Algorithms to identify radiotherapy intent in unresected non-metastatic non-small-cell lung cancer: an I-O Optimise analysis.

This study aimed to develop and evaluate the performance of algorithms for identifying radiotherapy (RT) treatment intent in real-world data from patients with non-metastatic non-small-cell lung cancer (NSCLC). Using data from IPO-Porto hospital (Portugal) and the REAL-Oncology database (England), three algorithms were developed based on available RT information (#1: RT duration, #2: RT duration and type, #3: RT dose) and tested versus reference datasets. Study results showed that all three algorithms had good overall accuracy (91-100%) for patients receiving RT plus systemic anticancer therapy (SACT) and algorithms #2 and #3 also had good accuracy (>99%) for patients receiving RT alone. These algorithms could help classify treatment intent in patients with NSCLC receiving RT with or without SACT in real-world settings where intent information is missing/incomplete.

One objective of many real-world studies is to evaluate which cancer treatments are given during routine visits to hospitals or cancer centers and assess how well the treatments work. This objective is easier to achieve when we know the reason for the cancer treatment (known as treatment intent), but doctors often do not record whether the treatment was given to actively treat the cancer (curative intent) or to slow down a cancer's growth or control symptoms in people with incurable cancer (palliative intent). In this article, we describe the development and testing of algorithms to determine treatment intent in people with lung cancer given radiotherapy (the controlled application of radiation to cancer cells). These algorithms involve following a step-by-step process based on three key questions: for how long was the radiotherapy given? what type of radiotherapy was given? and what dose of radiotherapy was given? Answers were then tested true or false against reference answers provided by doctors who know a lot about radiotherapy. We found that all three algorithms were able to determine the correct treatment intent in more than nine out of ten people given radiotherapy with systemic anticancer therapy (e.g., chemotherapy) and two algorithms were able to determine the correct treatment intent in more than nine out of ten people given radiotherapy alone. These algorithms may be helpful in determining treatment intent in people given radiotherapy to treat lung cancer in real-world settings, and may help us learn more about real-world lung cancer treatment.

Real-World Treatment Patterns and Survival Outcomes for Patients with Non-Metastatic Non-Small-Cell Lung Cancer in Sweden: A Nationwide Registry Analysis from the I-O Optimise Initiative.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with ~40-50% of patients diagnosed with non-metastatic disease (stages IA-IIIC). The treatment landscape is evolving rapidly as immunotherapies and targeted therapy are introduced in the non-metastatic setting, creating a need to assess patient outcomes prior to their introduction. This real-world study using Swedish National Lung Cancer Registry data examined outcomes (overall survival (OS) and time to next treatment or death (TTNTD)) and treatment patterns for adults diagnosed with non-metastatic NSCLC. Baseline characteristics and OS from diagnosis were described for all patients; OS, treatment patterns, and TTNTD from treatment start were described for the treatment subgroup (patients diagnosed from 2014 onwards), stratified by disease stage and initial treatment. OS and TTNTD were described using the Kaplan-Meier estimator. The overall population (2008-2019) included 17,433 patients; the treatment subgroup included 5147 patients. Median OS (interquartile range) overall ranged from 83.3 (31.6-165.3) months (stage I patients) to 10.4 (4.3-24.2) months (stage IIIB patients). Among the treatment subgroup, median OS and TTNTD were longest among patients receiving surgery versus other anticancer treatments. These findings provide a baseline upon which to evaluate the epidemiology of non-metastatic NSCLC as newer treatments are introduced.

Incidence and survival of transthyretin amyloid cardiomyopathy from a French nationwide study of in- and out-patient databases.

BACKGROUND: Precise data about ATTR-CM incidence rates at national level are scarce. Consequently, this study aimed to estimate the annual incidence and survival of transthyretin amyloid cardiomyopathy (ATTR-CM) in France between 2011 and 2019 using real world data. We used the French nationwide exhaustive data (SNDS database) gathering in- and out-patient claims. As there is no specific ICD-10 marker code for ATTR-CM, diagnosis required both amyloidosis (identified by E85. ICD-10 code or a tafamidis meglumine delivery) and a cardiovascular condition (identified by ICD-10 or medical procedure codes related to either heart failure, arrhythmias, conduction disorders or cardiomyopathies), not necessarily reported at the same visit. Patients with probable AL-form of amyloidosis or probable AA-form of amyloidosis were excluded. RESULTS: Between 2011 and 2019, 8,950 patients with incident ATTR-CM were identified. Incidence rates increased from 0.6 / 100,000 person-years in 2011 to 3.6 / 100,000 person-years in 2019 (p < 0.001), reaching 2377 new cases in 2019. Sex ratios (M/F) increased from 1.52 in 2011 to 2.23 in 2019. In 2019, median age at diagnosis was 84.0 years (85.5 for women and 83.5 for men). Median survival after diagnosis was 41.9 months (95% CI [39.6, 44.1]). CONCLUSIONS: This is the first estimate of nationwide ATTR-CM incidence in France using comprehensive real-world databases. We observed an increased incidence over the study period, consistent with an improvement in ATTR-CM diagnosis in recent years.

Real-world treatment patterns and survival outcomes for patients with stage III non-small cell lung cancer in Spain: a nationwide cohort study.

Background: The burden of non-small cell lung cancer (NSCLC) remains high in Spain, with lung cancer accounting for 20% of cancer-related deaths annually. Programs such as the Spanish Thoracic Tumour Registry (TTR) and the global I-O Optimise initiative have been developed to observe patients in clinical practice with the aim of improving outcomes. This analysis examined treatment patterns and survival in patients with stage III NSCLC from the TTR. These patients represent a heterogenous group with complex treatment pathways. Methods: The TTR is an ongoing, observational, prospective, and retrospective cohort multicentre study (NCT02941458) that follows patients with thoracic cancer in Spain. Adults aged ≥18 years with stage IIIA/IIIB NSCLC enrolled in the TTR between 01 Jan 2010 and 31 Oct 2019 were included in this analysis. Initial treatment received was described by cancer stage and histology (squamous and non-squamous NSCLC). Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated over a 5-year period. Results: A total of 1,838 patients were included in the cohort, including 1,082 with stage IIIA (58.9%) and 756 with stage IIIB (41.1%). Median follow-up was 18.3 months. The median age of patients was 66 years, and most had non-squamous NSCLC (54.0%), were male (81.2%), and were active or former smokers (93.4%). Overall, 26.3% of patients received surgical resection (37.0% for stage IIIA and 11.1% for stage IIIB). The most frequent initial treatment received was concurrent chemoradiotherapy for stage IIIA (30.2%) and stage IIIB (37.0%) patients. Median OS was lower in patients with stage IIIB than stage IIIA (28 vs. 37 months) disease and was lower for patients with squamous than non-squamous histology (19 vs. 26 months). Median PFS and OS varied when patients were stratified by initial treatment. Conclusions: This TTR analysis describes the clinical reality surrounding the initial management and survival outcomes for stage III NSCLC in Spain and presents survival outcomes comparable with other real-world evidence. It provides insights into the diverse approaches used before the availability of immunotherapies and targeted treatments in the non-metastatic NSCLC setting.

Patients with Metastatic Melanoma Receiving Anticancer Drugs: Changes in Overall Survival, 2010-2017.

Immune checkpoint inhibitors and targeted therapies have profoundly altered the management of several cancers over the past decade. Metastatic melanoma has been at the forefront of these changes. We provide here a nationwide overview and an assessment of changes in survival in France. We included 10,936 patients receiving a systemic treatment for metastatic cutaneous melanoma between 2010 and 2017 using the French National Health Insurance database (Système National des Données de Santé). Over the study period, there was a doubling of the number of new patients receiving a systemic treatment. Cytotoxic chemotherapy was progressively replaced by targeted therapy and immune checkpoint inhibitors. Patients having initiated a first-line treatment since June 2015 gained 46% overall survival compared with those initiating treatment before 2012. Overall survival at 24 months rose from 21% to 44%. We provide real-world evidence for the improvement of overall survival in the past decade among patients with metastatic melanoma. Although the characteristics of the patients treated can vary across periods, this type of exhaustive real-world data provides evidence from broader populations than those included in clinical trials.

Trends in sodium valproate prescriptions among children aged 0 to 14 years between 2010 and 2016: A study based on the French National Health Insurance Database.

PURPOSE: After a huge campaign of information on the teratogenic risk of sodium valproate (VPA) having taken place in France we aimed to evaluate the trend of its prescriptions in young epileptic girls. METHOD: Using the French National Health Insurance Database we searched for patients aged 0-14 years being supplied an antiepileptic drug (AED) between 2010 and 2016. RESULTS: 113,362 children received at least one AED, 61,259 boys and 52,103 girls. Compared to 2010-2014 years, VPA was less prescribed in 2016 as first AED (29% vs 37.3% respectively). The difference between the two periods was greater for girls (-41%) than for boys (-12%). CONCLUSION: The changing trend of VPA as first AED prescribed, particularly in girls, reflects published evidence in terms of safety.

Risk of suicide attempt associated with isotretinoin: a nationwide cohort and nested case-time-control study.

BACKGROUND: Isotretinoin is the only effective treatment for severe acne. An isotretinoin-related suicide risk is still debated and under scrutiny by regulatory agencies. Our objectives were: to assess the risk of suicide attempt before, during and after isotretinoin treatment; to detect any potential triggering effect of isotretinoin initiation on suicide attempt. METHODS: We implemented a cohort and nested case-time-control study of subjects treated with oral isotretinoin (course or initiation) aged 10-50 years, using the Nationwide French Health Insurance data (2009-2016). The main outcome was hospitalized suicide attempt. Standardized incidence ratios for hospitalized suicide attempts were calculated before, during and after isotretinoin treatment. The number of isotretinoin initiations was compared in risk and control periods of 2 months using a case-time-control analysis. RESULTS: In all, 443 814 patients (median age 20.0 years; interquartile range 17.0-27.0 years) were exposed to isotretinoin, amounting to 244 154 person-years, with a marked seasonality for treatment initiation. Compared with the French general population, the occurrence of suicide attempts under isotretinoin treatment was markedly lower, with a standardized incidence ratio of 0.6 [95% confidence interval (CI) = 0.53-0.67]; the same applied, to a lesser extent, before and after isotretinoin treatment. In the case-time-control analysis, among cases of suicide attempt, 108 and 127 isotretinoin initiations were observed in the risk and control periods respectively (i.e. 0-2 months and 2-4 months before the date of suicide attempt). The comparison with the 1199 and 1253 initiations observed among matched controls in the same two periods yielded a case-time-control odds ratio of 0.89 (95% CI = 0.68-1.16). A sensitivity analysis using three-month periods and a complementary analysis adding completed suicides for case definition showed consistent results. CONCLUSION: Compared with the general population, a lower risk of suicide attempt was observed among patients exposed to isotretinoin and there was no evidence for a triggering effect of isotretinoin initiation on suicide attempt. A selection of patients at lower risk for suicidal behaviour and appropriate treatment management could explain these findings. Risk management plans should therefore be maintained.

Safety of Oral Propranolol for Infantile Hemangioma.

OBJECTIVES: The safety of oral propranolol for infantile hemangioma has not yet been studied at population level since the pediatric use marketing authorization was obtained in Europe. METHODS: A survey of a nationwide, claim-based observational cohort of children <3 years old, with at least 1 delivery of oral propranolol between July 2014 and June 2016, was performed by using the database of the French National Health Insurance system. Standardized morbidity ratios (SMRs) were calculated by using, from the same database, a representative random sample of nonexposed subjects. The main outcomes were hospitalizations for cardiovascular (conduction disorders, bradycardia, and hypotension), respiratory (bronchial hyperactivity and bronchospasm), or metabolic events (hypoglycemia and hyperkalaemia), identified through the hospitalization diagnostic codes of the International Classification of Diseases, 10th Revision. The main analysis was conducted separately on "healthy" children (N = 1484), that is, free from of any prespecified underlying disease and on children with 1 of these underlying diseases (N = 269). RESULTS: In all, 1753 patients <3 years of age had at least 2 deliveries of oral propranolol. In the healthy population, we observed 2 cardiovascular events (SMR = 2.8 [0-6.7]), 51 respiratory events (SMR = 1.7 [1.2-2.1]), and 3 metabolic events (SMR = 5.1 [0-10.9]). In the population with an underlying disease (mainly congenital heart disease), we observed 11 cardiovascular events leading to an SMR of 6.0 (2.5-9.6). SMRs were not significantly raised for respiratory or metabolic events in this "nonhealthy" population. CONCLUSIONS: In this study on a large continuous nationwide claims database, we confirm the safety profile of oral propranolol in healthy children to be good.