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Item does not contain fulltext OBJECTIVE: To investigate the relationship between obesity and sarcopenia in relation to overall survival (OS) and disease-specific survival (DSS) in high-grade endometrial cancer patients. METHODS: We conducted a retrospective study in women diagnosed with high-grade endometrial cancer (EC) between February 2006 and August 2017 in the Royal Cornwall Hospital who had abdominal computerized tomography (CT)-scan as part of routine staging work-up. Sarcopenia was assessed by measuring psoas-, paraspinal- and abdominal wall muscles on CT and defined by skeletal muscle index ≤41 cm(2) /m(2) . Sarcopenic obesity was defined as sarcopenia combined with body mass index (BMI) ≥30 kg/m(2) . RESULTS: A total of 176 patients with median age of 70 years and median BMI of 29.4 kg/m(2) were included in the study. The majority of patients (38%) had endometrioid type histology. Sarcopenia was not associated with OS (P = 0.951) or DSS (P = 0.545) However, in multivariate analysis, sarcopenic obesity was associated with reduced OS in endometrioid endometrial cancer (EEC) patients (P = 0.048). CONCLUSION: Sarcopenic obesity is associated with OS in high-grade EEC patients, while sarcopenia without obesity is not related to OS or DSS in high-grade EC. In non-endometrioid endometrial cancer, there is no association between sarcopenic obesity and survival.

Purpose: Small cell carcinoma of the bladder (SCCB) is rare, accounting for less than 1% of all bladder carcinomas. It is aggressive, and outcomes are poor as a result of its early metastatic spread. Owing to its rarity, there are limitations on data to propose standardized management pathways. Methods and Materials: We conducted a retrospective analysis of patients presenting with pure or predominant-histology SCCB to 26 institutions in the United Kingdom between 2006 and 2016. The data cutoff date was February 1, 2018. We report patient characteristics, treatment received, and subsequent clinical outcomes. Results: A total of 409 eligible patients were included. Among these, 306 (74.8%) were male, the median age was 71 years (range, 35-96 years), and 189 patients (46.2%) had pure-histology SCCB. At data cutoff, 301 patients (73.6%) had died. The median overall survival (OS) was 15.9 months (95% CI, 13.2-18.7 months). Two hundred patients (48.9%) were confirmed to have bladder-confined disease (N0, M0), with a median OS of 28.3 months (95% CI, 20.9-35.8 months), versus a median OS of 12.7 months (95% CI, 10.9-14.6 months) for the 172 patients (42.1%) with confirmed N1-3 and/or M1 disease (hazard ratio [HR], 2.03; 95% CI, 1.58-2.60; P < .001). A total of 247 patients (61.5%) received primary chemotherapy, with a median OS of 21.6 months (95% CI, 15.5-27.6 months), versus a median OS of 9.1 months (95% CI, 5.4-12.8 months) in patients who did not receive primary chemotherapy (HR, 0.46; 95% CI, 0.37-0.59; P < .001). Choice of chemotherapy agent did not alter outcomes. For those with bladder-confined disease, 61 (30.5%) underwent cystectomy, and 104 (52.0%) received radiation therapy. Survival outcomes were similar for both cystectomy and radiation therapy. Only 6 patients (1.5%) were identified as having brain metastases at any time point. Conclusions: To our knowledge, this is the largest retrospective study of all-stage SCCB to date. Patients have a poor prognosis overall, but survival is improved in those able to receive chemotherapy and with organ-confined disease. Brain metastases are rare.

Objective: Enzalutamide is effective in treating metastatic castrate-resistant prostate cancer (mCRPC) but can have side effects that require treatment breaks (TB). We conducted a retrospective analysis of outcomes of patients who had extended TB due to toxicity compared to continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC from September 2011 to February 2018 were included. TB was defined as an interruption of four weeks or more. Overall survival (OS) from enzalutamide start, time to prostate-specific antigen failure (TTF) and total enzalutamide treatment time (TTT) were analysed for TB and continuous responders (>50% PSA drop), and a significance level of 0.05 was assigned. Results: A total of 110 patients were continuous responders, and 29 had TB. The median number of interruptions was one (range 1–7), and time on treatment was 70% in the TB group. The TB group had significantly improved OS (100 vs. 60 months; hazard ratio=1.8, 95% confidence interval 1.17–2.77, p=0.02), prolonged TTF (median 11 vs. 6 months; p=0.008) and TTT (median 15 vs. 8 months; p=0.0001). Conclusion: Extended TB do not seem to impact OS or treatment duration adversely in patients who are responding and experiencing toxicity, and may be a useful option in managing toxicity. Prospective trials could explore this further. Level of evidence: Level 2c.

Background: Obesity is an important risk factor for the development of endometrial cancer (EC). Recent data showed that body fat distribution might be more relevant than Body Mass Index (BMI). High visceral fat percentage was shown to be an independent predictor for survival in EC, but mainly included grade 12 EC.Objective: To evaluate body fat distribution and its relation to outcome in high-grade endometrial cancer.Methods: Retrospective study in women diagnosed with high-grade EC between February 2006 and August 2017 at the Royal Cornwall Hospital who had abdominal CT-scan as part of routine diagnostic work-up. Subcutaneous abdominal fat volumes and visceral abdominal fat volumes were quantified based on CT-scan measurements, and visceral fat percentage calculated.Results: A total of 176 patients with high-grade EC were included. The median age was 70 years and median BMI was 29.4 kg/m(2). The majority of patients had non-endometrioid endometrial cancer (NEEC; 62 %). High visceral fat percentage was associated with poor overall- and disease-specific survival (p = 0.006 and p = 0.026 respectively) in NEEC patients, but not in high-grade endometrioid EC (EEC). The most frequent obesity comorbidities hypertension and diabetes mellitus were significantly associated with high BMI and high visceral fat percentage.Conclusion: In high-grade EC, high visceral fat percentage was an independent predictor of poor survival only in NEEC. The strong correlation between high visceral fat and obesity-related comorbidities might be reflective of an unhealthy macroenvironment. (C) 2020 Published by Elsevier B.V.

Background: We investigated our institution’s mCRPC enzalutamide or abiraterone patients examining PSA responses and impact of sequencing of these drugs. Methods: All enzalutamide / abiraterone mCRPC patients (2011-2018) were included. Rates of PSA >50% response (PSA50) were compared. Time to treatment failure (TTF) and overall survival (OS) was analysed as per lines of previous therapy and timing of chemotherapy. Results: 363 patients included (Enza n=236, Abi n=127), with 15.6 months median follow-up. PSA50 was greater in enzalutamide group (58% vs 31% p

We present a case of prostate-specific antigen (PSA) bounce in a 76 year old man who underwent salvage radiotherapy to the prostate bed following biochemical relapse 6 years post-radical prostatectomy for a T2N0 Gleason grade 3 + 3 prostate adenocarcinoma; 10 months following completion of salvage radiotherapy for biochemical PSA recurrence of 0.2 μg/L. Following undetectable results (

631 Background: Combination therapy with A + Ax in patients with previously untreated aRCC has shown superior progression-free survival (PFS) and objective response rate (ORR) vs sunitinib across all International Metastatic RCC Database Consortium (IMDC) risk groups. This study reports 24-month real-world outcomes in patients with aRCC receiving A + Ax in the UK. Methods: Patients were recruited from 9 UK sites. Inclusion criteria were diagnosis of aRCC, initiation of A + Ax on or after August 1, 2019, via the Early Access to Medicines Scheme, and age ≥18 years. The primary endpoints were overall survival (OS), PFS, ORR, and best response at 24 months post-A + Ax initiation. Data were analyzed descriptively. Total recruitment was 130 patients. Follow-up will continue until July 2023. Results: This analysis includes 78 patients with a minimum follow-up of 24 months. Median age at baseline was 66.6 years (range, 39.8-84.1 years); 76% (n=59) of patients were male, 63% (n=49) were White, 5% (n=4) were Asian/Asian British, and ethnicity was not recorded in 32% (n=25); 91% (n=71) had an Eastern Cooperative Oncology Group score of 0 or 1. IMDC risk status was favorable in 42% (n=33) of patients, intermediate in 41% (n=32), and poor in 17% (n=13). Median time between aRCC diagnosis and A + Ax initiation was 2.5 months (range, 0.03-90.4 months; n=77). Clear cell histology was the most prevalent (81% [n=63]); 68% (n=53) of patients had undergone nephrectomy, and 74% (n=58) had 1 or 2 metastatic sites at the index date. The OS rate at 24 months was 60% (95% CI, 49.4%-71.1%). The OS rates by IMDC risk status were: favorable, 76% (95% CI, 61.1%-90.4%); intermediate, 63% (95% CI, 45.7%-79.3%); and poor, 15% (95% CI, 0%-35.0%). The PFS rate at 24 months was 31% (95% CI, 20.5%-41.0%); median PFS was 9.1 months (95% CI, 7.9-13.4 months). ORR (n=76) at 24 months was 59% (95% CI, 48.2%-70.3%), with 4% (n=3) achieving complete response (CR) and 55% (n=42) partial response (PR). Best responses observed within 24 months were CR in 4% (n=3), PR in 54% (n=42), stable disease in 29% (n=23), and progressive disease in 10% (n=8) (2 not recorded). Median duration of response was 11.9 months (range, 0.4-23.7 months). Median time to discontinuation (TTD) of either A or Ax was 5.5 months (range, 0.5-20.5 months; n=50). Median TTD of A + Ax combined was 5.6 months (range, 0.8-20.5 months; n=43). Of 78 patients, 62 experienced an adverse event (AE) due to A + Ax treatment, 8 of whom had 14 serious AEs in total. The most common AEs were diarrhea (n=31), fatigue (n=22), and rash or oral mucositis (n=18 each); 3 patients discontinued Ax due to AEs including diarrhea (n=2), abnormal hepatic function (n=1), and abdominal pain (n=1). Conclusions: This UK-based real-world study of A + Ax treatment reports 24-month clinical outcomes in patients with aRCC. OS, PFS, ORR, and best response were in line with findings from prior clinical trials, with no new emerging AEs.

689 Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over recent years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. There is ongoing discussion amongst oncology professionals about how best to optimise treatments in terms of sequencing to maximise the potential number of lines or to give the best treatments first. A previous south-west UK audit was completed in 2021 reviewing the drop off rates across 5 UK sites identifying that 69% of patients were able to receive second line therapy and 34% were able to receive third line therapy. Methods: In this study we conducted retrospective analysis of all patients who commenced treatment with SACT for mRCC between 1st January 2018 and 30th June 2021 in 18 centres across the 4 nations of the United Kingdom. All NHS reimbursed treatment options including the COVID interim treatment guideline options were included. Patients who received SACT as part of a clinical trial were also included. Patients who continued on their respective lines of treatment were censored. We also identified patients who had been on a period of active surveillance before staring SACT in this cohort. Results: 1549 patients (71% male: 29% female) were included. IMDC subgroup patients included 21.6% favourable, 52.3% intermediate, 25.1% poor and 1% unavailable. 9.1% of patients had been on active surveillance before starting SACT – defined as a period of longer than 3 months from mRCC diagnosis to starting SACT. Of those patients that started SACT 60.5% of eligible patients had 2nd line therapy, 25.3% had 3rd line, 7.2% received 4th line therapy and only 1% had 5th line therapy. In the 1st line setting 58.9% received single agent VEGF TKI, 24.5% received combination ipilimumab and nivolumab (IO-IO) immunotherapy, 14 % received IO/ VEGF TKI combination and 2.6% received other/trial treatment. The single agent VEGF TKI ratio for 1st line SACT declined year by year with rising IO-IO and IO/VEGF TKI combination ratios seen. In the second- and third-line settings cabozantinib (33.2% 2nd line and 44.4% 3rd line) and nivolumab (32.8% 2nd line and 22.6% 3rd line) were the most common options. Disease progression or death was the most common cause of SACT discontinuation amounting to 57.4%, 62.5% and 79% of SACT cessation in the 1st, 2nd and 3rd lines respectively. Treatment toxicity SACT discontinuation rates were 22.8%, 21.4% and 10.9% for 1st, 2nd and 3rd lines respectively. Conclusions: These results suggest that with more treatment options available, including combination/immunotherapy therapies, more patients are able to receive second- and third-line therapies. That said there remains significant drop off rates mostly driven by disease progression that would support the use of our most effective therapies in the upfront setting.

Objectives To assess the association between risk factors, including socioeconomic deprivation, and mortality, recurrence and chemo- or radiation toxicity in cervical cancer patients. Methods Retrospective study of cervical cancer patients diagnosed between January 2007 and July 2018. Patient characteristics and mortality data, including recurrence, were assessed, together with socioeconomic deprivation measures evaluated using the English Indices of Multiple Deprivation. Markov multi-state models were used to model mortality and recurrence, and logistic regression models were used to model chemo- or radiation toxicity. Results Included were 243 women with a median age of 49 years. A total of 57 patients died (23%), of which 41 due to cervical cancer, and 21 (9%) had recurrent disease. Hazard ratios (HR) showed no evidence of association between socioeconomic deprivation and cancer-specific hazard of mortality from diagnosis or recurrence, hazard of mortality due to other causes or hazard of cancer recurrence. Furthermore, there was no evidence of association between socioeconomic deprivation and chemo- or radiation toxicity (bowel, bladder or vaginal stenosis). Conclusions No associations were found between socioeconomic deprivation and cancer mortality or recurrence in cervical cancer patients in the population of Cornwall. In addition, no association was found between socioeconomic deprivation and chemo- or radiation toxicity.

Background Obesity is an important risk factor for the development of endometrial cancer and is associated with poor outcomes. However, the impact of body fat distribution on survival and surgical outcomes in endometrial cancer patients is unclear. Methods This is a retrospective study in women diagnosed with primary endometrial cancer between February 2006 and August 2017 at the Royal Cornwall Hospital who had abdominal CT-scan as part of routine diagnostic work-up. Subcutaneous abdominal fat volumes and visceral abdominal fat volumes were quantified, and visceral fat percentage calculated. Results A total of 302 patients with high grade endometrial cancer were included. The median age was 70 years and median Body Mass Index (BMI) was 29.7 kg/m2. The majority of patients (60%) had endometrioid type histology. High visceral fat percentage was associated with poor overall- and disease-free survival (p Conclusion Obesity with high visceral fat percentage is an independent negative prognostic factor in endometrial cancer and high visceral fat volumes are associated with increased postoperative complication rates. The additional association of high visceral fat with multiple comorbidities might be reflecting an unhealthy macroenvironment.

358 Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over the last few years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. A previous real world study in the UK had demonstrated a significant attrition rate between each line of therapy suggesting less than half of patients who received first line SACT then received second line therapy and less than a fifth of first line SACT patients reach third line. Methods: We conducted a retrospective analysis of all patients treated between January 2018 and end of June 2021 to see if advancement in treatment options had impacted on the drop-off rates. Data was collected from 5 UK sites. Patients were identified from electronic SACT database. All reimbursed treatment options including the COVID interim treatment guidelines options were included. Patients who received SACT as part of a clinical trial were also included. Patients who remained on the respective lines of treatment were censored. Results: Data for 515 patients (372 male: 143 female) who received first-line SACT for mRCC were included in the analyses. IMDC prognostic groups were 103 favourable, 236 intermediate, 127 poor (49 not available). On progression 69% of patients were able to receive second-line therapy and 34% were able to receive third-line therapy. Of the 515 first-line therapies, 24% of patients received frontline ipilimumab and nivolumab, 10% received TKI and IO combination and 63% received single agent VEGF TKI. Second-line nivolumab or cabozantinib (43% and 40% respectively) were the most commonly prescribed options. Third-line cabozantinib 61% and nivolumab 16% remain the most used options. Across all lines of therapy progressive disease was the primary reason for discontinuation. 5% switched treatment due to toxicity. Conclusions: These results suggest that, with more treatment options available, including combination/ immunotherapy therapies, more patients are able to receive second and third-line therapies. Despite this, nearly one third of patients only receive one line of treatment which highlights the need to deliver the most efficacious treatments first to optimise patient outcomes. Moreover, single agent TKI was the most commonly used first-line SACT despite advances in the management pathway. Data analysing the impact of COVID on treatment selection will be presented.[Table: see text]

Objective: To develop a simulation model to identify key bottlenecks in the bladder cancer pathway at Royal Cornwall Hospital and predict the impact of potential changes to reduce these delays. Materials and methods: The diagnosis and treatment of muscle-invasive bladder cancer can suffer numerous delays, which can significantly affect patient outcomes. We developed a discrete event computer simulation model of the flow of patients through the bladder cancer pathway at the hospital, using anonymised patient records from 2014 and 2015. The changes tested in the model were for patients suspected to have muscle-invasive disease on flexible cystoscopy. Those patients were ‘fast-tracked’ to receive their transurethral resection of bladder tumour (TURBT) treatment using operating slots kept free for these patients. A staging computed tomography scan was booked in the haematuria clinic. Pathology requests were marked as 48 hour turnaround. The nurse specialist would then speak to the patient whilst they were on the ward following their TURBT to give information about their ongoing treatment and provide support. Results: The model predicted that if the changes were implemented, delays in the system could be reduced by around 5 weeks. The changes were implemented, and analysis of 3 months of the data post-implementation shows that the average time in the system was reduced by 5 weeks. The environment created by the changes in the pathway improved referral to treatment times in both muscle-invasive and non-muscle-invasive groups. Conclusion: The simulation model proved an invaluable tool for facilitating the implementation of changes. Simple changes to the pathway led to significant reductions in delays for bladder cancer patients at Royal Cornwall Hospital. Level of evidence: Not applicable for this cohort study.

Contains fulltext : 182380.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To assess the impact of body mass index (BMI) on radiotherapy toxicities in endometrial cancer patients. METHODS: This was a retrospective cohort study of women diagnosed with endometrial cancer between January 2006 and December 2014 at the Royal Cornwall Hospital Trust. Women who received radiotherapy as part of their treatment, including external beam radiotherapy (EBRT) and/or vaginal brachytherapy were included. Radiation-related toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) guidelines. Toxicity outcomes were compared across BMI groups-non-obese (BMI /=30 kg/m(2))-according to radiotherapy treatment received (EBRT, brachytherapy or a combination). RESULTS: Of a total of 159 women who received radiotherapy, 110 were eligible for inclusion in the study. Sixty-three women had a BMI

81 Background: Intermittent hormone manipulation in castrate-sensitive prostate cancer can improve quality of life whilst maintaining comparable disease outcomes with continuous scheduling. Enzalutamide is effective in metastatic castrate-resistant prostate cancer (mCRPC) treatment but can have significant side-effects. We conducted a retrospective analysis of patients treated with intermittent enzalutamide compared with continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC at Royal Cornwall Hospital from September 2011 to February 2018 were included. Data was collected from electronic medical records, selecting patients with at least a 1 month treatment break. Kaplan-Meier analysis of overall survival from enzalutamide start (OS), time to PSA failure (TTF) and total enzalutamide treatment time (TTT) was calculated for intermittent and continuous responders (>50% PSA drop), assigned significance level of 0.05. Results: 243 patients received enzalutamide, 110 (45%) were continuous responders and 29 (12%) had intermittent dosing. All patients treated intermittently had a PSA response prior to first treatment break, which was most commonly for fatigue (60%). 25% were still receiving enzalutamide. Median number of breaks was 1 (range 1-7), time on treatment was 70% and time to first break was 5 months. The intermittent group had significantly improved OS with median not reached, median OS for continuous responders was 19 months (HR 2.39, 95% CI 1.53-3.76, p=0.002). The intermittent group had prolonged TTF (median 13 vs 6 months, p=0.001) and TTT (median 30 vs 10 months, p=0.0003). Conclusions: Intermittent dosing of enzalutamide in these mCRPC patients does not adversely impact OS, increasing time patients remain on treatment. However, this was a small, retrospective, single-centre study; prospective trials are necessary to clarify the role of intermittent enzalutamide.[Table: see text]

Approximately one quarter of patients receiving neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer will be anemic at presentation. The outcomes of these anemic patients have historically been less favorable. We assessed the potential of anemia to act as an independent biomarker for a poor prognosis in patients with locally advanced rectal cancer.We performed a retrospective, observational study of consecutive patients with locally advanced rectal adenocarcinoma who underwent NCRT from 2004 to 2009 at 3 English National Health Service trusts. The main outcomes were Rectal Cancer Regression Grade, mortality rate, and disease-free survival. These were compared between the anemic and nonanemic patients.A total of 273 patients were included. Of these patients, 63 (23%) had a hemoglobin level of 120 g/L (anemic) at presentation. The Rectal Cancer Regression Grades were higher (less regression) in the anemic patients than in the nonanemic patients (χThe present large UK study examined patients receiving NCRT for magnetic resonance imaging-proven, locally advanced rectal adenocarcinoma. Our findings have demonstrated that patients who were anemic at presentation have higher regression grades (less regression) in response to the treatment than nonanemic patients. This trend appeared to persist despite radiologic disease stage at presentation. Anemia at presentation was also associated with increased mortality rates compared with that of nonanemic patients.

Introduction Complete pathological response is widely accepted to be an independent predictor for better prognosis after neo-adjuvant chemoradiotherapy treatment (NCRT) of locally-advanced adenocarcinoma of the rectum. 1 Less is known about the role of the Rectal Cancer Regression Grades (RCRGs) in predicting prognosis where partial tumour regression is seen. The aim of this study was to examine the relationship between RCRG and mortality in patients with locally-advanced adenocarcinoma of the rectum treated with NCRT. Method A retrospective study of all patients treated with NCRT for locally-advanced rectal cancer between 2004–2009 in 3 UK centres was undertaken. Data was collected from oncology, radiology and laboratory databases as well as patient records. Differences in mortality rates were compared for patients within the 3 different RCRG groups using univariate and multivariate analysis. The multivariate analysis adjusted for the known confounders of age, sex and stage of disease at presentation. A subset analysis was performed on patients with partial tumour regression by excluding those patients with a complete pathological response. Results Of 273 patients treated, 183 (67%) were male. Median follow up time was 3.60 years (2.58–4.99). Univariate analysis demonstrated an association between higher RCRGs and increased mortality with hazard ratios (HRs) for RCRG1:RCRG2 of 2.05 (95% CI 1.67–3.59) and RCRG1:RCRG3 of 3.25 (95% CI 1.82–5.82). This association persisted when multivariate analysis was performed, with HRs for mortality of RGRC1:RCRG2 2.12 (95% CI 1.20–3.74) and RCRG1:RCRG3 of 3.14 (95% CI 1.74–5.67). Fifty-five patients demonstrated a complete pathological response and were excluded from the analysis of patients with partial tumour regression. Of the remaining 218 patients, univariate analysis demonstrated a HR for mortality in RCRG1:RCRG2 of 1.40 (95% CI 0.77–2.56) and RCRG1:RCRG3 of 2.30 (95% CI 1.24–4.26). Multivariate analysis of mortality gave HRs of 1.52 (95% CI 0.82–2.81) and 2.38 (95% CI 1.27–4.45) respectively. Conclusion This study demonstrated an association between higher rectal cancer regression grades and an increased risk of mortality. This association, although weakened, appeared to persist amongst the subset of rectal cancer patients who only demonstrated partial tumour regression following chemoradiation. Disclosure of interest None Declared. Reference Maas M, Nelemans PJ, Valentini V, et al . Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11:835–44