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Abstract: Transcalcaneal talonavicular dislocation is a rare injury, with very few reported cases. Of these, most have been the result of high-energy mechanisms such as road traffic collisions or falls from a height. The management of this injury is challenging, and treatment is fraught with a high rate of disability, infection, and amputation. We describe the successful management of the first reported case of a low-energy transcalcaneal talonavicular dislocation in a 71-year-old female. Combined external and internal fixation was used to reduce and maintain the injury, with a resultant good functional and complication-free outcome at 1 year after the injury. Our experience highlights the prevalence of these devastating injuries caused by relatively benign mechanisms in an increasingly older population with osteoporotic bone. It also indicates that operative stabilization of a low-energy injury can be more successful than that with the traditional high-velocity trauma. [Copyright &y& Elsevier]

Objectives The objective of this study is to explore how the UK versus the USA compare in patient characteristics, treatment patterns and overall survival (OS) of patients with advanced non-small cell lung cancer (aNSCLC) initiating first-line (1L) treatment.Design Retrospective cohort study.Setting Oncology treatment centres in the USA and UK.Participants People in the USA and UK diagnosed with aNSCLC and treated in the 1L setting between 2016 and 2018. The US cohort was obtained from a nationwide electronic health record-derived deidentified database. The UK cohort information was derived from a published study exploring the patient characteristics, treatments and outcomes of people with aNSCLC in the UK.Interventions 1L chemotherapy, immunotherapy monotherapy or targeted therapy.Primary outcome measure The primary outcome was OS—defined as the time from treatment initiation to death from any cause.Results There were 1003 patients in the UK and 3819 in the US cohorts receiving 1L therapy for aNSCLC. After standardising the US cohort to the UK cohort, median OS in the USA and UK was similar across 1L drug classes: chemotherapies (7.7 (95% CI 7.1 to 8.3) vs 8.1 (95% CI 7.4 to 8.9) months), immunotherapies (13.9 (95% CI 11.0 to 17.1) vs 14.0 (95% CI 10.7 to 20.6)) and targeted therapies (21.6 (95% CI 18.5 to 23.7) vs 20.2 (95% CI 16.0 to 30.5)). OS curves for 1L immunotherapy and targeted therapy were almost overlapping after standardisation. OS after around 12 months was higher in US patients compared with UK patients receiving 1L chemotherapy regimens. Of those receiving 1L chemotherapy, the proportion receiving any second-line therapy appeared higher for patients in the USA versus UK.Conclusions The results suggest that in aNSCLC patients receiving 1L treatment, US data have the potential to be used in technology evaluations to understand long-term OS where UK data are unavailable or sparse.

Purpose: External beam radiation therapy (EBRT) with brachytherapy boost reduces cancer recurrence in patients with prostate cancer compared with EBRT monotherapy. However, randomized controlled trials or large-scale observational studies have not compared brachytherapy boost types directly.Methods and Materials: This observational cohort study used linked national cancer registry data, radiation therapy data, administrative hospital data, and mortality records of 54,642 patients with intermediate-risk, high-risk, and locally advanced prostate cancer in England. The records of 11,676 patients were also linked to results from a national patient survey collected at least 18 months after diagnosis. Competing risk regression analyses were used to compare gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, skeletal-related events (SRE), and prostate cancer-specific mortality (PCSM) at 5 years with adjustment for patient and tumor characteristics. Linear regression was used to compare Expanded Prostate Cancer Index Composite 26-item version domain scores (scale, 0-100, with higher scores indicating better function).Results: Five-year GI toxicity was significantly increased after low-dose-rate brachytherapy boost (LDR-BB) (32.3%) compared with high-dose-rate brachytherapy boost (HDR-BB) (16.7%) or EBRT monotherapy (18.7%). Five-year GU toxicity was significantly increased after both LDR-BB (15.8%) and HDR-BB (16.6%), compared with EBRT monotherapy (10.4%). These toxicity patterns were matched by the mean patient-reported bowel function scores (LDR-BB, 77.3; HDR-BB, 85.8; EBRT monotherapy, 84.4) and the mean patient-reported urinary obstruction/irritation function scores (LDR-BB, 72.2; HDR-BB, 78.9; EBRT monotherapy, 83.8). Five-year incidences of SREs and PCSM were significantly lower after HDR-BB (2.4% and 2.7%, respectively) compared with EBRT monotherapy (2.8% and 3.5%, respectively).Conclusions: Compared with EBRT monotherapy, LDR-BB has worse GI and GU toxicity and HDR-BB has worse GU toxicity. HDR-BB has a lower incidence of SREs and PCSM than EBRT monotherapy. [ABSTRACT FROM AUTHOR]

Objectives Examine whether data from early access to medicines in the USA can be used to inform National Institute for Health and Care Excellence (NICE) health technology assessments (HTA) in oncology.Design Retrospective cohort study.Setting Oncology-based community and academic treatment centres in the USA.Participants Patients present in a nationwide electronic health record (EHR)-derived deidentified database.Interventions Cancer drugs that underwent NICE technology appraisal (TA) between 2014 and 2019.Primary and secondary outcome measures The count and follow-up time of US patients, available in the EHR, who were exposed to cancer drugs of interest in the period between Food and Drug Administration (FDA) approval and dates relevant to the NICE appraisal process.Results In 59 of 60 TAs analysed, the cancer therapy was approved in the USA before the final appraisal by NICE. The median time from FDA approval to the publication of NICE recommendations was 18.5 months, at which time the US EHR-derived database had, on average, 269 patients (SD=356) exposed to the new therapy, with a median of 75.3 person-years (IQR: 13.1–173) in time-at-risk. A case study generated evidence on real-world overall survival and treatment duration.Conclusions Across different cancer therapies, there was substantial variability in US real-world data accumulated between FDA approval and NICE decision milestones. The applicability of these data to generate evidence for HTA decision-making should be assessed on a case-by-case basis depending on the intended HTA use case.

The relationship between prostate-specific antigen (PSA) and prostate cancer (PCa) grade was traditionally thought to be linear but recent reports suggest this is not true in high-grade cancers. We aimed to compare the association between PSA and PCa-specific mortality (PCSM) in clinically localised low/intermediate and high-grade PCa. Retrospective cohort study using the National Prostate Cancer Audit database in England of men treated with external beam radiotherapy (EBRT), EBRT and brachytherapy boost (EBRT + BT), radical prostatectomy or no radical local treatment between 2014 and 2018. Multivariable competing-risk regression was used to examine the association between PSA, Gleason, and PCSM. Multivariable restricted cubic spline regression was used to explore the non-linear associations of PSA and PCSM. 102,089 men were included, of whom 71,138 had low/intermediate-grade and 22,425 had high-grade PCa. In high-grade, 4-year PCSM was higher with PSA ≤5 than PSA 5.1–10 for men treated with EBRT (hazard ratio 1.96 (95% confidence interval 1.15–3.34) or no radical local treatment (hazard ratio 1.99 (95% confidence interval 1.33–2.98). Restricted cubic spline regression showed that PSA and PCSM have a non-linear association in high-grade but a linear association in low/intermediate-grade PCa. The low-PSA/high-grade combination in M0 PCa treated with EBRT has a higher PCSM than those with high-grade and intermediate PSA levels. In high-grade disease, the PSA association was non-linear; by contrast, low/intermediate-grade had a linear relationship. This confirms a more aggressive biology in low PSA secreting high-grade PCa and a worse outcome following treatment. • Large dataset describing the prognostic value of prostate-specific antigen (PSA) in localised prostate cancer. • In high-grade prostate cancer, a low or high PSA predicts poor outcomes. • In low/intermediate-grade prostate cancer, the higher the PSA the worse the outcome. • This confirms a more aggressive biology in low PSA secreting high-grade PCa. [ABSTRACT FROM AUTHOR]

Purpose There is debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation in addition to prostate bed radiotherapy when used to treat disease recurrence following radical prostatectomy. We compared toxicity from radiation therapy (RT) to the prostate bed and pelvic lymph nodes (PBPLN-RT) with prostatebed only radiation therapy (PBO-RT) following radical prostatectomy. Methods and Materials Patients with prostate cancer who underwent post-prostatectomy RT between 2010 and 2016 were identified by using the National Prostate Cancer Audit (NPCA) database. Follow-up data was available up to December 31, 2018. Validated outcome measures, based on a framework of procedural and diagnostic codes, were used to capture ≥Grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity. An adjusted competing-risks regression analysis estimated subdistribution hazard ratios (sHR). A sHR > 1 indicated a higher incidence of toxicity with PBPLN-RT than with PBO-RT. Results 5-year cumulative incidences in the PBO-RT (n = 5,087) and PBPLNRT (n = 593) groups was 18.2% and 15.9% for GI toxicity, respectively. For GU toxicity it was 19.1% and 20.7%, respectively. There was no evidence of difference in GI or GU toxicity after adjustment between PBO-RT and PBPLN-RT (GI: adjusted sHR, 0.90, 95% CI, 0.67–1.19; P = 0.45); (GU: adjusted sHR, 1.19, 95% CI, 0.99–1.44; P = 0.09). Conclusions This national population-based study found that including PLNs in the radiation field following radical prostatectomy is not associated with a significant increase in rates of ≥Grade 2 GI or GU toxicity at 5 years.

Objectives: To develop and validate a coding framework to identify interventions for upper tract obstructive uropathy (UTOU) in men with locally advanced and metastatic prostate cancer (PCa) using administrative hospital data to assess clinical outcomes. There are no population‐based studies on the incidence, treatment, and outcomes of this complication. Patients and Methods: Patients newly diagnosed with PCa between April 2014 and March 2019 were identified in the English cancer registry. A coding framework based on procedure (Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures fourth edition) and diagnostic (International Classification of Diseases, 10th edition) codes was developed and validated. Subsequent clinical outcomes were determined using Hospital Episodes Statistics to determine the utility of the intervention. Results: A total of 77 010 patients newly diagnosed with locally advanced, and 30 083 patients with metastatic PCa were identified. Of these, 1951 (1.8%) patients underwent an intervention for UTOU according to our coding framework: 830 (42.5%) had locally advanced disease and 1121 (57.5%) had metastatic disease. In all, 844 (43.3%) had a percutaneous nephrostomy (PCN), 473 (24.2%) had a PCN with antegrade stent, and 634 (32.5%) had a retrograde stent. The mean follow‐up was 43.2 months. The cumulative incidence of the use of these interventions at 1, 3, and 5 years was 2.5%, 3.6% and 4.2% in men with metastases compared to 0.5%, 0.9% and 1.4% in men with locally advanced disease. Conclusion: A new coding framework, developed to identify procedures for UTOU was applied in the largest study to date of UTOU in men with primary locally advanced and metastatic PCa. Results demonstrated that 2% of men with locally advanced PCa and 4% of men with metastatic PCa require an intervention to resolve UTOU within 5 years of their PCa diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of the COVID‐19 pandemic on diagnostic and treatment activity in 2020 across hospital providers of prostate cancer (PCa) care in the English National Health Service. Methods: Diagnostic and treatment activity between 23 March (start of first national lockdown in England) and 31 December 2020 was compared with the same calendar period in 2019. Patients newly diagnosed with PCa were identified from national rapid cancer registration data linked to other electronic healthcare datasets. Results: There was a 30.8% reduction (22 419 vs 32 409) in the number of men with newly diagnosed PCa in 2020 after the start of the first lockdown, compared with the corresponding period in 2019. Men diagnosed in 2020 were typically at a more advanced stage (Stage IV: 21.2% vs 17.4%) and slightly older (57.9% vs 55.9% ≥ 70 years; P < 0.001). Prostate biopsies in 2020 were more often performed using transperineal (TP) routes (64.0% vs 38.2%). The number of radical prostatectomies in 2020 was reduced by 26.9% (3896 vs 5331) and the number treated by external beam radiotherapy (EBRT) by 14.1% (9719 vs 11 309). Other changes included an increased use of EBRT with hypofractionation and reduced use of docetaxel chemotherapy in men with hormone‐sensitive metastatic PCa (413 vs 1519) with related increase in the use of enzalutamide. Conclusion: We found substantial deficits in the number of diagnostic and treatment procedures for men with newly diagnosed PCa after the start of the first lockdown in 2020. The number of men diagnosed with PCa decreased by about one‐third and those diagnosed had more advanced disease. Treatment patterns shifted towards those that limit the risk of COVID‐19 exposure including increased use of TP biopsy, hypofractionated radiation, and enzalutamide. Urgent concerted action is required to address the COVID‐19‐related deficits in PCa services to mitigate their impact on long‐term outcomes. [ABSTRACT FROM AUTHOR]