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Background: Recruitment rates to rehabilitation trials are variable among cancer survivors, and deeper investigation into the causes for declining participation is needed. The aim of this study was to qualitatively explore the experiences of people with myeloma referred for autologous stem cell transplant who were approached to take part in a physiotherapist-led exercise trial but declined. Methods: Participants were asked to participate in this qualitative study after declining to participate in a trial conducted at a UK tertiary cancer center. Semi-structured interviews were conducted. Data was analyzed inductively using reflexive thematic analysis. Results: Interviews from 18 myeloma patients (56% male, mean age 62 years) were analyzed. Four themes were identified: 1) Traveling to the specialist center is challenging, not just logistically; 2) Individualized approach valued but recall of research information variable; 3) Being less active has profound impact yet ameliorative support is lacking; and 4) Common side-effects of treatment are expected and endured but personal impact underestimated and unaddressed. Conclusion: A number of barriers to participation were identified. Travel, a commonly cited reason for declining research participation, is more than a logistical issue for cancer survivors experiencing side-effects and the time burden of clinical appointments. Expectation or knowledge of the typical side-effects from myeloma and its treatment may lead to under-reporting of concerns to care providers, despite their impact upon daily activities and quality of life. Approaches used for research recruitment should consider the timing and consequences of ongoing cancer treatment to reduce potential barriers to participation. [ABSTRACT FROM AUTHOR]

Gastric malignancies will probably never attract the same attention as breast, prostate or lung carcinomas. Yet their prognosis is often bleak. But recent advances raise the prospect of transforming outcomes in this notoriously difficult‐to‐treat malignancy into a cancer manageable by precision medicine. [ABSTRACT FROM AUTHOR]

Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov , NCT02040272 , and is closed to new participants. Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3–30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0–33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6–37·4]), and the difference in restricted mean survival time at 2 years was –1·9 months (95% CI –3·4 to –0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895). [ABSTRACT FROM AUTHOR]

Featured Application: This opinion piece discusses the limitations of the current cytotoxic dosing methods and how advanced body measurement techniques could be used by oncology practitioners to determine cytotoxic chemotherapy dosages for patients, regardless of their body size. Within chemotherapy, estimates of a patient's body surface area (BSA) are used to calculate drug dosages. However, the use of BSA for calculating chemotherapy dosage has been heavily criticised in previous literature, with potentially significant implications for the effectiveness and toxicity of treatment. BSA has been found to be a poor indicator of optimal drug exposure that does not account for the complex processes of cytotoxic drug distribution and elimination. In addition, differences in BSA estimates between existing formulae have been shown to be so large that they can affect patients' mortality, particularly in patients with atypical body types. This uncertainty associated with BSA prediction may decrease the confidence of practitioners when determining chemotherapy dosages, particularly with regards to the risk of excess toxicity from over-dosing, or a reduced anti-cancer effect due to under-dosing. The use of national dose-banding in the UK may in some cases account for possible inaccuracies, but the threshold of variance in this case is small (+/−6%). Advanced body measurement techniques, utilising digital tools such as three-dimensional (3D) surface imaging, capture accurate external dimensions and detailed shape characteristics of the human body. Measures of body shape describe morphological variations that cannot be identified by traditional anthropometric techniques and improve the prediction of total body fat and distribution. It is our view that the use of advanced body measurement techniques can provide practitioners with tools for prescribing chemotherapy dosages that are valid for individuals, regardless of their body type. [ABSTRACT FROM AUTHOR]

Phyllodes tumours and breast sarcomas are uncommon tumours and their rarity poses significant challenges in diagnosis and management. This cross-sectional study was conducted to evaluate the multidisciplinary clinical practice for these tumours across the UK and Ireland, with the aim of identifying gaps in knowledge and providing direction for establishing national guidelines. An international survey was adapted and circulated to breast and/or sarcoma surgeons and oncologists in the UK and Ireland through national organisations. Multidisciplinary team (MDT) responses were analysed anonymously. Twenty-eight MDTs participated in this study, predominately from high-volume units (85.5%). Although only 43% of the surveyed units were part of a trust that holds a sarcoma MDT, 68% of units managed malignant phyllodes and angiosarcoma, whereas 64.5% managed soft-tissue sarcoma of the breast. Across all subtypes, axillary surgery was recommended by 14–21% of the MDTs and the most recommended resection margins for breast surgery were 'no tumour on ink' in benign phyllodes (39%) and 10 mm in the remaining subtypes (25–29%). Immediate breast reconstruction was supported by 11–18% of MDTs for breast sarcoma subtypes, whereas 36% and 32% advocated this approach in benign and borderline phyllodes tumours, respectively. Adjuvant radiotherapy and chemotherapy were recommended by up to 29% and 11% of the MDTs, respectively. The results of this study demonstrate a wide variation in clinical practice across the surveyed MDTs. As only 28 MDTs participated in our study, with under-representation from low-volume units, our results might be an underestimation of the variability in practice across the UK and Ireland. This multi-institutional study sheds light on controversial aspects in the management of phyllodes tumours and breast sarcoma, identifies the need for national guidelines to inform best practice, and calls for the centralisation of the management of breast sarcoma within specialist centres. • Considerable variation in the management of phyllodes tumours and breast sarcoma. • A proportion of breast sarcomas are managed in trusts that do not hold sarcoma MDT. • Lack of consensus on breast surgical margins and axillary surgery indications. • Diverse practice with regards to adjuvant radiotherapy and chemotherapy indications. • Urgent need for consensus-based guidelines and centralisation of management. [ABSTRACT FROM AUTHOR]

Simple Summary: Here, we report real-world treatment patterns and the overall survival of 104 patients with relapsing/refractory (R/R) MF who had received first-line therapy between 1984 and 2016. Our study found that second- and third-line therapies for R/RMF were heterogeneous, including systemic therapies, radiotherapy and topical therapies. More than two-thirds of patients at second- and third-line treatment received chemotherapy, and we observed that the median overall survival was longer with non-chemotherapy (not reached) vs. chemotherapy (6.5 years) treatment, suggesting that non-chemotherapy options may be more beneficial to patients. (1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lymphoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analyzed patient records (1984–2016) from 27 clinical sites in Europe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS) and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. The median (range) times from the start of first-line therapy to the first R/R MF and from the first to the second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radiotherapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). The median (95% confidence interval [CI]) OS from the diagnosis of the first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); the estimated median PFS (95% CI) from the time of the first R/R MF was 1.3 (1.0–2.1) years. (4) Conclusions: High rates of R/R disease were observed after second- and third-line treatments in this real-world cohort, with longer median OS in patients receiving non-chemotherapy treatment versus chemotherapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF. [ABSTRACT FROM AUTHOR]

Background: Real‐world evidence is increasingly used to guide treatment and regulatory decisions for non‐small cell lung cancer (NSCLC). Real‐world treatment patterns and clinical outcomes among patients with advanced/metastatic NSCLC in France, Germany, Italy, Spain, and the UK (EU5) were assessed. Methods: This retrospective physician‐completed patient chart review assessed treatment patterns (regimen, duration of treatment [DOT], time to discontinuation), and clinical outcomes (duration of response [DOR], progression‐free survival [PFS], and overall survival [OS]) of patients with stage IIIB/C or IV NSCLC who received pembrolizumab‐based first‐line induction chemotherapy. Results: Overall, 322 patients were included; at first‐line maintenance (1LM), 92% had stage IV NSCLC, 68% had nonsquamous histology, and 89% had no central nervous system (CNS)/brain metastasis. The two most common 1LM regimens were pembrolizumab monotherapy (76% overall) and pembrolizumab + pemetrexed (21% overall). Docetaxel monotherapy was the most common second‐line regimen in all countries except Germany (54% overall). For 1LM therapy, the overall median DOT and DOR were 5 and 10 months, respectively; PFS was 7 months and OS was 8 months. Germany had a longer duration of each outcome except for DOR which was longer in Spain. Clinical outcomes were generally poorer for patients with squamous histology and CNS/brain metastases. Conclusions: This study demonstrated differences in treatment patterns and clinical outcomes in NSCLC across the EU5 and patient subgroups. Improved survival was generally associated with response to first‐line therapy, nonsquamous histology, and CNS/brain metastases absence. These real‐world data provide valuable insights which may aid treatment decision‐making and clinical trial design. [ABSTRACT FROM AUTHOR]

Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19–27). We present the impact of these changes on patient outcomes. The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I–III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I–II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations. • Patients with stage I–III NSCLC had changes to treatment due to the COVID-19 pandemic. • Patients who had a change to radiotherapy had no increased risk of death or relapse. • Rates of toxicity were higher for patients who had a change to their radiotherapy. • Patients who had a change to their radiotherapy received a higher dose per fraction. [ABSTRACT FROM AUTHOR]

Background: Continuous androgen deprivation therapy ± first-generation non-steroidal antiandrogen was previously the standard-of-care for patients with metastatic castration-sensitive prostate cancer (mCSPC). Treatment intensification with novel hormonal therapy (NHT) or taxane chemotherapy is now approved and guideline-recommended for these patients. Methods: Physician-reported data on adult patients with mCSPC from the Adelphi Prostate Cancer Disease Specific Programme were analyzed descriptively. We evaluated real-world treatment trends for patients with mCSPC in 5 European countries (United Kingdom, France, Germany, Spain, and Italy) and the United States (US), looking at differences between patients initiating treatment in 2016-2018 and in 2019-2020. We also investigated treatment trends by ethnicity and insurance status in the US. Results: This study found that most patients with mCSPC do not receive treatment intensification. However, greater use of treatment intensification with NHT and taxane chemotherapy was observed in 2019-2020 than in 2016-2018 across 5 European countries. In the US, greater use of treatment intensification with NHT in 2019-2020 than in 2016-2018 was observed for all ethnicity groups and those with Medicare and commercial insurance status. Conclusions: As the number of patients with mCSPC who receive treatment intensification increases, more patients who progress to metastatic castration-resistant prostate cancer (mCRPC) will have been exposed to intensified treatments. Treatment options for patients with mCSPC and mCRPC overlap, suggesting that an unmet need will emerge for new therapies. Further studies are needed to understand optimal treatment sequencing in mCSPC and mCRPC. This study evaluated real-world metastatic castration-sensitive prostate cancer (mCSPC) treatment trends between 2016 to 2020 across a large, diverse patient population. The study also investigated whether treatment trends vary by ethnicity and insurance status. [ABSTRACT FROM AUTHOR]

The article focuses on the launch of the BOPA Digital SACT Verification Passport, a collaborative effort by BOPA and Tefogo, providing a standardized and digitally accessible accreditation record for oncology pharmacy training in the UK. Topics include the passport's benefits, such as ease of access and portability, its role in minimizing duplication of training efforts, and the collaborative achievements of over 100 pharmacists in establishing a unified approach.

Why you should read this article: • To enhance your understanding of the benefits of a nurse-led clinic for patients receiving PARP inhibitors and other systemic anticancer treatments • To recognise that those responsible for leading and delivering a nurse-led service require the relevant training and competencies • To appreciate the importance of creating a business case when setting up a nurse-led clinic Nurse-led chemotherapy clinics are an essential part of UK oncology services. The approval of oral poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors as maintenance treatment for people with platinum-responsive advanced ovarian cancer has provided patients with a new treatment option. However, due to their side effect profile, patients on these treatments require additional monitoring which can necessitate changes to the design of outpatient services. Nurse-led clinics designed specifically for patients receiving PARP inhibitors have been effective in addressing the additional monitoring requirements. This article provides a practical guide to developing a nurse-led clinic for patients receiving PARP inhibitors for advanced ovarian cancer and other systemic anticancer treatments. [ABSTRACT FROM AUTHOR]

Social scientists have argued that a treatment imperative shapes experiences of biomedicine. This is evident within oncology, where discourses of hope are tempered by persistent fears surrounding cancer. It is within this context that genomic decision‐making tools are entering routine care. These may indicate that a treatment is not appropriate for a particular disease profile. We draw on qualitative interviews and observations centred on gene expression profiling to consider the implications of this technique for the treatment imperative in early breast cancer. Influenced by sociological perspectives on medical technologies, we discuss how fallibilities of established tools have forged a space for the introduction of genomic testing into chemotherapy decision‐making. We demonstrate how high expectations shaped patients' interpretations of this tool as facilitating the 'right' treatment choice. We then unpick these accounts, highlighting the complex relationship between gene expression profiling and treatment decision‐making. We argue that anticipations for genomic testing to provide certainty in treatment choice must account for the sociocultural and organisational contexts in which it is used, including the powerful entwinement of chemotherapy and cancer. Our research has implications for sociological perspectives on treatment decision‐making and clinical expectations for genomic medicine to resolve the 'problem' of overtreatment. [ABSTRACT FROM AUTHOR]

Introduction: This study examined real-world data from patients who received eribulin for metastatic breast cancer (MBC) collected from 14 hospitals across the UK. Methods: Anonymized data were collected retrospectively from patients with MBC who had received eribulin. The data included the hormone-receptor status, histological diagnosis, age, prior chemotherapy, response to eribulin, progression-free survival (PFS), and overall survival (OS). Results: Among 577 patients analyzed, the median age was 56 years, and most patients (73%) were estrogen-receptor positive. The median OS was 288 days (95% confidence interval [CI]: 261–315), and the PFS was 117 days (95% CI: 105–129). The median OS was higher among older patients (≥65 vs. <65 years: 325 days [95% CI: 264–385] vs. 285 days [95% CI: 252–317]; p = 0.028). The median OS was also higher in patients who received eribulin after fewer prior lines of chemotherapy (≤2 vs. >2 prior: 328 days [95% CI: 264–385] vs. 264 days [95% CI: 229–298]; p = 0.042). Discussion/Conclusion: These retrospective data suggest that eribulin can be successfully used in older patients with MBC. Eribulin treatment was more effective in earlier-line settings, which, while predictable, supports consideration of eribulin as a second-line treatment option. [ABSTRACT FROM AUTHOR]

Introduction: This real-world study assessed the breast cancer susceptibility gene 1 or 2 mutation (BRCA1/2mut) status on treatment patterns, safety, and patient-reported outcomes (PROs) in women with human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) in the USA, the UK, and EU4 countries. Methods: Oncologists abstracted data from medical charts of adult women who presented with HER2− ABC from February to May 2015 and from March to July 2017. Data were collected using a physician-reported form and a patient-reported form, which included questions on breast cancer history/treatment and questions from PRO instruments (EuroQol 5-Dimensions 3-Levels [EQ-5D-3L], Brief Pain Inventory [BPI], European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core 30 and its breast cancer module). Results: In total, 742 oncologists provided data for 6,161 patients; 27.5% were tested for BRCA1/2mut. Out of the total patient population, 3.8% had BRCA1/2mut, 16.6% BRCA1/2 wild-type (BRCA1/2wt), and 79.5% were BRCA1/2 unknown (BRCA1/2unk). Hormone receptor-positive (HR+)/HER2− ABC was more frequent within the BRCA1/2wt versus BRCA1/2mut group and triple-negative breast cancer (TNBC) within the BRCA1/2mut versus BRCA1/2wt group. More patients with HR+/HER2− ABC with BRCA1/2mut received chemotherapy (with or without targeted or endocrine therapy) versus BRCA1/2wt (66.0% vs. 50.4%; p < 0.01); more patients had ≥1 AE (58.0% vs. 39.1%; p < 0.001). Among patients with BRCA1/2mut versus BRCA1/2wt, a significantly higher proportion had some problems or worse pain discomfort (p = 0.021) and anxiety/depression (p = 0.007) as measured by the EQ-5D-3L; role functioning (p < 0.01) and dyspnea (p < 0.05) measured by EORTC were worse with BRCA1/2mut. Pain scores by BPI were similar between groups. Conclusions: In patients with HER2− ABC in the real-world setting, more patients with BRCA1/2mut had TNBC; received chemotherapy; had >1 AE; and experienced increased discomfort, anxiety, and dyspnea and diminished role functioning versus patients with BRCA1/2wt. [ABSTRACT FROM AUTHOR]

Background. Randomized studies of neoadjuvant (NA) trastuzumab and pertuzumab combined with chemotherapy for HER2-positive breast cancers (BC) have reported pathological complete response (pCR) rates of 39 to 61%. This study aimed to determine the real-world efficacy and toxicity of NA trastuzumab and pertuzumab combined with chemotherapy in a UK tertiary referral cancer centre. Methods. HER2-positive early BC patients given neoadjuvant chemotherapy with trastuzumab and pertuzumab between October 2016 and February 2018 at our tertiary referral cancer centre were identified via pharmacy records. Clinico-pathological information, treatment regimens, treatment-emergent toxicities, operative details, and pathological responses and outcomes were recorded. Results. 78 female patients were identified; 2 had bilateral diseases and 48 of 78 (62%) were node positive at presentation. 55 of 80 (71%) tumours were ER-positive. PCR occurred in 37 of 78 (46.3%; 95% CI: 35.3–57.2%) patients. 14 of 23 (60.8%) patients with ER-negative tumours achieved pCR; 23 of 55 (41.8%) were ER-positive and 6 of 19 (31.6%) were ER-positive and PgR-positive. No cardiac toxicity was documented. Diarrhoea occurred in 53 of 72 (74%) patients. Grade 3–4 toxicity occurred in ≥2% patients. These were diarrhoea, fatigue, and infection. The Median follow up period was 45.2 months (95% CI 43.8–46.3) with 71 of 78 (91.0%) remaining disease-free and 72 of 78 (92.3%) alive. Estimated OS at 2 years 86% (95% CI: 75–99%). Conclusion. This data confirms the efficacy of neoadjuvant chemotherapy combined with dual HER2 directed therapy. While no cardiac toxicity was observed, diarrhoea occurred frequently. The low pCR rate observed in ER and PgR-positive BCs warrants further investigation and consideration of strategies to increase the pCR rate. [ABSTRACT FROM AUTHOR]

Background: Systemic anti-cancer treatments (SACTs) are high-risk medications with narrow therapeutic indexes and complex dosing used to treat many haematological and oncological cancers. SACT can interact with a variety of non-chemotherapy medications used by patients, thus leading to the potential ineffectiveness of treatment and/or significant side effects.1,2 A recent study suggests that 2% of hospitalisations of cancer patients arise as a consequence of drug interactions.3 However, data to define the incidence and severity of SACT interactions is less well defined, with the most recent systematic review citing limitations in the underpinning evidence base.4 Current practice involves a medicine reconciliation at the point of diagnosis, or when patients change regimens, conducted by the prescribing clinician and/or the validating pharmacist. While this serves to identify drug interactions on initiation of SACT, there is no provision for ongoing identification of interactions within the current service model. An audit was conducted to investigate this issue. Aim: To identify the incidence and severity of SACT: non-SACT drug interactions within a sample of cancer patients receiving ongoing treatment. Methodology: A retrospective, single-centre audit of patients receiving ongoing SACT within the preceding year was conducted. A sample of 10 patients per disease state was selected randomly using data captured within Chemocare (n = 100). Patients receiving a first cycle of SACT were excluded. Patients’ most recent, ongoing SACT treatment was identified via Chemocare and prescribed non-SACT treatments were identified using summary care records (SCRs) and electronic hospital records. Interactions were identified using Stock leys online and the University of Liverpool cancer drug interaction checker, and severity was defined using BNF classifications. Interactions were identified by two independent researchers, and differences were resolved through review by an independent third researcher. Results were analysed using Microsoft Excel®. Results: 52% of patients sampled experienced an interaction (Table 1), with 284 potential SACT: non-SACT interactions identified. Of these 3.5% were classified as mild, 39.1% were moderate and 57.4% were severe (Figure 1). A breakdown of these interactions per tumour site is provided in Figure 2. An outline of the five most commonly occurring interaction subtypes per severity grade is provided in Table 2. Discussion: This audit has highlighted a significant unmet clinical issue regarding the identification of SACT: non-SACT drug interactions for patients with ongoing treatments. The data presented is subject to a number of limitations. A small sample size may bias the results and provide an unrepresentative picture. This audit did not examine SACT: OTC or SACT: food interactions, the inclusion of these factors would likely increase the number of interactions identified.5 A larger scale project to identify SACT: non-SACT drug interactions, with the inclusion of patient interviews to establish the impact of interactions identified, may provide a more robust methodology for future research. This evidence suggests that cancer patients should receive more regular medicine reconciliations to identify interactions. Embedding pharmacy staff within clinics and on-day units would likely facilitate this process and increase the team’s ability to identify interactions, contributing to patient safety. A business case is being considered to support this development. [ABSTRACT FROM AUTHOR]

Objectives: To assess the cost-effectiveness of selective internal radiation therapy (SIRT) compared with sorafenib for the treatment of patients with advanced hepatocellular carcinoma in the United Kingdom, including a selected subgroup of patients who have been identified as benefiting from treatment with SIRT.Methods: A de novo economic model was developed comparing SIRT with sorafenib using data from two large randomized controlled trials. The model structure comprised a decision tree representing the outcome of the work-up procedure, transitioning into a 3-state partitioned survival model to project long-term survival outcomes. Cost-effectiveness in a post hoc defined subgroup with low tumor burden and good liver function was explored.Results: At list price, SIRT was predicted to be less costly but less effective than sorafenib with an estimated saving of £156 089 per quality-adjusted life-year forgone, with cost savings of £4589 and 0.029 fewer quality-adjusted life-years than sorafenib. Accounting for existing confidential discounts for sorafenib, two SIRTs were cost-effective at a £30 000 willingness-to-pay threshold compared with sorafenib when a discount for the technologies was introduced. In the subgroup with low tumor burden and good liver function, SIRT may be associated with greater survival benefits and cost savings.Conclusions: Accounting for confidential discounts, on average, SIRT technologies represent value for money in the whole advanced hepatocellular carcinoma population, being less effective but less costly than sorafenib. Results from a subgroup with low tumor burden and good liver function suggest that the cost-effectiveness of SIRTs may be maximized in this group, but further research is required to demonstrate the validity of effectiveness benefits. [ABSTRACT FROM AUTHOR]

• Patient-reported outcomes were assessed using EQ-5D and LCSS-Meso measures in CheckMate 743. • Nivolumab + ipilimumab maintained overall health status in patients vs chemo. • The risk of deterioration in symptoms was decreased with nivolumab + ipilimumab vs chemo. • Nivolumab + ipilimumab delayed time to definitive deterioration in quality-of-life vs chemo. • PRO data confirm clinical benefit of 1L nivolumab + ipilimumab vs chemo in unresectable MPM. In CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient-reported outcomes (PROs). Patients (N = 605) were randomized to nivolumab + ipilimumab or chemotherapy. Changes in disease-related symptom burden and health-related quality of life (HRQoL) were evaluated descriptively using the Lung Cancer Symptom Scale (LCSS)-Mesothelioma (Meso) average symptom burden index (ASBI), LCSS-Meso 3-item global index (3-IGI), 3-level EuroQol 5-dimensional (EQ-5D-3L) visual analog score (VAS), and EQ-5D-3L utility index. PROs were assessed at baseline and every 2 (nivolumab + ipilimumab) or 3 weeks (chemotherapy) through 12 weeks, every 6 weeks through 12 months, every 12 weeks thereafter, and at specified follow-ups. Mixed-effect model repeated measures (MMRM) and time to deterioration analyses were conducted. Completion rates were generally >80%. LCSS-Meso ASBI mean changes from baseline trended to improve over time with nivolumab + ipilimumab and deteriorate with chemotherapy, but did not meet clinically important difference thresholds [±10 score change]. EQ-5D-3L VAS mean scores improved over time with nivolumab + ipilimumab; by week 60, patients had scores consistent with United Kingdom normal population values. MMRM analyses favored nivolumab + ipilimumab for all individual symptoms except cough. Nivolumab + ipilimumab delayed time to definitive deterioration in HRQoL (hazard ratio 0.52 [95% confidence interval 0.36–0.74]) and showed a trend in symptom delay versus chemotherapy. Nivolumab + ipilimumab decreased the risk of deterioration in disease-related symptoms and HRQoL versus chemotherapy and maintained QoL in patients with unresectable MPM. [ABSTRACT FROM AUTHOR]

Objectives: Electrochemotherapy uses electric fields to facilitate the influx of chemotherapy into cancer cells, producing a targeted effect. For head and neck cancer, it is mainly used for palliation of non-skin-origin metastases. It is used infrequently in the UK. This paper presents our experience and a UK survey to identify its frequency of use. Methods: Between 2016 and 2019, a prospective database was created and reviewed. Only patients with non-skin-origin metastatic head and neck cancer, with no other palliative options, were included. Survival length, complications and symptomatic benefit were assessed. The survey was conducted via e-mail. Results: Five patients were included: three with squamous cell carcinoma, one with esthesioneuroblastoma and one with hepatocellular carcinoma. Survival ranged from 1 month to over 20 months. Minor complications were seen. Only 15 out of 69 UK head and neck multidisciplinary teams offer electrochemotherapy. Conclusion: Electrochemotherapy is a well-tolerated adjunct to standard palliation of metastatic head and neck cancer, and is offered by a limited number of UK multidisciplinary teams. [ABSTRACT FROM AUTHOR]

Summary: Patients with haematological malignancies have a high risk of severe infection and death from SARS‐CoV‐2. In this prospective observational study, we investigated the impact of cancer type, disease activity, and treatment in 877 unvaccinated UK patients with SARS‐CoV‐2 infection and active haematological cancer. The primary end‐point was all‐cause mortality. In a multivariate analysis adjusted for age, sex and comorbidities, the highest mortality was in patients with acute leukaemia [odds ratio (OR) = 1·73, 95% confidence interval (CI) 1·1–2·72, P = 0·017] and myeloma (OR 1·3, 95% CI 0·96–1·76, P = 0·08). Having uncontrolled cancer (newly diagnosed awaiting treatment as well as relapsed or progressive disease) was associated with increased mortality risk (OR = 2·45, 95% CI 1·09–5·5, P = 0·03), as was receiving second or beyond line of treatment (OR = 1·7, 95% CI 1·08–2·67, P = 0·023). We found no association between recent cytotoxic chemotherapy or anti‐CD19/anti‐CD20 treatment and increased risk of death within the limitations of the cohort size. Therefore, disease control is an important factor predicting mortality in the context of SARS‐CoV‐2 infection alongside the possible risks of therapies such as cytotoxic treatment or anti‐CD19/anti‐CD20 treatments. [ABSTRACT FROM AUTHOR]

In the community there are about 200 000 people with a stoma. Some of these may have been performed as a palliative procedure to relieve a bowel obstruction, for example. Alternatively, the condition of the patient may have altered. A person with a stoma may, for many reasons, be approaching the end of life. There are a number of stoma-related issues that can occur at the end of life as a result of cancer treatment, such as skin around the stoma being damaged as a result of chemotherapy or changes in weight. In the palliative setting, patients may no longer be able to independently care for their stoma and may require assistance from the community nurse. Input from the community nurse may include information on changing stool consistency, as a result of disease progression or cancer treatment. Alternatively, nursing input might be necessary to train carers to perform stoma care. Community nurses can also provide knowledge to patients to improve understanding and decrease anxiety at the end of life. [ABSTRACT FROM AUTHOR]

Background: Guideline‐recommended antiemetic prophylaxis improves nausea and vomiting control in most patients undergoing chemotherapy. Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO) antiemetic guidelines recommend prophylaxis with a neurokinin‐1 receptor antagonist (NK1RA), a 5‐hydroxytryptamine‐3 receptor antagonist (5‐HT3RA), and dexamethasone for patients receiving highly emetogenic chemotherapy (HEC), including anthracycline‐cyclophosphamide (AC)‐ and carboplatin (considered moderately emetogenic chemotherapy)‐based chemotherapy. Here, we analyze the use of NK1RA–5‐HT3RA–dexamethasone for antiemetic prophylaxis associated with HEC and carboplatin. Methods: The data source was the Global Oncology Monitor (Ipsos Healthcare). Geographically representative physicians from France, Germany, Italy, Spain, and the U.K. were screened for treatment involvement and number of patients treated per month. Patients' data from January to December 2018 were collected from medical charts and extrapolated on the basis of the total number of physicians who prescribe chemotherapy. The emetic risk of chemotherapy was classified per MASCC/ESMO guidelines. Results: Data from 45,324 chemotherapy‐treated patients were collected, representing a total extrapolated prevalence of 1,394,848 chemotherapy treatments included in the analysis. NK1RAs were used in 45%, 42%, and 19% of patients receiving cisplatin‐, AC‐, and carboplatin‐based chemotherapy, respectively; 18%, 24%, and 7% received the guideline‐recommended NK1RA–5‐HT3RA–dexamethasone combination; no antiemetics were prescribed for 12% of the treatments. Often, physicians' perception of the emetic risk of chemotherapy did not follow MASCC/ESMO guideline classification. Conclusion: Low adherence to antiemetic guidelines was revealed in clinical practice in five European countries, with 15% of all HEC‐/carboplatin‐based treatments receiving guideline‐recommended NK1RA–5‐HT3RA–dexamethasone prophylaxis and 12% of them receiving no antiemetics. New strategies for improving guideline adherence are urgently needed. Implications for Practice: Despite recent advances in antiemetic therapy, a substantial proportion of patients experience nausea and vomiting associated with chemotherapy in daily clinical practice. Antiemetic guidelines aim at prevention of chemotherapy‐induced nausea and vomiting (CINV), and guideline‐consistent antiemetic therapy can effectively prevent vomiting and, to a lesser extent, nausea in most patients with cancer. This study reports low adherence to antiemetic guidelines in the highly emetogenic chemotherapy setting in daily clinical practice across five European countries. Opportunity exists to increase adherence to antiemetic guideline recommendations. Implementation of strategies to facilitate guideline adherence can potentially improve CINV control. Adherence to antiemetic guidelines is associated with improved control of chemotherapy‐induced nausea and vomiting. This article analyzes the use of guideline‐recommended NK1RA‐based regimens for antiemetic prophylaxis of highly emetogenic chemotherapy and carboplatin regimens in real‐world clinical practice across Europe. [ABSTRACT FROM AUTHOR]

Aim: Delay to closure of ileostomy following anterior resection for rectal cancer may impair postoperative bowel function and quality of life. We analysed time to ileostomy closure across the UK and investigated factors delaying closure. Methods: For the retrospective cohort we assessed time to closure and incidence of non‐closure for patients who underwent anterior resection with defunctioning ileostomy during 2015. Multivariate linear/Cox regression analyses were performed. For the prospective cohort we captured patients undergoing ileostomy closure during a 3‐month period in 2018 to validate retrospective findings. Results: The retrospective cohort involved 788 patients of whom 669 (84.9%) had bowel continuity restored, median time to closure 259 days. Recognized factors associated with delay and risk of non‐closure included anastomotic leak (hazard ratio [HR] 3.65, 2.61–5.08), chemotherapy (HR 2.62, 2.17–3.15) and cancer progression (HR 2.05, 1.62–2.58). Crucially, specific aspects of the surgical pathway were associated with time to closure; for example, waiting list entry prior to outpatient clinic review/imaging was associated with an estimated 133‐day shorter interval to closure (P < 0.001). In the prospective cohort 288 patients underwent closure, at a median of 271 days. Chemotherapy use and cancer progression were associated with delay to closure while listing for surgery prior to clinic and imaging was associated with an estimated shorter interval to closure of 168 days (P = 0.008). Conclusions: Delays to closure of ileostomy are common in the UK. Listing patients for surgery only after follow‐up outpatient appointment, imaging or chemotherapy delays closure. Findings will inform consensus guidelines towards an optimum treatment pathway to reduce delay and improve post‐closure quality of life. [ABSTRACT FROM AUTHOR]

Purpose: Taxane chemotherapy is commonly used in the management of breast cancer. Hair loss (alopecia) is an expected side effect which may have a significant effect on quality of life. Alopecia is normally temporary but permanent chemotherapy‐induced alopecia (pCIA) is increasingly recognised especially following docetaxel chemotherapy. However, the prevalence following docetaxel is not well understood and there is no published literature for paclitaxel chemotherapy. The aim of this study is to investigate the prevalence and patterns of pCIA resulting from both docetaxel and paclitaxel chemotherapy at two tertiary UK cancer centres. Methods: In collaboration between Clatterbridge Cancer Centre and The Christie NHS Foundation Trusts, a retrospective survey was conducted for breast cancer patients who had received taxane chemotherapy in the neoadjuvant and adjuvant settings. Patients who had concluded chemotherapy at least a year previously were contacted by post and invited to participate by completing a questionnaire and returning it to their treatment centre. Data collected included the incidence and pattern of pCIA using the Savin pictorial hair loss scale, and the methods used by patients to manage it. Fisher's exact test was used to compare pCIA between the docetaxel and paclitaxel cohorts. Results: 383 patients responded to the survey (a 63.3% overall response rate). These comprised 245 patients receiving docetaxel and 138 patients treated with paclitaxel. pCIA was reported by 23.3% of patients receiving docetaxel and 10.1% paclitaxel (p < 0.01). Overall 16.7% of patients in both groups reported the ongoing use of products or appliances such as wigs to camouflage their pCIA. In the docetaxel group, pCIA appeared to be more frequent in post‐menopausal women than peri‐ or pre‐menopausal women (37.8%, 12.3% and 19.6% respectively [Chi‐square test p < 0.01]). Also in the docetaxel group, there appeared to be a trend for more severe scalp alopecia when the patient also received an aromatase inhibitor (AI) or tamoxifen and this difference was most marked in those who had received both an AI and tamoxifen as components of their treatment regime (p = 0.04). The use of scalp cooling was only recorded in the Christie paclitaxel group (n = 12). Of these 12 patients, 83.3% reported no hair loss. While overall rates of permanent eyebrow, eyelash and nostril hair loss were low, this pattern of hair loss appeared more frequent in the paclitaxel than the docetaxel group 4.3% vs. 1.8% (p = 0.29). Conclusions: Both docetaxel and paclitaxel may cause permanent scalp hair loss, but it is significantly more prevalent with docetaxel compared with paclitaxel. Implications for Cancer Survivors: Clinicians should counsel patients regarding the risk of permanent alopecia prior to embarking upon taxane chemotherapy and routinely offer scalp cooling if available. More research is required to understand the pathobiology of this important and previously under recognised long‐term side effect to enable more active preventive and management approaches. [ABSTRACT FROM AUTHOR]

Background: Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer.Methods: The ABC-06 clinical trial was a phase 3, open-label, randomised trial done in 20 sites with expertise in managing biliary tract cancer across the UK. Adult patients (aged ≥18 years) who had histologically or cytologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line cisplatin and gemcitabine chemotherapy and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (1:1) centrally to active symptom control (ASC) and FOLFOX or ASC alone. FOLFOX chemotherapy was administered intravenously every 2 weeks for a maximum of 12 cycles (oxaliplatin 85 mg/m2, L-folinic acid 175 mg [or folinic acid 350 mg], fluorouracil 400 mg/m2 [bolus], and fluorouracil 2400 mg/m2 as a 46-h continuous intravenous infusion). Randomisation was done following a minimisation algorithm using platinum sensitivity, serum albumin concentration, and stage as stratification factors. The primary endpoint was overall survival, assessed in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. The study is complete and the final results are reported. This trial is registered with ClinicalTrials.gov, NCT01926236, and EudraCT, 2013-001812-30.Findings: Between March 27, 2014, and Jan 4, 2018, 162 patients were enrolled and randomly assigned to ASC plus FOLFOX (n=81) or ASC alone (n=81). Median follow-up was 21·7 months (IQR 17·2-30·8). Overall survival was significantly longer in the ASC plus FOLFOX group than in the ASC alone group, with a median overall survival of 6·2 months (95% CI 5·4-7·6) in the ASC plus FOLFOX group versus 5·3 months (4·1-5·8) in the ASC alone group (adjusted hazard ratio 0·69 [95% CI 0·50-0·97]; p=0·031). The overall survival rate in the ASC alone group was 35·5% (95% CI 25·2-46·0) at 6 months and 11·4% (5·6-19·5) at 12 months, compared with 50·6% (39·3-60·9) at 6 months and 25·9% (17·0-35·8) at 12 months in the ASC plus FOLFOX group. Grade 3-5 adverse events were reported in 42 (52%) of 81 patients in the ASC alone group and 56 (69%) of 81 patients in the ASC plus FOLFOX group, including three chemotherapy-related deaths (one each due to infection, acute kidney injury, and febrile neutropenia). The most frequently reported grade 3-5 FOLFOX-related adverse events were neutropenia (ten [12%] patients), fatigue or lethargy (nine [11%] patients), and infection (eight [10%] patients).Interpretation: The addition of FOLFOX to ASC improved median overall survival in patients with advanced biliary tract cancer after progression on cisplatin and gemcitabine, with a clinically meaningful increase in 6-month and 12-month overall survival rates. To our knowledge, this trial is the first prospective, randomised study providing reliable, high-quality evidence to allow an informed discussion with patients of the potential benefits and risks from second-line FOLFOX chemotherapy in advanced biliary tract cancer. Based on these findings, FOLFOX should become standard-of-care chemotherapy in second-line treatment for advanced biliary tract cancer and the reference regimen for further clinical trials.Funding: Cancer Research UK, StandUpToCancer, AMMF (The UK Cholangiocarcinoma Charity), and The Christie Charity, with additional funding from The Cholangiocarcinoma Foundation and the Conquer Cancer Foundation Young Investigator Award for translational research. [ABSTRACT FROM AUTHOR]

Anthracycline chemotherapy administered via a peripheral cannula results in severe anthracycline chemotherapy-induced phlebitis (ACIP) in about 20–30% of patients. Administering chemotherapy via a central venous catheter (CVC) prevents ACIP. However, CVCs are associated with an increased risk of thrombosis and sepsis. Our aim was to identify risk factors associated with severe ACIP and to provide evidence about the individual risk of developing symptoms. A prospective observational study of 263 women with breast cancer receiving peripheral administration of anthracycline chemotherapy at a UK cancer centre was conducted between May 2016 and January 2018. Data were collected at baseline and every 3 weeks following each chemotherapy treatment, using both healthcare professional- and participant-reported symptom assessments. After three cycles of chemotherapy, 27% of participants experienced severe ACIP. Factors associated with symptom severity were identified as: arm used for chemotherapy administration, epirubicin dose, age, pre-existing hypertension, comorbidity, ethnic group and pain during chemotherapy administration. The sequence of arm used for chemotherapy administration was the single most significant factor (P < 0.001). When alternating arms were used no other risk factor was influential. Where alternating arms were not used, younger age and higher dose were associated with higher-grade symptoms, with age being more influential than dose. The cumulative effect of increasing symptom severity with repeated cycles was also identified (P < 0.001). It is recommended that a CVC is not routinely required for women with breast cancer who have not undergone an axillary node clearance and receive chemotherapy in alternate arms. The need for a CVC for women who are planned to receive all anthracycline chemotherapy cycles in the same arm should be assessed in the light of peripheral venous access assessment and the key risk factors of age, dose and number of cycles. • Peripheral administration of anthracycline chemotherapy can result in phlebitis. • Phlebitis severity increases with the number of cycles administered. • After three cycles of epirubicin 27% of patients experienced high-grade symptoms. • Alternating arms for administration significantly reduces the risk of phlebitis. • Younger age and higher doses are key risk factors for anthracycline phlebitis. [ABSTRACT FROM AUTHOR]

Objective: There are limited data on the efficacy and tolerability of VCD chemotherapy in transplant‐non‐eligible (TNE) newly diagnosed myeloma (NDMM) patients. In this retrospective study, we set out to evaluate this triplet combination in this setting across Thames Valley Cancer Network (UK). Methods: The primary end point was overall response rate (ORR). Secondary outcomes included event‐free survival (EFS), overall survival (OS) and adverse events (AEs). Results: In a total cohort of 158 patients, ORR for total cohort was 72.1%. Median EFS was 10.5 months, and for subgroups by age (<75:11.7 vs ≥75:10.3 months, P =.124), by Charlson Co‐morbidity Index (CCI) (<5:11.1 vs ≥5:8.2 months, P =.345). The 4‐month landmark analysis showed the following median EFS results: by cumulative bortezomib dose (≥26 mg/m2: 9.0 months vs <26 mg/m2: 6.4, P =.13), by cumulative cyclophosphamide dose (≥7000 mg: 9.2 vs <7000 mg: 7.0 months, P =.02) and by cumulative dexamethasone dose (>600 mg: 7.8 vs ≤600 mg: 8.3 months, P =.665). Median OS was 46.9 months. The incidence rate of AE was as follows: any grade (76.8%), ≥G3 (27.1%), ≥G3 haematological AEs (7.9%), any grade infections (31.1%) and ≥G3 infections (11.9%). Conclusion: This study demonstrated a good ORR achieved from fixed duration VCD, which was reasonably well tolerated. This was followed by modest median EFS. We envisage that the latter may be improved in this patient group with the use of a higher cumulative bortezomib dose (≥26 mg/m2) which showed a trend for improved EFS although without statistical significance (P =.13), and with the use of a higher cumulative cyclophosphamide doses (≥7000 mg, P =.02), subject to tolerability and close monitoring. [ABSTRACT FROM AUTHOR]

Older patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study. A prospective, multicentre, observational study of EBC patients ≥70 years old was conducted in 2013–2018 at 56 UK hospitals. Demographics, patient, tumour characteristics, treatments and adverse events were recorded. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires (EORTC-QLQ) C30, BR23 and ELD 15 plus the Euroqol-5D (eq-5d) over 24 months and analysed at each time point using baseline adjusted linear regression analysis and propensity score-matching. Three thousand and four hundred sixteen patients were enrolled in the study; 1520 patients undergoing surgery and who had high-risk EBC were included in this analysis. 376/1520 (24.7%) received chemotherapy. At 6 months, chemotherapy had a significant negative impact in several EORTC-QLQ-C30 domains, including global health score, physical, role, social functioning, cognition, fatigue, nausea/vomiting, dyspnoea, appetite loss, diarrhoea and constipation. Similar trends were documented on other scales (EORTC-QLQ-BR23, EORTC-QLQ-ELD15 and EQ-5D-5L). Its impact was no longer significant at 18–24 months in unmatched and matched cohorts. The negative impact of chemotherapy on quality-of-life is clinically and statistically significant at 6 months but resolves by 18 months, which is crucial to inform decision-making for older patients contemplating chemotherapy. 46099296. • This is a multicentre, cohort study of 3416 women (aged >70 years) with breast cancer. • In older women with high-risk, early breast cancer, chemotherapy reduces quality of life. • The relevant affected domains include cognition, fatigue, physical, role and social functioning. • Chemotherapy QoL impacts are transient and largely resolve completely by 18–24 months. [ABSTRACT FROM AUTHOR]

Background: Hemophagocyti.c lymphohistiocytosis (HLH) is a rare and severe disorder characterized by abnormal activation of the immune system. Primary HLH causes prolonged fever, spleen and liver enlargement, and organ dysfunction, usually in infancy and early childhood and is fatal if left untreated. As effective treatment options emerge, such as emapalumab-lzsg, Health Technology Assessment bodies around the world will assess them in terms of cost-effectiveness. This study was designed to estimate quality of life weights (utilities) for such analyses. Methods: Vignettes were developed describing HLH treatment related health states. Health states included active HLH, HLH plus neurological symptoms, receiving chemotherapy, undergoing stem cell transplant (SCT), graft versus host disease (GVHD), cure and end of life care. The vignettes were based on information from in depth interviews with clinical specialists; and qualitative research with four parents of children with primary HLH aged between 1 and 18 years old. The vignettes were then assessed in time trade off (TTO) interviews with members of the UK general public in one on one face to face interviews with trained, experienced interviewers. Preference data were analysed using the generalised estimating equations framework. Results: Detailed qualitative data captured the substantial burden of this disease for young children. One hundred participants completed the TTO interviews. The utility score for Active HLH was estimated as 0.32 (95% CI, 0.24 to 0.39). Values for other states were HLH plus neurological symptoms (0.27, 95%CI 0.18–0.35), receiving chemotherapy (0.26, 95%CI 0.17–0.34), undergoing SCT (0.18, 95%CI 0.07–0.28), GVHD (0.07, 95%CI -0.04-0.17), cure (0.72, 95%CI 0.67–0.77) and end of life care (− 0.17, 95%CI -0.27- -0.07). Conclusions: This study has estimated utility weights for seven different HLH related states which are based on detailed input from carers and physicians and have good face validity. There are few other options for collecting these data in an ultra-rare setting. [ABSTRACT FROM AUTHOR]

Objective: Platinum-based chemotherapy drugs are associated with substantial ototoxicity. The hearing of children treated with these drugs should be closely monitored. Method: A questionnaire was sent out to the 19 audiology departments associated with national paediatric cancer specialist centres in the UK looking at current practice in ototoxicity monitoring. Results: Responses were received from 17 of 19 centres (89 per cent). All offered some form of audiometric monitoring service. Extended high-frequency testing (9–20 kHz) was only utilised by 7 services (29 per cent). A majority of respondents were reluctant to consider self-test devices in paediatric ototoxicity monitoring (n = 9; 53 per cent). Provision of long-term audiological follow up is sporadic with only 4 (23 per cent) respondents keeping all children with normal hearing under review once treatment is completed. Conclusion: While some good practice in paediatric ototoxicity was identified, opportunities exist to improve clinical practice and protocols, promote multidisciplinary team working and to utilise technologies such as extended high frequency and self-test audiometry. [ABSTRACT FROM AUTHOR]

More than one quarter (28%) of the 350,000 people diagnosed with cancer every year in the UK undergo chemotherapy, according to Cancer Research UK data. [ABSTRACT FROM AUTHOR]

Real-world evidence of radium 223 (Ra-223) for the treatment of men with metastatic castration-resistant prostate cancer is emerging. In this prospective single-centre service evaluation, we report for the first time in the UK, real-world quality of life (QoL) and survival outcomes, including the sequencing impact, in 228 treated patients. We aim to share our 5-year experience on how to optimise Ra-223 treatment. Patients who received Ra-223 therapy between 2014 and 2018 at the Northern Centre for Cancer Care, Newcastle upon Tyne, UK were included in this evaluation. Demographics, clinical characteristics, blood parameters, treatment sequencing and QoL data using abbreviated Functional Assessment of Cancer Therapy-Prostate questionnaires were prospectively collected and analysed. In total, 228 patients were included; median age 72 years (51–87). The medium overall survival was 11.1 months. Overall survival in post-chemotherapy and chemotherapy-naïve patients was 8.1 and 12.3 months, respectively (P = 0.02, hazard ratio 1.52, 95% confidence interval 1.06–2.17); in pre-enzalutamide and post-enzalutamide patients was 11.3 and 10.4 months, respectively (P = 0.65, hazard ratio 0.92, 95% confidence interval 0.63–1.33); in pre-abiraterone and prednisolone and post-abiraterone and prednisolone patients was 11.8 and 10.5 months, respectively (P = 0.08, hazard ratio 0.74, 95% confidence interval 0.51–1.06); in this latter group, the fracture rate was 24% (15/63). QoL post Ra-223 (n = 101 evaluated) showed that pain scores improved in 54%, there was no change in 17% and pain scores worsened in 30% of treated patients. Overall QoL scores showed a similar trend. QoL was not significantly associated with overall survival. Ra-223 palliates pain and improves disease-related QoL in most patients in the real-world setting. Our survival outcome is comparable with other real-world studies. Chemotherapy-naïve patients seemed to have better survival than those who received prior chemotherapy. No significant survival differences were observed between pre- and post-abiraterone and prednisolone or enzalutamide patients. The fracture rate in the post-abiraterone and prednisolone group seemed to be high. Bone health evaluation and protection should be incorporated as standard of care. • Radium 223 (Ra-223) palliates pain and improves disease-related quality of life (QoL) in most treated patients in the real-world setting. • Post Ra-223 therapy, prostate-specific antigen (PSA) reduction (≥30 %) is a better predictor than ALP reduction (≥30 %) for QoL improvement. • Chemotherapy-naïve patients seemed to have a better survival outcome than those who received chemotherapy prior to Ra-223. • Compared with ERA223 control cohort (placebo+ abiraterone and predinisolone), fracture rate remains elevated in men treated with Ra-223 sequentially post-abiraterone and prednislone. • Fitness but not age was significant in predicting better survival outcome. [ABSTRACT FROM AUTHOR]

Objective: To determine patterns of nurse-patient communication in fulfilling patients' informational/psychosocial needs, effects of longer consultation/operational aspects on person-centred care experiences.Methods: Mixed-method design; secondary analysis of transcripts of nurse-patient communication within nurse-led chemotherapy clinics in UK [3]. Purposive sampling (13 nurses); non-participant observations (61 consultations). Qualitative content analysis of audio-recorded transcripts. Quantitative analysis using the Medical Interview Aural Rating Scale [14] to compare mean differences in the number of cues and level of responding using one-way ANOVA, and correlational analyses of discursive spaces.Results: Nurses responded positively to informational cues, but not psychosocial cues. Longer consultations associated with more informational and psychosocial cues (p <  .0001), but not nurses' cue-responding behaviours. Four main themes emerged: challenges/opportunities for person-centred communication in biomedical contexts; patients' "life world" versus the "medical world"; three-way communication: nurse, patient and family; implications of continuity of care.Conclusions: The challenges/opportunities for cue-responding in nurse-led chemotherapy clinics were evident for informational and psychosocial support of patients. Shifting from a biomedical to biopsychosocial focus is difficult.Practice Implications: Further evaluation is needed to integrate biopsychosocial elements into communication education/training. Careful planning is required to ensure continuity and effective use of time for person-centred care. [ABSTRACT FROM AUTHOR]

Background: Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation is widespread, although evidence that it improves outcomes is lacking and there exist concerns about morbidity. The impact of TACE on outcomes after transplantation was evaluated in this study. Methods: Patients with HCC who had liver transplantation in the UK were identified, and stratified according to whether they received TACE between 2006 and 2016. Cox regression methods were used to estimate hazard ratios (HRs) for death and graft failure after transplantation adjusted for donor and recipient characteristics. Results: In total, 385 of 968 patients (39·8 per cent) received TACE. Five‐year patient survival after transplantation was similar in those who had or had not received TACE: 75·2 (95 per cent c.i. 68·8 to 80·5) and 75·0 (70·5 to 78·8) per cent respectively. After adjustment for donor and recipient characteristics, there were no differences in mortality (HR 0·96, 95 per cent c.i. 0·67 to 1·38; P = 0·821) or graft failure (HR 1·01, 0·73 to 1·40; P = 0·964). The number of TACE treatments (2 or more versus 1: HR 0·97, 0·61 to 1·55; P = 0·903) or the time of death after transplantation (within or after 90 days; P = 0·291) did not alter the outcome. The incidence of hepatic artery thrombosis was low in those who had or had not received TACE (1·3 and 2·4 per cent respectively; P = 0·235). Conclusion: TACE delivered to patients with HCC before liver transplant did not affect complications, patient death or graft failure after transplantation. [ABSTRACT FROM AUTHOR]

The Christie NHS Foundation Trust is a leader in adapting patient care in response to treatment advances and new patient-centred care/efficiency initiatives. Due to extended waiting times in cancer clinics, The Christie developed an at-home treatment service to help reduce the pressure on clinics and improve patient experience. This article provides a detailed examination of the requirements necessary to successfully develop a home service for the delivery of systemic anticancer treatment. The authors discuss the criteria used to identify suitable at-home treatments, as well as necessary resources and equipment. The success of the Christie at Home service was examined using a patient survey to assess the standard of this care. Details are given regarding the challenges of implementing a homecare service and potential future challenges. As an example, systemic treatment with eribulin as a 'Christie at Home' therapy demonstrates the practicalities of introduction of new therapies in a homecare service. [ABSTRACT FROM AUTHOR]

Background: Metastatic urothelial cancer (UC) is the eighth most common cause of cancer death in the UK. Standard first-line treatment, for most patients, is cytotoxic chemotherapy. Although UC is initially sensitive to chemotherapy, relapse is almost inevitable and outcomes are poor; median overall survival is 8 months. Therefore, there is an urgent need for novel therapies to improve outcomes for this patient group.Methods: ATLANTIS is a randomised phase II umbrella-design screening trial of maintenance therapy in biomarker-defined subgroups of patients with advanced UC. The primary end point is progression-free survival, and the study involves over 30 UK cancer centres.Discussion: ATLANTIS is the first study in the UK to employ a precision-medicine approach to patients with UC for maintenance treatment. Agents with a positive efficacy signal will proceed to randomised phase III trials to confirm the activity of novel, biologically stratified therapies in UC.Registration: ATLANTIS trial EudraCT number 2015-003249-25. ISRCTN25859465. [ABSTRACT FROM AUTHOR]

Background: Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs.Methods: We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve [AUC]4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants.Findings: Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30-0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0-47·5). 3-year event-free estimates were 71% (95% CI 61-78) and 46% (36-56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported.Interpretation: Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population.Funding: Cancer Research UK. [ABSTRACT FROM AUTHOR]

To report the outcomes of nasopharyngeal carcinoma in adults across three large centres in a non-endemic region in the era of intensity-modulated radiotherapy (IMRT). Adult patients with nasopharyngeal carcinoma treated in three large cancer centres with IMRT ± chemotherapy with curative intent between 2009 and 2016 were identified from institutional databases. Radiotherapy was delivered with 70 Gy in 33–35 daily fractions. A univariable analysis was carried out to evaluate the relationship of patient, tumour and treatment factors with progression-free survival (PFS) and overall survival. In total, 151 patients were identified with a median follow-up of 5.2 years. The median age was 52 years (range 18–85). Seventy-five per cent were of Caucasian origin; 75% had non-keratinising tumours; Epstein Barr virus status was only available in 23% of patients; 74% of patients had stage III or IV disease; 54% of patients received induction chemotherapy; 86% of patients received concurrent chemotherapy. Five-year overall survival, PFS, local disease-free survival, regional disease-free survival and distant disease-free survival were 70%, 65%, 91%, 94% and 82%, respectively. Keratinising squamous cell carcinoma, older age, worse performance status, smoking and alcohol intake were associated with inferior overall survival and PFS. Local, regional and distant disease control are relatively high following IMRT ± chemotherapy in a non-endemic population. There was considerable heterogeneity in terms of radiotherapy treatment and the use of chemotherapy, encouraging the development of treatment protocols and expert peer review in non-endemic regions. • Multicentre UK outcomes of treatment of nasopharyngeal carcinoma. • Comparable local, regional and distant disease control with other non-endemic series. • Variation identified in radiotherapy and chemotherapy treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: The IDEAL-CRT phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiation for stage II/III non-small cell lung cancer investigated two 30-fraction schedules of 5 and 6 weeks' duration. We report toxicity, tumor response, progression-free survival (PFS), and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule.Methods and Materials: Patients received isotoxically individualized tumor radiation doses of 63 to 71 Gy in 5 weeks or 63 to 73 Gy in 6 weeks, delivered concurrently with 2 cycles of cisplatin and vinorelbine. Eligibility criteria were the same for both schedules.Results: One-hundred twenty patients (6% stage IIB, 68% IIIA, 26% IIIB, 1% IV) were recruited from 9 UK centers, 118 starting treatment. Median prescribed doses were 64.5 and 67.6 Gy for the 36 and 82 patients treated using the 5- and 6-week schedules. Grade ≥3 pneumonitis and early esophagitis rates were 3.4% and 5.9% overall and similar for each schedule individually. Late grade 2 esophageal toxicity occurred in 11.1% and 17.1% of 5- and 6-week patients. Grade ≥4 adverse events occurred in 17 (20.7%) 6-week patients but no 5-week patients. Four adverse events were grade 5, with 2 considered radiation therapy related. After median follow-up of 51.8 and 26.4 months for the 6- and 5-week schedules, median OS was 41.2 and 22.1 months, respectively, and median PFS was 21.1 and 8.0 months. In exploratory analyses, OS was significantly associated with schedule (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.32-0.98; P = .04) and fractional clinical/internal target volume receiving ≥95% of the prescribed dose (HR, 0.88; 95% CI, 0.77-1.00; P = .05). PFS was also significantly associated with schedule (HR, 0.53; 95% CI, 0.33-0.86; P = .01).Conclusions: Toxicity in IDEAL-CRT was acceptable. Survival was promising for 6-week patients and significantly longer than for 5-week patients. Survival might be further lengthened by following the 6-week schedule with an immune agent, motivating further study of such combined optimized treatments. [ABSTRACT FROM AUTHOR]

Background: A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement. Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.Methods/design: CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.Discussion: The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.Trial Registration: ISRCTN, ISRCTN92755158, Registered on 17 February 2016. [ABSTRACT FROM AUTHOR]

Introduction: Drug treatment for cancer has changed dramatically over the past decade with many new drugs often with multiple applications. More recently, the detailed pathway for approval from the National Institute for Health and Care Excellence (NICE) in the UK has been simplified. To explore how these changes have impacted on systemic anti-cancer therapy tumour site-specific prescribing and workload activities, we have reviewed the prescribing records for 2014–2018 in a UK cancer network. Methods: Information about the numbers of new systemic anti-cancer therapy drugs and NICE approvals were obtained from print editions of the British National Formulary (BNF) and the NICE website. Data on the numbers of new chemotherapy courses and individual treatment-related attendances were obtained from the cancer network Chemocare electronic prescribing system. Results: During the five-year study period, there were 49 new systemic anti-cancer therapy drugs for all tumour types, and a total of 65 NICE technology approvals for solid tumour indications. Overall numbers of treatment courses increased by 40.7% and total treatment-related visits by 80.6%. There was a wide variation across tumour types with the highest number of increased visits seen for melanoma (349.3%) and prostate cancer (242.3%), but in contrast, no appreciable increases were seen for lower gastrointestinal cancers or small cell lung cancer. Conclusion: The study confirms the major impact of the arrival of new drug technology and positive NICE appraisals on increasing systemic anti-cancer therapy prescribing and chemotherapy unit activity. The data in this study may be of help in planning for future service delivery planning and workforce configurations. [ABSTRACT FROM AUTHOR]