Objective Radiotherapy modalities such as iodine-125 (I125) and ruthenium-106 (Ru106) brachytherapy and proton beam radiotherapy (PBR) are well established for the treatment of choroidal melanoma. This study aimed to evaluate the rates of local tumour control, globe retention and visual acuity (VA) outcomes in patients with choroidal melanoma treated with I125 or Ru106 brachytherapy or PBR.Methods and analysis A review was conducted of all cases of choroidal melanoma treated with Ru106 or I125 brachytherapy or PBR over a 10-year period. Patient demographics, comorbidities, tumour characteristics, treatment parameters and VA outcomes were analysed. A predictive nomogram was developed to estimate final VA based on baseline clinical, tumour and radiation parameters.Results A total of 310 eyes from 310 patients were included, comprising 175 patients (56.5%) treated with Ru106, 72 (23.2%) treated with I125 brachytherapy and 63 (20.3%) treated with PBR. Local tumour control was achieved in 95.8% of cases. The recurrence rates were 4.0%, 4.2% and 4.8% for Ru106, I125 and PBR, respectively. Retention rates were 96.0% for Ru106, 94.4% for I125 and 95.2% for PBR. LogMAR VA of 1.0 or better was maintained in 50.9% of Ru106patients, 27.8% of I125patients and 39.7% of those treated with PBR. Baseline LogMAR VA, tumour volume, radiation dose to the fovea, radiotherapy modality and follow-up duration were significant predictors of final VA and were incorporated into the nomogram.Conclusions Each radiotherapy modality demonstrated high rates of local tumour control and globe retention. The predictive nomogram may serve as a practical tool to support individualised visual prognostication and patient counselling in the management of choroidal melanoma.

Objective: In this study we analyzed the impact of centralization on key metrics, outcomes and patterns of care at the Irish National Center. Summary Background Data: Overall survival rates in esophageal cancer in the West have doubled in the last 25 years. An international trend towards centralization may be relevant, however this model remains controversial with Ireland, centralizing esophageal cancer surgery in 2011 Study design: All patients (n=1245) with adenocarcinoma of the esophagus or junction treated with curative intent involving surgery, including endoscopic surgery, were included (n= 461 from 2000-2011, and 784 from 2012-2022). All data entry was prospectively recorded. Overall survival was measured (i) for the entire cohort; (ii) patients with locally advanced disease (cT2-3N0-3); and (iii) patients undergoing neoadjuvant therapy. All complications were recorded as per Esophageal Complication Consensus Group (ECCG) definitions, and the Clavien Dindo (CD) severity classification. Statistical analysis: Data were analyzed using GraphPad Prism (v.6.0) for Windows and SPSS (v.23.0) software (SPSS,Chicago,IL) RStudio (Rversion4.2.2). Survival times were calculated using log-rank test and a Cox-regression analysis, and Kaplan-Meier curves generated. Results: Endotherapy for cT1a/IMC adenocarcinoma increased from 40 (9% total) to 245 (31% total) procedures between the pre-centralization (pre-C) and post-centralization (post-C) periods. A significantly (P<0.001) higher proportion of patients with cT2-3N0-3 disease in the post-C period underwent neoadjuvant therapy (66% vs 53%). Operative mortality was lower (P=0.02) post-C, at 2% vs 4.5%, and>IIIa CD major complications decreased from 33% to 25% (P<0.01). Recurrence rates were lower post-C (38% vs 53%, P<0.01). Median overall survival was 73.83 versus 47.23 months in the 2012-22 and 2000-11 cohorts respectively (P<0.001). For those who received neoadjuvant therapy, the median survival was 28.5 months pre-C and 42.5 months post-C (P<0.001). Conclusion: These data highlight improvements in both operative outcomes and survival from the time of centralization, and a major expansion of endoscopic surgery. Although not providing proof, the study suggests a positive impact of formal centralization with governance on key quality metrics, and an evolution in patterns of care.

Background One of the key components of training in Radiation Oncology is gaining knowledge in contouring tumour volumes and organs at risk for radiotherapy planning. Trainees rotate through different tumour sites during their training and are expected to acquire competencies in contouring skills in tumour sites appropriate to their year of training. These skills are mostly acquired in an unstructured manner during supervised clinical work. We report on our institutional experience of introducing structured contouring workshops and on the feedback obtained from trainees. Methods Eight contouring workshops in different tumour sites - Head & Neck (n=3), Prostate (n=1), SABR Lung (n=2), Breast (n=1) and Oesophagus (n=1) were conducted between April 2019 and March 2022.Six were in-person workshops pre-COVID. Two were run virtually during the pandemic. The workshops were of 2-hour duration, limited to around 12 trainees each with varying degrees of experience in that particular tumour site. All workshops were similar in format with a tutorial on the tumour site followed by a contouring demonstration on an anonymised index case on the Eclipse planning platform referencing published contouring atlases. The trainees had access to a copy of the same case throughout the workshop. Their contours were reviewed individually and collectively. Feedback on the contouring experience was collected through a questionnaire after the workshop from each trainee. This feedback was incorporated into subsequent workshops where relevant. Results An average of 12 trainees (range 10 -14) attended the workshops. All trainees, irrespective of year of training, rated the content, format of the workshops highly and felt that they were relevant to their daily practice. Their reported subjective level of confidence in contouring improved significantly from an average score of 5.6 out of 10 (range 4-7) before the workshop to a score of 8.7 (range 8-9) after, over the 8 workshops. There was no cost associated with conducting these workshops as these were done on our existing planning software. Discussion Based on the feedback obtained from the trainees, the workshops were of definite educational benefit. They favoured the inclusion of this approach to the teaching of contouring skills in their curriculum. In keeping with this feedback and the recent implementation of the new radiation oncology training curriculum in Ireland efforts are currently underway in incorporating these contouring workshops into the training programme on a structured basis. This will ensure that trainees develop progressive expertise in contouring skills in keeping with highest international standards. One of the key components of training in Radiation Oncology is gaining knowledge in contouring tumour volumes and organs at risk for radiotherapy planning. Trainees rotate through different tumour sites during their training and are expected to acquire competencies in contouring skills in tumour sites appropriate to their year of training. These skills are mostly acquired in an unstructured manner during supervised clinical work. We report on our institutional experience of introducing structured contouring workshops and on the feedback obtained from trainees. Eight contouring workshops in different tumour sites - Head & Neck (n=3), Prostate (n=1), SABR Lung (n=2), Breast (n=1) and Oesophagus (n=1) were conducted between April 2019 and March 2022.Six were in-person workshops pre-COVID. Two were run virtually during the pandemic. The workshops were of 2-hour duration, limited to around 12 trainees each with varying degrees of experience in that particular tumour site. All workshops were similar in format with a tutorial on the tumour site followed by a contouring demonstration on an anonymised index case on the Eclipse planning platform referencing published contouring atlases. The trainees had access to a copy of the same case throughout the workshop. Their contours were reviewed individually and collectively. Feedback on the contouring experience was collected through a questionnaire after the workshop from each trainee. This feedback was incorporated into subsequent workshops where relevant. An average of 12 trainees (range 10 -14) attended the workshops. All trainees, irrespective of year of training, rated the content, format of the workshops highly and felt that they were relevant to their daily practice. Their reported subjective level of confidence in contouring improved significantly from an average score of 5.6 out of 10 (range 4-7) before the workshop to a score of 8.7 (range 8-9) after, over the 8 workshops. There was no cost associated with conducting these workshops as these were done on our existing planning software. Based on the feedback obtained from the trainees, the workshops were of definite educational benefit. They favoured the inclusion of this approach to the teaching of contouring skills in their curriculum. In keeping with this feedback and the recent implementation of the new radiation oncology training curriculum in Ireland efforts are currently underway in incorporating these contouring workshops into the training programme on a structured basis. This will ensure that trainees develop progressive expertise in contouring skills in keeping with highest international standards.

Background The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently).Methods Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe. Patients aged 18 years or older with clinical tumour stage T2-3, nodal stage N0-3, and M0 adenocarcinoma of the oesophagus and oesophagogastric junction were randomly assigned to perioperative chemotherapy (three preoperative and three postoperative 3-week cycles of intravenous 50 mg/m(2) epirubicin on day 1 plus intravenous 60 mg/m(2) cisplatin or intravenous 130 mg/m2 oxaliplatin on day 1 plus continuous infusion of 200 mg/m(2) fluorouracil daily or oral 625 mg/m(2) capecitabine twice daily up to 2018, with four preoperative and four postoperative 2-week cycles of 2600 mg/m(2) fluorouracil, 85 mg/m2 oxaliplatin, 200 mg/m(2) leucovorin, and 50 mg/m(2) docetaxel intravenously on day 1 as an option from 2018) or trimodality therapy (41.4 Gy in 23 fractions on days 1-5, 8-12, 15-19, 22-26, and 29-31 with intravenous area under the curve 2 mg/mL per min carboplatin plus intravenous 50 mg/m(2) paclitaxel on days 1, 8, 15, 22, and 29). The primary endpoint was overall survival, assessed in all randomly assigned patients who received at least one dose of study drug, regardless of which study drug they received, by intention to treat. Secondary endpoints were disease-free survival, site of treatment failure, operative complications, toxicity, pathological response (complete [ypT0N0] and major [tumour regression grade 1 and 2]), margin-free resection (R0), and health-related quality of life. Toxicity and safety data were analysed in the safety population, defined as patients who took at least one dose of study drug, according to treatment actually received. The initial power calculation was based on superiority of trimodality therapy (n=366 patients); it was adjusted after FLOT became an option to a non-inferiority design with a margin of 5% for perioperative chemotherapy (n=540). This study is registered with ClinicalTrials.gov, NCT01726452.Findings Between Jan 24, 2013, and Dec 23, 2020, 377 patients were randomly assigned, of whom 362 were included in the intention-to treat population (327 [90%] male and 360 [99%] White): 184 in the perioperative chemotherapy group and 178 in the trimodality therapy group. The trial closed prematurely in December, 2020, after the second interim futility analysis (143 deaths), on the basis of similar survival metrics and the impact of the COVID-19 pandemic. At a median follow-up of 38 center dot 8 months (IQR 16.3-55.1), median overall survival was 48 center dot 0 months (95% CI 33.6-64.8) in the perioperative chemotherapy group and 49 center dot 2 months (34.8-74.4) in the trimodality therapy group (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]; hazard ratio 1.03 [95% CI 0.77-1.38]; log-rank p=0.82). Median disease-free survival was 32.4 months (95% CI 22.8-64.8) in the perioperative chemotherapy group and 24 center dot 0 months (18 center dot 0-40.8) in the trimodality therapy group [hazard ratio 0.89 [95% CI 0.68-1.17]; log-rank p=0.41). The pattern of recurrence, locoregional or systemic, was not significantly different (odds ratio 1.35 [95% CI 0.63-2.91], p=0.44). Pathological complete response (odds ratio 0.33 [95% CI 0.14-0.81], p=0.012), major pathological response (0.21 [0.12-0.38], p<0.0001), and R0 rates (0.21 [0.08-0.53], p=0.0003) favoured trimodality therapy. The most common grade 3-4 adverse event was neutropenia (49 [27%] of 183 patients in the perioperative chemotherapy group vs 11 [6%] of 178 patients in the trimodality therapy group), followed by diarrhoea (20 [11%] vs none), and pulmonary embolism (ten [5%] vs nine [5%]). One (1%) patient in the perioperative chemotherapy group and three (2%) patients in the trimodality therapy group died from serious adverse events, two (one in each group) of which were possibly related to treatment. No differences were seen in operative mortality (five [3%] deaths in the perioperative chemotherapy group vs four [2%] in the trimodality therapy group), major morbidity, or in global health status at 1 and 3 years.Interpretation Although underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise.

472 Background: The rates of gastric (GC) and esophageal adenocarcinoma (EA) among individuals younger than age 50 years have increased by 30% and 50%, respectively, over the past three decades in the US. There is limited information on incidence and demographics for EO esophageal and gastric cancer in Europe. Methods: We conducted a retrospective review of the prospectively maintained upper gastrointestinal (UGI) cancer database in St James’s Hospital (SJH), the National Centre for Oesophageal and Gastric Cancer in Ireland. We reviewed all cases diagnosed with esophageal cancer (EC) and gastric cancer (GC) less than or equal to 50 years of age from 2000 to 2021. Results: From 2000 to 2021, 374 EO EA & GC cases were identified, 8% of the 4663 total EC & GC cases. The results are presented in the table. Conclusions: The major presenting symptoms for EO-UGI cancer were dysphagia, weight loss and dyspepsia, further investigation is warranted in young patients presenting with these symptoms, even in the absence of elevated BMI or other known risk factors for malignancy. A high proportion have advanced disease at diagnosis despite good PS and clinical outcomes are poor. There is a critical need to understand the pathogenesis of EO-UGI cancers to determine optimal strategies for prevention and management.[Table: see text]

295 Background: The optimum combination curative approach to locally advanced adenocarcinoma of the esophagus and esophago-gastric junction (AEG) remains controversial, specifically whether multimodal therapy or perioperative chemotherapy is superior. Neo-AEGIS was designed as the first randomized clinical trial (RCT) to directly compare the multimodal CROSS regimen (carboplatin/paclitaxel, 41.4Gy radiation therapy) with a modified MAGIC (epirubicin, cisplatin (oxaliplatin), 5-FU (capecitabine)) regimen (pre-2018) and more latterly the FLOT (docetaxel, 5-FU, leucovorin, oxaliplatin) regimen. Methods: 377 patients with cT2-3N0-3M0 AEG were randomly assigned to CROSS or peri-operative chemotherapy (ECF/ECX/EOF/EOX pre-2018, FLOT option 2019/20) at 24 sites (Ireland, UK, Denmark, France, Sweden). The primary outcome was overall survival. The initial power calculation was based on CROSS superiority of 10%. This was modified after the first futility analysis (70 events) to a non-inferiority margin of 5% for peri-operative chemotherapy. Secondary end points included toxicity, pathologic measures of response, and postoperative complications as per the Esophageal Complications Consensus Group (ECCG) definitions and Clavien-Dindo severity grade. Results: Of 362 evaluable patients, 178 CROSS, 184 MAGIC/FLOT (157/27), 90% were male, median (range) age 64 (35-83), 84% were cT3, and 58% cN1. At a median (range) follow up of 34.2 (0.43-111.8) months, there were 186 deaths, 91 CROSS and 95 MAGIC/FLOT arm, with 3-year estimated survival probability of 57% (95% CI 49,64) and 55% (95% CI 47,62), respectively [(HR 1.03 (95%CI. 0.77-1.38))]. Conclusions: This RCT reveals no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy in the primary outcome of overall survival, notwithstanding greater proxy markers of local tumor response in the CROSS arm. Oncologic and operative outcomes were consistent with optimum modern benchmarks. These data strongly suggest non-inferiority and support equipoise in clinical decision making in modern practice. Clinical trial information: NCT01726452 . [Table: see text]

Purpose All patients living with cancer, including those with metastatic cancer, are encouraged to be physically active. This paper examines the secondary endpoints of an aerobic exercise intervention for men with metastatic prostate cancer. Methods ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells), was a multi-centre randomised control trial with a 6-month aerobic exercise intervention arm or a standard care control arm. Exercise adherence data was collected via heart rate monitors. Quality of life (FACT-P) and physical activity (self-administered questionnaire) assessments were completed at baseline, at 3 months and at 6 months. Results A total of 61 patients were included (69.4 ± 7.3 yr, body mass index 29.2 ± 5.8 kg/m 2 ). The median time since diagnosis was 34 months (IQR 7–54). A total of 35 (55%) of participants had > 1 region affected by metastatic disease. No adverse events were reported by participants. There was no effect of exercise on quality of life (Cohen’s d = − 0.082). Overall adherence to the supervised sessions was 83% (329 out of 396 possible sessions attended by participants). Overall adherence to the non-supervised home exercise sessions was 72% (months 1–3) and 67% (months 3–6). Modelling results for overall physical activity scores showed no significant main effect for the group ( p -value = 0.25) or for time ( p -value = 0.24). Conclusion In a group of patients with a high burden of metastatic prostate cancer, a 6-month aerobic exercise intervention did not lead to change in quality of life. Further exercise studies examining the role of exercise for people living with metastatic prostate cancer are needed. Trial Registration The trial was registered at clinicaltrials.gov (NCT02453139) on May 25th 2015.

Background: The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics. Methods: Two hundred and twenty-two patients, 111 in each arm, were included from 2 high-volume centers. Computed tomography-measured sarcopenia, and pulmonary function (forced expiratory volume in first second/forced vital capacity/diffusion capacity for carbon monoxide) were compared pretherapy and posttherapy. Operative complications were defined as per the Esophageal Complications Consensus Group (ECCG) criteria, and severity per Clavien-Dindo. Tumor regression grade and R status were measured, and survival estimated per Kaplan-Meier. Results: A total of 83% were male, cT3/cN+ was 92%/68% for FLOT, and 86%/60% for CROSS. The full prescribed regimen was tolerated in 40% of FLOT patients versus 92% for CROSS. Sarcopenia increased from 16% to 33% for FLOT, and 14% to 30% in CROSS (P<0.01 between arms). Median decrease in diffusion capacity for carbon monoxide was -8.25% (-34 to 25) for FLOT, compared with -13.8%(-38 to 29), for CROSS (P=0.01 between arms). Major pathologic response was 27% versus 44% for FLOT and CROSS, respectively (P=0.03). In-hospital mortality, respectively, was 1% versus 2% (P=0.9), and Clavien Dindo >III 22% versus 27% (P=0.59), however, respiratory failure was increased by CROSS, at 13% versus 3% (P<0.001). Three-year survival was similar at 63% (FLOT) and 60% (CROSS) (P=0.42). Conclusions: Both CROSS and FLOT resulted in equivalent survival. Operative outcomes were similar, however, the CROSS regimen increased postoperative respiratory failure and atrial fibrillation. Less than half of patients received the prescribed FLOT regimen, although toxicity rates were acceptable. These data support clinical equipoise, caution, however, may be advised with CROSS in patients with greatest respiratory risk.

Radiotherapy is being used increasingly in the treatment of prostate cancer. However, ionising radiation may confer a small risk of a radiation-induced secondary malignancy. We aim to assess the risk of rectal cancer following pelvic radiotherapy for prostate cancer. A search was conducted of the PubMed/MEDLINE, EMBASE and Web of Science databases identifying studies reporting on the risk of rectal cancer following prostatic radiotherapy. Studies must have included an appropriate control group of non-irradiated prostate cancer patients. A meta-analysis was performed to assess the risk of prostatic radiotherapy on subsequent rectal cancer diagnosis. In total, 4757 articles were screened with eight studies meeting the predetermined criteria. A total of 796,386 patients were included in this meta-analysis which showed an increased odds ratio (OR) for subsequent rectal cancer in prostate cancer patients treated with radiotherapy compared to those treated by non-radiotherapy means (OR 1.45, 1.07–1.97, p = 0.02). These findings confirm that prostate radiotherapy significantly increases the risk of subsequent rectal cancer. This risk has implications for treatment selection, surveillance and patient counselling. However, it is crucial that this information is presented in a rational and comprehensible manner that does not disproportionately frighten or deter patients from what might be their most suitable treatment modality.

Purpose There have been significant advancements in the specialty of radiation oncology (RO) in recent years. This has been reflected in the modernisation of RO infrastructure in Ireland. Two large satellite units connected to our largest training centre in Dublin opened in 2011. The other two national training sites in Cork and Galway have also been expanded which has introduced the capability to treat with advanced techniques. RO trainee numbers have also significantly increased over this time, in parallel with these developments. Methods An RO curriculum development subcommittee of the Irish Faculty of Radiologists was established. This included faculty representatives, the national training coordinator, the local training coordinators for each of the three sites, and 2 trainee representatives. The subcommittee reviewed the current curriculum and identified areas for modernisation using Grant's 6 steps method for guidance. These steps include needs assessment, curriculum purpose, learning outcomes, curriculum organisation, educational experience and curriculum evaluation. Multiple sources were referenced to aid content generation. For example, the Medical Council of Ireland's 8 domains of Good Clinical Practice were followed to ensure that the goals of the training scheme were in keeping with the highest professional standards. Training curricula from North America, ESTRO, Australia and the UK were used as references to guide the clinical aspects of training. The subcommittee divided work and met regularly to review progress over a 12-month period. More broad surveys of stakeholders including trainees and trainers were undertaken for some aspects. Results The new curriculum was agreed by the members of the subcommittee and approved by the Faculty. Due to the nature of post graduate RO training, the curriculum design is overlapping between the modular and the spiral design Several new documents are now in place including introductory guidelines to help new trainees through the training scheme. Non-clinical aspects related to management and communication skills have been introduced. Formal processes for evaluating clinical skills related to radiotherapy planning, and a reference to modern treatment techniques including SABR and SRS, have also been incorporated. Discussion We have created a new national training scheme, based on the 6 steps method, which reflects modern RO practice in Ireland. This should facilitate the training of ROs with excellent professional and clinical skills and allow for international recognition of the training programme. There have been significant advancements in the specialty of radiation oncology (RO) in recent years. This has been reflected in the modernisation of RO infrastructure in Ireland. Two large satellite units connected to our largest training centre in Dublin opened in 2011. The other two national training sites in Cork and Galway have also been expanded which has introduced the capability to treat with advanced techniques. RO trainee numbers have also significantly increased over this time, in parallel with these developments. An RO curriculum development subcommittee of the Irish Faculty of Radiologists was established. This included faculty representatives, the national training coordinator, the local training coordinators for each of the three sites, and 2 trainee representatives. The subcommittee reviewed the current curriculum and identified areas for modernisation using Grant's 6 steps method for guidance. These steps include needs assessment, curriculum purpose, learning outcomes, curriculum organisation, educational experience and curriculum evaluation. Multiple sources were referenced to aid content generation. For example, the Medical Council of Ireland's 8 domains of Good Clinical Practice were followed to ensure that the goals of the training scheme were in keeping with the highest professional standards. Training curricula from North America, ESTRO, Australia and the UK were used as references to guide the clinical aspects of training. The subcommittee divided work and met regularly to review progress over a 12-month period. More broad surveys of stakeholders including trainees and trainers were undertaken for some aspects. The new curriculum was agreed by the members of the subcommittee and approved by the Faculty. Due to the nature of post graduate RO training, the curriculum design is overlapping between the modular and the spiral design Several new documents are now in place including introductory guidelines to help new trainees through the training scheme. Non-clinical aspects related to management and communication skills have been introduced. Formal processes for evaluating clinical skills related to radiotherapy planning, and a reference to modern treatment techniques including SABR and SRS, have also been incorporated. We have created a new national training scheme, based on the 6 steps method, which reflects modern RO practice in Ireland. This should facilitate the training of ROs with excellent professional and clinical skills and allow for international recognition of the training programme.

Background: Radiotherapy offers an attractive treatment option for many men with prostate cancer. However it has been suggested that such ionising radiation may incur a small risk of a radiation induced secondary malignancy. This meta-analysis aims to investigate the risk of rectal cancer following radiation to the prostate. Methods: PubMed, Web of Science and Embase databases were searched to identify articles assessing the risk of rectal cancer following prostatic radiotherapy. Articles without a valid control group of prostate cancer patients treated without radiotherapy were excluded. A meta-analysis was carried out quantifying the risk of rectal cancer following radiotherapy to the prostate. Results: A total of 4,757 articles were screened with eight papers meeting the predetermined inclusion criteria. Our analysis of these 796,386 patients showed an increased risk of subsequent rectal cancer in men with prostate cancer treated with radiotherapy in comparison to those treated without radiotherapy (odds ratio: 1.45, 1.07–1.97, P=0.02). Conclusions: These findings confirm an increased risk of rectal cancer associated with prior radiotherapy to the prostate. Such a risk has important implications for treatment selection, patient counselling and post-treatment surveillance. Nonetheless, it is imperative that this information is presented in a rational, balanced and comprehensible form that does not disproportionately frighten or deter men with prostate cancer from what might be their most appropriate treatment modality.

Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or <25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples (n = 29). CTC count positively correlated with absolute total lymphocyte count (r2 = 0.1709, p = 0.0258) and NK-cell count (r2 = 0.49, p < 0.0001). There was also a positive correlation between platelet count and CTC count (r2 = 0.094, p = 0.0001). Correlation was also demonstrated within the overweight/obese group (n = 123, p < 0.0001), the non-exercise group (n = 79, p = 0.001) and blood draw samples lacking platelet cloaking (n = 128, p < 0.0001). By flow cytometry, blood samples from the exercise group (n = 15) had a higher proportion of CD3+ T-lymphocytes (p = 0.0003) and lower proportions of B-lymphocytes (p = 0.0264) and NK-cells (p = 0.015) than the non-exercise group (n = 14). These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis.

Anal cancer is a relatively rare cancer with 660 cases diagnosed in 2000–2015 in Ireland (1). The current standard treatment is radical chemoradiotherapy (CRT). The aim of our study was to review the treatment and outcomes of patients with localised anal squamous cell carcinoma (SCC), who received radical treatment in our radiation oncology network between 2008 and 2014 inclusive. Data were collected retrospectively from ARIA® oncology information system and patient charts. Statistical analyses were performed using IBM® SPSS® statistical software version 25.0. Seventy-nine cases of anal SCC were identified. Mean age of patients at commencement of radiotherapy (RT) was 60.2 years (standard deviation: 13.1 years). The most common total RT dose was 50.4 Gy in 28 fractions (N = 58; 73.4%). Median follow-up was 5.6 years. Two (2.6%) patients had persistent disease, seventeen (21.8%) patients developed loco-regional recurrence and nine (11.5%) patients developed solid organ metastases, four of whom had complete treatment response at the primary site. Eight patients underwent salvage anal surgery following completion of RT. Median overall survival was 10.5 years (95% confidence interval (CI) 5.1–15.8 years), median loco-regional relapse-free survival was 10.4 years (95% CI 4.4–16.3 years) and median disease-free survival was 9.3 years (95% CI 6.3–12.2 years). Our study demonstrates that treatment for anal SCC and outcomes following definitive CRT in Ireland during the study period were comparable to international standards.

4004 Background: The optimum combination curative approach to locally advanced adenocarcinoma of the esophagus and esophago-gastric junction (AEG) is unknown. A key question is whether neoadjuvant multimodal therapy, specifically CROSS (carboplatin/paclitaxel, 41.4Gy radiation therapy), is superior to optimum peri-operative chemotherapeutic regimens including modified MAGIC (epirubicin, cisplatin (oxaliplatin), 5-FU (capecitabine)) and more latterly FLOT (docetaxel, 5-FU, leucovorin, oxaliplatin). Neo-AEGIS was designed as the first randomised controlled trial to address this question. Methods: 377 patients with cT2-3N0-3M0 AEG were randomly assigned to CROSS or peri-operative chemotherapy (ECF/ECX/EOF/EOX pre-2018, FLOT option 2019/20) at 24 sites (Ireland, UK, Denmark, France, Sweden). The primary outcome was overall survival. The initial power calculation was based on CROSS superiority of 10%. This was modified after the first futility analysis (70 events) to a non-inferiority margin of 5%. Secondary end points included toxicity, pathologic measures of response, and postoperative complications as per the Esophageal Complications Consensus Group (ECCG) definitions and Clavien-Dindo severity grade. Results: Of 362 evaluable patients, 178 CROSS, 184 MAGIC/FLOT (157/27), 90% were male, median (range) age 64 (35-83), 84% were cT3, and 58% cN1. At a median (range) follow up of 24.5 (1-92) months, at the second futility analysis (60% of planned events), there were 143 deaths, 70 CROSS and 73 MAGIC/FLOT arm, with 3-year estimated survival probability of 56% (95% CI 47,64) and 57% (95% CI 48,65), respectively [(HR 1.02 (95%CI. 0.74-1.42))]. Based on the absence of futility evidenced in this data the DSMB recommended closure of recruitment in December 2020. Conclusions: This RCT reveals no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy, notwithstanding greater proxy markers of local tumour response in the CROSS arm. Oncologic and operative outcomes were consistent with optimum modern benchmarks. These data strongly suggest non-inferiority and support equipoise in decision making in modern practice. Clinical trial information: NCT01726452. [Table: see text]

Introduction: The objective of this pilot study was to obtain preliminary data on the efficacy and feasibility of incorporating geriatric assessment (GA) into radiation oncology (RO) with regard to patient outcomes and treatment decisions. Materials and Methods: Feasibility was assessed via the percentage of patients able to complete certain aspects of the assessment on their own, or with the assistance of a carer before appointments, was recorded. Consultation times and referrals were also documented. All participants (n=30) underwent GA at baseline, before randomisation to the intervention/control arm and commencement of radiotherapy treatment planning procedures. The results of GA were relayed to the Radiation Oncologist (RO) for the intervention arm only. GA was repeated for each participant three months after the completion of radiotherapy. Results: There was some evidence of increasing dependence, at three month follow-up, in ADLs and IADLs, less mobility (TUG score), higher GDS scores and increased vulnerability. However, these were not statistically significant. All patients underwent their predefined radiotherapy treatment plan, without modification. A number of deficits on GA were identified that may be considered significant for older patients. Conclusion: The impact on decision making may reflect a lack of experience and familiarity with GA and how to interpret it, as well as an obvious gap in the literature as to how it affects radiotherapy patient outcomes.

Background Circulating tumour cells (CTCs) represent a morphologically distinct subset of cancer cells, which aid the metastatic spread. The ExPeCT trial aimed to examine the effectiveness of a structured exercise programme in modulating levels of CTCs and platelet cloaking in patients with metastatic prostate cancer. Methods Participants (n = 61) were randomised into either standard care (control) or exercise arms. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analysed for the presence of CTCs, CTC clusters and platelet cloaking. CTC data was correlated with clinico-pathological information. Results Changes in CTC number were observed within group over time, however no significant difference in CTC number was observed between groups over time. Platelet cloaking was identified in 29.5% of participants. A positive correlation between CTC number and white cell count (WCC) was observed (p = 0.0001), in addition to a positive relationship between CTC clusters and PSA levels (p = 0.0393). Conclusion The presence of platelet cloaking has been observed in this patient population for the first time, in addition to a significant correlation between CTC number and WCC. Trial registration ClincalTrials.gov identifier NCT02453139 .

Background: Uveal melanoma and its treatment can influence the physical and psychological well-being of patients in a way that differs from other cancers. Factors influencing quality of life (QOL) include visual impairment, changes in appearance, day-to-day functioning, ocular discomfort, and worry regarding disease recurrence. Objective: We aimed to study both general and disease-specific QOL in uveal melanoma patients in Ireland and compare QOL between a plaque radiotherapy group and an enucleation treatment group. This information was sought to enhance our understanding of QOL issues for uveal melanoma patients, in the context of improving care and providing appropriate psychosocial support. Method: The European Organisation for Research and Treatment of Cancer (EORTC) QOL questionnaires QLQ-C30 and QLQ-OPT30 were completed by patients with uveal melanoma treated by enucleation or brachytherapy. Results: 138 of 206 patients completed the questionnaires. There was no significant difference in QOL scores between treatment groups. Thirty-two percent of patients reported concerns about tumour recurrence elsewhere in the body. The brachytherapy group had a significantly higher "role functioning" score (p = 0.030). Enucleation patients were more likely to have problems with appearance (p < 0.0005). Younger patients (12-54 years of age) were more likely to report headaches (p < 0.0005) and problems with reading (p = 0.042), and they had a lower cognitive functioning score (p = 0.003) than those aged >= 55 years. Conclusions: There was no significant difference in reported QOL between treatment groups. Our data identified a number of vulnerable patient subgroups. By anticipating which patients are more likely to suffer in terms of certain aspects of their QOL, we are better able to provide appropriate and timely psychosocial support.

Abstract Background: Globally, prostate cancer (PrCa) is the fourth most common cancer type. Obesity and inflammation have been shown to play significant roles in PrCa disease progression. Obesity and a high body mass index (BMI) are associated with increased PrCa-specific mortality in patients with advanced disease. Furthermore, proinflammatory cytokines can aid metastatic potential and promote angiogenesis. The ExPeCT (Exercise, Prostate Cancer and Circulating Tumor Cells) trial seeks to examine the effectiveness of a structured exercise program in modulating inflammatory mediators and obesity in patients with metastatic PrCa. Methods: ExPeCT (CTRIALIE 15-21 (ClincalTrials.gov identifier NCT02453139)) is a multicenter, randomized trial for patients with metastatic PrCa (n=67). Participants were randomized to either control or exercise arms. Participants in the exercise arm completed six months of prescribed aerobic exercise, which was monitored using percentage heart-rate reserve. Serum samples were collected for all participants at baseline (T0), three months (T3), and six months (T6), and assayed for 16 interlinked adipokines and cytokines using the Meso Scale Discovery platform. An interim statistical analysis was performed (n=26) comparing median change in serum analyte levels between control (n=13) and exercise (n=13) arms using non-parametric Wilcoxon rank-sum tests. Results: Among 26 patients included in our interim analysis, mean age at baseline was 71 years, median BMI was 29.1 kg/m2, and median waist circumference (WC) was 107 cm, with no significant differences between arms (all p>0.3). Between T0 and T6, WC decreased by a median of 3.8 cm in the exercise group and 2.6 cm in the control group (p=0.412), with a similar trend for BMI. Interim serum cytokine analysis showed a 3-fold increase in IL-10 levels in the exercise arm at T3 when compared to the control arm (p=0.036). No significant change in IL-10 levels was recorded at T6 between arms (p=0.776). Similarly, CXCL8 (IL-8) levels were increased by 1.8-fold at T3 in the exercise arm in comparison to the control arm (p=0.017), with no significant change reported at T6 (p=0.191). While changes were evident in serum TNFα, IL-6, VEGF, IL-17a, MMP9 and CCL5 (RANTES) levels, these did not reach significance. Differences in levels of adipokines leptin and resistin were also reported. A 1.5-fold increase in resistin expression was observed in the exercise arm at T6; however, it was not significant (p=0.293). A 2-fold decrease in leptin in the control arm relative to the exercise arm at T6 was also detected (p=0.676). Analysis of adiponectin, MMP2, and CCL2 is ongoing. Conclusion: Our interim analysis of ExPeCT trial participants demonstrated a significant increase in serum CXCL8 and IL-10 levels after three months of a supervised exercise intervention. These preliminary data suggest that a structured exercise program has the potential to modify inflammatory status in patients with metastatic PrCa. Citation Format: Lauren Brady, Grainne Sheill, Anne-Marie Baird, Emma H. Allott, Tatjana Vlajnic, John Greene, Orla Casey, Brian Hayes, Emer Guinan, Juliette Hussey, Fidelma Cahill, Mieke Van Hemelrijck, Nicola Peat, Sarah Rudman, Moya Cunningham, Liam Grogan, Thomas Lynch, Rustom P. Manecksha, John McCaffrey, Orla Sheils, Dearbhaile M. O’Donnell, John O’Leary, Ray McDermott, Stephen P. Finn. Examining the link between obesity, inflammation, and exercise in patients with metastatic prostate cancer—An interim analysis from the ExPeCT trial [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A057.