Evaluating comprehensive cancer networks; a review of standards and evaluation methods for care networks to inform a comparison with the OECI comprehensive cancer network standards.

INTRODUCTION: To ensure that all citizens have equal access to high-quality cancer diagnosis and care, the EU4Health Programme, Europe's Beating Cancer Plan, and Horizon Europe's Cancer Mission propose Comprehensive Cancer Infrastructures in every European Union Member State. It is therefore important to establish the basic principles for high-performing cancer networks and a methodology for evaluating their quality and effectiveness. This article describes methods and standards/indicators for network evaluation found in literature, gives a comparative overview of the new OECI European Cancer Network Quality standards, and proposes principles for evaluating the performance of Comprehensive Cancer Networks as a basis for continuous improvement. MATERIALS AND METHODS: We performed a scoping literature review on methods and standards/indicators for care-network evaluation. We then compared the OECI set with literature findings, categorised standards that were similar, reflected on standards that were different, and deduced principles for quality standards for cancer networks. RESULTS: Of 1002 articles identified, 17 reported on evaluation methods and/or (mostly) qualitative indicators. Sixteen studies described indicators/standards for evaluating care networks, critical success factors or desirable outcomes. Of the 54 present OECI standards, 32 had a literature equivalent. No literature equivalent was found for 22 standards, especially on those related to the combination of care and research. The proposed OECI evaluation methods (survey, document review, and interviews) were all reported in the literature. From the conformity of these results, we deduced 8 principles for standards evaluating the effectiveness of Comprehensive Cancer Networks. CONCLUSIONS: Research on the evaluation of the effectiveness of care networks is scarce. Evaluation methods vary and are often single time-point assessments. The OECI set contributes to establishing clear principles and standards to evaluate the effectiveness of Comprehensive Cancer Networks.

Cancer Cure and Consequences on Survivorship Care: Position Paper from the Italian Alliance Against Cancer (ACC) Survivorship Care Working Group.

A multidisciplinary panel of experts and cancer patients developed a position paper to highlight recent evidence on "cancer cure" (ie, the possibility of achieving the same life expectancy as the general population) and discuss the consequences of this concept on follow-up and rehabilitation strategies. The aim is to inform clinicians, patients, and health-care policy makers about strategies of survivorship care for cured cancer patients and consequences impacting patient lives, spurring public health authorities and research organizations to implement resources to the purpose. Two identifiable, measurable, and reproducible indicators of cancer cure are presented. Cure fraction (CF) is >60% for breast and prostate cancer patients, >50% for colorectal cancer patients, and >70% for patients with melanoma, Hodgkin lymphoma, and cancers of corpus uteri, testis (>90%), and thyroid. CF was >65% for patients diagnosed at ages 15-44 years and 30% for those aged 65-74 years. Time-to-cure was consistently <1 year for thyroid and testicular cancer patients and <10 years for patients with colorectal and cervical cancers, melanoma, and Hodgkin lymphoma. The working group agrees that the evidence allows risk stratification of cancer patients and implementation of personalized care models for timely diagnosis, as well as treatment of possible cancer relapses or related long-term complications, and preventive measures aimed at maintaining health status of cured patients. These aspects should be integrated to produce an appropriate follow-up program and survivorship care plan(s), avoiding stigma and supporting return to work, to a reproductive life, and full rehabilitation. The "right to be forgotten" law, adopted to date only in a few European countries, may contribute to these efforts for cured patients.

Prevalence and determinants of quitting smoking after cancer diagnosis: a prospective cohort study.

OBJECTIVE: To describe smoking behaviours of patients with incident cancer attending an Italian cancer centre and to examine changes in their smoking habits within 12 months from cancer diagnosis, evaluating determinants of smoking cessation. METHODS: A hospital-based prospective cohort included patients hospitalized in an Italian cancer centre (2016-2018). Patients were mostly female (74%) and included a limited proportion of aerodigestive cancers (7%). Face-to-face interviews were performed during hospital stay to gather information on patient characteristics and smoking history. Changes in smoking habits were assessed through telephone interviews at 3, at 6, and at 12 months after cancer diagnosis. RESULTS: Among 1011 enrolled patients, 222 (22%) were current smokers at cancer diagnosis. Smoking prevalence was high in male patients (30%), in patients <50 years old (28%), in those with aerodigestive cancers (50%), and in those diagnosed at advanced stages (26%). Among current smokers at cancer diagnosis, 38% quit smoking after 12 months, 26% reduced intensity, and 36% did not modify smoking habits. Smoking cessation was associated with chemotherapy and, although not statistically significant, with female sex, older age, and advanced cancer stage. Patients with gastrointestinal, breast, or genitourinary cancer and those treated with surgery were less likely to quit smoking. CONCLUSIONS: Our results highlighted that 62% of smoking patients with cancer did not quit the habit. Smoking cessation programs targeted to patients with cancer need intensification, particularly for those who may underestimate smoking effects after diagnosis.

Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.

A moonshot approach toward the management of cancer patients in the COVID-19 time: what have we learned and what could the Italian network of cancer centers (Alliance Against Cancer, ACC) do after the pandemic wave?

If we focus our attention on seven main features of COVID-19 infection (heterogeneity, fragility, lack of effective treatments and vaccines, "miraculous cures", psychological suffering, deprivation, and globalization), we may establish parallelism with the challenges faced in the steep road to the understanding and treatment of neoplastic diseases. How the similarities between these two conditions can help us cope with the emergency effort represented by the management of cancer patients in the COVID-19 era, today and in the future? In a manner similar to the Cancer Moonshot initiative in the United States, we can hypothesize a multinational moonshot project towards the management of cancer patients during COVID-19 pandemic. In particular, we believe that the main road to elaborate meaningful scientific evidence is represented by the collection of all the data on COVID-19 and cancer comorbidity that are and will become available in cancer centers, coupled with the design of large clinical studies. To address this goal, it is essential to identify the entity that can produce this scientific evidences and the potentially most successful research strategy to undertake. The largest Italian organization for cancer research, Alliance Against Cancer (Alleanza Contro il Cancro, ACC), is called to play a scientific leadership in addressing these challenges, which requires the coordination of oncology teams at regional, national, and international levels. To fulfill this commitment, ACC will create a liaison with health government agencies in order to develop "dynamic" indications able to fight such an unpredictable pandemic.

Patients and caregivers' unmet information needs in the field of patient education: results from an Italian multicenter exploratory survey.

Patient education and empowerment (PEE) is aimed at improving competence of patients during their clinical path and enabling healthcare providers with specific communication strategies. We investigated the interest of Italian Cancer Research & Care Centers (CRCI) users (patients and caregivers) in being involved in PEE activities. An anonymous questionnaire addressed to users was distributed between June 2013 and February 2014. The questionnaire gathered information on the following: health-related topics; 13 different PEE initiatives/modalities of learning already active at CRCI; personal demographic data; the willingness to be more involved in the organization of health services provided and in which context; and five preferred info-educational activities. Frequency distribution and chi-square analysis were computed. Statistical significance (p value) was set at < 0.05. A total of 875 (29%) users responded to the 3000 distributed questionnaires. The first three priorities of interest were "early diagnosis" (18%), "prevention" (17%), and "diagnosis explanation" (13%). The first three priorities on informational activity were as follows: "classes on cancer-related topics with healthcare professionals" (28%); "cancer information service" (22%); "drug information point" (7%). Forty-nine percent of the respondents stated that they would like to be involved in the organization of PEE activities, particularly caregivers and users older than 55 years of age. The preferred educational activities were "classes on cancer-related topics with healthcare professionals" and "cancer information service" on a face-to-face modality. Patients were more interested than caregivers in "prevention." The extension of PEE programs to all CRCI users into routine care will be the next step of the present research.

The perceived severity of a disease and the impact of the vocabulary used to convey information: using Rasch scaling in a simulated oncological scenario.

BACKGROUND: Healthcare staff should be aware of the importance that patients may attach to the words that are used to convey information. This is relevant in terms of the patients' understanding. Modeling how people understand the information conveyed in a medical context may help health practitioners to better appreciate the patients' approach. PURPOSE: 1) Analyze the participants' self-reported perception of the type of information provided in an oncological scenario in terms of three dimensions: impairment to their health, risks associated with the disease itself and commitment required to undergo the treatment; and 2) show the benefits of using Rasch scaling for the analysis of the data. Starting from a survey, Rasch scaling produces a unidimensional logit-interval scale relating to the extent to which each item conveys a latent dimension. These were related to structure, in particular concerning communication by means of opposite vs. unipolar language. SUBJECTS AND METHODS: The participants rated 82 items of information in a questionnaire regarding their perception of impairment to their health (H) and the risks (R) and commitment relating to the treatment prescribed (T). RESULTS: The scaling produced an item bank for healthcare staff to consult in order to estimate the importance the recipient would be likely to attach to the vocabulary used and the likely impact of the information in terms of the patient's condition. Furthermore, the use of opposites was generally associated with a clearer impression of whether the information given was generally only very negative or slightly negative, whereas 'neutral' information was often perceived as being very negative. ACTUAL FINDINGS: Is possible to estimate people's understanding more precisely (in terms of H, R and T) which can help healthcare practitioners to modulate the way they convey information. LIMITATIONS: The participants in the study were healthy volunteers and the context was simulated.

Coffee consumption is not associated with ovarian cancer risk: a dose-response meta-analysis of prospective cohort studies.

BACKGROUND: Coffee consumption has been associated with numerous cancers, but evidence on ovarian cancer risk is controversial. Therefore, we performed a meta-analysis on prospective cohort studies in order to review the evidence on coffee consumption and risk of ovarian cancer. METHODS: Studies were identified through searching the PubMed and MEDLINE databases up to March 2017. Risk estimates were retrieved from the studies, and dose-response analysis was modelled by using restricted cubic splines. Additionally, a stratified analysis by menopausal status was performed. RESULTS: A total of 8 studies were eligible for the dose-response meta-analysis. Studies included in the analysis comprised 787,076 participants and 3,541 ovarian cancer cases. The results showed that coffee intake was not associated with ovarian cancer risk (RR = 1.06, 95% CI: 0.89, 1.26). Stratified and subgroup analysis showed consisted results. CONCLUSIONS: This comprehensive meta-analysis did not find evidence of an association between the consumption of coffee and risk of ovarian cancer.

The effects of presenting oncologic information in terms of opposites in a medical context.

BACKGROUND: An extensive body of literature has demonstrated that many patients who have been asked to participate in clinical trials do not fully understand the informed consent forms. A parallel independent study has demonstrated that opposites have a special status in human cognitive organization: they are common to all-natural languages and are intuitively and naturally understood and learnt. PURPOSE: The study investigates whether, and how, the use of opposites impacts on doctor-patient communication: does using the terms "small-large" to describe a nodule (ie, bipolar communication) rather than speaking in terms of centimeters (ie, unipolar communication) affect a patient's understanding of the situation? And is it better to speak of "common-rare" side effects (ie, bipolar communication) instead of the number of people who have suffered from particular side effects (ie, unipolar communication)? METHODS: Two questionnaires were created and used, one presenting the information in terms of opposites (ie, bipolar communication) and another using unipolar communication. RESULTS: The participants' perception of their situation (in terms of feeling healthy-ill, being at high-low risk, and their treatment requiring high-low commitment) varied in the two conditions. Moreover, self-reported levels of understanding and satisfaction with how the information was communicated were higher when opposites were used. LIMITATIONS: Since this is the first study that addresses the merits of using bipolar structures versus unipolar structures in doctor-patient communication, further work is needed to consolidate and expand on the results, involving not only simulated but also real diagnostic contexts. CONCLUSION: The encouraging results imply that further testing of the use of opposites in informed consent forms and in doctor-patient communication is strongly advisable.

Can the addition of radiotherapy postoperatively increase clinical outcome of patients with gastric cancer? A systematic review of the literature and meta-analysis.

BACKGROUND: Although several studies have been carried out to determine the best treatment for gastric carcinoma, the data on survival rate still remain inconclusive. OBJECTIVE: To evaluate the effects of postoperative radio-chemotherapy on overall and disease-free survival. DATA SOURCES: MEDLINE and CANCERLIT searches of reference lists (for the period 1970 to 2016) were supplemented with hand search of reference lists. STUDY SELECTION: The present work includes randomized controlled trials comparing postoperative radio-chemotherapy to postoperative chemotherapy or to surgery alone in patients with resected gastric carcinoma without evidence of metastatic disease. Ten randomized controlled trials were analyzed in total: four compared postoperative radiochemotherapy to surgery alone (708 patients), and six compared postoperative radiochemotherapy to postoperative chemotherapy (1020 patients). DATA EXTRACTION: According to "intention to treat" method, three independent observers have extracted from each trial, the data on patients, intervention, and outcomes. These data were subsequently combined using DerSimonian and Laird methods. RESULTS: Postoperative radiochemotherapy significantly increases 3-year and 5-year overall survival and 3-year and 5-year disease free survival rate compared to postoperative chemotherapy (RR 0.89; 95%CI 0.81-0.97 and RR 0.82; 95%CI 0.71-0.95) or surgery alone (RR 0.83; 95% CI 0.77-0.91 and RR 0.80; 95% CI 0.65-0.98). CONCLUSIONS: In patients with resected gastric cancer, postoperative radiochemotherapy obtains: 1) an increase in overall survival, 2) an increase in disease free survival, and 3) a gain in 5 year disease free survival independent of surgical procedure.

Coffee Intake Decreases Risk of Postmenopausal Breast Cancer: A Dose-Response Meta-Analysis on Prospective Cohort Studies.

Aim: A dose-response meta-analysis was conducted in order to summarize the evidence from prospective cohort studies regarding the association between coffee intake and breast cancer risk. Methods: A systematic search was performed in electronic databases up to March 2017 to identify relevant studies; risk estimates were retrieved from the studies and linear and non-linear dose-response analysis modelled by restricted cubic splines was conducted. A stratified and subgroup analysis by menopausal and estrogen/progesterone receptor (ER/PR) status, smoking status and body mass index (BMI) were performed in order to detect potential confounders. Results: A total of 21 prospective studies were selected either for dose-response, the highest versus lowest category of consumption or subgroup analysis. The dose-response analysis of 13 prospective studies showed no significant association between coffee consumption and breast cancer risk in the non-linear model. However, an inverse relationship has been found when the analysis was restricted to post-menopausal women. Consumption of four cups of coffee per day was associated with a 10% reduction in postmenopausal cancer risk (relative risk, RR 0.90; 95% confidence interval, CI 0.82 to 0.99). Subgroup analyses showed consistent results for all potential confounding factors examined. Conclusions: Findings from this meta-analysis may support the hypothesis that coffee consumption is associated with decreased risk of postmenopausal breast cancer.

Cancer Targeted Therapy Strategy: The Pathologist's Perspectives.

The effectiveness of new personalized treatment procedures in oncology is based on the fact that certain tumors exhibit specific molecular features. More in detail, neoplastic tissues of patients should display a specific biomarker, most often a specific genetic alteration and/or under/overexpression of a definite protein, that could be the target of its respective drug. Immunohistochemical and molecular analyses, which usually include examination of nucleic acids from either tissues or fluids, are common tests to define the status of a tumor. This review focuses on the pathologist's role in carefully controlling pre- analytic procedures and standard operating procedures that are a crucial prerequisite to reach reliable and reproducible results. Six paradigmatic applications of targeted therapy, for which pathological diagnosis plays a fundamental role, are summarized. Traditional and next-generation sequencing are also addressed from the pathologist's perspective as well as the importance pathologists have in this shift to more accurate definition of disease risk and prognostication of therapy response in the personalized medicine era.

Liquid dynamic medicine and N-of-1 clinical trials: a change of perspective in oncology research.

The increasing use of genomics to define the pattern of actionable mutations and to test and validate new therapies for individual cancer patients, and the growing application of liquid biopsy to dynamically track tumor evolution and to adapt molecularly targeted therapy according to the emergence of tumor clonal variants is shaping modern medical oncology., In order to better describe this new therapeutic paradigm we propose the term "Liquid dynamic medicine" in the place of "Personalized or Precision medicine". Clinical validation of the "Liquid dynamic medicine" approach is best captured by N-of-1 trials where each patient acts as tester and control of truly personalized therapies.

Probe-based confocal laser endomicroscopy for in vivo evaluation of the tumor vasculature in gastric and rectal carcinomas.

Probe-based Confocal Laser Endomicroscopy (pCLE) is a powerful imaging technique that allows to perform gastrointestinal endomicroscopy at subcellular resolution. The aim of this study was to assess the use of pCLE to evaluate tumor angiogenesis in rectal and gastric cancers. A total of 35 consecutive patients with gastric and 91 with rectal carcinomas underwent endoscopy and pCLE during the same examination. Vascular assessment was based on vessel shape and size, vessel permeability and blood flow, and allowed the creation of an angiogenic score ranging from 0, for normal vasculature, to 4, for aberrant vasculature. A significant difference for the presence of vessels with large diameter and defective blood flow was found between rectal and gastric cancers. Overall, rectal cancers displayed a higher angiogenic score compared to gastric cancers. Conventional therapy induced a striking reduction in the angiogenic score only in rectal cancer patients. Taken together, our findings suggest that the pCLE technology is suitable for the evaluation of the tumor microvasculature abnormalities. Therefore, the real-time assessment of the vasculature status may represent a promising approach to predict the efficacy of the treatments and improve the clinical management of patients with gastric or rectal carcinomas.

Teaching Digital Pathology: The International School of Digital Pathology and Proposed Syllabus.

Digital pathology is an interdisciplinary field where competency in pathology, laboratory techniques, informatics, computer science, information systems, engineering, and even biology converge. This implies that teaching students about digital pathology requires coverage, expertise, and hands-on experience in all these disciplines. With this in mind, a syllabus was developed for a digital pathology summer school aimed at professionals in the aforementioned fields, as well as trainees and doctoral students. The aim of this communication is to share the context, rationale, and syllabus for this school of digital pathology.

Cross-cultural validation of health literacy measurement tools in Italian oncology patients.

BACKGROUND: The aim of this study was to assess the psychometric characteristics of four Health Literacy (HL) measurement tools, viz. Newest Vital Sign (NVS), Short Test of Functional Health Literacy in Adults (STOFHLA), Single Item Literacy Screener (SILS) and Single question on Self-rated Reading Ability (SrRA) among Italian oncology patients. METHODS: The original version of the tools were translated from the English language into Italian using a standard forward-backward procedure and according to internationally recognized good practices. Their internal consistency (reliability) and validity (construct, convergent and discriminative) were tested in a sample of 245 consecutive cancer patients recruited from seven Italian health care centers. RESULTS: The internal consistency of the STOFHLA-I was Chronbach's α=0.96 and that of NVS-I was α=0.74. The STOFHLA-I, NVS-I, SILS-I and SrRA-I scores were in a good relative correlation and in all tools the discriminative known-group validity was confirmed. The reliability and validity values were similar to those obtained from other cultural context studies. CONCLUSION: The psychometric characteristics of the Italian version of NVS, STHOFLA, SILS and SrRA were found to be good, with satisfactory reliability and validity. This indicates that they could be used as a screening tool in Italian patients. Moreover, the use of the same cross-cultural tools, validated in different languages, is essential for implementing multicenter studies to measure and compare the functional HL levels across countries.

Multiple viral infections in primary effusion lymphoma: a model of viral cooperation in lymphomagenesis.

INTRODUCTION: Primary effusion lymphoma (PEL) is a rare B-cell lymphoid neoplasm mainly associated with HIV infection, presenting as pleural, peritoneal, and pericardial effusions. A defining property of PEL is its consistent association with Kaposi sarcoma associated herpesvirus (KSHV) infection, and, in most cases, Epstein Barr virus (EBV) co-infection. On these grounds, a review of the literature related to viral cooperation and lymphomagenesis can help to understand the complex interplay between KSHV and EBV in PEL pathogenesis. Areas covered: In this review, the authors highlight clinical, pathologic, genetic and proteomic features of PEL, in the context of viral cooperation in PEL lymphomagenesis. Expert commentary: Tumour cells are characterized by the overexpression of genes that are involved in inflammation and invasion. Coherently, PEL secretomes are enriched in proteins probably responsible for the particular tropism (cell adhesion and migration) of PEL cells. The development of PEL in HIV+ patients is multifactorial and involves a complex interplay among co-infection with oncogenic viruses (EBV and KSHV), inflammatory factors, and environmental conditions.

The angiostatic molecule Multimerin 2 is processed by MMP-9 to allow sprouting angiogenesis.

Angiogenesis is a crucial process occurring under physiological and pathological conditions, including cancer. The development of blood vessels is tightly regulated by a plethora of cytokines, endothelial cell (EC) receptors and extracellular matrix (ECM) components. In this context, we have shown that Multimerin 2 (MMRN2), an ECM molecule specifically secreted by ECs, exerts angiostatic functions by binding VEGFA and other pro-angiogenic cytokines. Here, we demonstrate that during angiogenic stimuli MMRN2 mRNA levels significantly decrease. Furthermore, we provide evidence that MMRN2 is processed by matrix metalloproteinases (MMPs) including MMP-9 and, to a lesser degree, by MMP-2. This proteolytic cleavage correlates with an increased migration of ECs. Accordingly, MMRN2 down-regulation is associated with an increased number of EC pseudopodia at the migrating front and this effect is attenuated using specific MMP-9 inhibitors. The down-modulation of MMRN2 occurs also in the context of tumor-associated angiogenesis. Immunofluorescence performed on tumor sections indicate a broad co-localization of MMP-9 and MMRN2, suggesting that the molecule may be extensively remodeled during tumor angiogenesis. Given the altered expression in tumors and the key role of MMRN2 in blood vessel function, we postulate that analyses of its expression may serve as a marker to predict the efficacy of the treatments. In conclusion, these data further support the role of MMRN2 as a key molecule regulating EC function and sprouting angiogenesis.

Use of Complementary and Alternative Medicine (CAM) in cancer patients: An Italian multicenter survey.

INTRODUCTION: Complementary and Alternative Medicine (CAM) include a wide range of products (herbs, vitamins, minerals, and probiotics) and medical practices, developed outside of the mainstream Western medicine. Patients with cancer are more likely to resort to CAM first or then in their disease history; the potential side effects as well as the costs of such practices are largely underestimated. PATIENTS AND METHOD: We conducted a descriptive survey in five Italian hospitals involving 468 patients with different malignancies. The survey consisted of a forty-two question questionnaire, patients were eligible if they were Italian-speaking and receiving an anticancer treatment at the time of the survey or had received an anticancer treatment no more than three years before participating in the survey. RESULTS: Of our patients, 48.9% said they use or have recently used CAM. The univariate analysis showed that female gender, high education, receiving treatment in a highly specialized institute and receiving chemotherapy are associated with CAM use; at the multivariate analysis high education (Odds Ratio, (OR): 1.96 95% Confidence Interval, CI, 1.27-3.05) and receiving treatment in a specialized cancer center (OR: 2.75 95% CI, 1.53-4.94) were confirmed as risk factors for CAM use. CONCLUSION: Roughly half of our patients receiving treatment for cancer use CAM. It is necessary that health professional explore the use of CAM with their cancer patients, educate them about potentially beneficial therapies in light of the limited available evidence of effectiveness, and work towards an integrated model of health-care provision.