An Italian Real-World Study Highlights the Importance of Some Clinicopathological Characteristics Useful in Identifying Metastatic Breast Cancer Patients Resistant to CDK4/6 Inhibitors and Hormone Therapy.

Background: Cyclin-dependent kinase 4 and 6 (CDK4 and CDK6) inhibitors have changed the therapeutic management of hormone receptor-positive (HR+) metastatic breast cancer (mBC) by targeting the cell cycle machinery and overcoming endocrine resistance. However, a large number of patients present disease progression due to cancer cells resisting CDK4/6 inhibitors. Our research considers which clinicopathological characteristics could be useful in identifying patients who might respond to CDK4/6 inhibitors by analyzing a retrospective case series of patients with HR+ mBC who were treated with hormone therapy plus CDK4/6 inhibitors. Methods: Approximately 177 mBC patients were enrolled, of whom 66 were treated with CD4/6 inhibitors plus letrozole and 111 were treated with CDK4/6 inhibitors and fulvestrant. A multistate model was used. Results: A low body surface area and older age were associated with an increased risk of developing neutropenia. A high Ki67 index, the presence of visceral metastases, and not having previously undergone adjuvant chemotherapy were prognostic factors of disease progression/death. As expected, some of the neutropenic patients who had previously undergone multiple lines of treatment were at a higher risk of disease progression/death. Furthermore, neutropenia status was associated with a more than doubled risk of progression/death compared to patients without neutropenia (HR = 2.311; p = 0.025). Conclusions: Having identified certain factors that could be associated with the development of neutropenia and considering that neutropenia itself is associated with an increased risk of progression, we believe that the baseline characteristics should be taken into account to reduce cases of neutropenia and disease progression.

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.

European value-based healthcare benchmarking: moving from theory to practice.

BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.

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.

Appropriateness and Economic Analysis of Conventional Circulating Biomarkers Assessment in Early Breast Cancer: A Real-World Experience from the E.Pic.A Study.

The risk of relapse for early breast cancer (BC) patients persists even after decades and to date, no specific and sensitive effective circulating biomarker for recurrence prediction has been identified yet. The international guidelines do not recommend the assessment of the serum tumor markers CEA and CA15-3 in the follow-up of asymptomatic early BC patients. In our institute, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", as part of the E.Pic.A study, which was designed to assess the economic appropriateness of integrated care pathways in early BC, the use of CEA and CA15-3 as circulating tumor biomarkers in early BC patients was evaluated in 1502 patients one year after surgery, from 2015 to 2018, with an overall expense of EUR 51,764. A total of EUR 47,780 (92%) was used for execution of circulating tumor markers in early BC patients with stage 0, I and II tumors, neglecting the current guidelines and considered inappropriate by our professional board. We found that no patients with stage I BC experienced relapse in the 365 days after surgery, and in any case examination of the circulating markers CEA and CA15-3 was considered crucial for diagnosis of relapse. Our findings suggest that this inadequacy is a low-value area, supporting the reallocation of economic resources for interventions of a higher value for patients.

Chronological age or biological age: What drives the choice of adjuvant treatment in elderly breast cancer patients?

Ma and colleagues reported in their study on 12,004 elderly patients published on Breast J. 2020, that adjuvant chemotherapy was not associated with overall survival. Given the toxicities associated with systemic treatments, caution recommendation or omission of chemotherapy may be considered in elderly patient selection especially when comorbidities are present. We agree with authors final conclusions but we want to highlight that to define the adjuvant therapy in BC elderly patients several factors need to be taken into account. One of the main issues is the lack of universal and unique guidelines to define elderly patients. In clinical practice it can be very difficult to estimate the benefit/risk ratio in elderly patients because chemotherapy-induced toxicity is worse than in younger individuals. For these reasons, beyond comorbidities, the choice of adjuvant therapy for elderly patients must also be based both on chronological and biological age. Moreover, the multidisciplinary team for the elderly patient evaluation should include both the geriatrician and the molecular biologist.

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.

Incidence and Prevalence Analysis of Non-Small-Cell and Small-Cell Lung Cancer Using Administrative Data.

Treatment of lung cancer depends on the stage of the tumor and the histological type. In recent years, the histological confirmation of lung non-small-cell lung cancer has become crucial since the availability of selective target therapeutic approaches. The aim of the study was to develop a validated procedure to estimate the incidence and prevalence of non-small-cell and small-cell lung cancer from healthcare administrative data. A latent class model for categorical variables was applied. The following observed variables were included in the analysis: ICD-9-CM codes in the Hospital Discharge Registry, ATC codes of medications dispensed present in the Drugs Prescriptions Registry, and the procedure codes in the Outpatient Registry. The proportion of non-small-cell lung cancer diagnoses was estimated to be 85% of the total number of lung cancer on the cohort of incident cases and 89% on the cohort of prevalent cases. External validation on a cohort of 107 patients with a lung cancer diagnosis and histological confirmation showed a sensitivity of 95.6% (95%CI: 89-98.8%) and specificity of 94.1% (95%CI: 71.3-99.9%). The procedure is an easy-to-use tool to design subpopulation-based studies on lung cancer and to better plan resource allocation, which is important since the introduction of new targeted therapies in non-small-cell lung carcinoma.

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.

The challenge of sustainability in healthcare systems: cost of radiotherapy in the last month of life in an Italian cancer center.

PURPOSE: Cost evaluation is becoming mandatory to support healthcare sustainability and optimize the decision-making process. This topic is a challenge, especially for complex and rapidly evolving treatment modalities such as radiotherapy (RT). The aim of the present study was to investigate the cost of RT in the last month of life of patients in an Italian cancer center. METHODS: This was a retrospective study on a cancer population (N= 160) who underwent RT or only an RT planning simulation in an end of life (EOL) setting. The cost of RT procedures performed on patients was collected according to treatment status, care setting, and RT technique used. Costs were valued according to the sum of reimbursements relating to all procedures performed and assessed from the perspective of the National Health System. RESULTS: The total cost of RT in the last month of life was €244,774, with an average cost per patient of €1530. Around 7.7% and 30.3% of the total cost was associated with patients who never started RT or who discontinued RT, respectively, while the remaining 62.0% referred to patients who completed treatment. Costs associated with outpatient and inpatient settings represented 54.3% and 38.6% of the total cost, respectively. The higher average cost per patient for the never-started and discontinued groups was correlated with patients who had a poor ECOG Performance Status. CONCLUSION: Improved prognostic accuracy and a better integration between radiotherapy and palliative care units could be a key to a better use of resources and to a reduction in the cost of EOL RT.

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.

The challenge of sustainability in healthcare systems: frequency and cost of diagnostic procedures in end-of-life cancer patients.

BACKGROUND: Literature data on the overuse and misuse of diagnostic procedures leading to end-of-life aggressiveness are scarce due to the limited amount of estimated economic waste. This study investigated the potential overuse of diagnostic procedures in a population of end-of-life patients. METHODS: This is a retrospective study on consecutive advanced patients admitted into two Italian hospices. Frequency and relative costs of X-ray imaging, CT scans, MRI, and interventional procedures prescribed in the 3 months before admission were collected in patient electronic charts and/or in administrative databases. We conducted a deeper analysis of 83 cancer patients with a diagnosis of at least 1 year before admission to compare the number of examinations performed at two distant time periods. RESULTS: Out of 541 patients, 463 (85.6%) had at least one radiological exam in the 3 months before last admission. The mean radiological exam number was 3.9 ± 3.2 with a relative mean cost of 278.60 ± 270.20 € per patient with a statistically significant (p < 0.001) rise near death. In the 86-patient group, a higher number of procedures was performed in the last 3 months of life than in the first quarter of the year preceding last admission (38.43 ± 28.62 vs. 27.95 ± 23.21, p < 0.001) with a consequent increase in cost. CONCLUSIONS: Patients nearing death are subjected to a high level of "diagnostic aggressiveness." Further studies on the integration of palliative care into the healthcare pathway could impact the appropriateness of interventions, quality of care, and, ultimately, estimated costs.

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.