Endometriosis and endometrial cancer: A propensity score-adjusted real-world data study.

Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. Our study investigated the effect of endometriosis on the risk of endometrial cancer (EC) and the prognosis of endometriosis-associated EC. In our study, 197,196 patients with endometriosis and without a previous diagnosis of EC were compared with 6,455,556 females encountering health services for examinations, with body mass index (BMI) data, and without endometriosis or EC. A propensity score generated 197,141 matched pairs. In the endometriosis cohort, 875 cases of EC were seen, whereas 558 were in the control group: the hazard ratio (HR) was 1.56 (95% CI 1.40-1.73, p < 0.001). Women with endometriosis were more likely to develop invasive endometrioid (p = 0.005) and clear cell (p < 0.001) EC. There was no difference in overall survival between endometriosis-associated EC and EC without endometriosis. Our epidemiological findings were consistent with the evidence of an association between endometriosis and EC.

Healthcare Costs and Resource Utilisation of Italian Metastatic Non-Small Cell Lung Cancer Patients.

This study evaluated the economic burden of metastatic non-small cell lung cancer patients before and after the availability of an immuno-oncology (IO) regimen as a first-line (1L) treatment. Patients from 2014 to 2020 were categorized according to mutational status into mutation-positive and negative/unknown groups, which were further divided into pre-1L IO and post-1L IO sub-groups depending on the availability of pembrolizumab monotherapy in 1L. Healthcare costs and HCRU for a 1L treatment and overall follow-up were reported as the mean total and per-month cost per patient by groups. Of 644 patients, 125were mutation-positive and 519 negative/unknown (229 and 290 in pre- and post-1L IO, respectively). The mean total per-patient cost in 1L was lower in pre- (EUR 7804) and post-1L IO (EUR 19,301) than the mutation-positive group (EUR 45,247), persisting throughout overall disease follow-up. However, this difference was less when analyzing monthly costs. Therapy costs were the primary driver in 1L, while hospitalization costs rose during follow-up. In both mutation-positive and post-IO 1L groups, the 1L costs represented a significant portion (70.1% and 66.3%, respectively) of the total costs in the overall follow-up. Pembrolizumab introduction increased expenses but improved survival. Higher hospitalisation and emergency room occupation rates during follow-up reflected worsening clinical conditions of the negative/unknown group than the mutation-positive population.

Real-World Outcomes and Treatments Patterns Prior and after the Introduction of First-Line Immunotherapy for the Treatment of Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: This study provides insights into the treatment use and outcomes of metastatic non-small cell lung cancer (NSCLC) patients in a real-world setting prior to and after the availability of immuno-oncology (IO) regimens in the first line (1L). METHODS: Metastatic NSCLC patients, who initiated systemic 1L anticancer treatment from 2014 to 2020, were identified from health records. Patients were grouped into Pre-1L IO and Post-1L IO, according to the availability of pembrolizumab 1L monotherapy at the date of initiating 1L systemic anticancer treatment. Patient characteristics, treatment patterns and outcomes were assessed by the cohort. Overall survival (OS) and real-world progression-free survival (rwPFS) were calculated using the Kaplan-Meier method. RESULTS: The most common 1L treatment was platinum-based chemotherapy regimens in both groups (≥46%), followed by single-agent chemotherapy (27.0%) in Pre-1L IO and pembrolizumab (26.0%) in Post-1L IO. Median OS was 6.2 (95% CI 5.5-7.4) in Pre- and 8.9 months (95% CI 7.5-10.6) in Post-1L IO, while rwPFS was 3.7 (95% CI 3.3-4.2) and 4.7 months (95% CI 3.9-5.7), respectively. CONCLUSIONS: Even if a small proportion of patients received a 1L IO, the data showed an improved survival outcomes in the Post-1L IO group.

Emilia-Romagna Surgical Colorectal Cancer Audit (ESCA): a value-based healthcare retro-prospective study to measure and improve the quality of surgical care in colorectal cancer.

PURPOSE: Surgery is the main treatment for non-metastatic colorectal cancer. Despite huge improvements in perioperative care, colorectal surgery is still associated with a significant burden of postoperative complications and ultimately costs for healthcare organizations. Systematic clinical auditing activity has already proven to be effective in measuring and improving clinical outcomes, and for this reason, we decided to evaluate its impact in a large area of northern Italy. METHODS: The Emilia-Romagna Surgical Colorectal Audit (ESCA) is an observational, multicentric, retro-prospective study, carried out by 7 hospitals located in the Emilia-Romagna region. All consecutive patients undergoing surgery for colorectal cancer during a 54-month study period will be enrolled. Data regarding baseline conditions, preoperative diagnostic work-up, surgery and postoperative course will be collected in a dedicated case report form. Primary outcomes regard postoperative complications and mortality. Secondary outcomes include each center's adherence to the auditing (enrolment rate) and evaluation of the systematic feedback activity on key performance indicators for the entire perioperative process. CONCLUSION: This protocol describes the methodology of the Emilia-Romagna Surgical Colorectal Audit. The study will provide real-world clinical data essential for benchmarking and feedback activity, to positively impact outcomes and ultimately to improve the entire healthcare process of patients undergoing colorectal cancer surgery. CLINICAL TRIAL REGISTRATION: The study ESCA is registered on the clinicaltrials.gov platform (Identifier: NCT03982641).

How has COVID-19 pandemic changed flu vaccination attitudes among an Italian cancer center healthcare workers?

A retrospective study was conducted among Italian cancer healthcare workers (HCWs) to describe how influenza vaccination attitudes have changed during the COVID-19 pandemic. The analysis was conducted on the last three influenza seasons (2018/19, 2019/20 and 2020/21). To account for different relationships and proximity with patients, the study population was grouped into three main professional categories: health personnel, administrative staff and technicians. Moreover, to explore the factors affecting the coverage of influenza vaccine, a multinomial regression analysis was performed.Over the years, the influenza vaccination uptake showed a gradual increase across the overall staff, the highest coverage (53.8%) was observed in the season 2020/21, in particular, for health personnel (57.7%). In general, males resulted in more adherent to vaccination campaigns; nevertheless, this gap decreased in the last season. A total of 28.6% workers were always vaccinated throughout the past three seasons, a remarkable 25.2% (mainly young and females) received for the first time the influenza vaccination in 2020/21.In this dramatic health crisis, the attitudes of HCWs toward flu vaccination have changed. The COVID-19 outbreak increased adherence to flu vaccination, reaching the highest coverage in the campaign 2020/21. However, further efforts should be made to achieve greater vaccination coverage.

The Challenge of Sustainability of High-Cost Oncological Drugs: A Budgeting Model in an Italian Cancer Center.

In Italy, drug expenditure governance is achieved by setting caps based on the percentage increase in hospital spending compared to the previous year. This method is ineffective in identifying issues and opportunities as it does not consider an analysis of the number of treated cases and per capita consumption in local and regional settings. The IRCCS (Scientific hospitalization and treatment institute) Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" in Meldola, has developed and adopted an effective management model designed to oversee pharmaceutical expenditure, guarantee prescription appropriateness and quality of care to patients. The budget setting follows a structured process which evaluates determining factors of the expenditure such as expected patients calculated according to the epidemiology and to national and regional indications of appropriateness, mean cost per patient calculated on the average period of demonstrated efficacy of the drug and use of drugs with the best cost-effectiveness ratio. Strict monitoring and integrated purchasing processes allow for immediate corrective actions on expenditures, as well as a continuous dialogue with the region in order to guarantee consistent funding of IRST activities. The model, presented in this article is efficient and implements concepts beyond the conventional "silos" approach and national and regional governance tools, in terms of patient centricity.

How to discriminate non-small cell lung cancer (NSCLC) cases from an Italian administrative database? A retrospective, secondary data use study for evaluating a novel algorithm performance.

OBJECTIVES: To evaluate an algorithm developed for identifying non-small cell lung cancer (NSCLC) candidates among patients with lung cancer with a diagnosis International Classification of Diseases: ninth revision (ICD-9) 162.x code in administrative databases. Algorithm could then be applied for identifying the NSCLC population in order to assess the appropriateness and quality of care of the NSCLC care pathway. DESIGN: Algorithm discrimination capacity to select both NSCLC or non-NSCLC was carried out on a sample for which electronic health record (EHR) diagnosis was available. A bivariate frequency distribution and other measures were used to evaluate algorithm's performances. Associations between possible factors potentially affecting algorithm accuracy were investigated. SETTING: Administrative databases used in a specific geographical area of Emilia-Romagna region, Italy. PARTICIPANTS: Algorithm was carried out on patients aged >18 years, with a lung cancer diagnosis from January to December 2017 and resident in Emilia-Romagna region who have been hospitalised at IRST or in one of the hospitals placed in the Forlì-Cesena area and for which EHR diagnosis data were available. OUTCOME MEASURES: Overall accuracy, positive (PPV) and negative (NPV) predictive values, sensitivity and specificity, positive and negative likelihood ratios and diagnostic OR were calculated. RESULTS: A total of 430 patients were identified as lung cancer cases based on ICD-9 diagnosis. Focusing on the total incident cases (n=314), the algorithm had an overall accuracy of 82.8% with a sensitivity of 88.8%. The analysis confirmed a high level of PPV (90.2%), but lower specificity (53.7%) and NPV (50%). Higher length of stay seemed to be associated with a correct classification. Hospitalisation regimen and a supply of antiblastic therapy seemed to increase the level of PPV. CONCLUSION: The algorithm demonstrated a strong validity for identifying NSCLC among patients with lung cancer in hospital administrative databases and can be used to investigate the quality of cancer care for this population. TRIAL REGISTRATION NUMBER: NCT04676321.

Is it possible to conduct clinical trials during a pandemic? The example of a trial of hydroxychloroquine.

OBJECTIVES: to examine the factors that, in the context of the current pandemic, have influenced the conduct of a randomized clinical trial on hydroxychloroquine in Italy. DESIGN: the trend of enrolment in the PROTECT study, "A randomized study with Hydroxychloroquine versus observational support for prevention or early phase treatment of Coronavirus disease (COVID-19)" (Eudract number: 2020-001501-24, NCT04363827), conducted in the period from May to September 2020, was analysed to evaluate the possible association of the enrolment rate with the amount of information published in the national and local press on hydroxychloroquine. SETTING AND PARTICIPANTS: the PROTECT clinical study is an Italian interventional superiority study, open label, with cluster randomization, aimed at evaluating whether treatment with hydroxychloroquine can reduce the percentage of symptomatic subjects compared to observation only in a population of subjects exposed to SARS-CoV-2 virus consisting of cohabitants/contacts of COVID-19 patients and asymptomatic or paucisymptomatic subjects diagnosed with COVID-19. MAIN OUTCOME MEASURES: the number of asymptomatic or paucisymptomatic COVID-19 patients and the number of contacts/cohabitants of COVID-19 patients enrolled in the Protect study from May to September 2020. RESULTS: from May to September 2020, the number of patients diagnosed with COVID-19 enrolled in the PROTECT clinical trial showed a decrease consistent with the number of news on hydroxychloroquine appearing in the national and local press, starting from the time when the first criticisms of the efficacy of hydroxychloroquine were made known; the number of contacts/cohabitants of COVID-19 patients showed a more marked and more timely decrease. CONCLUSIONS: in the context determined by the current COVID-19 pandemic, conducting a controlled clinical trial is strongly influenced by public opinion on scientific issues. Adherence to a clinical study can become highly problematic and invalidate the possibility of answering a scientific question and the validity of a project. In the current pandemic situation, randomized controlled trials may not always be the optimal tool to reach the expected scientific evidence, due to a number of problems. It is preferable to use a sequential or adaptive design. Furthermore, study protocols should implement innovative approaches that also include the involvement of participants in the decision-making process. In any case, the influence of public information on scientific issues is an extremely important factor to consider in the design of clinical trials in exceptional situations such as a pandemic.

The challenge of sustainability in healthcare systems: economic and organizational impact of subcutaneous formulations for rituximab and trastuzumab in onco-hematology.

Background: This study estimated the economic and organisational impact of using subcutaneous injection (SC) formulations of two monoclonal antibodies (rituximab and trastuzumab) in patients with non-Hodgkin's lymphoma (NHL) and HER2 + breast cancer (BC).Methods: The database of the Unit of Oncology and Haematology of the IRST of Meldola was used. The analysis was structured as follows: i) measurement of the volume of Day-Hospital activity; ii) identification of activities and time to complete the administration; iii) estimate the mean cost of an SC or IV (intravenous infusion); iv) estimate the impact of SC formulations on the volumes of activities provided; v) estimate the social impact of SC or IV formulations.Results: The use of an SC formulation was associated a significant reduction in the time that the patient takes to complete the administration (trastuzumab -1 hr 18 min; rituximab -2 hr 24 min) and in consumption of healthcare resources and related costs for trastuzumab (IV: € 1781; SC: € 1701) and rituximab (IV: € 2116; SC: € 1941).Conclusion: The adoption of the SC formulation for rituximab and trastuzumab can generate a greater value for both the national healthcare system and the patient compared to an IV formulation.

Radiology imaging management in an Italian cancer center (IRST IRCCS) during the COVID-19 pandemic.

In Italy, the first case of the coronavirus disease 2019 (COVID-19) was officially reported on 20.02.2020. The disease has since rapidly evolved, causing a public health emergency throughout the country but especially in our region, one of the most widely affected areas. We reorganized the daily routine of our cancer center to reduce the risk of contagion. A temporary tensile structure was set up as an entry-point triage, and a COVID-19 route was created with a dedicated CT scanner. A pre-access telephonic triage was performed the day before a patient was scheduled to come in for an examination. At the time of writing (May 4), 4053 patients had been to our center since the emergency officially began (9.03.2020) and the COVID-19 route had been activated for only 9 paucisymptomatic outpatients and 7 symptomatic inpatients. We also re-evaluated patient radiology examination lists and rescheduled non-urgent tests in consensus with the referring oncologist. Out of a total of 1438 patients scheduled for radiological examinations, 456 were postponed for a total volume reduction of 29.1%. Nine asymptomatic patients with typical CT findings of COVID-19 were identified during routine CTs, but none were RT-PCR-positive for SARS-CoV-2. We guaranteed all urgent and semi-urgent examinations, including those to stage newly diagnosed cancers and to evaluate response to treatment, ensuring the continuation of the diagnostic and therapeutic pathway of our patients. The measures we took were instrumental in keeping the institute COVID-19-free. We also describe the planned measures to resume normal clinical practice at the center.

Assessment of Cancer Care Costs in Disease-Specific Cancer Care Pathways.

In view of an efficient use of the Italian National Health Service-funded healthcare resources, a novel data-processing strategy combining information from multiple sources was developed in a regional cancer network of northern Italy. The goal was to calculate the annual overall cost of care pathways of six disease groups in 10,486 patients. The evaluation was conceived as a population-based cost description from the perspective of the Italian National Health Service. Costs occurred during a defined time period for a cross-section of patients at varying stages of their disease were measured. The total cancer care cost was €81,170,121 (11.1% of total local health expenditure), with a cost per patient of €7741.17 and a cost per capita of €204.62. Surgical, inpatient and day-hospital medical admissions, radiotherapy, drugs, outpatient care, emergency admissions, and home and hospice care accounted for 21.2%, 24.1%, 6.2%, 28.2%, 14.0%, 0.9%, and 5.4% of the total cost, respectively. The highest cost items included drugs (cost per capita, €22.95; 11.2% of total cost) and medical admissions (€14.51; 7.1%) for blood cancer, and surgical (€14.56; 7.1%) and medical admissions (€13.60; 6.6%) for gastrointestinal cancer. The information extracted allows multidisciplinary cancer care teams to be more aware of the costs of their clinical decisions.

Performances of a Solution to Semi-Automatically Fill eCRF with Data from the Electronic Health Record: Protocol for a Prospective Individual Participant Data Meta-Analysis.

Clinical trial data collection still relies on a manual entry from information available in the medical record. This process introduces delay and error risk. Automating data transfer from Electronic Health Record (EHR) to Electronic Data Capture (EDC) system, under investigators' supervision, would gracefully solve these issues. The present paper describes the design of the evaluation of a technology allowing EHR to act as eSource for clinical trials. As part of the EHR2EDC project, for 6 ongoing clinical trials, running at 3 hospitals, a parallel semi-automated data collection using such technology will be conducted focusing on a limited scope of data (demographic data, local laboratory results, concomitant medication and vital signs). The evaluation protocol consists in an individual participant data prospective meta-analysis comparing regular clinical trial data collection to the semi-automated one. The main outcome is the proportion of data correctly entered. Data quality and associated workload for hospital staff will be compared as secondary outcomes. Results should be available in 2020.

Increased frequency of acute reactions to iodinated contrast media in cancer patients treated with anti-CTLA-4 immunomodulatory antibodies.

Contrast-enhanced computed tomography (CECT) is an indispensable tool in the management of cancer patients. However, this procedure can be complicated by the development of acute adverse reactions (ARs) to iodinated contrast media (ICM). On the basis of the hypothesis that cancer immunotherapy, in particular with immune checkpoint inhibitors, increases the incidence of allergic-like immediate ARs to ICM with respect to "standard" cancer chemotherapy/targeted therapy (CHT) we retrospectively evaluated the incidence of CECT-related immediate ARs in cancer patients undergoing cancer treatments. All patients who underwent at least one CECT scan after starting any cancer treatment between 2006 and 2014 were included in a mono-institutional radiological database. The staff of the Radiology Unit recorded any ARs that occurred within 30 min of the ICM injection and classified them as "allergic-like" or "physiologic" and graded as mild, moderate, or severe according to the American College of Radiology (ACR) Manual on Contrast Media, version 10.1. Fifty-nine of the 3,521 patients included in the database received ipilimumab (Ipi), 75 received cytokines (Cys), and the remaining 3,387 received non-immunologic agents (CHT). Overall, 71 (2%) patients suffered ICM-related ARs. The incidence of ICM-related ARs was higher in Ipi- and Cy-treated patients than in those who received CHT (12%, 5%, and 2%, respectively). Our data show that immunological cancer treatments, particularly Ipi, considerably increase the proportion of patients suffering CECT-related immediate ARs with respect to non-immunologic agents. Although these findings need to be validated in larger prospective studies, they serve as a "wake-up call" for radiologists to closely monitor patients who have previously received cancer immunotherapy with anti-cytotoxic T-lymphocyte antigen-4 antibodies when using ICM in order to reduce the risk of potentially severe immediate ARs.

Chemotherapy and palliative care near end-of life: examining the appropriateness at a cancer institute for colorectal cancer patients.

BACKGROUND: Appropriate cessation of chemotherapy and timely referral of patients to hospice services are crucial for the quality of care near death. We investigated the quality of care in our Cancer Institute in very advanced metastatic colorectal cancer patients treated in real life. PATIENTS AND METHODS: We performed a retrospective analysis of electronic medical data of patients with metastatic colorectal cancer who were candidates for chemotherapy during the study period (1 January 2007-30 June 2014) and died before 31 December 2014. Quality-of-cancer-care indicators were calculated for the overuse of chemotherapy and referral to hospice. Predictive factors of chemotherapy discontinuation and hospice referral in end-of life care were investigated using parametric and nonparametric methods. RESULTS: Of the 365 patients who died before 31 December 2014, 26 (7.1%) received chemotherapy in the last 14 days of life and 36 (9.8%) started a new chemotherapy regimen in the last 30 days of life. Factors associated with the overuse of chemotherapy were being < 70 years of age for both indicators and not having received advanced chemotherapy treatments for the former indicator. The majority of patients (74.7%) had access to hospice services, of whom only a small percentage (7.2%) accessed them very near to death. CONCLUSIONS: According to the criteria used, our Institute provides a good quality of cancer care for dying colorectal cancer patients, measured by the use of chemotherapy and referral to hospice in their last days of life.

The challenge of sustainability in healthcare systems: Frequency and cost of inappropriate patterns of breast cancer care (the E.Pic.A study).

OBJECTIVES: In a context of decreasing economic health resources and a rise in health needs, it is urgent to face this sustainability crisis through the analysis of healthcare expenditures. Wastages, deriving from inappropriate interventions, erode resources which could be reallocated to high-value activities. To identify these areas of wastages, we developed a method for combining and analyzing data from multiple sources. Here we report the preliminary results of a retrospective cohort study evaluating the performance of breast cancer (BC) care at IRST, an Italian cancer institute. MATERIALS AND METHODS: Four data sources gathered in a real-world setting (a clinical database, two administrative databases and a cancer registry) were linked. Essential Key Performance Indexes (KPIs) in the pattern of BC diagnosis (KPI 1 and 2) and treatment (KPI 3 and 4) based on current guidelines were developed by a board of professionals. The costs of inappropriate examinations were associated with the diagnostic KPIs. RESULTS: We found that 2798 patients treated at IRST from January 2010 to June 2016 received a total of 2516 inappropriate examinations accounting for € 573,510.80. Linkage from multiple routine healthcare data sources is feasible: it allows the measurement of important KPIs specifically designed for BC care, and the identification of areas of low-value use of the resources. CONCLUSION: If systematically applied, this method could help provide a complete picture of inappropriateness and waste, redirect these resources to higher-value interventions for patients, and fill the gap between proper use of the resources and the best clinical results.

Does the time between CT scan and chemotherapy increase the risk of acute adverse reactions to iodinated contrast media in cancer patients?

BACKGROUND: Cancer patients undergo routine computed-tomography (CT) scans and, therefore, iodinated contrast media (ICM) administration. It is not known whether a time-dependent correlation exists between chemotherapy administration, contrast enhanced CT and onset of acute ICM-related adverse reactions (ARs). METHODS: All consecutive contrast-enhanced CTs performed from 1 January 2010 to 31 December 2012 within 30 days of the last chemotherapy administration were retrospectively reviewed. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. We analyzed time to CT evaluation calculated as the time elapsed from the date of the CT performed to the date of the last chemotherapy administration. Patients were classified into 4 groups based on the antineoplastic treatment: platinum-based, taxane-based, platinum plus taxane and other group. RESULTS: Out of 10,472 contrast-enhanced CTs performed, 3,945 carried out on 1,878 patients were considered for the study. Forty acute ICM-related ARs (1.01%; 95% CI, 0.70-1.33) were reported. No differences were seen among immediate (within 10 days of the last chemotherapy administration), early (11-20 days) and delayed (21-30 days) CTs. Median time to CT in patients who experienced an acute ICM-related AR by treatment group was not statistically different: 20 days (range 6-30), 17 days (range 5-22), 13 days (range 8-17), 13 days (range (2-29) for the platinum, taxane, platinum plus taxane and other group, respectively (P =0.251). CONCLUSIONS: Our results did not reveal any correlation between time to CT and risk of acute ICM-related ARs in cancer patients.

Taxanes as a risk factor for acute adverse reactions to iodinated contrast media in cancer patients.

BACKGROUND: The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. METHODS: We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. RESULTS: Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI: 0.74-1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane groups (p = .007), whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting. Multivariate analysis confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14-2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02-4.16). CONCLUSION: Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs.