BACKGROUND: Estimates of the cost of cancer care are crucial for the economic evaluation of screening interventions and other early cancer diagnosis initiatives. However, data on the cost of cancer is scarce. This study...BACKGROUND: Estimates of the cost of cancer care are crucial for the economic evaluation of screening interventions and other early cancer diagnosis initiatives. However, data on the cost of cancer is scarce. This study estimated National Health Service (NHS) hospital care costs for eight cancer types by stage at diagnosis in England. METHODS: This national, retrospective, population-based cohort study used individual patient-level data collated by the National Disease Registration Service, NHS England. We included patients aged 50-79 years who were diagnosed with a colorectal, head and neck, liver and bile duct, lung, lymphoma, oesophageal, ovarian, or pancreatic cancer in England between Jan 1, 2014, and Dec 31, 2017. For each patient, we obtained linked national health-care records, incorporating all inpatient hospital care, outpatient activity, and accident and emergency department attendances, and costed these using a payer perspective. Patients were excluded if registration was death certificate only, records related only to a secondary metastatic site, sex and cancer type were incompatible, death status or date were uncertain, or there were zero health-care costs from 6 months before diagnosis to end of follow-up. Net, cancer-related, regression-adjusted hospital care costs were reported for each cancer type and stage overall, annually, and by phase of care. Within each annual period and phase, mean monthly costs were also estimated. FINDINGS: Of 359 106 cancer records registered, 345 629 cancers were available for analysis, and 333 657 cancers were included in the analysis (147 334 [44·2%] occurred in female patients and 186 323 [55·8%] in male patients; 303 227 [90·9%] among participants of White ethnicity, 4452 [1·3%] among participants of mixed or other ethnicity, 7870 [2·3%] among participants of Asian ethnicity, 4179 [1·3%] among participants of Black ethnicity, and 13 929 [4·2%] among participants of unknown ethnicity). Overall costs were higher at later stages for colorectal, head and neck, lymphoma, and ovarian cancers with mean stage IV costs of £37 838, £36 657, £42 667, and £45 871, respectively. Costs for liver and bile duct, lung, oesophageal, and pancreatic cancers were highest for those diagnosed at stage II (£28 356, £29 553, £33 640, and £39 351, respectively), and slightly lower at stages I, III, and IV. Health-care costs were highest in the initial treatment and the end-of-life phases of care. Within each phase, mean cost per month increased with stage for most cancer types studied, though fewer months of follow-up were observed in each phase for liver and bile duct, lung, oesophageal, and pancreatic cancers. INTERPRETATION: Cancer-related NHS hospital care costs by stage at diagnosis differed between cancer types; this heterogeneous pattern could inform detailed and nuanced economic evaluations of early detection initiatives. FUNDING: GRAIL Bio UK.
BACKGROUND: Combination therapy with vibostolimab plus pembrolizumab has previously shown promising antitumor activity in melanoma. We aimed to evaluate the efficacy and safety of vibostolimab coformulated with pembroliz...BACKGROUND: Combination therapy with vibostolimab plus pembrolizumab has previously shown promising antitumor activity in melanoma. We aimed to evaluate the efficacy and safety of vibostolimab coformulated with pembrolizumab as adjuvant therapy for high-risk resected melanoma. METHODS: This randomised, double-blind, phase 3 study was done at 205 global sites (hospitals and cancer centres). Participants aged 12 years or older with surgically resected, stage IIB-IV cutaneous melanoma per the American Joint Committee on Cancer Cancer Staging Manual 2017 (8th edition), with no evidence of metastatic disease after resection, were randomly assigned (1:1) to receive vibostolimab 200 mg coformulated with pembrolizumab 200 mg or pembrolizumab 200 mg alone intravenously every 3 weeks. Randomisation was done using an interactive response technology system and was stratified by risk-based staging and geographical region. Participants, investigators, and site staff were masked to group assignment. The primary endpoint was recurrence-free survival assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the study treatment. The protocol-prespecified first interim analysis was an event-driven nonbinding futility analysis of recurrence-free survival that was planned for when 111 events had occurred (futility bar of observed HR 0·95). This study is registered with ClinicalTrials.gov (NCT05665595), and is closed to recruitment. FINDINGS: Between Jan 19, 2023, and March 6, 2024, 1402 participants were randomly assigned to receive coformulated vibostolimab-pembrolizumab (n=701) or pembrolizumab (n=701). At the first interim analysis, median study follow-up, defined as time from randomisation to data cutoff, was 4·2 months (IQR 1·9-6·7). The median age was 61·0 years (IQR 51·0-70·0), 829 (59%) of 1402 participants were male and 573 (41%) were female. 1107 (79%) of participants were White, 273 (19%) were Asian, and 22 (2%) were of other race or race was missing. At the time of the first interim analysis, a total of 119 (8%) of 1402 participants had had a recurrence-free survival event, including 67 (10%) of 701 in the vibostolimab-pembrolizumab group and 52 (7%) of 701 in the pembrolizumab alone group. The median recurrence-free survival was not reached in either group; the hazard ratio for recurrence-free survival in the vibostolimab-pembrolizumab group versus pembrolizumab alone group was 1·25 (95% CI 0·9-1·8). The most common (occurred in more than five participants) grade 3 or higher treatment-related adverse events were adrenal insufficiency in 13 (2%) participants, hepatitis in 11 (2%) participants, rash in 9 (1%) participants, maculopapular rash in 7 (1%) participants, and pruritus in 6 (1%) participants in the vibostolimab-pembrolizumab group and increased alanine aminotransferase in 7 (1%) participants in the pembrolizumab alone group. Treatment-related serious adverse events occurred in 74 (11%) participants and 30 (4%) participants, respectively. Treatment-related adverse events led to death in two (<1%) participants in the vibostolimab-pembrolizumab group (myasthenia gravis and myocarditis) and one participant (<1%) in the pembrolizumab group (myositis). The external data monitoring committee decided to discontinue the study according to prespecified futility criteria. INTERPRETATION: Vibostolimab coformulated with pembrolizumab did not provide additional clinical benefit versus pembrolizumab as adjuvant therapy in participants with resected stage IIB-IV melanoma. Pembrolizumab monotherapy remains a standard of care for resected high-risk melanoma. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.
Nilsson P, Gunnlaugsson A, Beckman L
… +16 more, Widmark A, Fransson P, Hoyer M, Lagerlund M, Kindblom J, Johansson B, Björnlinger K, Ginman C, Olsson M, Agrup M, Kjellén E, Zackrisson B, Tavelin B, Franzén L, Anderson H, Thellenberg Karlsson C
BACKGROUND: HYPO-RT-PC is a phase 3 trial comparing ultra-hypofractionated and conventionally fractionated radiotherapy in intermediate-to-high-risk localised prostate cancer. This 10-year update reports long-term effica...BACKGROUND: HYPO-RT-PC is a phase 3 trial comparing ultra-hypofractionated and conventionally fractionated radiotherapy in intermediate-to-high-risk localised prostate cancer. This 10-year update reports long-term efficacy and toxicity outcomes. METHODS: In this open-label, randomised, phase 3, non-inferiority trial done in ten centres in Sweden and two in Denmark, we recruited men aged 75 years or younger with intermediate-risk or high-risk prostate cancer and a WHO performance status between 0 and 2. Previous or current androgen deprivation therapy was not permitted. Patients were randomly assigned (1:1) to ultra-hypofractionated radiotherapy (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventionally fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). Randomisation was performed with a minimisation algorithm balancing T stage, Gleason score, prostate-specific antigen, and trial centre. The primary endpoint was failure-free survival, defined as time from randomisation to the first occurrence of biochemical failure, evidence of clinical progression, initiation of androgen deprivation therapy, or death from prostate cancer, analysed in the per-protocol population. The non-inferiority margin was 4% at 5 years and had previously been met, corresponding to a critical hazard ratio (HR) limit of 1·338. Toxicity was assessed using the Radiation Therapy Oncology Group morbidity scale. Here, we report long-term efficacy and safety results at 10 years. The trial is registered with the ISRCTN registry, ISRCTN45905321, and is closed. FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionated radiotherapy (n=602) or ultra-hypofractionated radiotherapy (n=598). Ten patients withdrew consent, eight were found to be ineligible, and two died of reasons unrelated to prostate cancer. 1180 patients constituted the per-protocol population (591 in the conventional fractionation group and 589 in the ultra-hypofractionation group). After a median follow-up of 10·6 years (IQR 9·0-13·0) in the conventional fractionation group and 10·7 years (9·1-12·7) in the ultra-hypofractionation group, 205 and 178 primary events were observed, respectively. 10-year failure-free survival was 65% (95% CI 61-69) in the conventionally fractionated group and 72% (68-76) in the ultra-hypofractionated group. The adjusted HR for the primary endpoint was 0·84 (95% CI 0·69-1·03; Cox regression analysis), confirming non-inferiority. The 10-year cumulative incidence of late grade 2 or worse genitourinary toxic effects was 30% (95% CI 26-34) in the conventional fractionation group and 28% (24-32) in the ultra-hypofractionated group (HR 1·01, 95% CI 0·81-1·25; p=0·95). For late grade 2 or worse gastrointestinal toxic effects, the corresponding figures were 14% (95% CI 11-18) and 14% (11-17; HR 0·94, 95% CI 0·70-1·28; p=0·72). INTERPRETATION: This 10-year follow-up confirms the non-inferiority of the ultra-hypofractionated radiotherapy regimen compared with the conventionally fractionated, with similar toxicity profiles. The findings support the seven-fraction schedule as a safe, effective, and practical standard-of-care option for patients with intermediate-risk prostate cancer. FUNDING: The Nordic Cancer Union, the Swedish Cancer Society, the Swedish Research Council, the Swedish Prostate Cancer Association, and Cancerforskningsfonden i Norrland.
Kaye EC, Bogetz J, Barton KS
… +9 more, Bell CJ, Johnston EE, Pozzar RA, Superdock A, Thorne S, Weaver MS, Wiener L, Graetz DE, Applied Qualitative Research Working Group 2
Qualitative research is essential in addressing unresolved problems in oncology, yet high-yield strategies to bolster qualitative approaches in cancer research are scarce. To promote the unique strengths of qualitative r...Qualitative research is essential in addressing unresolved problems in oncology, yet high-yield strategies to bolster qualitative approaches in cancer research are scarce. To promote the unique strengths of qualitative research and increase uptake in the field of oncology, qualitative methods should show quality and credibility on par with quantitative methods. This Review presents recommendations for applied qualitative cancer research generated by multidisciplinary experts who were invited to attend the Symposium on Applied Qualitative Research, held on Nov 11-12, 2024, based on their contributions to the field. First, we describe the interplay between quantitative and qualitative methods and discuss how current research standards for qualitative data reporting are necessary but insufficient for establishing rigour. Second, we propose expert recommendations comprising five key pillars-engagement, flexibility, transparency, transferability, and impact-with actionable examples for application across the cancer research continuum. We advocate for use of these recommendations in the design, conduct, analysis, dissemination, and appraisal of qualitative research in oncology to advance outcomes.
This Review underscores qualitative research as an indispensable facet of scientific inquiry to improve provision of safe, effective, and affordable care for patients with cancer worldwide. Representing a global working...This Review underscores qualitative research as an indispensable facet of scientific inquiry to improve provision of safe, effective, and affordable care for patients with cancer worldwide. Representing a global working group of applied qualitative researchers, our multidisciplinary authorship team defines qualitative research, characterises its purpose and value, and describes specific ways in which qualitative inquiry is central to advancing cures, treatment, and quality of life in oncology. In this Review, we put forward an imperative for the use of qualitative methods to assess context, understand population needs, design interventions, optimise implementation, and investigate mechanisms of action underpinning changes in health outcomes. We highlight the ways in which qualitative methods capture cultural context, making them crucial for scientific inquiry, and discuss the importance of using qualitative research to define research priorities, uncover and address understudied topics, and elevate marginalised voices globally. Ultimately, this Review serves as a call to action for improved integration of qualitative scholarship across each stage of cancer research and establishes a roadmap for collaboration among clinicians, scientists, publishers, and funders to recognise qualitative research as essential for scientific advancement in the field of oncology.