barriers and contributes to lack of trust in health care services. Educational interventions and an implementation of person-centric cancer policies are urgently needed.

Hydrocarbons removal from real marine sediments: Analysis of degradation pathways and microbial community development during bioslurry treatment.

In this study, real marine sediments polluted by petroleum compounds were treated by means of a bioslurry pilot scale reactor. The treatment performance was evaluated by measuring the removal of total petroleum hydrocarbon (TPH), coupled to further analyses required to understand the mechanisms involved in the biodegradation process. The maximum TPH-removal efficiency reached 86 % at the end of experiments. Moreover, high throughput 16S RNA gene sequencing was used to describe the microbiome composition in sediment prior to, and after, bioslurry treatment, in order to identify the taxa mostly entailed in the TPH removal process. The raw sediment was mostly colonized by members of Sulfurimonas genus; after bioslurry treatment, it was noticed a shift in the microbial community composition, with Proteobacteria phylum dominating the remediation environment (high increase in terms of growth for Hydrogenophaga and Sphingorhabdus genera) along with the Phaeodactylibacter genus (Bacteroidetes). Furthermore, the assessment of gaseous emissions from the system allowed to quantify the volatile hydrocarbon component and, consequently, to obtain a more accurate evaluation of TPH-removal pathway by the bioslurry system. Finally, phytotoxicity tests on sediment samples highlighted an increase of the treated sample quality status compared to the untreated one.

Quantifying geographical accessibility to cancer clinical trials in different income landscapes.

BACKGROUND: Clinical trials are increasingly perceived as a therapeutic opportunity for cancer patients. Favoring their concentration in few high-expertise academic centers maximizes quality of data collection but poses an issue of access equality. Analytical tools to quantify trial accessibility are needed to rationalize resources. MATERIALS AND METHODS: We constructed a distance-based accessibility index (dAI) using publicly available data on demographics, cancer incidence and trials. Multiple strategies were applied to mitigate or quantify clear sources of bias: reporting biases by text mining multiple registries; reliability of simple geographical distance by comparison with high-quality travel cost data for Italy; index inflation due to highly heterogeneous cancer incidence by log-transformation. We studied inequalities by Gini index and time trend significance by Mann-Kendall test. We simulated different resource allocation models in representative countries and identified locations where new studies would maximally improve the national index. RESULTS: The dAI approximated well a more realistic but not widely applicable travel cost-based index. Accessibility was unevenly distributed across and within countries (Gini index ∼0.75), with maximal inequalities in high- and upper-middle-income countries (China, United States, Russian Federation). Over time, accessibility increased but less than the total number of trials, most evidently in upper-middle-income countries. Simulations in representative countries (Italy and Serbia) identified ideal locations able to maximally raise the national index. CONCLUSIONS: Access to clinical trials is highly uneven across and within countries and is not mitigated by simple increase in the number of trials; a rational algorithmic approach can be used to mitigate inequalities.

Risk-adapted modulation through de-intensification of cancer treatments: an ESMO classification.

BACKGROUND: The landscape of clinical trials testing risk-adapted modulations of cancer treatments is complex. Multiple trial designs, endpoints, and thresholds for non-inferiority have been used; however, no consensus or convention has ever been agreed to categorise biomarkers useful to inform the treatment intensity modulation of cancer treatments. METHODS: An expert subgroup under the European Society for Medical Oncology (ESMO) Precision Medicine Working Group shaped an international collaborative project to develop a classification system for biomarkers used in the cancer treatment de-intensification, based on a tiered approach. A group of disease-oriented clinical, translational, methodology and public health experts, and patients' representatives provided an analysis of the status quo, and scanned the horizon of ongoing clinical trials. The classification was developed through multiple rounds of expert revisions and inputs. RESULTS: The working group agreed on a univocal definition of treatment de-intensification. Evidence of reduction in the dose-density, intensity, or cumulative dose, including intermittent schedules or shorter treatment duration or deletion of segment(s) of the standard regimens, compound(s), or treatment modality must be demonstrated, to define a treatment de-intensification. De-intensified regimens must also portend a positive impact on toxicity, quality of life, health system burden, or financial toxicity. ESMO classification categorises the biomarkers for treatment modulation in three tiers, based on the level of evidence. Tier A includes biomarkers validated in prospective, randomised, non-inferiority clinical trials. The working group agreed that in non-inferiority clinical trials, boundaries are highly dependent upon the disease scenario and endpoint being studied and that the absolute differences in the outcomes are the most relevant measures, rather than relative differences. Biomarkers tested in single-arm studies with a threshold of non-inferiority are classified as Tier B. Tier C is when the validation occurs in prospective-retrospective quality cohort investigations. CONCLUSIONS: ESMO classification for the risk-guided intensity modulation of cancer treatments provides a set of evidence-based criteria to categorise biomarkers deemed to inform de-intensification of cancer treatments, in risk-defined patients. The classification aims at harmonising definitions on this matter, therefore offering a common language for all the relevant stakeholders, including clinicians, patients, decision-makers, and for clinical trials.

Distribution of the workforce involved in cancer care: a systematic review of the literature.

BACKGROUND: A skilled health workforce is instrumental for the delivery of multidisciplinary cancer care and in turn a critical component of the health systems. There is, however, a paucity of data on the vast inequalities in cancer workforce distribution, globally. The aim of this study is to describe the global distribution and density of the health care workforce involved in multidisciplinary cancer management. METHODS: We carried out a systematic review of the literature to determine ratios of health workers in each occupation involved in cancer care per 100 000 population and per 100 cancer patients (PROSPERO: protocol CRD42018095414). RESULTS: We identified 33 eligible papers; a majority were cross-sectional surveys (n = 16). The analysis of the ratios of health providers per population and per patients revealed deep gaps across the income areas, with gradients of workforce density, highest in high-income countries versus low-income areas. Benchmark estimates of optimal workforce availability were provided in a secondary research analysis: mainly high-income countries reported workforce capacities closer to benchmark estimates. A paucity of literature was defined for critical health providers, including for pediatric oncology, surgical oncology, and cancer nurses. CONCLUSION: The availability and distribution of the cancer workforce is heterogeneous, and wide gaps are described worldwide. This is the first systematic review on this topic. These results can inform policy formulation and modelling for capacity building and scaleup.

Benefit of adjuvant chemotherapy in patients with special histology subtypes of triple-negative breast cancer: a systematic review.

PURPOSE: Breast cancer (BC) is a leading cause of morbidity, disability, and mortality in women, worldwide; triple-negative BC (TNBC) is a subtype traditionally associated with poorer prognosis. TNBC special histology subtypes present distinct clinical and molecular features and sensitivity to antineoplastic treatments. However, no consensus has been defined on the best adjuvant therapy. The aim of the review is to study the evidence from literature to inform the choice of adjuvant treatments in this setting. METHODS: We systematically searched literature assessing the benefit of adjuvant chemotherapy in patients with TNBC special histotypes (PROSPERO: CRD42020153818). RESULTS: We screened 6404 records (15 included). All the studies estimated the benefit of different chemotherapy regimens, in retrospective cohorts (median size: 69 patients (range min-max: 17-5142); median follow-up: 51 months (range: 21-268); mostly in Europe and USA). In patients with early-stage adenoid cystic TNBC, a marginal role of chemotherapy was reported. Similar for apocrine TNBC. Medullary tumors exhibited an intrinsic good prognosis with a limited role of chemotherapy, suggested to be modulated by the presence of tumor-infiltrating lymphocytes. A significant impact of chemotherapy on the overall survival was estimated in patients with metaplastic TNBC. Limitations were related to the retrospective design of all the studies and heterogeneous treatments received by the patients. CONCLUSIONS: There is potential opportunity to consider treatment de-escalation and less intense therapies in some patients with early, special histology-type TNBC. International efforts are indispensable to validate prospective clinical decision models.

Benefit of adjuvant chemotherapy in patients with lobular breast cancer: A systematic review of the literature and metanalysis.

The role of adjuvant chemotherapy (aCT) for patients with localized lobular breast cancer (ILC) is still controversial. It is unclear what is the magnitude of benefit of the CT in this setting. In this systematic review of the literature and metanalysis, we aimed to estimate the benefit of aCT in addition to the standard treatments in the early ILC setting. We identified the records by searching Medline, CENTRAL, Web of Science, SCOPUS, and Google Scholar, and the meeting proceeding of the principal oncology meetings of the last 10 years, with no language or time restriction. A research strategy was developed with mapped and MeSH terms. Studies on the clinical use of aCT reporting survival outcomes in the ILC setting were double-screened and tabulated. PRISMA methodology was used for data extraction and synthesis. We extracted information on the study design and setting, eligible population and population size, histology variants, menopausal status, treatment regimens, follow-up duration. Hazard ratios (HR) and 95% confidence interval (CI) were extracted and transformed into logHR and corresponding standard error to obtain the Summary HR (SHR). Heterogeneity (I2 statistics) and publication bias (Macaskill test) were tested; a random effect models provided by SAS Proc Mixed was used for data analysis. Sensitivity analysis was conducted to examine the impact of inclusion criteria on the summary results. Disease-free (DFS), overall (OS) and cancer-specific survival (BCSS) were the primary endpoints of the investigation. The systematic review and metanalysis included 38,387 patients across 8 clinical studies. aCT was not associated with an improvement of OS (SHR 0.99; 95%CI 0.86-1.14), with low heterogeneity (I2 = 28%) and no publication bias (p = 0.43). Sensitivity analysis resulted in unchanged conclusions. We did not perform a metanalysis of the DFS estimates, as only reported in 3 studies. The value of aCT in improving DFS was unconfirmed, consistently with the OS results. Our research did not confirm a certain role of aCT for patients with ILC. Research gaps were identified, warranting the development of prospective, controlled ad hoc investigations.

Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring.

BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment. METHODS: As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment. RESULTS: Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data. CONCLUSION: Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, implementation, and data analysis that may have biased results and conclusions. These will be addressed in future iterations of the ESMO-MCBS.

The global landscape of availability, accessibility and affordability of essential diagnostics and therapeutics for the management of HER2-positive breast cancer: The ONCOLLEGE-001 survey.

AIM OF THE STUDY: Barriers in access to essential care are key determinants of disparities in cancer survival. Breast cancer (BC) is the most common cancer and lead cause of mortality among women, 60 % occurring in low- and middle-income countries (LMs). A quarter of BC are characterized by an over-expression of the epidermal growth factor receptor 2 (HER2). Valuable strategies to diagnose and manage patients with HER2-positive BC have been determined and some considered essential health interventions. ONCOLLEGE-001 is a global survey of availability, accessibility, and affordability of essential HER2 diagnostics and therapeutics. METHOD: A self-administered questionnaire was shared electronically to oncologists, identified from oncology networks. Data were analyzed using descriptive statistics, per income areas and geographic regions. RESULTS: We received 191 responses (84 % response rate). The majority of the responders were from LMs (n = 153) and were physician providers. Immunohistochemistry was the most common HER2 diagnostics available (n = 185). A third of the responders from low/lower-middle and a half of upper-middle income countries had HER2 testing only in the private sector. Trastuzumab was not available for 8 %: when available, 15%-21% reported accessibility only as out-of-pocket expenditure; when not reimbursed, only 10 % of the providers could significantly offer this intervention. Availability of trastuzumab biosimilars was reported in more than a half of the responders (n = 107). CONCLUSION: Stark disparities are reported, with high out-of-pocket expenses for HER2 testing and significant financial barriers to access trastuzumab treatments. Policy solutions are urgently warranted for the selection, prioritization, and reimbursement of essential health interventions, to result in improved population health. POLICY SUMMARY STATEMENT: the inclusion of essential services for cancer management should be assured and financed in the benefit packages of healthcare to all. Prioritizing high-value health interventions, including medicines and medical devices, is critical to deliver impactful programs on population health.

The global landscape of drug development for kidney cancer.

Renal cell cancer (RCC) is the third most diagnosed genitourinary malignancy in the world. Nearly a half of the diagnoses and 60% of related deaths occur in low-middle income countries (LMs), where prognosis is generally poor. We conducted a systematic research of ClinicalTrials.gov, searching RCC ongoing studies for adult patients. We included 205 trials in the final analysis. The enrolling centers were mainly distributed in high-income settings (88.9%). We estimated 94.6% of the trial population was enrolled in only five countries and none in LMs. Clinical drug development for RCC is driven by early phase studies, mainly assessing small molecule tyrosine kinase inhibitors and immunotherapy or the combination. Sixty percent of the trials were industry sponsored. Only a minority of the trials were in the early setting of care, adjuvant or neoadjuvant therapy. Disparities in drug development in LMs mirror a common underestimation of the value of research among the national priorities in cancer health planning, resulting in poor ethnic diversity and inclusiveness. This commonly results in incomplete knowledge of activity and safety of medicines across different ethnic groups, with consequences on priorities for cancer interventions and estimates of benefit in LMs patients. The use of RCC as a case study for inclusiveness suggests poor inclusion of non- Caucasian populations in the trials, especially trials testing new immunotherapy and targeted agents where RCC drug development is more pronounced, resulting in issues of generalizability in other ethnic groups when these compounds are approved with no ethnic restrictions or specifications.

Biogas from municipal solid waste landfills: a simplified mathematical model.

Municipal solid waste (MSW) landfills now represent one of the most important issues related to the waste management cycle. Knowledge of biogas production is a key aspect for the proper exploitation of this energy source, even in the post-closure period. In the present study, a simple mathematical model was proposed for the simulation of biogas production. The model is based on first-order biodegradation kinetics and also takes into account the temperature variation in time and depth as well as landfill settlement. The model was applied to an operating landfill located in Sicily, in Italy, and the first results obtained are promising. Indeed, the results showed a good fit between measured and simulated data. Based on these promising results, the model can also be considered a useful tool for landfill operators for a reliable estimate of the duration of the post-closure period.