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.

Assessment of bone-targeting agents use in patients with bone metastasis from breast, lung or prostate cancer using structured and unstructured electronic health records from a regional UK-based hospital.

ObjectiveTo assess use of bone-targeting agents (BTA) in patients with confirmed bone metastases (BM) from breast cancer (BC), non-small cell lung cancer (NSCLC) or prostate cancer (PC). DESIGN: Retrospective cohort study. SETTING: Regional hospital-based oncology database of approximately 2 million patients in England. PARTICIPANTS: Patients aged ≥18 years with a diagnosis of BC, NSCLC or PC as well as BM between 1 January 2007 and 31 December 2018, with follow-up to 30 June 2020 or death; BM diagnosis ascertained from recorded medical codes and unstructured data using natural language processing (NLP). MAIN OUTCOMES MEASURES: Initiation or non-initiation of BTA following BM diagnosis, time from BM diagnosis to BTA initiation, time from first to last BTA, time from last BTA to death. RESULTS: This study included 559 BC, 894 NSCLC and 1013 PC with BM; median age (Q1-Q3) was 65 (52-76), 69 (62-77) and 75 (62-77) years, respectively. NLP identified BM diagnosis from unstructured data for 92% patients with BC, 92% patients with NSCLC and 95% patients with PC. Among patients with BC, NSCLC and PC with BM, 47%, 87% and 88% did not receive a BTA, and 53%, 13% and 12% received at least one BTA, starting a median 65 (27-167), 60 (28-162) and 610 (295-980) days after BM, respectively. Median (Q1-Q3) duration of BTA treatment was 481 (188-816), 89 (49-195) and 115 (53-193) days for patients with BC, NSCLC and PC. For those with a death record, median time from last BTA to death was 54 (26-109) for BC, 38 (17-98) for NSCLC and 112 (44-218) days for PC. CONCLUSION: In this study identifying BM diagnosis from both structured and unstructured data, a high proportion of patients did not receive a BTA. Unstructured data provide new insights on the real-world use of BTA.

Ovarian Real-World International Consortium (ORWIC): A multicentre, real-world analysis of epithelial ovarian cancer treatment and outcomes.

Introduction: Much drug development and published analysis for epithelial ovarian cancer (EOC) focuses on early-line treatment. Full sequences of treatment from diagnosis to death and the impact of later lines of therapy are rarely studied. We describe the establishment of an international network of cancer centers configured to compare real-world treatment pathways in UK, Portugal, Germany, South Korea, France and Romania (the Ovarian Real-World International Consortium; ORWIC). Methods: 3344 patients diagnosed with EOC (2012-2018) were analysed using a common data model and hub and spoke programming approach applied to existing electronic medical records. Consistent definition of line of therapy between sites and an efficient approach to analysis within the limitations of local information governance was achieved. Results: Median age of participants was 53-67 years old and 5-29% were ECOG >1. Between 62% and 84% of patients were diagnosed with late-stage disease (FIGO III-IV). Sites treating younger and fitter patients had higher rates of debulking surgery for those diagnosed at late stage than sites with older, more frail patients. At least 21% of patients treated with systemic anti-cancer therapy (SACT) had recurrent disease following second-line therapy (2L); up to 11 lines of SACT treatment were recorded for some patients. Platinum-based SACT was consistently used across sites at 1L, but choices at 2L varied, with hormone therapies commonly used in the UK and Portugal. The use (and type) of maintenance therapy following 1L also varied. Beyond 2L, there was little consensus between sites on treatment choice: trial compounds and unspecified combinations of other agents were common. Discussion: Specific treatment sequences are reported up to 4L and the establishment of this network facilitates future analysis of comparative outcomes per line of treatment with the aim of optimizing available options for patients with recurrent EOC. In particular, this real-world network can be used to assess the growing use of PARP inhibitors. The real-world optimization of advanced line treatment will be especially important for patients not usually eligible for involvement with clinical trials. The resources to enable this analysis to be implemented elsewhere are supplied and the network will seek to grow in coverage of further sites.

Treatment patterns and survival outcomes for patients with non-small cell lung cancer in the UK in the preimmunology era: a REAL-Oncology database analysis from the I-O Optimise initiative.

OBJECTIVES: To report characteristics, treatment and overall survival (OS) trends, by stage and pathology, of patients diagnosed with non-small cell lung cancer (NSCLC) at Leeds Teaching Hospital NHS Trust in 2007-2018. DESIGN: Retrospective cohort study based on electronic medical records. SETTING: Large NHS university hospital in Leeds. PARTICIPANTS: 3739 adult patients diagnosed with incident NSCLC from January 2007 to August 2017, followed up until March 2018. MAIN OUTCOME MEASURES: Patient characteristics at diagnosis, treatment patterns and OS. RESULTS: 34.3% of patients with NSCLC were clinically diagnosed (without pathological confirmation). Among patients with known pathology, 45.2% had non-squamous cell carcinoma (NSQ) and 33.3% had squamous cell carcinoma (SQ). The proportion of patients diagnosed at stage I increased (16.4%-27.7% in 2010-2017); those diagnosed at stage IV decreased (57.0%-39.1%). Surgery was the most common initial treatment for patients with pathologically confirmed stage I NSCLC. Use of radiotherapy alone increased over time in patients with clinically diagnosed stage I NSCLC (39.1%-60.3%); chemoradiation increased in patients with stage IIIA NSQ (21.6%-33.3%) and SQ (24.2%-31.9%). Initial treatment with systemic anticancer therapy (SACT) increased in patients with stages IIIB-IV NSQ (49.0%-67.5%); the proportion of untreated patients decreased (30.6%-15.0%). Median OS improved for patients diagnosed with stage I NSQ and SQ and stage IIIA NSQ over time. Median OS for patients with stages IIIB-IV NSQ and SQ remained stable, <10% patients were alive 3 years after diagnosis. Median OS for clinically diagnosed stages IIIB-IV patients was 1.2 months in both periods. CONCLUSIONS: OS for stage I and IIIA patients improved over time, likely due to increased use of stereotactic ablative radiation, surgery (stage I) and chemoradiation (stage IIIA). Conversely, OS outcomes remained poor for stage IIIB-IV patients despite increasing use of SACT for NSQ. Many patients with advanced-stage disease remained untreated.

Trends in the prescription of systemic anticancer therapy and mortality among patients with advanced non-small cell lung cancer: a real-world retrospective observational cohort study from the I-O optimise initiative.

OBJECTIVES: To assess how a decade of developments in systematic anticancer therapy (SACT) for advanced non-small cell lung cancer (NSCLC) affected overall survival (OS) in a large UK University Hospital. DESIGN: Real-world retrospective observational cohort study using existing data recorded in electronic medical records. SETTING: A large National Health Service (NHS) university teaching hospital serving 800 000 people living in a diverse metropolitan area of the UK. PARTICIPANTS: 2119 adults diagnosed with advanced NSCLC (tumour, node, metastasis stage IIIB or IV) between 2007 and 2017 at Leeds Teaching Hospitals NHS Trust. MAIN OUTCOMES AND MEASURES: OS following diagnosis and the analysis of factors associated with receiving SACT. RESULTS: Median OS for all participants was 2.9 months, increasing for the SACT-treated subcohort from 8.4 months (2007-2012) to 9.1 months (2013-2017) (p=0.02); 1-year OS increased from 33% to 39% over the same period for the SACT-treated group. Median OS for the untreated subcohort was 1.6 months in both time periods. Overall, 30.6% (648/2119) patients received SACT; treatment rates increased from 28.6% (338/1181) in 2007-2012 to 33.0% (310/938) in 2013-2017 (p=0.03). Age and performance status were independent predictors for SACT treatment; advanced age and higher performance status were associated with lower SACT treatment rates. CONCLUSION: Although developments in SACT during 2007-2017 correspond to some changes in survival for treated patients with advanced NSCLC, treatment rates remain low and the prognosis for all patients remains poor.

Current Treatment and Outcomes Benchmark for Locally Advanced or Metastatic Urothelial Cancer From a Large UK-Based Single Centre.

Objectives: To characterize treatment patterns and survival outcomes for patients with locally advanced or metastatic malignancy of the urothelial tract during a period immediately preceding the widespread use of immune checkpoint inhibitors in the UK. Patients and Methods: We retrospectively examined the electronic case notes of patients attending the Leeds Cancer Center, UK with locally advanced or metastatic urothelial carcinoma, receiving chemotherapy between January 2003 and March 2017. Patient characteristics, treatment patterns, and outcomes were collected. Summary and descriptive statistics were calculated for categorical and continuous variables as appropriate. The Kaplan-Meier method was used to estimate median survival and Cox regression proportional hazards model was used to explore relationships between clinical variables and outcome. Results: Two hundred and sixteen patients made up the study cohort, with a median age of 66 years (range: 35-83) and 72.7% being male. First-line treatment consisted of either a cisplatin- (44%) or carboplatin-based regimen (48%) in the majority of patients. Twenty seven percent of patients received a second-line of treatment (most commonly single-agent paclitaxel) following a first-line platinum containing regimen. Grade 4 neutropenia was observed in 19 and 27% of those treated with a first-line cisplatin- and carboplatin-based regimen, respectively. The median overall survival (mOS) of the study cohort was estimated to be 16.2 months (IQR: 10.6-28.3 months). Receipt by patients of cisplatin-based chemotherapy was associated with a longer mOS and this association persisted when survival analysis was adjusted for age, sex, performance status and presence of distant metastases. Conclusions: This study provides a useful benchmark for outcomes achieved in a real-world setting for patients with locally advanced or metastatic UC treated with chemotherapy in the immediate pre-immunotherapy era.

Systemic treatment of hormone receptor positive, human epidermal growth factor 2 negative metastatic breast cancer: retrospective analysis from Leeds Cancer Centre.

BACKGROUND: Study aimed to characterise treatment and outcomes for patients with hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (MBC) within a large regional cancer centre, as a benchmark for evaluating real-world impact of novel therapies. METHODS: Retrospective longitudinal cohort, using electronic patient records of adult females with a first diagnosis of HR+/HER2- MBC January 2012-March 2018. RESULTS: One hundred ninety-six women were identified with HR+/HER2- MBC. Median age was 67 years, 85.2% were post-menopausal and median time between primary diagnosis and metastasis was 5.4 years. Most (75.1%) patients received endocrine therapy as first line systemic treatment (1st LoT); use of 1st LoT chemotherapy halved between 2012 and 2017. Patients receiving 1st LoT chemotherapy were younger and more likely to have visceral metastasis (p < 0.01). Median OS was 29.5 months and significantly greater for patients with exclusively non-visceral metastasis (p < 0.01). The adjusted hazard ratio for death of patients with visceral (or CNS) metastasis was 1.91 relative to those with exclusively non-visceral metastasis. CONCLUSIONS: Diverse endocrine therapies predominate as 1st LoT for patients with HR+/HER2- MBC, chemotherapy being associated with more aggressive disease in younger patients, emphasising the importance of using effective and tolerable therapies early.

Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer.

BACKGROUND: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. METHODS: Patients were randomised (2 : 1) to IMM-101 (10 mg ml(-l) intradermally)+GEM (1000 mg m(-2) intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. RESULTS: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44-1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33-0.87, P=0.01). CONCLUSIONS: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.