BACKGROUND:Textbook outcome (TBO) has been proposed as a composite measure of quality in esophagogastric surgery, and achieving a TBO has been associated with improved overall survival (OS). The Dutch Upper Gastrointestinal Cancer Audit group determined their TBO rate for gastrectomy to be 32.1%, using 10 parameters. Our study aimed to assess the TBO rate in patients who had a gastrectomy for cancer in an Australian Upper GI unit, allowing for comparisons with international specialist centers. METHODS:Retrospective analysis of a prospectively maintained database of patients who had a gastrectomy for cancer performed by the surgeons in a single Australian center between 2013 and 2018. Postoperative complications were analyzed using Clavien-Dindo (CD) ≥2 and CD ≥3 definitions. Baseline factors and their association with TBO were analyzed using multivariable logistical regression. The association between TBO and survival rates was determined by Cox proportional hazards regression analysis. RESULTS:In 136 patients, 84 (62%) achieved a TBO when complications were graded as CD ≥2. Greatest negative impact on TBO was the complication rate, lymph node yield, and length of stay. Patients more likely to achieve a TBO were younger, with an increased body mass index and absence of underlying respiratory disease. A nonsignificant trend toward improved OS was seen when TBO was achieved. CONCLUSION:Our TBO rate compares favorably with published data from high-volume centers. Assessment of a unit's TBO may provide a stronger evaluation of quality when assessing where complex surgery should be performed within Australia.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.

PURPOSE The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors ( P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women ( P = .003, .012, respectively). CONCLUSION Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

Introduction: In 2017 the Dutch Upper Gastrointestinal Cancer Audit Group proposed a ten-item composite measure for a 'textbook outcome' (TBO) following oesophagogastric resection. Studies have shown associations between TBO and improved conditional and overall survival. The aim of this study was to evaluate the use of TBO to assess the outcomes from a single specialist unit in a country, with low incidence of disease, allowing comparisons with international specialist centres.Materials and methods: Retrospective analysis of prospectively collected oesophageal cancer surgery data at a single centre, in Australia, between 2013 and 2018. Multivariable logistical regression assessed association between baseline factors and TBO. Post-operative complications were analysed in two separate groups as Clavien-Dindo >= 2 (CD >= 2) and Clavien-Dindo >= 3 (CD >= 3). Cox-proportional hazards regression analysis determined the association between TBO and survival.Results: 246 patients were analysed, with 50.8% (n = 125) achieving a TBO when complications were defined as CD >= 2 and 58.9% (n = 145) when using CD >= 3. Patients aged >= 75, and those with a pre-operative respiratory co-morbidity were less likely to achieve a TBO. Overall survival was not influenced by TBO when complications were defined as CD >= 2, however it was higher when a TBO was achieved, and complications were defined as CD >= 3 (HR 0.54, 95% CI, 0.35 to 0.84, P = 0.007).Conclusion: TBO is a multi-parameter metric that allowed benchmarking of the quality of oesophageal cancer surgery in our unit, providing favourable outcomes compared with other published data. There was an association between TBO and improved overall survival when the definition of severe complications was CD >= 3.(c) 2023 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Abstract Oesophageal adenocarcinoma (OAC) is a deadly disease with an increasing incidence globally. Treatment outcomes with traditional therapy have largely plateaued and responses to immunotherapy are modest at best, necessitating the need for better biomarker driven selection. We aimed to unravel the tumour neoantigen landscape and immune microenvironment in OAC patients to aid improved patient selection and inform novel immunotherapy trials. To characterise the tumour immune microenvironment and neoantigen landscape of OACs, we performed DNA sequencing (n = 117) and RNA sequencing (n = 115) on biopsies taken at pre-treatment endoscopy. Using expression-based computational methods we analysed transcriptomic data to profile infiltration levels of 28 immune cell populations and their functional orientation, as well as stromal signatures and immune checkpoint molecules. TCGA data was used for as a validation cohort. Tumour neoantigens were predicted using the pVAC-Seq pipeline. Using an immune based classification based on the tumour microenvironment composition, we identified three distinct phenotypes; immune-enriched (IE), heterogeneously-infiltrated (HI), and immune-cold (IC). The IE group showed improved survival compared to both HI and IC, with HI showing the worst survival. The HI-group showed no difference in stromal scores to the IE group, but showed significantly decreased adaptive-immune cell infiltration, indicating that an immunosuppressive stromal compartment may be driving outcomes for these patients. No difference was seen in total or quality neoantigen load between groups, but high correlation with antigen processing machinery is seen. Our analysis expands the knowledge of the relatively unknown tumour immune microenvironment of OAC. We have identified three immune TME-phenotypes with prognostic utility with current standard of care therapies; which may also act as potential immunotherapy biomarkers. This is being explored further in ongoing immune microenvironment research and will guide future translational studies.

e16028 Background: : Prognosis of oesophageal adenocarcinoma (OAC) remains poor globally. Traditional histopathology classifications have minimal impact on clinical management and outcomes. To improve patient outcomes, prognostic and therapeutic stratification is required within this cohort of morphologically homogenous cancers. Identification and validation of candidate prognostic and therapeutic biomarkers may contribute to personalisation of therapy for patients with OAC. Methods: We used RNAseq of OAC tumour tissues to classify OAC into subgroups which were associated with patient survival and the immune infiltrate in the tumour micro-environment. We identified genes that discriminate each group and selected thirteen to perform IHC against the protein products of these genes using the same OAC samples. The IHC markers that best discriminate the immune-clusters were applied to an independent set of OAC in tissue micro-arrays (TMAs) to validate the prognostic significance of the immune-clusters. Results: Using RNA-seq we identified four candidate immune-clusters namely, immune hot, immune cold, immune suppressed and immune moderate, that correlate with progression free and overall patient survival. IHC revealed a correlation of five of thirteen of these IHC markers with the RNAseq data, and the IHC was able to corroborate the classification of OAC immune-clusters. The best markers predictive of these immune-clusters underwent IHC in an independent OAC TMA cohort to confirm the prognostic significance of these markers. The TMAs contain matched primary and nodal disease, so we will also report on the presence of the four subgroups within nodal disease. To date, two of the IHC markers are associated with survival benefit in the TMAs patient group. Conclusions: We anticipate that validating IHC markers to reliably identify the four immune-clusters of OAC will be useful in predicting prognosis, survival and therapeutic classification of OAC in precision oncology of the OAC.

Abstract Definitive chemoradiotherapy (dCRT) for oesophageal cancer is recommended in selected patients who are unfit for surgery, or where doctor and/or patient prefers to surgery. Salvage oesophagectomy after dCRT is reportedly a morbid procedure compared to oesophagectomy following neoadjuvant chemoradiotherapy (nCRT). If indications for dCRT expand, there will be a larger pool of patients requiring salvage oesophagectomy. We aimed to assess the post-operative clinical outcomes of patients who had dCRT compared with nCRT in our unit. Data were obtained from a prospectively maintained database of patients receiving curative treatment for oesophageal cancer from January 2010 until February 2022. Patients receiving a salvage oesophagectomy after dCRT were compared to those receiving nCRT and planned oesophagectomy. An comparison of differences in group characteristics, post-operative outcomes and survival rates was made. Analysis was completed using t-test, chi-square, log rank and Kaplan–Meier methods. 216 patients had dCRT with 24 undergoing salvage oesophagectomy. 228 had nCRT followed by surgery. The salvage group had more SCC (47% versus 16%; p = 0.002), higher blood loss (434 versus 280 mL; p = 0.033) and more surgeon-rated technical problems (e.g. pleural adhesions or mediastinal fibrosis) (30% versus 11%; p = 0.010). Operative times were not significantly different (357 versus 330 minutes; p = 0.232). There was a trend towards higher complications in the dCRT group (83 versus 63%; p = 0.057). Operative mortality was 0% in both groups. As expected the median survival was worse in the dCRT group (26 versus 66 months; p = 0.040). Patients selected to dCRT who require and are fit for salvage oesophagectomy have worse outcomes compared with those who have nCRT. However, this subgroup still have a modest potential for cancer survival. Our dataset adds to the existing literature and will help to counsel patients being considered for salvage oesophagectomy. The possible future increase in number of patients being offered dCRT makes improving the understanding of peri-operative and cancer-specific outcomes after salvage oesophagectomy a priority.

Background AGITG DOCTOR was a randomised phase 2 trial of pre-operative cisplatin, 5 fluorouracil (CF) followed by docetaxel (D) with or without radiotherapy (RT) based on poor early response to CF, detected via PET, for resectable oesophageal adenocarcinoma. This study describes PROs over 2 years. Methods Participants ( N = 116) completed the EORTC QLQ-C30 and oesophageal module (QLQ-OES18) before chemotherapy (baseline), before surgery, six and 12 weeks post-surgery and three-monthly until 2 years. We plotted PROs over time and calculated the percentage of participants per treatment group whose post-surgery score was within 10 points (threshold for clinically relevant change) of their baseline score, for each PRO scale. We examined the relationship between Grade 3+ adverse events (AEs) and PROs. This analysis included four groups: CF responders, non-responders randomised to DCF, non-responders randomised to DCF + RT, and “others” who were not randomised. Results Global QOL was clinically similar between groups from 6 weeks post-surgery. All groups had poorer functional and higher symptom scores during active treatment and shortly after surgery, particularly the DCF and DCF + RT groups. DCF + RT reported a clinically significant difference (−13points) in mean overall health/QOL between baseline and pre-surgery. Similar proportions of patients across groups scored +/− 10 points of baseline scores within 2 years for most PRO domains. Instance of grade 3+ AEs were not related to PROs at baseline or 2 years. Conclusions By 2 years, similar proportions of patients scored within 10 points of baseline for most PRO domains, with the exception of pain and insomnia for the DCF + RT group. Non-responders randomised to DCF or DCF + RT experienced additional short-term burden compared to CF responders, reflecting the longer duration of neoadjuvant treatment and additional toxicity. This should be weighed against clinical benefits reported in AGITG DOCTOR. This data will inform communication of the trajectory of treatment options for early CF non-responders. Trial registration Australia New Zealand Clinical Trials Registry (ANZCTR), ACTRN12609000665235 . Registered 31 July 2009.

Background and Objective Isolated limb infusion (ILI) and intralesional PV-10 are well described locoregional therapies for in-transit melanoma. The objective of this study was to assess the effect of these treatments on survival outcomes within a cohort matched for key characteristics. Methods Patients were treated using ILI or intralesional PV-10 at a single institution and the data prospectively recorded. Propensity score matching was performed using key covariates within a logistic regression model. The primary outcome was the melanoma-specific survival. Results Seventy-two patients nonrandomized were successfully matched. Both treatments produced similar best overall responses. The median melanoma-specific survival (MSS) was 74.4 months from ILI and 36.4 months from PV-10 treatments (P = 0.164). Within the ILI subgroup, the 12-, 24-, 36- and 60-month MSS rates were 85.3%, 75.3%, 60.1%, and 60.1%, respectively. From the time of PV-10 the corresponding 12-, 24-, 36-, and 60-month MSS rates were 82.6%, 70.0%, 53.9%, and 35.9%. On multivariate analysis, there was a significant difference in survival comparing completely with noncomplete responders (P = 0.031). Conclusions These findings demonstrate that ILI and PV-10 treatments for in-transit disease produce comparable long-term survival. Both therapies have reproducible response rates and predominantly localized and tolerable side-effects.

BACKGROUND:Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. PATIENTS AND METHODS:Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) ≥35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). RESULTS:Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. CONCLUSIONS:EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy. TRIAL REGISTRATION:ACTRN12609000665235.

Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC.

Neoadjuvant therapy (NAT) for oesophageal cancer may reduce cardiopulmonary function, assessed by cardiopulmonary exercise testing (CPEX). Impaired cardiopulmonary function is associated with mortality following esophagectomy. We sought to assess the impact of NAT on cardiopulmonary function using CPEX and assessing the clinical relevance of any change in particular if changes were associated with post-operative morbidity. This was a prospective, cohort study of 40 patients in whom CPEX was performed before and after NAT. Thirty-eight patients underwent surgery and follow-up with perioperative outcomes measured. The primary variables derived from CPEX were the anaerobic threshold (AT) and peak oxygen uptake (<(V)over dot>O(2)peak). There were significant reductions in the AT (pre-NAT: 12.4 +/- 3.0 vs. post-NAT 10.6 +/- 2.0 mL kg(-1). min(-1); p = 0.001). This reduction was also evident for <(V)over dot>O(2)peak (pre-NAT: 16.6 +/- 3.6 vs. post-NAT 14.9 +/- 3.7 mL kg(-1). min(-1); p = 0.004). The relative reduction in <(V)over dot>O(2)peak was greater in chemotherapy patients who developed any peri-operative morbidity (p = 0.04). For patients who underwent chemoradiotherapy, there was a significantly greater relative reduction in AT (p = 0.03) for those who encountered a respiratory complication. Cardiopulmonary function significantly declined as a result of NAT prior to oesophagectomy. The reduction in AT and <(V)over dot>O(2)peak was similar in both the chemotherapy and chemoradiotherapy groups.

Abstract Background The presence of signet ring cells (SRC) is associated with poorer survival in multiple cancer types. Here we aimed to determine the predictive and prognostic value of SRC in oesophageal and junctional adenocarcinoma (OAC) for patients treated with neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). Methods Patients who underwent nCRT and nCT followed by surgery for OAC between 2000 and 2016 were identified from two institutional prospective databases. Pre-treatment biopsy and surgical resection pathology reports were used to determine the presence of SRC morphology. The association between SRC histology and clinicopathological characteristics including pathological response was assessed. The prognostic impact of SRC on disease-free survival (DFS) and overall survival (OS) was determined. Survival was calculated with Kaplan Meier method and differences tested with log rank test. Results Of the 689 study patients, 129 had SRC (nCRT; n = 65, nCT; n = 64) and 560 patients had no evidence of SRC (nCRT; n = 326, nCT; n = 234). The SRC group had higher pT stage (P = 0.004) and median number of involved nodes (P = 0.004) following nCT compared with the non-SRC group. There were no significant differences between the two groups with respect to age, gender, tumour site, pN, R status or pathological complete response. For the 129 in the SRC group, nCT patients had significantly worse DFS (median [IQR]; 12 months [50–5]) compared with nCRT patients (median [IQR]; 26 months [111–9], P = 0.021). Moreover, nCT had a worse loco-regional recurrence-free survival (P = 0.004), but not distant recurrence-free survival (P = 0.74), in the SRC group. In contrast, there were no differences in DFS (P = 0.245) or recurrence patterns between nCRT and nCT among the 560 non-SRC patients. However, there was no significant difference in OS according to SRC status following nCT (P = 0.076) or nCRT (P = 0.541). Conclusion For SRC OAC, nCRT is associated with better DFS and loco-regional control compared with nCT. However, the presence of SRC in OAC was not prognostic for OS following nCT or nCRT. Disclosure All authors have declared no conflicts of interest.

Background: Multimodality treatments of patients with esophageal adenocarcinoma (EAC) improve survival, but the optimal treatment strategy remains undetermined. This study aimed to compare response, local recurrence and survival outcomes in patients undergoing neoadjuvant paclitaxel and carboplatin chemoradiotherapy with 41Gy (CROSS) with neoadjuvant cisplatin and 5-fluoruracil (CF)-based chemoradiotherapy with 45Gy (CFRT) or CF chemotherapy followed by oesophagectomy for EAC. Methods: Patients who underwent CROSS, CFRT or CF followed by surgery for EAC were identified from two single institution prospective databases from Australia and the Netherlands (2000-2018) and included in this study. After pair-wise propensity score matching (caliper 0.2) using pre-treatment variables (age, gender, year of treatment, tumor length and site, and clinical T stage), we compared the impact of the treatments on pathological outcomes, patterns of recurrence and overall survival. Results: Of the 637 eligible patients, 429 patients were analysed following propensity score matching. This resulted in 143 patients in each group with median follow up 61 months. CROSS and CFRT demonstrated significantly higher pathological complete response rates (p < 0.001), lower ypT stage (p < 0.001) and lower ypN stage (p < 0.001) compared with CF. There were no statistically significant differences in 5-year local recurrence-free survival between the three treatment groups: CROSS 76% (95%CI: 68-85); CFRT 71% (95%CI: 64-81); and CF 66% (95%CI: 65-76). Similarly, there were no significant differences in 5-year overall survival rates between groups: CROSS 52% (95%CI: 44-62); CFRT 40% (95%CI: 32-49); and 46% (95%CI: 38-55)(p = 0.18, log rank). Median overall survival for CROSS was 69 months (95%CI: 47-139), for CFRT 32 months (95%CI: 26-52), and for CF 47 months (95%CI: 33-66) (p = 0.33, log rank). Conclusions: In this study, there were higher pathological response rates and lower pathological stage associated with CROSS and CFRT. However, overall survival and local recurrence was similar for CROSS, CF and CFRT. Legal entity responsible for the study: The University of Queensland. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

BackgroundThe optimal treatment strategy for patients with esophageal adenocarcinoma (EAC) remains undetermined. This study compared outcomes in patients undergoing neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) for EAC.MethodsPatients who underwent nCT or nCRT followed by surgery for EAC were identified from a prospective database (2000‐2017) and included. After propensity score matching, the impact of the treatments on postoperative complications, in‐hospital mortality, pathological outcomes, and survival rates were compared.ResultsOf the 396 eligible patients, 262 patients were analysed following matching with 131 patients in both groups. There were no significant differences between the nCT and nCRT groups for overall complications (59% vs 57%, P = 0.802) or in‐hospital mortality (2% vs 0%, P = 0.156). Patients who had nCRT had more R0 resections (93% vs 83%, P = 0.013), and higher pathological complete response rates (15% vs 5%, P < 0.001). No differences in 5‐year overall survival rates (nCT vs nCRT; 44% vs 33%, P = 0.645) were found.ConclusionIn this study no differences between nCT and nCRT were seen in postoperative complications and in‐hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities.

Background: Resectable oesophageal and gastro-oesophageal junction adenocarcinoma patients (pts) without early metabolic response (EMR) to chemotherapy as defined by 18-FDG-PET (PET) show poor survival and major histological response rates (RR) <5%. This multicentre trial previously reported changing neoadjuvant therapy improved major histological RR for early metabolic non-responders (MNR). Grade 3/4 toxicities were seen in 27% of pts on 5-FU + cisplatin (CF); 42% on docetaxel + CF (DCF) and 71% on DCF + concurrent 45Gy radiotherapy (DCFRT). Updated results now report progression-free survival (PFS) and local recurrence. Methods: Pts had a day 15 PET scan after induction CF. Early metabolic responders (SUVmax decreasing by ≥ 35% from baseline to day 15 PET) received a 2nd CF cycle then oesophagectomy. Early metabolic non-responders were centrally randomised 1:1 to 2 cycles of DCF or DCFRT then oesophagectomy. Primary endpoint was major histological RR (<10% residual tumour). Seconday endpoints were PFS and local recurrence. Results: From 2009 -2016, 124 pts were recruited. 45 were deemed early metabolic responders. 77 were deemed early metabolic non-responders and 31 allocated DCF and 35 to DCFRT. 11 were not randomised (progression, toxicity, refusal). 2 were not evaluable. Major histological response rates: 7% EMR (CF); 20% DCF; 63% DCFRT. Local recurrence: 5/45 (11%) EMR (CF); 10/31 (32%) MNR allocated DCF; 4/35 (11%) MNR allocated DCFRT. PFS at 36m: 46% (95% CI 31-60%) for EMR; 31% (95% CI 16-48%) for MNR allocated DCF; 46% (95% CI 29- 61%) MNR allocated to DCFRT. Conclusions: Early metabolic response to CF alone is associated with favourable PFS and low local recurrence rate despite a low major histological RR. The addition of docetaxel in MNR group may augment histological RR but PFS & local recurrence outcomes remained inferior. Further addition of RT to DCF produced the highest histological RR and PFS/local recurrence outcomes matching EMR group. Early PET can enable tailoring of therapy to 'close the gap' in outcomes between early metabolic response and early metabolic non-response patients. Clinical trial identification: Australian New Zealand Clinical Trials Registry: 12609000665235. Legal entity responsible for the study: The Australasian Gastro-Intestinal Trials Group (AGITG). Funding: The National Health and Medical Research Council, Australia. Disclosure: All authors have declared no conflicts of interest.

BackgroundPatients with in‐transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi‐center study, PV‐10 treatment was continued at our institution for patients with in‐transit disease.MethodologyAn open‐label, non‐randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV‐10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions.ResultsForty‐five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV‐10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow‐up duration was 22 months and the median overall survival was 25 months from first PV‐10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response (P = 0.03).ConclusionsIntralesional PV‐10 provided rapid lesion‐specific ablation of melanoma metastases with well‐tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume.

Abstract Background MIE is becoming more common and is considered safe. There are few studies supporting laparoscopy in favor of laparotomy for the abdominal part of a three-field esophagectomy and long term survival data are scarce. The objective was to compare open esophagectomy (OE), with hybdrid thoracoscopic-laparotomic esophagectomy (HMIE) and minimally invasive esophagectomy (MIE) with regard to surgical outcomes, postoperative complications and survival. Methods A prospective database of esophageal resection for cancer at a single centre identified 243 OE, 688 HMIE and 80 MIE procedures. Propensity scores were used to match 80 patients in each group adjusting for age, gender, weight, clinical stage, neoadjuvant treatment, and year of surgery. Results Respiratory complications were more common after OE (49%) than after MIE (31%, P = 0.02). Median operative time was longer for MIE (330 minutes) versus HMIE or OE (both 300 minutes, P < 0.001). Median length of stay was shorter following MIE (12 days) compared with HMIE (14 days) and OE (15 days), P = 0.001. There were no significant differences between groups with respect to other complications, median number of lymph nodes examined (22–23 for all groups), or R0 resection rate (range 85–91%) for all groups. There was no difference in 5-year overall survival between groups. Conclusion Compared with OE and HMIE, MIE was associated with shorter length of stay and fewer respiratory complications, but longer operative time. Thus, there may be additional benefit for MIE without comprising oncological outcomes. Disclosure All authors have declared no conflicts of interest.

Aims: To analyse outcomes and patterns of failure following dose-escalated definitive chemoradiotherapy (CRT) for oesophageal squamous cell carcinoma using fluorodeoxyglucose positron emission tomography for staging and treatment planning. Materials and methods: A retrospective review of patients with oesophageal squamous cell carcinoma receiving definitive CRT to a dose of >= 56 Gy was conducted. Patient and tumour characteristics, treatment received and first sites of relapse were analysed. Results: Between 2003 and 2014, 72 patients were treated with CRT to a median dose of 60 Gy (range 56-66 Gy). The median age was 63 years; most (61%) were stage III/IVa. The median follow-up was 57 months. Three year in-field control, relapse-free survival and overall survival was 64% (95% confidence interval 50-75%), 38% (95% confidence interval 27-50%) and 42% (95% confidence interval 30-53%), respectively. Of the 41 failures prior to death or at last follow-up date, isolated locoregional relapse occurred in 16 patients (22%) with isolated in-field recurrence in 11 patients (15%). Distant failure as first site of relapse was present in 25 patients (35%). No in-field failures occurred in the 11 patients with cT1-2, N0-1 tumours. The median survival for cT4 tumours was 8 months, with five of eight patients developing local progression within the first 6 months. Conclusions: Dose-escalated radiotherapy was associated with promising rates of in-field local control, with the exception of cT4 tumours. Distant failure remains a significant competing risk. Our data supports the need for current trials re-examining the role of dose escalation in the modern era. (C) 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.