Now showing items 21-40 of 8564

    • Brigatinib versus crizotinib in anaplastic lymphoma kinase (ALK) inhibitor-naive advanced alk-positive non-small cell lung cancer: final results of the Phase 3 ALTA-1L trial

      Camidge, D. R.; Kim, H. R.; Ahn, M. J.; Yang, J. C.; Han, J. Y.; Hochmair, M. J.; Lee, K. H.; Delmonte, A.; Garcia Campelo, M. R.; Kim, D. W.; et al. (2021)
      Introduction: In the phase 3 ALTA-1L study of brigatinib in anaplastic lymphoma kinase (ALK) inhibitor-naive advanced ALK+ NSCLC, brigatinib demonstrated superior progression-free survival (PFS) versus crizotinib in 2 planned interim analyses. We report final efficacy, safety, and exploratory results. Methods: Patients were randomized to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. Primary endpoint was blinded independent review committee (BIRC)-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy. Results: 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up: 40.4 months), 3-year PFS by BIRC was 43% (brigatinib) versus 19% (crizotinib; median, 24.0 vs 11.1 months; HR: 0.48; 95% CI: 0.35-0.66). Median overall survival (OS) was not reached in either group (HR: 0.81; 95% CI: 0.53-1.22). Post hoc analyses suggested an OS benefit for brigatinib in patients with baseline brain metastases (HR: 0.43; 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib demonstrated efficacy superior to crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed. Conclusions: At ALTA-1L final analysis, with longer follow-up brigatinib continued to demonstrate superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study.
    • Inhibition of WEE1 is effective in TP53- and RAS-mutant metastatic colorectal cancer: a randomized trial (FOCUS4-C) comparing adavosertib (AZD1775) with active monitoring

      Seligmann, J. F.; Fisher, D. J.; Brown, L. C.; Adams, R. A.; Graham, J.; Quirke, P.; Richman, S. D.; Butler, R.; Domingo, E.; Blake, A.; et al. (2021)
      Purpose: Outcomes in RAS-mutant metastatic colorectal cancer (mCRC) remain poor and patients have limited therapeutic options. Adavosertib is the first small-molecule inhibitor of WEE1 kinase. We hypothesized that aberrations in DNA replication seen in mCRC with both RAS and TP53 mutations would sensitize tumors to WEE1 inhibition. Methods: Patients with newly diagnosed mCRC were registered into FOCUS4 and tested for TP53 and RAS mutations. Those with both mutations who were stable or responding after 16 weeks of chemotherapy were randomly assigned 2:1 between adavosertib and active monitoring (AM). Adavosertib (250 mg or 300 mg) was taken orally once on days 1-5 and days 8-12 of a 3-week cycle. The primary outcome was progression-free survival (PFS), with a target hazard ratio (HR) of 0.5 and 80% power with a one-sided 0.025 significance level. Results: FOCUS4-C was conducted between April 2017 and Mar 2020 during which time 718 patients were registered; 247 (34%) were RAS/TP53-mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib = 44; AM = 25). Adavosertib was associated with a PFS improvement over AM (median 3.61 v 1.87 months; HR = 0.35; 95% CI, 0.18 to 0.68; P = .0022). Overall survival (OS) was not improved with adavosertib versus AM (median 14.0 v 12.8 months; HR = 0.92; 95% CI, 0.44 to 1.94; P = .93). In prespecified subgroup analysis, adavosertib activity was greater in left-sided tumors (HR = 0.24; 95% CI, 0.11 to 0.51), versus right-sided (HR = 1.02; 95% CI, 0.41 to 2.56; interaction P = .043). Adavosertib was well-tolerated; grade 3 toxicities were diarrhea (9%), nausea (5%), and neutropenia (7%). Conclusion: In this phase II randomized trial, adavosertib improved PFS compared with AM and demonstrates potential as a well-tolerated therapy for RAS/TP53-mutant mCRC. Further testing is required in this sizable population of unmet need.
    • Author Correction: Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population

      Westphalen, C. B.; Krebs, Matthew G; Le Tourneau, C.; Sokol, E. S.; Maund, S. L.; Wilson, T. R.; Jin, D. X.; Newberg, J. Y.; Fabrizio, D.; Veronese, L.; et al. (2021)
    • Progress and pitfalls with the use of image-guided personalised approaches in lymphoma

      Illidge, Timothy M; Phillips, Elizabeth H; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, NIHR Biomedical Research Centre, Manchester Academic Health Sciences Centre, Christie Hospital NHS Foundation Trust, Manchester, UK. (2021)
      The use of 18F-FDG PET CT has become an essential part of the management of patients with lymphoma. The last decade has seen unrivalled progress in research efforts to personalise treatment approaches using PET as a predictive imaging biomarker. Critical to this success has been the standardisation of PET methods and reporting, including the 5-point Deauville scale, which has enabled the delivery of robust clinical trial data to develop response-adapted treatment approaches.(1, 2) The utility of PET as a predictive imaging biomarker in assessing treatment success or failure has been investigated extensively in malignant lymphomas. Considerable progress has been made over the last decade, in using PET to direct more personalised "risk-adapted" approaches, as well as an increased understanding of some of the limitations. Arguably the greatest success has been in Hodgkin Lymphoma (HL) where PET was initially demonstrated to be a powerful predictive biomarker (3) and is now routinely used in both early-stage and advanced HL to reduce or escalate the use of chemotherapy as well as guiding the delivery of more selective radiotherapy to patients.
    • Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence

      Heydt, Q.; Xintaropoulou, C.; Clear, A.; Austin, M.; Pislariu, I.; Miraki-Moud, F.; Cutillas, P.; Korfi, K.; Calaminici, M.; Cawthorn, W.; et al. (2021)
      The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance.
    • Survival outcomes associated with completion of adjuvant oxaliplatin-based chemotherapy for stage III colon cancer: a national population-based study

      Boyle, J. M.; Kuryba, A.; Cowling, T. E.; van der Meulen, J.; Fearnhead, N. S.; Walker, K.; Braun, Michael S; Aggarwal, A.; Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK (2021)
      The impact of cycle completion rates of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer in real-world practice is unknown. We assessed its impact, and that of treatment modification, on 3-year cancer-specific mortality. 4147 patients with pathological stage III colon cancer undergoing major resection from 2014 to 2017 in the English National Health Service were included. Chemotherapy data came from linked national administrative datasets. Competing-risk regression analysis for 3-year cancer-specific mortality was performed according to completion of <6, 6-11, or 12 FOLFOX cycles, or < 4, 4-7, or 8 CAPOX cycles, adjusted for patient, tumour and hospital-level characteristics. Median age was 64 years. 32% of patients had at least one comorbidity. 42% of patients had T4 disease, and 40% N2 disease. Compared to completion of 12 FOLFOX cycles, cancer-specific mortality was higher in patients completing <6 cycles (sHR 2.17; 95% CI, 1.56 to 3.03) or 6-11 cycles (sHR 1.40; 95% CI, 1.09 to 1.78) (P < 0.001). Compared to completion of 8 CAPOX cycles, cancer-specific mortality was higher in patients completing <4 cycles (sHR 2.02; 95% CI 1.53 to 2.67) or 4-7 cycles (sHR 1.63; 95% CI 1.27 to 2.10) (P < 0.001). Dose reduction and early oxaliplatin discontinuation did not impact mortality in patients completing all cycles. Completion of all cycles of chemotherapy was associated with improved cancer-specific survival in real-world practice. Poor prognostic factors may have affected findings, however, patients completing <50% of cycles had poor outcomes. Clinicians may wish to facilitate completion with treatment modification in those able to tolerate it.
    • Biopsy for advanced hepatocellular carcinoma: results of a multicentre UK audit

      Childs, A.; Zakeri, N.; Ma, Y. T.; O'Rourke, J.; Ross, P.; Hashem, E.; Hubner, Richard A; Hockenhull, Kimberley; Iwuji, C.; Khan, S.; et al. (2021)
      Background: Advanced hepatocellular carcinoma (HCC) is commonly diagnosed using non-invasive radiological criteria (NIRC) defined by the European Association for the Study of the Liver or the American Association for the Study of Liver Diseases. In 2017, The National Institute for Clinical Excellence mandated histological confirmation of disease to authorise the use of sorafenib in the UK. Methods: This was a prospective multicentre audit in which patients suitable for sorafenib were identified at multidisciplinary meetings. The primary analysis cohort (PAC) was defined by the presence of Child-Pugh class A liver disease and performance status 0-2. Clinical, radiological and histological data were reported locally and collected on a standardised case report form. Results: Eleven centres reported 418 cases, of which 361 comprised the PAC. Overall, 76% had chronic liver disease and 66% were cirrhotic. The diagnostic imaging was computed tomography in 71%, magnetic resonance imaging in 27% and 2% had both. Pre-existing histology was available in 45 patients and 270 underwent a new biopsy, which confirmed HCC in 93.4%. Alternative histological diagnoses included cholangiocarcinoma (CC) and combined HCC-CC. In cirrhotic patients, NIRC criteria had a sensitivity of 65.4% and a positive predictive value of 91.4% to detect HCC. Two patients (0.7%) experienced mild post-biopsy bleeding. Conclusion: The diagnostic biopsy is safe and feasible for most patients eligible for systemic therapy.
    • Determination of a cone-beam CT low-dose protocol for root fracture diagnosis in non-endodontically treated anterior maxillary teeth

      Andraws Yalda, F.; Theodorakou, Chrysoula; Clarkson, R. J.; Davies, J.; Feinberg, L.; Sengupta, A.; Horner, K.; College of Dentistry, Hawler Medical University, Erbil, Iraq (2021)
      Objectives: The aim of this study was to determine a "low-dose protocol" which provides acceptable diagnostic accuracy for detection of root fractures in unrestored anterior maxillary teeth, using an ex vivo model. Methods: 48 maxillary anterior teeth, half with horizontal or oblique root fractures, were imaged using CBCT in an anthropomorphic model. Nine X-ray exposure combinations were used, including the manufacturer's standard ("reference") exposure and high-resolution settings ("HiRes"), by varying kV, exposure time, and rotation angle. Measurements of Dose Area Product (DAP) were recorded. Five dental radiologists assessed the scans for root fractures and judged image quality. Parameters of diagnostic accuracy were calculated, including area under the Receiver Operating Characteristic curve (Az). Objective measures of image quality were made at the same exposure combinations using an image quality phantom. Results: Although there was a significant linear relationship between DAP and mean Az, only the lowest DAP exposure combination had a mean Az significantly different to the reference exposure. There was no significant effect on other diagnostic accuracy parameters when using HiRes compared with the reference exposure. There was a significant positive relationship between DAP and contrast resolution. HiRes did not significantly improve contrast resolution and made a small improvement to spatial resolution. Conclusions: Scope existed for radiation dose reduction compared with the manufacturer's guidance. There was no improvement in diagnostic accuracy using HiRes settings. A cautious recommendation for this CBCT machine is that it is possible to achieve a dose reduction of about 20% compared with the reference exposure parameters.
    • Radioguided surgery for gastroenteropancreatic neuroendocrine tumours: a systematic literature review

      Cockburn, K. C.; Toumi, Z.; Mackie, A.; Julyan, Peter J; Northern Medical Physics and Clinical Engineering, County Durham and Darlington NHS Foundation Trust, Hollyhurst Road, Darlington, DL3 6HX, UK. (2021)
      Background: Radioguided surgery (RGS) for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has been suggested as a way to improve intraoperative lesion detection. This systematic literature review of reports of the use of RGS for GEP-NETs was performed to determine if there is a benefit. Methods: A literature search was conducted using Google Scholar and PubMed, and snowballing from any relevant literature. Full-text studies were included if they were published in the English language and reported outcomes of RGS on human subjects with GEP-NETs. Qualitative data synthesis was performed. Results: Twenty-six papers including a total of 209 patients were included. The tracers used were predominantly indium-111 pentetreotide, gallium-68 DOTA-peptides, and technetium-99m EDDA/HYNIC-peptides. Heterogeneous protocols make comparisons difficult, but most papers reported a benefit from the use of RGS in tumours in the gastrointestinal tract; utility in localisation of pancreatic tumours was less clear. Time between tracer administration and operation varied: from 16 h to 8 days with indium-111, 0-24 h with technetium-99m, and 19-193 min with gallium-68. Eight teams reported the thresholding technique used for discrimination-four used a ratio, four statistical methods, and one looked at the sensitivity and specificity of different cut-offs. Six teams performed follow-up of 24 patients (three pancreas, eight gastrinoma, 13 gastrointestinal tract) for between 3 months and 3 years. Two patients relapsed (one pancreas, one gastrinoma) between 6 and 12 months post-surgery. Conclusions: RGS appears to aid in localisation of gastrointestinal NETs, but the benefit is more equivocal in pancreatic NETs. Further work into outcomes is warranted.
    • Combination of pembrolizumab with electrochemotherapy in cutaneous metastases from melanoma: a comparative retrospective study from the InspECT and Slovenian Cancer Registry

      Campana, Luca G; Peric, B.; Mascherini, M.; Spina, R.; Kunte, C.; Kis, E.; Rozsa, P.; Quaglino, P.; Jones, R. P.; Clover, A. J. P.; et al. (2021)
      Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC-IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.
    • Centralised RECIST assessment and clinical outcomes with lenvatinib monotherapy in recurrent and metastatic adenoid cystic carcinoma

      Feeney, Laura; Jain, Yatin; Beasley, M.; Donnelly, O.; Kong, A.; Moleron, R.; Nallathambi, C.; Rolles, M.; Sanghera, P.; Tin, A.; et al. (2021)
      Adenoid cystic carcinoma (ACC) is a rare cancer of secretory glands. Recurrent or metastatic (R/M) ACC is generally considered resistant to cytotoxic chemotherapy. Recent phase II studies have reported improved objective response rates (ORR) with the use of the multi-kinase inhibitor lenvatinib. We sought to evaluate real-world experience of R/M ACC patients treated with lenvatinib monotherapy within the UK National Health Service (NHS) to determine the response rates by Response Evaluation Criteria of Solid Tumour (RECIST) and clinical outcomes. Twenty-three R/M ACC patients from eleven cancer centres were included. All treatment assessments for clinical decision making related to drug therapy were undertaken at the local oncology centre. Central radiology review was performed by an independent clinical trial radiologist and blinded to the clinical decision making. In contrast to previously reported ORR of 12-15%, complete or partial response was not observed in any patients. Eleven patients (52.4%) had stable disease and 5 patients (23.8%) had progression of disease as the best overall response. The median time on treatment was 4 months and the median survival from discontinuation was 1 month. The median PFS and OS from treatment initiation were 4.5 months and 12 months respectively. Multicentre collaborative studies such as this are required to evaluate rare cancers with no recommended standard of care therapy and variable disease courses.
    • Swiss germ-cell cancer consensus recommendations

      Beyer, J.; Berthold, D.; Bode, P. K.; Cathomas, R.; Fankhauser, Christian D; Fischer, S.; Gillessen, S.; Gross, T.; Hermanns, T.; Honecker, F.; et al. (2021)
      Approximately 420 men are diagnosed with germ-cell cancer (GCC) in Switzerland each year. Recent international guidelines outline management issues, but many aspects remain controversial in an area of highly individualised treatments. Even more than in other tumour types, in GCC the challenge is to choose exactly the correct treatment for an individual patient. Overtreatment in patients likely to be cured must be avoided to reduce long-term toxicities. On the other hand, treatment intensification is required in patients presenting with adverse prognostic factors. Therefore, referral to expert centres or consultations with an expert for a second opinion is strongly recommended. In 2020, Swiss experts discussed their strategies in a consensus meeting during the virtual Swiss Oncology and Haematology Congress (SOHC) in order to harmonise their concepts and to suggest optimal strategies for the management of GCC patients in Switzerland. Votes on controversial issues were obtained and are presented in this review wherever applicable.
    • Hospital volume and outcomes after radical prostatectomy: a national population-based study using patient-reported urinary continence and sexual function

      Nossiter, J.; Morris, M.; Cowling, T. E.; Parry, M. G.; Sujenthiran, A.; Aggarwal, A.; Payne, H.; van der Meulen, J.; Clarke, Noel W; Cathcart, P.; et al. (2021)
      Background: Improvements in short-term outcomes have been reported for hospitals with higher radical prostatectomy (RP) volumes. However, the association with longer-term functional outcomes is unknown. Methods: All patients diagnosed with non-metastatic prostate cancer in the English NHS between 2014 and 2016 who underwent RP (N = 10,089) were mailed a survey ≥18 months after diagnosis. Differences in patient-reported urinary continence and sexual function (EPIC-26 on scale from 0 to 100) by hospital volume group (≤60, 61-100, 101-140, >140 RPs/year) were estimated using multilevel linear regression. Results: Overall, 7702 men (76.3%) responded. There were no statistically significant differences in urinary continence (p = 0.08) or sexual function scores with increasing volume group (p = 0.2). When modelled as a linear function, we found a non-significant increase of 0.70 (95% CI -0.41 to 1.80; p = 0.22) in urinary continence and a significant increase of 1.54 (0.62-2.45; p = 0.001) in sexual function scores for a 100-procedure increase in hospital volume, which did not meet the threshold for a minimal clinically important difference (10-12 points). The results were similar for robotic-assisted RP (5529 men [71.8%]). Conclusions: These results do not support further centralisation of RP services beyond levels in England where four in five hospitals perform >60 RPs/year.
    • Determinants of variation in radical local treatment for men with high-risk localised or locally advanced prostate cancer in England

      Parry, M. G.; Boyle, J. M.; Nossiter, J.; Morris, M.; Sujenthiran, A.; Berry, B.; Cathcart, P.; Aggarwal, A.; van der Meulen, J.; Payne, H.; et al. (2021)
      Background: Many factors are implicated in the potential 'under-treatment' of prostate cancer but little is known about the between-hospital variation. Methods: The National Prostate Cancer Audit (NPCA) database was used to identify high-risk localised or locally advanced prostate cancer patients in England, between January 2014 and December 2017, and the treatments received. Hospital-level variation in radical local treatment was explored visually using funnel plots. The intra-class correlation coefficient (ICC) quantified the between-hospital variation in a random-intercept multivariable logistic regression model. Results: 53,888 men, from 128 hospitals, were included and 35,034 (65.0%) received radical local treatment. The likelihood of receiving radical local treatment was increased in men who were younger (the strongest predictor), more affluent, those with fewer comorbidities, and in those with a non-Black ethnic background. There was more between-hospital variation (P < 0.001) for patients aged ≥80 years (ICC: 0.235) compared to patients aged 75-79 years (ICC: 0.070), 70-74 years (ICC: 0.041), and <70 years (ICC: 0.048). Comorbidity and socioeconomic deprivation did not influence the between-hospital variation. Conclusions: Radical local treatment of high-risk localised or locally advanced prostate cancer depended strongly on age and comorbidity, but also on socioeconomic deprivation and ethnicity, with the between-hospital variation being highest in older patients.
    • Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists

      Lindsay, Colin R; Shaw, E. C.; Moore, D. A.; Rassl, D.; Jamal-Hanjani, M.; Steele, N.; Naheed, S.; Dick, C.; Taylor, F.; Adderley, Helen; et al. (2021)
      Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.
    • Impact of hypofractionated radiotherapy on patient-reported outcomes in prostate cancer: results up to 5 yr in the CHHiP trial (CRUK/06/016)

      Staffurth, J. N.; Haviland, J. S.; Wilkins, A.; Syndikus, I.; Khoo, V.; Bloomfield, D.; Parker, C.; Logue, John P; Scrase, C.; Birtle, A.; et al. (2021)
      Background: Moderate hypofractionation is the recommended standard of care for localised prostate cancer following the results of trials including Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP). Evaluation of long-term patient-reported outcomes (PROs) is important to confirm safety and enhance patient information. Objective: To determine whether 5-yr PROs from the CHHiP quality of life (QoL) substudy confirm 2-yr findings and assess patterns over follow-up. Design, setting, and participants: A phase III randomised controlled trial recruited from 2002 to 2011. The QoL substudy completed accrual in 2009; participants were followed up to 5 yr after radiotherapy. Analyses used data snapshot taken on August 26, 2016. A total of 71 radiotherapy centres were included in the study (UK, Republic of Ireland, Switzerland, and New Zealand); all 57 UK centres participated in the QoL substudy. CHHiP recruited 3216 men with localised prostate cancer (cT1b-T3aN0M0). Intervention: Conventional (74 Gy/37 fractions/7.4 wk) or hypofractionated radiotherapy (60 Gy/20 fractions/4 wk or 57 Gy/19 fractions/3.8 wk) was delivered with intensity-modulated techniques. Outcome measurements and statistical analysis: University of California Los Angeles Prostate Cancer Index, Short Form 36 and Functional Assessment of Cancer Therapy-Prostate, or Expanded Prostate Cancer Index Composite and Short Form 12 questionnaires were administered at baseline, before radiotherapy, at 10 wk, and at 6, 12, 18, 24, 36, 48, and 60 mo after radiotherapy. The QoL primary endpoint was overall bowel bother. Results and limitations: The QoL substudy recruited 2100 patients; 1141 5-yr forms were available from 1957 patients still alive (58%). There were no statistically significant differences in 5-yr prevalence of overall "moderate or big" bowel bother: 19/349 (5.4%), 29/381 (7.6%), and 21/393 (5.3%) for 74, 60, and 57 Gy, respectively; overall urinary or sexual bother at 5 yr was similar between schedules. Bowel and urinary symptoms remained stable from 2 to 5 yr for all schedules. Some evidence of worsening overall sexual bother from baseline to 5 yr was less likely in the hypofractionated schedules compared with 74 Gy (odds ratios for increase in bother score vs 74 Gy: 0.55 [0.30-0.99], p = 0.009 for 60 Gy, and 0.52 [0.29-0.94], p = 0.004 for 57 Gy). General QoL scores were similar between schedules at 5 yr. Conclusions: Longer follow-up confirms earlier findings, with similar patient-reported bowel, urinary, and sexual problems between schedules overall. The continued low incidence of moderate or high bother confirms that moderate hypofractionation should be the standard of care for intermediate-risk localised prostate cancer. Patient summary: We looked at patient-reported outcomes up to 5 yr after treatment in a trial of different radiotherapy schedules for prostate cancer. The findings confirmed that shorter radiotherapy schedules were as safe as standard radiotherapy in terms of bowel, urinary, and sexual problems. TAKE HOME MESSAGE: Bowel, urinary, and sexual symptoms were similar between schedules up to 5 yr. The continued low incidence of moderate/high bother confirms that moderate hypofractionated radiotherapy should be considered the standard of care for men with intermediate-risk prostate cancer.
    • Changes in treatment pattern and costs in advanced hepatocellular carcinoma (HCC)

      Muszbek, N.; Evans, R.; Remak, E.; Brennan, V. K.; Colaone, F.; Shergill, S.; Ross, P.; Mullan, Damian; Visible Analytics, Reading, UK. Visible Analytics, Oxford, UK. Visible Analytics, Budapest, Hungary. Health Economics, Pricing, Reimbursement & Market Access, SIRTEX Medical United Kingdom Ltd, London, UK. Department of Medical Oncology, Guy's & St Thomas' Nhs Foundation Trust, London, UK. Department of Radiology, The Christie NHS Foundation Trust, Manchester, UK. (2021)
      Introduction: While essential for cost-effectiveness analyses, there are no current resource use and cost data available for advanced hepatocellular carcinoma (HCC) and selective internal radiation therapy (SIRT). The study aims to assess current resource use and costs in HCC and for SIRT compared to historical survey data. Areas covered: To address this data gap, resource use was elicited via surveys and interviews with medical professionals experienced with HCC and SIRT in the United Kingdom. Unit costs were from publicly available databases. Resource use and costs were estimated and compared to prior surveys. Expert opinion: From eleven responses, pre-progression costs for SIRT and systemic therapy were £256.77 and £292.27/month, respectively. One-off progression and post-progression costs were £209.98 and £522.84/month. Monthly costs were 54%-79% lower than in previous surveys, due to reduction in hospitalizations and funded social care. Furthermore, substantial differences in resource use associated with SIRT between clinical practice and clinical trials were found. In conclusion, increased availability and familiarity with systemic treatments has led to important changes in HCC care and SIRT administration. The uncertainty from the use of expert opinion and the limited number of hospitals with SIRT experience can be addressed with future research using large databases, registries.
    • Evaluating the potential utility of three-dimensional printed models in preoperative planning and patient consent in gastrointestinal cancer surgery

      Povey, M.; Powell, S.; Howes, N.; Vimalachandran, D.; Sutton, Paul A; Countess of Chester Hospital NHS Foundation Trust, Chester, UK (2021)
      Introduction: The Future of Surgery report from the Royal College of Surgeons of England acknowledges the important role that three-dimensional imaging will play in support of personalised surgical interventions. One component of this is preoperative planning. We investigated surgeons' and patients' perceptions of this evolving technology. Materials and methods: Ethical approval was obtained. From a normal computed tomography scan, three-dimensional models of the stomach, pancreas and rectum were rendered and printed on an Ultimaker™ three-dimensional printer. Semi-structured interviews were performed with surgeons and patients to explore perceived model effectiveness and utility. Likert scales were used to grade responses (1 = strongly disagree; 10 = strongly agree) and qualitative responses recorded. Results: A total of 26 surgeons (9 rectal, 9 oesophagogastric, 8 pancreatic) and 30 patients (median age 62 years, interquartile range, IQR, 68-72 years; 57% male) were recruited. Median surgeon scores were effectiveness for preoperative planning, 6 (IQR 3-7), authenticity, 5 (IQR 3-6), likability, 6 (IQR 4-7), promoting learning, 7 (IQR 5-8), utility, 6 (IQR 5-7) and helping patients, 7 (IQR 5-8). Median patient scores were usefulness to the surgeon, 8 (IQR 7-9), authenticity, 8 (IQR 6-8), likability, 8 (IQR 7-8), helping understanding of condition, 8 (IQR 8-9), helping understanding of surgery, 8 (IQR 7-9) and feeling uncomfortable, 1 (IQR 1-4). Median overall decisional conflict score (0 = no; 100 = high) was 22 (IQR 19-28) and decision effectiveness was 25 (IQR 19-30). Discussion: Overall, patients and surgeons considered that three-dimensional printed models were effective and had potential utility in education and, to a lesser extent, preoperative planning. Patient decisional conflict and effectiveness scores were weighted towards certainty in decision making but had room for improvement, which three-dimensional models may help to facilitate.
    • Examining the experiences and support needs of bereaved parents after the death of a child during early adulthood from cancer

      Law, Kate; Kirk, S.; The Christie Hospital (Ms Law), Manchester; and Division of Nursing, Midwifery and Social Work, School of Health Sciences, University of Manchester (Dr Kirk), UK. (2021)
      Background: Parents experience unique grief, which may be experienced differently by mothers and fathers. A lack of knowledge about the particular bereavement experiences of the parents of young adults exists. Objective: The aim of this study was to investigate experiences and support needs of parents after the death of a child (aged 16-29 years) from cancer, exploring changes over time. Methods: The study used a Charmazian constructivist grounded theory approach. Semistructured interviews were conducted with 11 parents (7 mothers and 4 fathers) purposefully sampled and bereaved between 15 months and 7 years. Data were analyzed inductively using the constant comparative approach for category development. Results: "Living with continual loss" emerged as the core category central to parents' experiences of bereavement. Feelings of continual loss were compounded by parents' lack of information ("grieving in the dark") and a perceived lack of understanding from families and friends ("grieving alone"). Parents discovered strategies to manage the feeling of loss: "changing routines," "preserving the meaning of home," "maintaining memories and presence," and "sharing experiences." Conclusions: This is the first study focusing solely on the experiences and support needs of bereaved parents of young adults who have died of cancer. Parents live with a continual sense of loss irrespective of the length of bereavement, and a lack of bereavement information and empathetic emotional support can exist. Implications for practice: The need for improved information giving and development of peer support for bereaved parents has been identified. Cancer centers have a continuing role in developing and providing this support.
    • The UK's contribution to cancer control in low-income and middle-income countries

      Stanway, S.; Lodge, M.; Sullivan, R.; Diprose, K.; Young, A. M.; Crisp, N.; Lewis, P.; Eden, T.; Aggarwal, A.; Nadin, A.; et al. (2021)
      Cancer mortality rates in low-income and middle-income countries (LMICs) are unacceptably high, requiring both collaborative global effort and in-country solutions. Experience has shown that working together in policy, clinical practice, education, training, and research leads to bidirectional benefit for LMICs and high-income countries. For over 60 years, the UK National Health Service has benefited from recruitment from LMICs, providing the UK with a rich diaspora of trained health-care professionals with links to LMICs. A grassroots drive to engage with partners in LMICs within the UK has grown from the National Health Service, UK academia, and other organisations. This drive has generated a model that rests on two structures: London Global Cancer Week and the UK Global Cancer Network, providing a high-value foundation for international discussion and collaboration. Starting with a historical perspective, this Series paper describes the UK landscape and offers a potential plan for the future UK's contribution to global cancer control. We also discuss the opportunities and challenges facing UK partnerships with LMICs in cancer control. The UK should harness the skills, insights, and political will from all partners to make real progress.