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  • The impact of atherosclerotic cardiovascular disease, dyslipidaemia and lipid lowering therapy on Coronavirus disease 2019 outcomes: an examination of the available evidence

    Adam, Safwaan; Ho, Jan Hoong; Bashir, B.; Iqbal, Z.; Ferdousi, M.; Syed, A. A; Soran, H.; The University of Manchester, Faculty of Biology, Medicine and Health Department of Endocrinology (2021)
    Purpose of review: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. Recent findings: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. Summary: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.
  • Antiproliferative systemic therapies for metastatic small bowel neuroendocrine tumours

    Dawod, Mohammed; Gordoa, T. A.; Cives, M.; De Mestier, L.; Crona, J.; Spada, F.; Oberg, K.; Pavel, Marianne; Lamarca, Angela; Department of Medical Oncology, ENETs, Centre of Excellence, The Christie NHS Foundation Trust, Manchester, UK. (2021)
    Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies with rising incidence and prevalence. Outcome and therapy of small bowel neuroendocrine tumours (SBNETs) is variable, depending on the grade, differentiation, tumour burden, as well as the site of the tumour origin. Because of this, multidisciplinary approach is essential. Large randomized clinical trials, with somatostatin analogues (PROMID, CLARINET) or with peptide receptor radionuclide therapy (PRRT) with 177-lutetium (NETTER-1 trial) as well as the mammalian target of rapamycin inhibitor (mTOR) everolimus (RADIANT trials), represent milestones for the medical management of unresectable grade 1 and 2 SBNETS over the last decade. Novel therapies, such as tyrosine kinase inhibitors (TKI), are on the cutting edge. However, multiple unsolved questions remain. This review provides a comprehensive review of the main systemic therapeutic options for advanced SBNETs and discusses the latest guideline recommendations for palliative treatment.
  • Single dose or fractionated SBRT for oligometastatic disease? Reply

    Zelefsky, M. J.; Greco, C.; Yamada, Y.; Powell, S. N.; Fuks, Z.; Cowling, T. E.; Patel, R. N.; Morris, M.; Berry, B.; Cathcart, P.; et al. (2021)
  • Is it time to look for better prognostic markers and reconsider adjuvant chemotherapy for locally advanced anal cancers?

    King, J; Swinton, Martin; Grant, G; Buckley, Lucy; Lavin, Victoria; Alam, Noreen; Saunders, Mark P; The Christie Hospital NHS Foundation Trust, Manchester, UK. (2021)
  • In reply to Langley et al

    Parry, M. G.; Nossiter, J.; Sujenthiran, A.; Cowling, T. E.; Patel, R. N.; Morris, M.; Berry, B.; Cathcart, P.; Clarke, Noel W; van der Meulen, J; et al. (2021)
  • Photons, protons, SBRT, brachytherapy-what is leading the charge for the management of prostate cancer? A perspective from the GU editorial team

    Choudhury, Ananya; Henry , A.; Mitin , D. T.; Chen , R.; Joseph , N; Spratt , D. D.; Department of Clinical Oncology, Christie NHS Foundation Trust, Manchester, United Kingdom (2021)
  • Remembering friends: exploring the bereavement support needs of teenagers and young adults experiencing the death of a friend in the cancer setting

    Mackland, Anna; Wright, Lorraine; Occupational Therapy, Salford University, Manchester, United Kingdom. (2021)
    Introduction: Bereavement is often difficult for adolescents to cope with particularly when the death experienced is a friend due to cancer, while the young person is undergoing their own cancer treatment. There is limited research on this specific type of bereavement. The Teenage & Young Adult (TYA) team at The Christie in Manchester recognized the complicated nature of bereavement in this cohort and identified the need to research this area further. Methods: A mixed method research strategy was used to explore bereavement experiences of young people, gathering qualitative and quantitative data from a TYA bereavement advisory group and an online survey. Inductive thematic analysis was used to establish themes from the qualitative data. Results: Data from the advisory group and survey elicited four main themes: prevalence and emotional impact; maintaining and valuing friendships; communication and conversations; and support and space to grieve. Young people experienced multiple exposures to death, long-term emotional reactions, reflections on mortality, and fears of making new friendships. How a death was communicated was difficult, and bereavement support was lacking. Young people want a formalized bereavement service, provided by specially trained staff, and their own "space" to grieve. Conclusion: Young people in this study highlight the complicated nature of bereavement when their friend dies, while undergoing their own cancer treatment. Bereavement support is essential at the time of a death. TYA services bring young people together for peer support so more emphasis needs to be focused on providing bereavement support to reduce the risk of young people experiencing long-term psychological difficulties and negative outcomes later in life.
  • The promise of proton beam therapy for oesophageal cancer: A systematic review of dosimetric and clinical outcomes

    Nicholas, O; Prosser S; Mortensen H R; Radhakrishna, Ganesh; Hawkins, M A; Gwynne, S H; South West Wales Cancer Centre, Swansea, (2021)
    Aims: Due to its physical advantages over photon radiotherapy, proton beam therapy (PBT) has the potential to improve outcomes from oesophageal cancer. However, for many tumour sites, high-quality evidence supporting PBT use is limited. We carried out a systematic review of published literature of PBT in oesophageal cancer to ascertain potential benefits of this technology and to gauge the current state-of-the-art. We considered if further evaluation of this technology in oesophageal cancer is desirable. Materials and methods: A systematic literature search of Medline, Embase, Cochrane Library and Web of Science using structured search terms was carried out. Inclusion criteria included non-metastatic cancer, full articles and English language studies only. Articles deliberating technical aspects of PBT planning or delivery were excluded to maintain a clinical focus. Studies were divided into two sections: dosimetric and clinical studies; qualitatively synthesised. Results: In total, 467 records were screened, with 32 included for final qualitative synthesis. This included two prospective studies with the rest based on retrospective data. There was heterogeneity in treatment protocols, including treatment intent (neoadjuvant or definitive), dose, fractionation and chemotherapy used. Compared with photon radiotherapy, PBT seemed to reduce dose to organs at risk, especially lung and heart, although not for all reported parameters. Toxicity outcomes, including postoperative complications, were reduced compared with photon radiotherapy. Survival outcomes were reported to be at least comparable with photon radiotherapy. Conclusion: There is a paucity of high-quality evidence supporting PBT use in oesophageal cancer. Wide variation in intent and treatment protocols means that the role and 'gold-standard' treatment protocol are yet to be defined. Current literature suggests significant benefit in terms of toxicity reduction, especially in the postoperative period, with comparable survival outcomes. PBT in oesophageal cancer holds significant promise for improving patient outcomes but requires robust systematic evaluation in prospective studies.
  • Alpelisib in combination with everolimus ± exemestane in solid tumours: Phase Ib randomised, open-label, multicentre study

    Curigliano, G.; Martin, M.; Jhaveri, K.; Beck, J. T.; Tortora, G.; Fazio, N.; Maur, M.; Hubner, Richard A; Lahner, H.; Donnet, V.; et al. (2021)
    Background and purpose: Combined mTORC1 inhibition with everolimus (EVE) and phosphatidylinositol 3-kinase catalytic subunit p110α blockade with alpelisib (ALP) has demonstrated synergistic efficacy in preclinical models and supports testing the combination of ALP and EVE in the clinical setting. The primary objective was to determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) of ALP in combination with EVE and in combination with EVE and exemestane (EXE) and subsequently assess safety, preliminary efficacy and effect of ALP on the pharmacokinetics of EVE and determine the magnitude of the drug-drug interaction. Patients and methods: Dose escalation phases were conducted in patients with advanced solid tumours and in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). The dose expansion phase was conducted in patients with pancreatic neuroendocrine tumour and renal cell carcinoma (RCC) (both mechanistic target of rapamycin inhibitor [mTORi]-naive), in patients with mTORi-pretreated solid tumours and in postmenopausal women with HR+, HER2- ABC. Results: During the doublet escalation phase, dose-limiting toxicities (DLTs) were reported in 5 of 10 (50%) patients: one patient had grade (Gr) 2 hyperglycemia and one patient had Gr 3 diarrhoea in the 300 mg dose group, one patient had Gr 2 hyperglycemia and one patient had Gr 4 hypocalcaemia in the 250 mg dose group, and one patient in the 200 mg dose group had Gr 3 diarrhoea and Gr 3 stomatitis. The combination of ALP 250 mg + EVE 2.5 mg was declared as the MTD/RDE in subjects with advanced solid tumours. In the triplet escalation phase, one patient who received ALP 200 mg + EVE 2.5 mg + EXE 25 mg had a DLT of Gr 3 acute kidney injury. This dose combination was declared as the MTD and RDE in subjects with advanced HR-positive HER2-negative BC. The common adverse events (≥30% patients), occurring across all phases, were hyperglycaemia, stomatitis, diarrhoea, nausea, asthenia, decreased appetite and fatigue. The sixteen-week progression-free survival rate was 52.4% (90% confidence interval [CI]: 32.8, 71.4) in the RCC cohort, 35.3% (90% CI: 16.6, 58.0) in the prior pNET cohort and 30.0% (90% CI: 8.7, 60.7) in the prior mTORi cohort. The pharmacokinetics of 2.5 mg of EVE was largely unchanged in the presence of ALP, independent of the dose (250 mg or 300 mg). There were no clinically relevant drug-drug interactions observed between ALP and EVE. Conclusion: The overall safety profile of ALP with EVE and EXE is manageable and reversible; no unexpected safety signals were noted compared with the individual safety profiles. Pharmacokinetics of ALP, EVE and EXE was largely unchanged in combination with each other.
  • Twice-daily chemoradiotherapy in limited-stage small-cell lung cancer

    Levy, A.; Le Péchoux, C; Faivre-Finn, Corinne; Department of Radiation Oncology, Institut d'Oncologie Thoracique, Gustave Roussy, Villejuif, France (2021)
  • HALT: targeted therapy with or without dose-intensified radiotherapy in oligo-progressive disease in oncogene addicted lung tumours

    McDonald, F.; Guckenberger, M.; Popat, S.; Faivre-Finn, Corinne; Andratschke, N.; Riddell, A.; Hanna, G.; Prakash, V.; Nair, A.; Diez, P.; et al. (2021)
    Background: Following initial response to TKI, advanced NSCLC patients with actionable mutations ultimately develop treatment resistance. In a proportion of patients (15-40%), initial, limited pro gression (≤3 lesions) is observed, termed oligoprogressive disease (OPD). SBRT offers hypofractionated, targeted radiotherapy treatment hypothesised to prolong clinical benefit from TKI prior to widespread disease development. The potential benefit offered by SBRT to ablate OPD sites prior to change in systemic therapy is an important question to address, particularly during the current pandemic, where reducing clinic visits is particularly advantageous. Method: HALT is a randomised, multi-centre, phase II/III international trial with seamless transition to phase III incorporated. Eligible patients (stage IV NSCLC, actionable mutation, TKI response prior to OPD) are randomised 2:1 to SBRT/continued TKI or continued TKI alone. Eligibility is confirmed by a virtual MDT comprising trial clinicians and radiologists (OPD, SBRT suitability). Follow-up assessments aligned with routine care at 3-monthly intervals until change in systemic therapy is clinically indicated, imaging and toxicity assessment at each visit. Current status: Recruitment commenced November 2017; 27 centres (16 UK; 11 non-UK) open to date (09/03/2021), 94 patients registered and 50 randomised. Because of the COVID-19 pandemic, recruitment was temporarily paused on 20/03/2020 and restarted in accordance with national guidelines on 16/06/2020. Of 94 patients registered, vMDT review performed for 74 patients (18 screen fails prior to vMDT); 50 randomised, 22 confirmed ineligible via vMDT (inc. >3 lesions, lesion >5cm, intracranial disease identified). Conclusion: The vMDT remains an important, novel aspect of the trial, ensuring robust patient selection ahead of randomisation. As the first randomised trial assessing SBRT benefit in this patient population, HALT will provide valuable treatment efficacy and safety information, informing subsequent trial design and contribute to the development of international guidelines for the identification and clinical management of oligoprogression in mutation positive lung cancer.
  • A real-world analysis of 30-day post systemic anti-cancer therapy mortality in patients with small cell lung cancer

    Carter, Louise; Church, Matt; Blackhall, Fiona H; The Christie NHS Foundation Trust, Manchester (2021)
    Introduction: Small cell lung cancer (SCLC) is highly aggressive with a poor prognosis. Chemo-immunotherapy is recommended as first-line treatment in patients of good performance status and has excellent response rates. However, patients frequently present late or with oncological emergencies such as superior vena cava obstruction (SVCO) where benefits of systemic anti-cancer therapy (SACT) are less clear. This study aimed to evaluate SCLC patients who died within 30 days of SACT administration to better understand this at-risk patient group. Methods: Patients with SCLC who died within 30 days of receiving SACT between August 2012 and September 2019 at the Christie Hospital, UK, were characterised for demographics, oncological history, clinical features and cause of death. A comparator cohort of patients who did not die within 30 days was randomly generated from health records and analysed for statistical differences and multivariate post-SACT survival. Results: There were 105 SCLC patients who died within 30 days of SACT. The majority were elderly and 81% were performance status 2 or 3 (Table 1). SVCO was present in 25%, 82% of patients were receiving first-line SACT, 42% received single-agent carboplatin and 38% died within ten days of SACT. Cause of death was determined to be progressive disease in 63% and neutropenic sepsis in 9.5%, with 28.6% possibly related to SACT. Comparison with 95 comparator patients showed significantly higher SVCO (p=0.01) and performance status (p<0.001) in the 30-day mortality cohort. Higher performance status, raised leukocytes and low serum sodium were associated with lower 30-day post-SACT survival on multivariate analysis (hazard ratio 1.77, 1.08, 0.96 respectively). Conclusions: International guidelines support combination SACT in SCLC patients of good performance status, but nuances remain regarding optimal SACT for frailer patients. These results highlight the high risk of 30-day post-SACT mortality in SCLC, particularly in those with markers of poor prognosis.
  • A predictive model for reactive tube feeding in head and neck cancer patients undergoing definitive (chemo) radiotherapy

    Gaito, Simona; France, A.; Foden, Philip; Abravan, Azadeh; Burnet, Neil G; Garcez, Kate; Kota, Vamsi R; Lee, Lip W; Price, J.; Sykes, Andrew J; et al. (2021)
    Aims: Careful management of a patient's nutritional status during and after treatment for head and neck squamous cell cancers (HNSCC) is crucial for optimal outcomes. The aim of this study was to develop a model for stratifying a patient's risk of requiring reactive enteral feeding through a nasogastric tube during radiotherapy for HNSCC, based on clinical and treatment-related factors. Materials and methods: A cohort of consecutive patients treated with definitive (chemo)radiotherapy for HNSCC between January 2016 and January 2018 was identified in the institutional electronic database for retrospective analysis. Patients requiring enteral feeding pretreatment were excluded. Clinical and treatment data were obtained from prospectively recorded electronic clinical notes and planning software. Results: Baseline patient characteristics and tumour-related parameters were captured for 225 patients. Based on the results of the univariate analysis and using a stepwise backwards selection process, clinical and dosimetric variables were selected to optimise a clinically predictive multivariate model, fitted using logistic regression. The parameters found to affect the probability, P, of requiring a nasogastric feeding tube for >4 weeks in our clinical multivariate model were: tumour site, tumour stage (early T0/1/2 stage versus advanced T3/T4 stage), chemotherapy drug (None versus any drug) and mean dose to the contralateral parotid gland. A scoring model using the regression coefficients of the selected variables in the clinical multivariate model achieved an area under the curve (AUC) of 0.745 (95% confidence interval 0.678-0.812), indicating good discriminative performance. Internal validation of the model involved splitting the dataset 80:20 into training and test datasets 10 times and assessing differences in AUC of the model fitted to these. Conclusions: We developed an easy-to-use prediction model based on both clinical and dosimetric parameters, which, once externally validated, can lead to more personalised treatment planning and inform clinical decision-making on the appropriateness of prophylactic versus reactive enteral feeding.
  • A real-world experience of second-line nivolumab in mesothelioma patients during the COVID-19 pandemic

    Church, M.; Taylor, Paul; Summers, Yvonne J; Califano, Raffaele; Rafee, Shereen; Dixon, M.; Clarke, L; Cove-Smith, Laura; Manchester University NHS Foundation Trust, Manchester (2021)
    Introduction: Treatment options beyond the first-line have traditionally been limited in mesothelioma patients, and include approaches such as re-challenge chemotherapy or clinical trials. The COVID-19 pandemic put pressure on oncology services worldwide and triggered numerous adaptations to traditional treatment strategies. In mid-2020, NHS England approved the use of nivolumab in the second-line for mesothelioma patients. While the recent results of the CONFIRM trial support this approach, the real-world implications of this decision remain to be fully evaluated. Methods: Mesothelioma patients who commenced nivolumab therapy in the second-line between August 2020 and February 2021 at Wythenshawe Hospital, UK, were included. Disease subtype, cycles administered, reported adverse events, radiological response and survival were collected from electronic patient records. Results: Twenty-one patients were identified (17 epithelioid, two sarcomatoid, one biphasic, one unknown); mean age 70 years (range 38-82). Adverse events included fatigue, nausea and vomiting, diarrhoea, skin rash, mucositis and anorexia. There was one myocardial infarction and another patient developed hyperthyroidism. One patient died during treatment; two ceased treatment due to clinical progression. Fifteen patients have received a post-treatment CT scan; 12 (80%) had progressive disease, two (13%) had a mixed response and one (7%) a partial response. Seven patients are ongoing with treatment. Patients who discontinued nivolumab received an average of 3.2 cycles of treatment (range 1–5); two subsequently received re-challenge chemotherapy, one watchful waiting and ten best supportive care. Conclusions: These results provide a real-world insight on nivolumab use in mesothelioma. Nivolumab was generally well tolerated, however the high proportion of patients with progressive disease on radiological assessment highlights the need for improved predictive biomarkers.
  • Real world outcomes in patients with lung oligometastases treated with SABR - a single-centre experience

    Fatimilehin, Abiola; Bewley, Michelle; Bowen Jones, Sarah; Chan, Clara; Coote, Joanna H; Harris, Catherine; Harris, Maggie A; Pemberton, Laura S; Salem, Ahmed; Sheikh, Hamid Y; et al. (2021)
    Introduction: Delivering Stereotactic Ablative Body Radiotherapy (SABR) to patients with extracranial oligometastatic disease has the potential to improve long-term disease control, survival and defer changes to systemic therapies [1]. We present the results from an audit of patients treated with SABR under the NHS Commissioning through Evaluation (CtE) scheme at The Christie Hospital, Manchester UK. Methods: The outcomes of patients who received SABR to lung lesions or thoracic nodes under CtE were analysed. Prescribed doses included 30-60Gy in 3-8 fractions to nodes and 54-60 Gy in 3-8 fractions to lung lesions. Patients were eligible if aged ≥18, had ≤3 metastatic lesions, WHO performance status of ≤2, onset of metastatic disease was ≥6 months from the primary tumour diagnosis and life expectancy estimated to be ≥6 months. The main outcomes evaluated included local control (assessed by local radiologists) and overall survival which were obtained from hospital records. Adverse events by CTCAE grade were recorded prospectively. Results: 52 patients treated between February 2016 and August 2019 were included. Median follow up was 28.5 months and median age was 72 (range 49-90 years). 51.9% were female and 75% had a performance status of 0-1. The most common primary was colorectal (n=23; (44.2%)). 5 patients received SABR to thoracic nodes, and 8 patients had >1 lesion treated. The median BED10 dose was 121 Gy. Local control was 96% at 1 year and 84.6% at 2 years. Overall survival was 94.2% at 1 year and 89.7% at 2 years. One patient had a toxicity graded ≥3, which was fatigue. Conclusion: The findings demonstrate high levels of local control and overall survival in these patients, with low rates of toxicity. Our findings are comparable to the overall national results, and SABR to oligometastatic lesions has now been commissioned.
  • Magnetic resonance-guided radiotherapy (MRgRT) for patients with lung cancer

    Crockett, Cathryn; Chuter, Robert; Cobben, D.; Dubec, Michael; Green, O.; Hackett, S.; McDonald, F.; Robinson, C.; Samson, P.; Shiarli, A. M.; et al. (2021)
    Background: Magnetic resonance-guided radiotherapy (MRgRT) offers improved soft tissue contrast, the ability to gate and track tumours and the option of adapting treatment daily to compensate for changing target volumes or anatomy (Sim et al., 2020). It may help to improve the therapeutic index of radiotherapy treatment for lung cancer thereby improving outcomes for patients, whose outcomes generally remain poor. Its implementation and use is not without its challenges, however. Method: An updated literature search on PubMed in January 2021 identified relevant papers. We also received personal correspondence from clinicians who have had experience with MRgRT in the lung cancer setting. Treatments on the ViewRay MRIdian or the Elekta Unity radiotherapy machines were reviewed. Results: Several centres around the world have now treated patients with lung cancer with MRgRT (Crockett et al., 2021). Most of the treatments were delivered on the MRIdian and involved the use of stereotactic ablative radiotherapy for early-stage or oligometastatic disease, including (ultra-) central tumours. The majority of centres adapted treatments daily based on anatomical changes. Low rates of severe toxicity (0-8% ≥ grade 3) have been reported and preliminary outcome data appears favourable. Technical issues relating to MRgRT treatment in lung cancer have been highlighted, including challenges relating to image quality, the magnetic field’s effect on dose distribution and accounting for both physiological respiratory and cardiac motion. Conclusion: The use of MRgRT for patients with lung cancer is still in its infancy. Long-term toxicity data is currently lacking. Future studies will focus on addressing technical issues surrounding its use and the feasibility of treating patients with stage III disease using adaptive RT, as this group is likely where the advantages of MRgRT may be best exploited. The first UK patient with lung cancer will be treated on a Unity MR-linac in April 2021.
  • Clinico-pathological features of MET exon 14 mutation positive NSCLC in the UK

    Benafif, S.; Greystoke, A.; Carter, Mathew; Bulusu, R.; Baijal, S.; Conibear, J.; Nintos, G.; Papadatos-Pastos, D.; Ahmad, T.; Lee, S. M; et al. (2021)
    Introduction: MET exon 14 skip mutation-driven lung cancer makes up 3-4% of non-small cell lung cancer (NSCLC). Unlike EGFR associated NSCLC, an association with a smoking history and older age has been described in this subset of NSCLC. Here, we describe a UK cohort of MET mutation positive NSCLC patients. Methods: A retrospective review of MET mutation positive NSCLC cases treated at 7 UK centres was carried out. Information collected included baseline characteristics, response to treatment and outcomes. Results: 30 patients were diagnosed with MET mutation positive NSCLC between 2013 and December 2020. Median follow-up duration from NSCLC diagnosis was 17.5 months. Median age was 76 years (42-86); male to female ratio was 1:1. 67% were current or ex-smokers. MET exon 14 skip mutation was present in 30 cases, 1 of which also carried MET amplification. The most common comutations were observed in TP53 (9/30). PDL1 IHC for 18 patients showed 61% had a score of ≥50%, 22% had a score of 1-49% and 17% were negative. Baseline staging was reported as M0 in 43% (13/30), M1a in 13% (4/30) and M1b/c in 43% (13/30). Brain metastases were diagnosed in 6/30 (20%), 2 of which were at baseline. Radical treatment was performed in 9 (30%) cases with either surgery or chemoradiation. 26 patients received systemic treatment for advanced NSCLC. The commonest first-line systemic treatment was immunotherapy in 35% (9/26), followed by chemotherapy in 27% (7/26). Table 1 summarises outcomes of patients treated with a MET inhibitor (METi). Conclusions: NSCLC characteristics in this UK cohort are similar to those described elsewhere. Of those patients who received a METi, most achieved PR. UK approval of METi agents is awaited, but with increasing access to extended molecular profiling for NSCLC, more patients that may benefit from these agents will continue to be identified.
  • A retrospective audit into the prophylactic use of antibiotics in patients receiving chemotherapy for lung cancer

    Crockett, Cathryn; Nillegoda, Hasanthi; Ooi, Kai Yun; Harris, Maggie A; The Christie, Manchester, (2021)
    Introduction: Patients with lung cancer are highly susceptible to infections due to their underlying malignancy and smoking-related comorbidities (e.g. COPD). Myelosuppressive chemotherapy use increases their risk and can result in hospitalisation, subsequent treatment disruption and even death. Prescribing prophylactic antibiotics (PA) following chemotherapy has been proposed as a strategy to mitigate this. Current literature reports that they are particularly beneficial in reducing morbidity in ‘high risk’ patients – those expected to have grade 4 neutropenia for >7-10 days (Kardas and Buraczewska, 2016). However concerns have been expressed around potential risks of allergic reactions, Clostridium Difficile infection and the development of antibiotic resistance. The Christie introduced a departmental guideline in 2009 outlining recommendations for PA use in this setting (Fig. 1). A local audit in 2010 showed only 54% compliance. Consequently, PA has begun to be routinely incorporated into relevant chemotherapy regimens on the electronic prescribing system. Methods: A re-audit was carried out in 2020. We identified and reviewed the notes of all patients diagnosed with lung cancer who received chemotherapy in September 2019. Results: Of 103 patients, 89 (86.4%) received PA including all patients with small cell lung cancer and all receiving concurrent chemoradiotherapy, regardless of histology. Eight (7.7%) patients had infections following cycle one and a further nine (8.7%) had infections following later cycles but only one patient was subsequently prescribed PA. In total, 79 of 96 eligible patients received PA meaning compliance was 82.3%. Reasons for withholding PA were poorly documented. No PA related adverse events were reported. Conclusion: Compliance with the departmental PA policy has greatly improved compared to the previous audit but prescribing in subsequent cycles for patients who have had infections was still poor and needs to be addressed. The lack of PA associated toxicity justifies our incorporation of routine PA into specific chemotherapy regimens
  • Treatment patterns and real-life response in patients with relapsed/refractory cutaneous t-cell lymphoma: clinical practice data in Spain

    Ortiz-Romero, P.; Pimpinelli, N.; Illidge, Timothy M; Bagot, M.; Waser, N.; He, M.; Zomas, A.; Gavini, F.; Trinchese, F.; Little, M.; et al. (2020)
    Introducción: Descripción de patrones de tratamiento y resultados en pacientes con R/R LCCT tras terapia sistémica previa en centros españoles. Métodos: Revisión retrospectiva multicéntrica de datos de 27 centros europeos (corte: 11-mar-2019), 7 en España. Los datos fueron anonimizados tras aprobación de los Comités de Ética centrales y locales. Los pacientes elegibles habían recibido terapia sistémica previa para LCCT con enfermedad R/R antes del 1-ene-2016. Los pacientes con linfoma anaplásico de células grandes primariamente cutáneo (LACGpc) con enfermedad R/R tras radioterapia también fueron elegibles. La respuesta al tratamiento se evaluó utilizando los métodos de la práctica clínica de cada centro. Resultados: Se incluyeron 39 pacientes de centros españoles. La mediana de edad en la fecha índice (R/R1; definida como la fecha de R/R al último estado conocido) fue de 58 años (rango: 28–84); El 59% tenía micosis fungoide, 21% LACGpc, 13% síndrome de Sézary y el 8% otros subtipos. La mediana de seguimiento fue 3.2 años (rango: 0–26) desde la fecha índice. 37 pacientes recibieron tratamiento adicional tras la fecha índice para R/R LCCT; 34 recibieron terapia sistémica/radioterapia/ ambas (con/sin terapia dirigida a la piel) y se evaluó respuesta/seguridad. Las terapias sistémicas más empleadas fueron regímenes basados en bexaroteno/metotrexato (41%), quimioterapia de agente único (16%) o combinada (14%). El 50% de los pacientes logró una respuesta (24% respuestas completas); El 26% experimentó progresión. Los síntomas cutáneos de prurito (50%), enrojecimiento/irritación/ardor (29%) y erupción cutánea (18%) continuaron tras tratamiento en R/R1. Los eventos adversos más frecuentes incluyeron neutropenia febril (9%), alopecia (6%) y astenia/fatiga (6%). La mediana de tiempo hasta próxima recaída fue 12.7 meses (rango: 0.7–52.9). 20 pacientes recibieron otra línea de terapia adicional (R/R2). Al final del seguimiento, 14 pacientes fallecieron. Se presentarán datos adicionales de población española y se compararán con datos europeos. Conclusiones: Este análisis reveló un uso heterogéneo de terapias sistémicas en los subtipos de LCCT en España; Las basadas en bexaroteno/metotrexato fueron las más utilizadas. A pesar del uso generalizado de quimioterapia, los eventos cutáneos siguieron siendo frecuentes, se lograron respuestas completas limitadas y 1/4 de los pacientes progresaron tras tratamiento para R/R1, recayendo/volviéndose refractarios dentro de ~1 año y recibiendo líneas posteriores. La carga clínica de LCCT podría ser, probablemente, considerable. En este contexto, las terapias dirigidas recientemente aprobadas pueden ayudar a abordar este problema.
  • Superficial HDR brachytherapy for skin lesions involving the finger - The Christie experience

    Rembielak, Agata; Bedford, J; Wilson, S.; The Christie NHS Foundation Trust, Clinical Oncology, Manchester (2021)
    Purpose or Objective The standard of care for treatment of skin cancer and refractory precancerous conditions located on the finger is largely surgical management. Surgery usually involves digits/finger amputation or wide local excision with reconstruction. Many patients are elderly and/or frail. Non-invasive methods of treatment are often the preferred option due to favourable cosmetic and/or functional outcomes and improved patient compliance. External beam radiotherapy in finger location is challenging due to depth-dose characteristics in curved surfaces and close target location to joints and bones. HDR brachytherapy (BT) is a well-established non-invasive alternative treatment option delivering high radiation dose to the target with rapid dose fall-off in normal surrounding tissues. We report The Christie experience with HDT BT in the finger location over the past 6 years. Materials and Methods From Jan 2014 to Sept 2020, 13 patients (7 males and 5 females) underwent radical superficial HDR BT to the finger. There were 9 skin SCCs: 5 postoperative and 4 definitive. One patient had BCC and 3 patients had progressive refractory Bowen’s disease. The median age at the time of BT was 71 years (range 52 – 95). The patients were treated with a total dose of 30–34 Gy at 100% isodose in 8 fractions twice a day at least 6 hours apart. Target area was marked out by visual inspection, palpation and high frequency skin ultrasound. All patients were treated with The Christie mould technique: a flap mounted over an individually designed mould composed of a pre-calculated number of layers of thermoplastic material. Patients were followed for at least 2-3 years for treatment toxicity, cosmetic results, and local failures. Acute toxicity was graded using the CTC AE, v. 4.0 and cosmetic outcomes were classified using the RTOG cosmetic rating scale. Results Average follow-up from completion of the treatment was 23.5 months (2-36 months). All patients had an acute reaction to the BT: desquamation, crusting and erythema grade 1 or 2. One patient developed acute grade 3 wet desquamation. All acute toxicity was resolved within 2 months after treatment. Late toxicity was reported in 6 patients: slight/moderate atrophy, pigmentation change and grade 1 or 2 teleangiectasia. No cosmetic or functional results worse than good were observed. 11 patients had no evidence of recurrence in follow-up. 2 patients proceeded to salvage surgery due to either no response to BT or local recurrence at 4 months after BT. 2/11 patients passed away due to non-cancer related causes. Conclusion HDR mould BT is a valid non-invasive alternative to surgical management of skin cancer and refractory precancerous conditions located on the finger. It has its role particularly in elderly where PS and comorbidities may preclude surgery and short treatment duration can help with patient compliance. With appropriate patient selection skin HDR BT with customized surface moulds offers a good outcome and favourable cosmetic results with function preservation.

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