Global application of National Comprehensive Cancer Network resource-stratified guidelines for systemic treatment of colon cancer: a population-based, customisable model for cost, demand, and procurement.

BACKGROUND: Resource-stratified guidelines (RSGs) can inform systemic treatment decisions in the face of limited resources. The objective of this study was to develop a customisable modelling tool to predict the demand, cost, and drug procurement needs of delivering National Comprehensive Cancer Network (NCCN) RSG-based systemic treatment for colon cancer. METHODS: We developed decision trees for first-course systemic therapy for colon cancer based on the NCCN RSGs. Decision trees were merged with data from the Surveillance, Epidemiology, and End Results programme, the International Agency for Research on Cancer's GLOBOCAN 2020 national estimates for colon cancer incidence, country-level income data, and data on drug costs from Redbook (USA), the Pharmaceutical Benefits Scheme (Australia), and the Management Sciences for Health 2015 International Medical Products price guide to estimate global treatment needs and costs, and forecast drug procurement. Simulations and sensitivity analyses were used to explore the effect of scaling up services globally and the effect of alternative stage distributions on treatment demand and cost. We generated a customisable model, in which estimates can be tailored to local incidence, epidemiological, and costing data. FINDINGS: First-course systemic therapy is indicated in 608 314 (53·6%) of 1 135 864 colon cancer diagnoses in 2020. Indications for first-course systemic therapy are projected to rise to 926 653 in 2040; the indications in 2020 might be as high as 826 123 (72·7%), depending on stage distribution assumptions. Adhering to NCCN RSGs, patients with colon cancer in low-income and middle income countries (LMICs) would constitute 329 098 (54·1%) of 608 314 global systemic therapy demands, but only 10% of global expenditure on systemic therapies. The total cost of NCCN RSG-based first-course systemic therapy for colon cancer in 2020 would be between about US$4·2 and about $4·6 billion, depending on stage distribution. If all patients with colon cancer in 2020 were treated according to maximal resources, global expenditure on systemic therapy for colon cancer would rise to around $8·3 billion. INTERPRETATION: We have developed a customisable model that can be applied at global, national, and subnational levels to estimate systemic treatment needs, forecast drug procurement, and calculate expected drug costs on the basis of local data. This tool can be used to plan resource allocation for colon cancer globally. FUNDING: None.

European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

Health service planning to assess the expected impact of centralising specialist cancer services on travel times, equity, and outcomes: a national population-based modelling study.

BACKGROUND: Centralisation of specialist cancer services is occurring in many countries, often without evaluating the potential impact before implementation. We developed a health service planning model that can estimate the expected impacts of different centralisation scenarios on travel time, equity in access to services, patient outcomes, and hospital workload, using rectal cancer surgery as an example. METHODS: For this population-based modelling study, we used routinely collected individual patient-level data from the National Cancer Registration and Analysis Service (NCRAS) and linked to the NHS Hospital Episode Statistics (HES) database for 11 888 patients who had been diagnosed with rectal cancer between April 1, 2016, and Dec 31, 2018, and who subsequently underwent a major rectal cancer resection in 163 National Health Service (NHS) hospitals providing rectal cancer surgery in England. Five centralisation scenarios were considered: closure of lower-volume centres (scenario A); closure of non-comprehensive cancer centres (scenario B); closure of centres with a net loss of patients to other centres (scenario C); closure of centres meeting all three criteria in scenarios A, B, and C (scenario D); and closure of centres with high readmission rates (scenario E). We used conditional logistic regression to predict probabilities of affected patients moving to each of the remaining centres and the expected changes in travel time, multilevel logistic regression to predict 30-day emergency readmission rates, and linear regression to analyse associations between the expected extra travel time for patients whose centre is closed and five patient characteristics, including age, sex, socioeconomic deprivation, comorbidity, and rurality of the patients' residential areas (rural, urban [non-London], or London). We also quantified additional workload, defined as the number of extra patients reallocated to remaining centres. FINDINGS: Of the 11 888 patients, 4130 (34·7%) were women, 5249 (44·2%) were aged 70 years and older, and 5005 (42·1%) had at least one comorbidity. Scenario A resulted in closures of 43 (26%) of the 163 rectal cancer surgery centres, affecting 1599 (13·5%) patients; scenario B resulted in closures of 112 (69%) centres, affecting 7029 (59·1%) patients; scenario C resulted in closures of 56 (34%) centres, affecting 3142 (26·4%) patients; scenario D resulted in closures of 24 (15%) centres, affecting 874 (7·4%) patients; and scenario E resulted in closures of 16 (10%) centres, affecting 1000 (8·4%) patients. For each scenario, there was at least a two-times increase in predicted travel time for re-allocated patients with a mean increase in travel time of 23 min; however, the extra travel time did not disproportionately affect vulnerable patient groups. All scenarios resulted in significant reductions in 30-day readmission rates (range 4-48%). Three hospitals in scenario A, 41 hospitals in in scenario B, 13 hospitals in scenario C, no hospitals in scenario D, and two hospitals in scenario E had to manage at least 20 extra patients annually. INTERPRETATION: This health service planning model can be used to to guide complex decisions about the closure of centres and inform mitigation strategies. The approach could be applied across different country or regional health-care systems for patients with cancer and other complex health conditons. FUNDING: National Institute for Health Research.

Survival outcomes associated with completion of adjuvant oxaliplatin-based chemotherapy for stage III colon cancer: A national population-based study.

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. Four thousand one hundred and forty-seven 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 5-fluoropyrimidine and oxaliplatin (FOLFOX) cycles, or <4, 4-7, or 8 capecitabine and oxaliplatin (CAPOX) cycles, adjusted for patient, tumour and hospital-level characteristics. Median age was 64 years. Thirty-two per cent of patients had at least one comorbidity. Forty-two per cent of patients had T4 disease, and 40% had N2 disease. Compared to completion of 12 FOLFOX cycles, cancer-specific mortality was higher in patients completing <6 cycles [subdistribution hazard ratios (sHR) 2.17; 95% CI 1.56-3.03] or 6-11 cycles (sHR 1.40; 95% CI 1.09-1.78) (P < .001). Compared to completion of 8 CAPOX cycles, cancer-specific mortality was higher in patients completing <4 cycles (sHR 2.02; 95% CI 1.53-2.67) or 4-7 cycles (sHR 1.63; 95% CI 1.27-2.10) (P < .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.

Towards an evidence-informed value scale for surgical and radiation oncology: a multi-stakeholder perspective.

Surgery and radiotherapy, two locoregional cancer treatments, are essential to help improve cancer outcomes, control, and palliation. The continued evolution in treatment processes, techniques, and technologies-often at substantially increased costs-demands for direction on outcomes that are most valued by patients, and the evidence that is required before clinical adoption of these practices. Three recently introduced frameworks-the European Society for Medical Oncology Magnitude of Clinical Benefit Scale, the American Society of Clinical Oncology Value Framework, and the National Comprehensive Cancer Network Blocks-which all help define the value of oncology treatments, were appraised with a focus on their methods and definition of patient benefit. In this Review, we investigate the applicability of these frameworks to surgical and radiotherapy innovations. Findings show that these frameworks are not immediately transferable to locoregional cancer treatments. Moreover, the lack of emphasis on patient perspective and the reliance on traditional, trial-based endpoints such as survival, disease-free survival, and safety, calls for a new framework that includes real-world evidence with focus on the whole spectrum of patient-centred endpoints. Such an evidence-informed value scale would safeguard against the proliferation of low-value innovation while simultaneously increasing access to treatments that show significant improvements in the outcomes of cancer care.

Prophylactic antibiotics do not affect cultures in the treatment of an infected TKA: a prospective trial.

UNLABELLED: Prophylactic antibiotics are frequently withheld until cultures are obtained in revision total knee arthroplasty (TKA). We undertook a prospective study to determine whether prophylactic preoperative intravenous antibiotics would affect the results of cultures obtained intraoperatively. We enrolled 25 patients with 26 infected TKAs, a known preoperative infecting organism, and no recent antibiotic therapy. Reaspiration of the infected TKA was performed after anesthesia and sterile preparation. Intravenous antibiotic prophylaxis was then administered and the tourniquet inflated. Intraoperative culture swabs and tissue were obtained at arthrotomy. The timing of events was recorded. Pre- and postantibiotic culture data were analyzed to determine the effect of intravenous preoperative prophylactic antibiotics on cultures obtained intraoperatively. Infections were acute postoperative (four), chronic (19), and acute hematogenous (three). The most common infecting organism was cloxacillin-sensitive Staphylococcus aureus (nine knees [35%]). Preoperative prophylactic antibiotics did not affect the results of intraoperative cultures and we therefore believe should not be withheld before surgery for an infected TKA when an organism has been identified on aspiration preoperatively, and there has been no recent (4 weeks) antimicrobial therapy. LEVEL OF EVIDENCE: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Effect of respiratory muscle endurance training in patients with COPD undergoing pulmonary rehabilitation.

BACKGROUND: Respiratory muscle endurance training (hyperpnea training) has been shown to have beneficial effects in patients with COPD. STUDY OBJECTIVES: The purpose of this study was to determine whether hyperpnea training, when added to an endurance exercise training program, would lead to additional benefits compared with endurance training alone in patients with COPD. SETTING AND PARTICIPANTS: Patients with COPD entering an 8-week outpatient pulmonary rehabilitation program. Fifteen patients (mean [+/- SE] FEV1, 45 +/- 6% predicted) were randomized to combined therapy, and 14 patients (mean FEV1, 44 +/- 4% predicted) were randomized to endurance training. METHODS: Peak exercise capacity, exercise endurance time during constant workload cycle exercise, 6-min walk distance, quality of life as measured by the chronic respiratory questionnaire, respiratory muscle strength and endurance, and quadriceps fatigability were measured before and after endurance or combined training. RESULTS: After rehabilitation, peak exercise capacity, exercise endurance time, 6-min walk distance, and quality of life all increased in both groups, but there was no significant difference in the extent of improvement between groups. Mean respiratory muscle endurance increased to a significantly greater extent in the combined therapy group (17.5 +/- 2.7 vs 8.5 +/- 2.5 min, respectively; p = 0.02). Respiratory muscle strength was significantly increased, and quadriceps fatigability was significantly reduced after rehabilitation in the combined therapy group but not in the endurance training group, but the difference between groups did not reach statistical significance. CONCLUSION: The endurance of the respiratory muscles can be improved by specific training beyond that achieved by endurance training alone in patients with COPD. However, this improvement did not translate into additional improvement in quality of life or exercise performance.