Strategies to decrease inequalities in cancer therapeutics, care and prevention: Proceedings on a conference organized by the Pontifical Academy of Sciences and the European Academy of Cancer Sciences, Vatican City, February 23-24, 2023.

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA-Cancer Moonshot and the EU-Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state-of-the-art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost-effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost-effective healthcare.

Self-Reported Assessment of the Socio-Economic Impact of Anticancer Chemotherapy-Related Neurotoxicity.

Chemotherapy-induced neurotoxicity is a well-known complication of several very effective systemic anticancer treatments, mainly presenting as cognitive impairment ("chemo-brain") and peripheral neuropathy. The social and economic effects of long-lasting chemotherapy-induced neurotoxicity on patients' lifestyles and their relationships are under-investigated, and their impact is, therefore, largely unknown. In this study, we used a web-based questionnaire to record the self-reported perception of chemotherapy-induced neurotoxicity on cancer patients' health status, but also on several different aspects of their daily life. From the study results, it emerged that the impact of chemotherapy-induced neurotoxicity on personal, social, and working activities is very high. A similar effect was also observed when the psychological impact is assessed. Moreover, there is evidence suggesting that the management of CIPN is suboptimal; this is partially due to a lack of effective drugs, but also of appropriate advice from healthcare providers. In conclusion, this study provides evidence for the relevance of the impact on the explored aspects of the daily life of cancer patients and spotlights the need for a larger and more structured investigation on these long-term side effects of anticancer chemotherapy.

Out-of-pocket costs sustained in the last 12 months by cancer patients: an Italian survey-based study on individual expenses between 2017 and 2018.

PURPOSE: Out of Pocket costs (OOP) sustained by cancer patients also in public NHS contribute to disease-related financial toxicity. Aim of the study was to investigate the amount and the types of OOP sustained by Italian cancer patients for care services. METHODS: A sample survey was conducted by FAVO in December 2017-June 2018, in 39 adhering hospitals and 1289 patients diagnosed from 1985 to 2018, by standardized questionnaire inquiring on: yearly expenditure by cancer service, age, year of diagnosis, disease phase, cancer site, sex, marital status, education, residence. Univariate and multivariable regression analyses were performed between OOP and each variable. Multilevel mixed-effects negative binomial regression was used to assess the combined effects of patients characteristics on the differences in acquiring health services. RESULTS: The yearly average OOP was 1841.81€, with the highest values for transports (359.34€) and for diagnostic examinations (259.82€). Significantly higher OOP were found in North and Centre than South and Islands (167.51 vs. 138.39). In the fully adjusted multivariable analysis, the variables significantly associated with higher than reference expenditure were: medium/high education (OR 1.22 [1.05-1.42], upper gastrointestinal tract cancer (OR 1.37 [1.06-1.77]), disease phase of treatments for cancer progression or pain therapy (OR 1.59 [1.30-1.93]). CONCLUSION: Italian cancer patients in 2018 sustained OOP quite similar to those measured in 2012 to supplement NHS services. The main component of the OOP costs were diagnostic examination and transportation. The NHS should pay attention to potentiate its ability to answer unmet needs of patients with advanced cancer who are the most fragile ones. IMPLICATIONS FOR CANCER SURVIVORS: Reinforcing the services where the main OOP expenses are located can help in promoting public health actions and reduce socio-economic needs that could compromise the receipt of optimal care along the whole disease course, from diagnosis to rehabilitation.

Clinical and economic value of oral nutrition supplements in patients with cancer: a position paper from the Survivorship Care and Nutritional Support Working Group of Alliance Against Cancer.

Malnutrition is a common clinical and public health problem that can frequently affect patients in hospital and community settings. In particular, cancer-related malnutrition results from a combination of metabolic dysregulation and anorexia, caused both by the tumor itself and by its treatment. Patients with head-neck cancer, or with gastroesophageal, pancreatic, lung, and colorectal cancer, are particularly at risk of developing malnutrition, with a prevalence varying between 30 and 50% depending on tumor location and anti-cancer treatment complications. Prevention and adequate management of malnutrition is now considered an essential key point of therapeutic pathways of patients with cancer, with the aim to enhance their quality of life, reduce complications, and improve clinical outcomes. Oral nutritional supplements (ONS) are part of the nutritional therapy and represent an effective tool to address cancer-related malnutrition, as supported by growing literature data. However, patients' access to ONS - which is regulated by different national and regional policies in terms of reimbursement - is quite heterogeneous. This narrative review aims to summarize the current knowledge about the role of ONS in terms of cost-effectiveness in the management of actively treated patients with cancer, following surgery and/or radiotherapy/chemotherapy treatment and to present the position on this issue of the Alliance Against Cancer, the Italian National Oncology Network, coming up from a focused virtual roundtable of the Survivorship Care and Nutritional Support Working Group.

Cancer Biomarkers in the era of precision oncology: Addressing the needs of patients and health systems.

Cancer Biomarkers are the key to unlocking the promise of precision oncology, selecting which patients will respond to a more personalised treatment while sparing non-responders the therapy-related toxicity. In this paper, we highlight the primacy of cancer biomarkers, but focus on their importance to patients and to health systems. We also highlight how cancer biomarkers represent value for money. We emphasise the need for cancer biomarkers infrastructure to be embedded into European health systems. We also highlight the need to deploy multiple biomarker testing to deliver the optimal benefit for patients and health systems and consider cancer biomarkers from the perspective of cost, value and regulation. Cancer biomarkers must also be situated in the context of the upcoming In Vitro Diagnostics Regulation, which may pose certain challenges (e.g. non-compliance of laboratory developed tests, leading to cancer biomarker shortages and increased costs) that need to be overcome. Cancer biomarkers must be embedded in the real world of oncology delivery and testing must be implemented across Europe, with the intended aim of narrowing, not widening the inequity gap for patients. Cancer patients must be placed firmly at the centre of a cancer biomarker informed precision oncology care agenda.

Cross-sectional study to develop and describe psychometric characteristics of a patient-reported instrument (PROFFIT) for measuring financial toxicity of cancer within a public healthcare system.

OBJECTIVES: To measure and explain financial toxicity (FT) of cancer in Italy, where a public healthcare system exists and patients with cancer are not expected (or only marginally) to pay out-of-pocket for healthcare. SETTING: Ten clinical oncological centres, distributed across Italian macroregions (North, Centre, South and Islands), including hospitals, university hospitals and national research institutes. PARTICIPANTS: From 8 October 2019 to 11 December 2019, 184 patients, aged 18 or more, who were receiving or had received within the previous 3 months active anticancer treatment were enrolled, 108 (59%) females and 76 (41%) males. INTERVENTION: A 30-item prefinal questionnaire, previously developed within the qualitative tasks of the project, was administered, either electronically (n=115) or by paper sheet (n=69). PRIMARY AND SECONDARY OUTCOME MEASURES: According to the protocol and the International Society for Pharmacoeconomics and Outcomes Research methodology, the final questionnaire was developed by mean of explanatory factor analysis and tested for reliability, internal consistency (Cronbach's α test and item-total correlation) and stability of measurements over time (test-retest reliability by intraclass correlation coefficient and weighted Cohen's kappa coefficient). RESULTS: After exploratory factor analysis, a score measuring FT (FT score) was identified, made by seven items dealing with outcomes of FT. The Cronbach's alpha coefficient for the FT score was 0.87 and the item-total correlation coefficients ranged from 0.53 to 0.74. Further, nine single items representing possible determinants of FT were also retained in the final instrument. Test-retest analysis revealed a good internal validity of the FT score and of the 16 items retained in the final questionnaire. CONCLUSIONS: The Patient-Reported Outcome for Fighting FInancial Toxicity (PROFFIT) instrument consists of 16 items and is the first reported instrument to assess FT of cancer developed in a country with a fully public healthcare system. TRIAL REGISTRATION NUMBER: NCT03473379.

A qualitative analysis and development of a conceptual model assessing financial toxicity in cancer patients accessing the universal healthcare system.

PURPOSE: This paper illustrates a conceptual model for a new patient-reported outcome measure (PROM) aimed at measuring financial toxicity (FT) in oncological setting in Italy, where citizens are provided universal healthcare coverage. METHODS: Focus groups with overall 34 patients/caregivers in three different Italian centers (from Northern, Centre, and Southern Italy) and an open-ended survey with 97 medical oncologists were undertaken. Transcripts from focus groups and the open-ended survey were analyzed to identify themes and links between themes. Themes from the qualitative research were supplemented with those reported in the literature; concepts identified formed the basis for item development that were then tested through the importance analysis (with 45 patients) and the cognitive debriefing (with other 45 patients) to test relevance and comprehension of the first draft PRO instrument. RESULTS: Ten domains were extracted by analyzing 156 concepts generated from focus groups and the open-ended survey. After controlling for redundancy, 55 items were generated and tested through the importance analysis. After controlling comprehension and feasibility through cognitive debriefing interviews, a first version of the questionnaire consisting of 30 items was devised. CONCLUSIONS: This qualitative study represents the first part of a study conducted to develop a new PROM to assess FT in Italy, by using a bottom-up approach that makes the most of patients' experiences and the health system analysis. TRIAL REGISTRATION: clinicaltrials.gov NCT03473379 first posted on March 22, 2018.

Development and validation of a patient-reported outcome tool to assess cancer-related financial toxicity in Italy: a protocol.

INTRODUCTION: Financial toxicity (FT) is a well-recognised problem in oncology. US-based studies have shown that: (a) cancer patients have a 2.7 times risk of bankruptcy; (b) patients who declare bankruptcy have a 79% greater hazard of death; (c) financial burden significantly impairs quality of life (QoL) and (d) reduces compliance and adherence to treatment prescriptions. The aim of the project is to develop and validate a patient-reported-outcome (PRO) measure to assess FT of cancer patients in Italy, where, despite the universal health coverage provided by the National Health Service, FT is an emerging issue. METHODS AND ANALYSIS: Our hypothesis is that a specific FT measure, which considers the relevant sociocultural context and healthcare system, would allow us to understand the main determinants of cancer-related FT in Italy, in order to address and reduce these factors. According to the International Society for Pharmaco-economics and Outcomes Research guidelines on PROs, the project will include the following steps: (1) concept elicitation (from focus groups with patients and caregivers; literature; oncologists; nurses) and analysis, creating a coding library; (2) item generation (using a format that includes a question and a response on a 4-point Likert scale) and analysis through patients' cognitive interviews of item importance within different coding categories to produce the draft instrument; (3) factor analysis and internal validation (with Cronbach's alpha and test-retest for reliability) to produce the final instrument; (4) external validation with QoL anchors and depression scales. The use of the FT measure in prospective trials is also planned. ETHICS AND DISSEMINATION: The protocol is approved by the ethical committees of all the participating centres. The project will tentatively produce a validated tool by the spring 2021. The project might also represent a model and the basis for future cooperation with other European countries, with different healthcare systems and socioeconomic conditions. TRIAL REGISTRATION NUMBER: NCT03473379.

Cancer Core Europe: A translational research infrastructure for a European mission on cancer.

Cancer Core Europe is a European legal alliance consisting of seven leading cancer centres - most of them Comprehensive Cancer Centres (CCCs) - with a single portal system to engage in various research projects with partners. Cancer Core Europe was established to create a sustainable, high-level, shared research infrastructure platform hosting research collaborations and task forces (data sharing, clinical trials, genomics, immunotherapy, imaging, education and training, and legal and ethical issues), with a controlled expansion agenda. Translational cancer research covers the cancer research continuum from basic to preclinical to early clinical, late clinical, and outcomes research. Basic-preclinical research serves as the 'engine' for early clinical research by bridging the early translational research gap and is the primary and current focus of the consortium as exemplified by the launching of the Basket of Baskets trial, Europe's largest precision cancer medicine trial. Inspired by the creation of Cancer Core Europe, the prevention community established Cancer Prevention Europe, a consortium of ten cancer prevention centres aimed at supporting the complete prevention research continuum. Presently, Cancer Core Europe and Cancer Prevention Europe are integrating therapeutics and prevention strategies to address in partnership the widening cancer problem. By providing innovative approaches for cancer research, links to healthcare systems, development of quality-assured multidisciplinary cancer care, and assessment of long-term outcomes, the virtual infrastructure will serve as a hub to connect and interact with other centres across Europe and beyond. Together, Cancer Core Europe and Cancer Prevention Europe are prepared to function as a central engine to tackle, in collaboration with various partners, a potential 'mission on cancer' addressing the cancer burden.

Out-of-pocket costs for cancer survivors between 5 and 10 years from diagnosis: an Italian population-based study.

PURPOSE: To illustrate the out-of-pocket (OOP) costs incurred by a population-based group of patients from 5 to 10 years since their cancer diagnosis in a country with a nationwide public health system. METHODS: Interviews on OOP costs to a sample of 5-10 year prevalent cases randomly extracted from four population-based cancer registries (CRs), two in the north and two in the south of Italy. The patients' general practitioners (GPs) gave assurance about the patient's physical and psychological condition for the interview. A zero-inflated negative binomial model was used to analyze OOP cost determinants. RESULTS: Two hundred six cancer patients were interviewed (48 % of the original sample). On average, a patient in the north spent €69 monthly, against €244 in the south. The main differences are for transport, room, and board (TRB) to reach the hospital and/or the cancer specialist (north €0; south €119). Everywhere, OOP costs without TRB costs were higher for patients with a low quality of life. CONCLUSIONS: Despite the limited participation, our study sample's characteristics are similar to those of the Italian cancer prevalence population, allowing us to generalize the results. The higher OOP costs in the south may be due to the scarcity of oncologic structures, obliging patients to seek assistance far from their residence. Implications for cancer survivors Cancer survivors need descriptive studies to show realistic data about their status. Future Italian and European descriptive studies on cancer survivorship should be based on population CRs and involve GPs in order to approach the patient at best.