To assess the feasibility and potential impact on target delineation of respiratory-gated (4D) contrast-enhanced 18Fluorine fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT), in the treatment planning position, for a prospective cohort of patients with lower third oesophageal cancer. Fifteen patients were recruited into the study. Imaging included 4D PET-CT, 3D PET-CT, endoscopic ultrasound and planning 4D CT. Target volume delineation was performed on 4D CT, 4D CT with co-registered 3D PET and 4D PET-CT. Planning target volumes (PTV) generated with 4D CT (PTV4DCT), 4D CT co-registered with 3D PET-CT (PTV3DPET4DCT) and 4D PET-CT (PTV4DPETCT) were compared with multiple positional metrics. Mean PTV4DCT, PTV3DPET4DCT and PTV4DPETCT were 582.4 ± 275.1 cm3, 472.5 ± 193.1 cm3 and 480.6 ± 236.9 cm3 respectively (no significant difference). Median DICE similarity coefficients comparing PTV4DCT with PTV3DPET4DCT, PTV4DCT with PTV4DPETCT and PTV3DPET4DCT with PTV4DPETCT were 0.85 (range 0.65–0.9), 0.85 (range 0.69–0.9) and 0.88 (range 0.79–0.9) respectively. The median sensitivity index for overlap comparing PTV4DCT with PTV3DPET4DCT, PTV4DCT with PTV4DPETCT and PTV3DPET4DCT with PTV4DPETCT were 0.78 (range 0.65–0.9), 0.79 (range 0.65–0.9) and 0.89 (range 0.68–0.94) respectively. Planning 4D PET-CT is feasible with careful patient selection. PTV generated using 4D CT, 3D PET-CT and 4D PET-CT were of similar volume, however, overlap analysis demonstrated that approximately 20% of PTV3DPETCT and PTV4DPETCT are not included in PTV4DCT, leading to under-coverage of target volume and a potential geometric miss. Additionally, differences between PTV3DPET4DCT and PTV4DPETCT suggest a potential benefit for 4D PET-CT. ClinicalTrials.gov Identifier – NCT02285660 (Registered 21/10/2014).

TPS4166 Background: There is increasing evidence suggesting benefit from a neoadjuvant approach to PC. However, the optimal regimen is unclear and will likely require a precision medicine approach, where patient and tumor attributes define therapy. Platinum-containing regimens have shown survival benefit for PC, with occasional exceptional responders, but biomarkers (BM) of response are not well defined and treatment decisions are often based on patient performance status (PS) and co-morbidity. Tumors with defects in BRCA1/2and other Fanconi Anemia genes show defective DNA damage response (DDR), conferring potential selective sensitivity to DNA-damaging agents (e.g. platinum) and newer targeted agents. We have shown that DDR deficiency (DDRd) is present in up to 20% of PC. This study aims to exploit DDRd as a therapeutic vulnerability, with integrated analysis to define candidate BM for FA and AG response. Methods: PRIMUS-002 will enroll patients registered on the Precision-Panc Master Protocol who are molecularly profiled using the Precision-Panc Clinical Cancer Genome including a novel DDRd assay, and the transcriptome with longitudinal sampling (pre-, during, and post-treatment). Patients receive either FA ( nab-paclitaxel 150mg/m²IV,oxaliplatin 85mg/m², folinic acid 350mg flat dose, fluorouracil infusion 2400mg/m²continuous IV infusion), orAG ( nab-paclitaxel 125mg/m², gemcitabine 1000 mg/m²) for 3 months,based on patient age and PS.Following initial safety analysis, chemoradiation may be introduced. The primary endpoint is disease progression (DP) during neoadjuvant therapy. The study is designed to detect a 20% difference in DP between the BM+ve (10%) and BM –ve (30%) in patients treated with FA (90% power, 5% 1-sided level of statistical significance)., Exploratory translational endpoints include surrogate therapeutic response assessment using CA19.9, PET-CT SUV, DWI-MRI and ctDNA. Current Enrolment: 2 patients enrolled to date: 1 to receive FA and 1 to AG treatment. Clinical trial information: ISRCTN34129115.

To outline the toxicity, tolerability, and efficacy of a 3D conformal computed tomography planned endoluminal brachytherapy (ELBT) treatment for esophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC). A retrospective single-center analysis of toxicity, tolerability, and outcomes for 65 consecutive patients with OAC/OSCC who received 6-8Gy in one fraction or 12-16Gy in two fractions of high-dose-rate ELBT as salvage postchemoradiotherapy (n = 7 and n = 14 respectively), or as a boost to external beam radiotherapy (n = 14 and n = 30, respectively). Median overall survival from the first brachytherapy application was 7.4 (IQR 5.0-14.7) months for the boost cohort and 9.2 (IQR 5.8-20.1) months for the salvage cohort. In a univariate analysis, use of a higher, fractionated dose of radiotherapy was associated with longer overall survival. At least one-third (33%; n = 7) of the salvage cohort and 28% (n = 12) of the boost cohort exhibited a local recurrence prior to death. Overall, 66.7% of the salvage and 56.8% of the boost cohort experienced odynophagia. Swallow function stabilized or improved early after treatment, with only 11.6% of the boost and 14.3% of the salvage cohort demonstrating a long-term decline in dysphagia score. 3D conformal planned ELBT is safe and tolerable. Most patients exhibit an early and sustained stabilization or improvement in their swallow function and greater survival is seen with higher brachytherapy doses. Further research is required to determine the place of brachytherapy in the management of esophageal cancer, particularly when planned using contemporary conformal approaches.

Background: Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) are accepted standards of care for the management of adenocarcinoma of the esophagus and gastroesophageal junction. Summary: The MRC-OEO2 study established the role of 2 cycles of neoadjuvant cisplatin/fluoropyrimidine. More recently, the FLOT-AIO4 study demonstrated the superiority of perioperative FLOT chemotherapy (5FU, oxaliplatin, and docetaxel) compared to ECX (epirubicin, cisplatin, and capecitabine) regime. The results from the pivotal CROSS study established neoadjuvant CRT as a new standard of care in OG cancer. The survival benefits observed in FLOT and CROSS studies are similar [FLOT – hazard ratio 0.75 (0.62–0.92); CROSS – 0.741 (0.55–0.98)]. Key Messages: Both nCT and nCRT have been shown to be associated with survival benefit compared to surgery alone. We have performed a comprehensive review of the available evidence to define the optimum treatment algorithm and identify specific patient sub-groups who may be appropriate for the use of one or more of these neoadjuvant options.

Background: The study purpose was to develop a machine learning (ML)-based predictive model for event-free survival (EFS) in patients with hepatocellular carcinoma (HCC) undergoing stereotactic ablative radiotherapy (SABR). Methods: Patients receiving SABR for HCC at a single institution, between 2017 and 2020, were included in the study. They were split into training and test (85%:15%) cohorts. Events of interest were HCC recurrence or death. Three ML models were trained, the features were selected, and the hyperparameters were tuned. The performance was measured using Harrell’s C index with the best-performing model being tested on the unseen cohort. Results: Overall, 41 patients were included (training = 34, test = 7) and 64 lesions were analysed (training = 50, test = 14), resulting in 30 events (60% rate) in the training set (death = 6, recurrence = 24) and 8 events (57% rate) in the test set (death = 5, recurrence = 3). A Cox regression model, using age at treatment, albumin, and intra-lesional fat identified through MRI as variables, had the best performance with a mean training score of 0.78 (standard deviation (SD) 0.02), a mean validation of 0.78 (SD 0.18), and a test score of 0.94. Conclusions: Predicting the outcomes in patients with HCC, following SABR, using a novel model is feasible and warrants further evaluation.

There is increasing interest in the potential benefits of reirradiation of recurrent or new primary cancer close to or within a previously irradiated region but there is a need for high-quality studies to evaluate this approach. This study aimed to understand clinician and NHS commissioner perspectives, methods for evidence generation, and the potential role of advanced technologies. Semi-structured interviews were conducted with UK clinical oncologists and commissioners. Analysis was informed by principles of thematic analysis. Interviews were conducted and analysed with 10 clinical oncologists and 2 commissioners. Six themes were developed: 1. Weighing potential benefits against uncertainties; 2. Considering patient preferences in clinical decision-making; 3. A desire for clear guidance on planning and delivering reirradiation; 4. Challenges in the availability of reirradiation; 5. A desire for a stronger evidence-base to guide clinical care; 6. Considerations for clinical trial design. Clinicians and commissioners were supportive of strengthening the evidence base and increasing availability of reirradiation. Some clinicians and both commissioners favoured doing so using clinical trials whereas others considered prospective registries or evaluative commissioning to be more feasible. The potential benefits that could be gained from advanced technologies were highlighted, but also that many patients could benefit from high-quality standard photon reirradiation. This study provides important insights into reirradiation practice and how to improve its availability. Perspectives regarding trials and advanced technologies should shape future study design to strengthen the evidence base.