Survival following adjuvant trastuzumab-based treatment among older patients with HER2-positive early invasive breast cancer: A national population-based cohort study using routine data.

Background: Randomised controlled trials (RCTs) reported adjuvant trastuzumab-based treatment improved overall survival (OS) among patients with HER2-positive early invasive breast cancer (EIBC). Few RCTs included older patients or those with comorbidity/frailty. This study aimed to determine whether the effect of adjuvant trastuzumab-based treatment on survival outcomes varies by patient age and fitness, using national data from routine care.

Survival outcomes after breast cancer surgery among older women with early invasive breast cancer in England: population-based cohort study.

Background: This study assessed the influence of age, co-morbidity and frailty on 5-year survival outcomes after breast conservation surgery (BCS) with radiotherapy (RT) versus mastectomy (with or without RT) in women with early invasive breast cancer.

Methods: Women aged over 50 years with early invasive breast cancer diagnosed in England (2014-2019) who had breast surgery were identified from Cancer Registry data. Survival estimates were calculated from a flexible parametric survival model.

Mastectomy patterns among older women with early invasive breast cancer in England and Wales: A population-based cohort study.

Introduction: Older women with early invasive breast cancer (EIBC) are more likely to receive a mastectomy compared with younger women. This study assessed factors associated with receiving a mastectomy among older women with EIBC, with a particular focus on comorbidity and frailty.

Materials And Methods: Women diagnosed with EIBC (stages I-IIIa) aged ≥50 years from 2014 to 2019 in English and Welsh NHS organisations who received breast surgery were identified from cancer registration datasets linked to routine hospital data.

Evidence into practice: a national cohort study of NICE-recommended oncological drug therapy utilisation among women diagnosed with invasive breast cancer in England.

Background: Multiple drug treatments are approved for invasive breast cancer (IBC). We investigated uptake of NICE-recommended oncological drugs and variation by age, comorbidity burden and geographical region.

Methods: Women (aged 50+ years) diagnosed with IBC from 2014 to 2019, were identified from England Cancer Registry data and drug utilisation from Systemic Anti-Cancer Therapy data.

Completeness of endocrine therapy information in the Primary Care Prescription Database (PCPD) and secondary care treatment datasets: A national population-based cohort study using routine healthcare data.

Background: Endocrine therapy (ET) is a widely used treatment for breast cancer. In the UK, use is typically initiated in secondary care, with subsequent treatment in primary care. Evaluating use of ET depends on data sources containing accurate and complete information.

Concordance of cancer drug therapy information derived from routinely collected hospital admissions data and the Systemic Anti-Cancer Therapy (SACT) dataset, for older women diagnosed with early invasive breast cancer in England.

Background: Evaluating uptake of oncological treatments, and subsequent outcomes, depends on data sources containing accurate and complete information about cancer drug therapy (CDT). This study aimed to evaluate the consistency of CDT information in the Hospital Episode Statistics Admitted Patient Care (HES-APC) and Systemic Anti-Cancer Therapy (SACT) datasets for early invasive breast cancer (EIBC).

Methods: The study included women (50 + years) diagnosed with EIBC in England from 2014 to 2019 who had surgery within six months of diagnosis.

The association between guideline adherence, age and overall survival among women with non-metastatic breast cancer: A systematic review.

Introduction: Conformity with treatment guidelines should benefit patients. Studies have reported variation in adherence to breast cancer (BC) guidelines, particularly among older women. This study investigated (i) whether adherence to treatment guideline recommendations for women with non-metastatic BC improves overall survival (OS), (ii) whether that relationship varies by age.

The influence of age, comorbidity and frailty on treatment with surgery and systemic therapy in older women with operable triple negative breast cancer (TNBC) in England: A population-based cohort study.

Background: Surgery and chemotherapy use were studied among older women with early stage triple negative breast cancer (TNBC) in a population-based cohort.

Methods: Women aged ≥50 years with unilateral early (stage 1-3a) TNBC diagnosed in 2014-2017 were identified from English cancer registration data. Information on surgery and chemotherapy was from linked Hospital Episode Statistics and Systemic Anti-Cancer Therapy datasets, respectively.

Costs of Early Invasive Breast Cancer in England Using National Patient-Level Data.

Objectives: This study aimed to use patient-level data to provide up-to-date estimates of early invasive breast cancer care costs by stage in England and to explore to what extent these costs varied based on patients' ages and geographic regions.

Methods: This study identified women aged 50 years and older who had been diagnosed with early invasive breast cancer between January 1, 2014, and December 31, 2015, using linked cancer registrations and routine hospital data sets generated from the usual care for all National Health Service trusts in England. Cost estimates were derived from hospital records in Hospital Episodes Statistics with additional chemotherapy and radiotherapy information from the national data sets.

Construction of the secondary care administrative records frailty (SCARF) index and validation on older women with operable invasive breast cancer in England and Wales: a cohort study.

Objectives: Studies that use national datasets to evaluate the management of older women with breast cancer are often constrained by a lack of information on patient fitness. This study constructed a frailty index for use with secondary care administrative records and evaluated its ability to improve models of treatment patterns and overall survival in women with breast cancer.

Design: Retrospective cohort study.

Adding new experimental arms to randomised clinical trials: Impact on error rates.

Background: Experimental treatments pass through various stages of development. If a treatment passes through early-phase experiments, the investigators may want to assess it in a late-phase randomised controlled trial. An efficient way to do this is adding it as a new research arm to an ongoing trial while the existing research arms continue, a so-called multi-arm platform trial.

Initiation of adjuvant chemotherapy and trastuzumab for human epidermal growth receptor 2-positive early invasive breast cancer in a population-based cohort study of older women in England.

Background: Clinical guidance on recommended treatment for older patients with breast cancer is often ambiguous, particularly in the context of comorbidities and poor functional status. Older patients, aged 70 years and over, account for a substantial proportion of women with breast cancer yet are underrepresented in randomized controlled trials. This paper investigates the initiation of adjuvant chemotherapy and trastuzumab in older patients in routine care.

Addressing frailty in patients with breast cancer: A review of the literature.

Various studies have documented variation in the management of older patients with breast cancer, and some of this variation stems from different approaches to balancing the expected benefit of different treatments, with the ability of patients to tolerate them. Frailty is an emerging concept that can help to make clinical decisions for older patients more consistent, not least by providing a measure of 'biological' ageing. This would reduce reliance on 'chronological' age, which is not a reliable guide for decisions on the appropriate breast cancer care for older patients.

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness.

Background: Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources.

Objective: To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting.

Changing platforms without stopping the train: experiences of data management and data management systems when adapting platform protocols by adding and closing comparisons.

Background: There is limited research and literature on the data management challenges encountered in multi-arm, multi-stage platform and umbrella protocols. These trial designs allow both (1) seamless addition of new research comparisons and (2) early stopping of accrual to individual comparisons that do not show sufficient activity. FOCUS4 (colorectal cancer) and STAMPEDE (prostate cancer), run from the Medical Research Council Clinical Trials Unit (CTU) at UCL, are two leading UK examples of clinical trials implementing adaptive platform protocol designs.

Surgery and adjuvant radiotherapy for unilateral ductal carcinoma in situ (DCIS) in women aged over 70 years: A population based cohort study.

Background: There is little clinical evidence to guide treatment decisions for ductal carcinoma in situ (DCIS) in older women. This study evaluated how the management of DCIS in women aged 70 or more compared with women aged 50-69 in England and Wales.

Method: The study identified women aged ≥50 years with new unilateral DCIS diagnosed between 2014 and 2016 from linked cancer registration and routine hospital datasets for England and Wales.

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.

Background: Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.

Methods: We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK.

Leishmania donovani amastigotes mobilize organic and inorganic osmolytes during regulatory volume decrease.

The protozoan parasite Leishmania donovani encounters large fluctuations in osmolality as it cycles between its insect vector and human host. The flagellated promastigote exhibits regulatory volume responses involving organic and inorganic osmolytes, but little is known about volume regulation in the clinically relevant amastigote that multiplies within the parasitophorous vacuoles of mammalian host cells. Using a combination of morphological, X-ray microanalytical, and biochemical approaches we determined that non-motile amastigotes respond to hypotonic stress with (1) an amino acid and l-alanine-mediated regulatory volume decrease, and (2) a parallel release of Na+, K+, P (presumably as negatively charged phosphates), and subsequently Cl- from cytoplasm and the cell as a whole.