Multicenter Real-World Study on Effectiveness and Early Discontinuation Predictors in Patients With Non-small Cell Lung Cancer Receiving Nivolumab.

BACKGROUND: Real-world (RW) evidence on nivolumab in pretreated patients with non-small cell lung cancer (NSCLC) by matching data from administrative health flows (AHFs) and clinical records (CRs) may close the gap between pivotal trials and clinical practice. METHODS: This multicenter RW study aims at investigating median time to treatment discontinuation (mTTD), overall survival (mOS) of nivolumab in pretreated patients with NSCLC both from AHF and CR; clinical-pathological features predictive of early treatment discontinuation (etd), budget impact (BI), and cost-effectiveness analysis were investigated; mOS in patients receiving nivolumab and docetaxel was assessed. RESULTS: Overall, 237 patients with NSCLC treated with nivolumab were identified from AHFs; mTTD and mOS were 4.2 and 9.8 months, respectively; 141 (59%) received at least 6 treatment cycles, 96 (41%) received < 6 (etd). Median overall survival in patients with and without etd were 3.3 and 19.6 months, respectively (P < .0001). Higher number, longer duration, and higher cost of hospitalizations were observed in etd cases. Clinical records were available for 162 patients treated with nivolumab (cohort 1) and 83 with docetaxel (cohort 2). Median time to treatment discontinuation was 4.8 and 2.6 months, respectively (P < .0001); risk of death was significantly higher in cohort 2 or cohort 1 with etd compared with cohort 1 without etd (P < .0001). Predictors of etd were body mass index <25, Eastern Cooperative Oncology Group performance status >1, neutrophile-to-lymphocyte ratio >2.91, and concomitant treatment with antibiotics and glucocorticoids. The incremental cost-effectiveness ratio of nivolumab was 3323.64 euros ($3757.37) in all patients and 2805.75 euros ($3171.47) for patients without etd. Finally, the BI gap (real-theoretical) was 857 188 euros ($969 050.18). CONCLUSION: We defined predictors and prognostic-economic impact of nivolumab in etd patients.

Quality management of cutaneous melanoma: impact on short-term outcomes and costs.

Promoting standardization and quality assurance (QA) may guarantee better outcomes for patients and ensure a better allocation of healthcare system resources. The present study tested the association between process quality indicators of the clinical pathway for melanoma and both patient short-term mortality and budget utilization. Specific indicators were selected to assess quality of processes in different phases of the pathway as well as the pathway as a whole. Cox regression models were run for each phase to test the association between adherence to the quality indicator and overall mortality. A Tobit regression analysis was used to identify any association between adherence to the quality indicators and total costs over the two years after melanoma was diagnosed. This retrospective cohort study concerned 1,222 incident cases of melanoma in the Veneto Region (north-east of Italy). Adherence to the clinical pathway as a whole was associated with a significant decrease in risk of death (HR= 0.40; 95% CI: 0,19 -0,77). Adherence to quality processes in the diagnostic phase (HR= 0.55 95% CI: 0.31- 0.95) and surgical phase (HR= 0.33 95% CI: 0.16- 0.61) significantly reduced the hazard risk. Tobit regression revealed a significant increase in overall costs for patients who adhered to the whole pathway in comparison with those who did not (ß= 2,393.24; p= 0.013). This study suggests that adherence to the quality of management of clinical pathways modifies short-term survival as well as mean cost of care for patients with cutaneous melanoma. Physicians should be encouraged to improve their compliance with clinical care pathways for their melanoma patients, and steadily growing associated costs emphasize the need for policy makers to invest exclusively in treatments of proven efficacy.

Use of Electronic Administrative Databases to Measure Quality Indicators of Breast Cancer Care: Experience of Five Regional Oncology Networks in Italy.

PURPOSE: Assuring quality of care, while maintaining sustainability, in complex conditions such as breast cancer (BC) is an important challenge for health systems. Here, we describe a methodology to define a set of quality indicators, assess their computability from administrative data, and apply them to a large cohort of BC cases. MATERIALS AND METHODS: Clinical professionals from the Italian Regional Oncology Networks identified 46 clinically relevant indicators of BC care; 22 were potentially computable using administrative data. Incident cases of BC diagnosed in 2016 in five Italian regions were identified using administrative databases from regional repositories. Each indicator was calculated through record linkage of anonymized individual data. RESULTS: A total of 15,342 incident BC cases were identified. Nine indicators were actually computable from administrative data (two structure and seven process indicators). Although most indicators were consistent with guidelines, for one indicator (blood tumor markers in the year after surgery, 44.2% to 64.5%; benchmark ≤ 20%), deviation was evident throughout the five regions, highlighting systematic overlooking of clinical recommendations. Two indicators (radiotherapy within 4 months after surgery if no adjuvant chemotherapy; 42% to 83.8%; benchmark ≥ 90%; and mammography 6 to 18 months after surgery, 55.1% to 72.6%; benchmark ≥ 90%) showed great regional variability and were lower than expected, possibly as result of an underestimation in indicator calculation by administrative data. CONCLUSION: Despite highlighting some limitations in the use of administrative data to measure health care performance, this study shows that evaluating the quality of BC care at a population level is possible and potentially useful for guiding quality improvement interventions.

Impact of breast cancer screening in a population with high spontaneous coverage with mammography.

OBJECTIVE: The impact of organized screening programs on breast cancer (BC) mortality is unclear in an era of high spontaneous referral of women to mammography. The aim of this study was to analyze if the introduction of mammographic screening programs reduced BC mortality in the Veneto region, Italy, despite already widespread spontaneous access to mammography. METHODS: In Veneto, screening was introduced in different years between 1999 and 2009 across 21 local health units (LHUs), inviting asymptomatic women aged 50-69 years to undergo mammography biennially. We compared BC mortality for the 1995-2014 period of women aged 40-49 and 50-74 years who were resident in LHUs where screening programs started in 2003 (early LHUs) with women resident in LHUs where screening was introduced later (late LHUs). Poisson regression models were applied to incidence-based mortality (IBM), including only deaths from BC arising within the screening period. RESULTS: In the prescreening period and until 2010, BC mortality rates in early and late LHUs were similar in both age groups. In the last study period (2010-2014), we observed a 10% decrease in overall BC mortality in early compared to late LHU, limited to women aged 50-74 years. IBM was reduced by 8% (95% CI 1%-16%) in the overall study period and by 16% (6%-25%) in 2010-2014. CONCLUSIONS: In the Veneto region, screening programs were associated with a significant impact on BC-specific mortality; such effect appeared at least 8 years after screening implementation.

Italian cancer figures--Report 2015: The burden of rare cancers in Italy.

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.

Estimates of cancer burden in Veneto.

AIMS AND BACKGROUND: In Veneto a regional cancer registry has been operating since 1987 which provides incidence and survival data for the region. It currently covers 48% of the regional population. The aim of this paper is to provide estimates of the incidence, mortality and prevalence of the major cancers for the whole Veneto region in the period 1970-2015. METHODS: The estimates were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Survival was modeled on the basis of published data from the Italian cancer registries. RESULTS: In 2012 the most frequent cancer sites were colon-rectum, prostate and breast with 4,677, 3,760 and 3,729 new diagnosed cases, respectively. The incidence rates were estimated to increase constantly for female lung cancer, prostate cancer, colorectal cancer and melanoma, while they were decreasing for cervical cancer and stomach cancer. For male lung cancer and female breast cancer the rates increased, reaching a peak, and then decreased. In the last years of the period of analysis, mortality declined for all cancers: the highest number of deaths (2,390 in both sexes) was estimated for lung cancer in 2012. Prevalence was increasing for all the considered cancer sites with the exception of lung cancer in men, for which the prevalence was estimated to increase until 2007 and then stabilize. By contrast, the cervical cancer decreased during the whole period. In 2012 breast cancer had the highest prevalence, with about 52,000 cases. CONCLUSION: This paper provides a description of the burden of the major cancers in Veneto until 2015. The estimates highlight the continuing reduction of cancer mortality. This decline can be related to the improvement of clinical treatments and to multidisciplinary treatment approaches. In order for this positive trend to continue, implementation and reinforcement of the screening programs is needed, especially for breast and colorectal cancer.

Probabilistic classifiers and automated cancer registration: an exploratory application.

A test of the performance of two probabilistic classifiers (random forests and multinomial logit models) in automatically defining cancer cases has been carried out on 5608 subjects, registered by the Venetian Tumour Registry (RTV) during the years 1987-1996 and manually checked for possible second cancers that occurred during the 1997-1999 period. An eightfold cross-validation was performed to estimate the classification error; 63 predictive variables were entered into the model fitting. The random forest allows to automatically classify 45% of subjects with a classification error lower than 5%, while the corresponding error is 31% for the multilogit model. The performance of the former classifier is appealing, indicating a potential drop of manually checked cases from 1750 to 960 per incidence year with a moderate error rate. This result suggests to refine the approach and extend it to other categories of manually treated cases.

Ovarian cancer in Europe: Cross-sectional trends in incidence and mortality in 28 countries, 1953-2000.

We have considered trends in incidence and mortality in 28 European countries using incidence data from successive volumes of Cancer Incidence in Five Continents and mortality from the WHO database. Countries with the highest rates in the early 1960s included the Nordic countries, Austria, Germany and the United Kingdom, but trends in these areas have tended to decline over recent calendar periods, particularly with regard to mortality. Southern European countries showed upward trends, at least until the early 1980s for France and Italy. Likewise, in most central and eastern European countries, ovarian cancer incidence and mortality rates were originally relatively low, but tended to rise over time. Falls in mortality, but not in incidence, over recent years were observed in the Czech Republic and Hungary. In several countries, mainly in northern Europe, trends were more favorable at younger age (25-49 years) than in the subsequent age groups. Thus, recent trends in ovarian cancer have led to a leveling of rates across various areas of the continent, although a 2.5-fold variation was still observed in the late 1990s between the highest mortality rate of 9.3/100,000 in Denmark and the lowest one of 3.6 in Portugal. These patterns should be viewed in the light of an observed reduction in parity, mainly in southern and eastern Europe, and the spread of oral contraceptive use, mainly in northern Europe, since these are the best recognized protective factors with regard to ovarian carcinogenesis. The declining mortality trends can also in part be ascribed to improvements in treatment.