Background/Objectives: (P)rehabilitation, comprising structured exercise, nutritional optimisation, and/or psychological support delivered pre- or postoperatively, has demonstrated efficacy in improving outcomes across the cancer care continuum. However, access remains limited. Technology-enabled (p)rehabilitation offers a novel solution with the potential to enhance equity and continuity of care. This systematic review aimed to evaluate the efficacy of technology-enabled (p)rehabilitation on perioperative and patient-reported outcomes among individuals undergoing thoracic and/or abdominopelvic cancer surgery. Methods: Six databases were search from inception to October 2024. Eligible studies were randomised controlled trials (RCTs) comparing technology-enabled (p)rehabilitation with usual care, placebo, or non-technology-based interventions in adults undergoing thoracic and/or abdominopelvic cancer surgery. Outcomes included postoperative complications, hospital readmissions, hospital length of stay (LOS), quality of life (QoL), pain, anxiety, depression, fatigue, distress, and satisfaction. Higher scores indicated improved QoL or worse symptom severity. Risk of bias was assessed using the revised Cochrane tool, and evidence strength was determined using GRADE methodology. Relative risks (RR) and mean differences (MD) were calculated using random-effects meta-analysis. Results: Seventeen RCTs (18 publications, n = 1690) were included. Trials most commonly evaluated application-based platforms (n = 8) and the majority exhibited some risk of bias. Technology-enabled (p)rehabilitation was associated with a significant reduction in LOS (MD = 1.33 days; 95% CI: 0.59-2.07; seven trials), and improvements in pain (MD = 6.12; 95% CI: 3.40-8.84; four trials), depression (MD = 2.82; 95% CI: 0.65-4.99; five trials), fatigue (MD = 10.10; 95% CI: 6.97-13.23; three trials) and distress (MD = 1.23; 95% CI: 0.30-2.16; single trial) compared with controls. Conclusions: Technology-enabled (p)rehabilitation shows promise in reducing LOS and improving selected patient-reported outcomes following thoracic and abdominopelvic cancer surgery. Although evidence is limited due to the small number of studies, modest sample sizes, methodological heterogeneity, and intervention variability, the overall findings justify further investigation. Large-scale, adequately powered clinical trials are required to confirm efficacy and guide clinical effectiveness and implementation studies.

BACKGROUND:The multicentre ALaCaRT and ACOSOG Z6051 randomized trials were unable to demonstrate non-inferiority of laparoscopic versus open surgery for rectal cancer with respect to a composite pathology metric indicating successful resection. Neither trial was individually powered to detect differences in long-term recurrence or survival. This planned meta-analysis determined long-term oncological outcomes of laparoscopic versus open proctectomy for rectal adenocarcinoma. METHODS:This prospective meta-analysis included individual patient data from patients with cT1-3 N0-2 M0 rectal adenocarcinoma enrolled in the ALaCaRT and ACOSOG Z6051 trials. Pathologically successful resection was defined as complete or near-complete total mesorectal excision, a clear circumferential resection margin (CRM; > 1 mm), and a clear distal resection margin (> 1 mm). The non-inferiority margin for disease-free survival (DFS) was an absolute difference of 5% at least 3 years after surgery. RESULTS:The combined data set included 935 patients (65.6% men, mean age 60.7 years, mean body mass index 26.7 kg/m2) randomized to open (457 patients) or laparoscopic (478 patients) proctectomy. Pathologically successful resection was lower in the laparoscopic than open group (85.1% versus 89.9%, respectively; pooled estimate 4.6% difference; 95% confidence interval (c.i.) -8.6% to -0.5%). The median follow-up was 60.2 (interquartile range 49.9-61.1) months. Three-year DFS was 75.2% (95% c.i. 71.1% to 79.2%) and 76.5% (95% c.i. 72.5% to 80.6%) for the laparoscopic and open groups, respectively (pooled estimate difference -1.5%; 95% c.i. -7.2% to 4.2%). Non-inferiority of laparoscopic surgery was not demonstrated because the lower one-sided 95% c.i. (-6.3% to 100%) crossed -5%. Three-year locoregional recurrence was higher in laparoscopic than open group (5.4% (95% c.i. 3.3% to 7.5%) versus 2.0% (95% c.i. 0.7% to 3.4%), respectively; pooled estimate 3.1% difference (95% c.i. 0.6% to 5.6%)). A clear CRM was the most significant and only pathological predictor of both DFS (P < 0.0001) and overall survival (P < 0.0001). CONCLUSION:Laparoscopic proctectomy led to a lower rate of pathologically successful resection and a higher rate of locoregional recurrence at 3 years. The possibility of subsequent poorer DFS or overall survival rate requires further evaluation, because this analysis was not specifically powered for these endpoints.

PURPOSE:This qualitative study explored barriers and facilitators to adherence among participants of a virtual multimodal (p)rehabilitation program for gastrointestinal cancer surgery and investigated how these aligned with constructs from Temporal Self-Regulation Theory (TST), a theoretical behaviour change framework. MATERIALS AND METHODS:Semi-structured interviews were conducted with participants of the PRIORITY-CONNECT 2 Pilot Trial, a virtual multimodal (p)rehabilitation program for patients undergoing major gastrointestinal cancer surgery. TST informed the development of the semi-structured interview questions to explore participants' experiences of barriers and facilitators to uptake of the program recommendations. Reflexive thematic analysis was conducted to identify patterns within participants' experiences and perceptions of the (p)rehabilitation program. RESULTS:13 interviews were conducted. Six themes were identified: (1) Trust in Healthcare Professionals; (2) Overall Program Perceptions; (3) Socioenvironmental Impacts; (4) Personal Characteristics and Motivation; (5) Prior Health Habits; (6) Symptoms Impacting Physical Capacity. These themes mapped to the constructs of TST, identifying how beliefs about program value, contextual barriers, and self-regulatory capacity shape adherence behaviour. CONCLUSIONS:Adherence to virtual (p)rehabilitation was influenced by trust, perceived benefit, and flexible, supervised delivery, but limited by competing demands and treatment-related fatigue. Integrating behaviour-change principles from TST may enhance adherence in future multimodal (p)rehabilitation programs.

AIM:To identify clinicians' perceived challenges and barriers in the management of low anterior resection syndrome (LARS) through exploration of attitudes and decision-making practices around screening, diagnosis and management. METHOD:Exploratory interpretive qualitative design. Semi-structured interviews were undertaken and a reflexive thematic qualitative analysis was conducted using an iterative-inductive approach. RESULTS:Eleven colorectal surgeons, six physiotherapists and three specialist nurses were interviewed. Data were grouped into four major themes and 13 sub-themes. Variation in clinician engagement with LARS was identified, with clinicians' knowledge, training and personal interest in managing patients raised by participants as contributing factors. An absence of standardized management pathways presented challenges in clinical practice with the lack of structured multidisciplinary approaches and referral pathways combined with a perceived lack of established treatment guidelines impacting on clinical decision-making. Inequities in access to specialist pelvic services and treatment were identified as systemic limitations which influence clinical decision-making in relation to clinical practice and implementation of patient care. The interpretation of the patient experience with LARS and perceptions of treatment acceptability were identified to influence clinical decision-making and demonstrated divergent perceptions of patient experience. CONCLUSION:This study identified several challenges in LARS management from a clinician's perspective. A lack of standardized treatment guidelines and pathways, limited treatment access, and inconsistent clinician engagement present challenges. Divergent perceptions of patient experience and treatment acceptability further complicate care. These findings highlight the urgent need to address these systemic limitations through enhanced surgeon education, standardized treatment/referral guidelines, improved patient resources and expanded access to multidisciplinary care.

BACKGROUND/AIM:To evaluate the efficacy of [177Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) plus capecitabine and temozolomide (CAPTEM) in participants(pts) with progressive WHO Grade 1-2 neuroendocrine tumours: pancreas(pNETs) and small bowel(SBNETs). METHODS:Non-comparative randomized open label parallel group phase II trial, 2:1 randomization to PRRT/CAPTEM (experimental arm) vs PRRT (SBNETs control) and CAPTEM (pNETs control). PRRT/CAPTEM:7.8 GBq [177Lu]Lu-DOTATATE i.v. Day 10, 8 weekly x 4, concurrent CAP 750 mg/m2 b.i.d. Days 1-14 and TEM 75 mg/m2 b.i.d. Days 10-14. CAPTEM Q 4 weekly (pNET control arm). PRIMARY ENDPOINT:Progression-free survival (PFS) @ 15 months (SBNETS) (target > 80%), and 12 months (pNETs) (target >75%). Other: Objective response rate (ORR), overall survival and adverse events (AE). Extended follow-up was undertaken after initial analysis. RESULTS:Seventy-two patients were enrolled and evaluable (27 pNETs, 45 SBNETs). The pNET 12 month PFS was 83.3% (PRRT/CAPTEM) and 88.9% (CAPTEM), and 27 month PFS was 61.1% (PRRT/CAPTEM) and 33.3% (CAPTEM). The SBNET 15 month PFS was 90.4% (PRRT/CAPTEM) and 92.3% (PRRT), and 36 month PFS was 60.4% (PRRT/CAPTEM) and 61.5% (PRRT). PFS HR was HR 0.41 (95% CI: 0.15-1.12, p = 0.08) for pNETs and 1.17 (95% CI: 0.51-2.68, p = 0.71) for SBNETs. ORR for pNETs was 72.2% (PRRT/CAPTEM) and 33.3% for CAPTEM, and for SBNETs 34% (PRRT/CAPTEM) and 23% for PRRT. PRRT treatment-related myeloid neoplasms were noted in 2/63 participants (3%). CONCLUSIONS:AGITG CONTROL NETs is the first randomized trial to demonstrate efficacy for PRRT/CAPTEM in pNETs. Extended follow-up confirms durable activity, with higher PFS and ORR in pNETs. The efficacy of CAPTEM/PRRT in pNETs should be tested in a phase III trial. CLINICAL TRIAL REGISTRATION:NCT02358356 / ACTRN12615000909527.

Previous stage I-III colon cancer trials demonstrated improved peri-operative and similar long-term oncological outcomes with minimally invasive approaches compared with open surgery. Subsequent technical developments, including intracorporeal anastomosis, complete mesocolic excision (CME), refined pathologic grading systems and robotic approaches are increasingly used despite minimal supporting evidence. This international phase II trial aims to assess patient, surgical and pathological outcomes following robotic (RRHC) with laparoscopic right hemicolectomy (LRHC) for right sided colon cancer. Prospective, international multicentre pilot randomised phase II trial for patients with right colon adenocarcinoma, randomised 2:1 to robotic (RRHC) or laparoscopic (LRHC) surgery performed by accredited surgeons. Primary outcome was 90-day surgical morbidity measured using the Comprehensive Complication Index (CCI). Standardised pathology reviews, patient reported quality of life and surgeon task load index data was captured. RRHC vs. LRHC surgery allocation was 19 vs. 10, mean operative time 3.8 vs. 3.1 h with no operative mortality, all had R0 resection, CME rate 53 vs. 50

Introduction As a result of improving survival rates, the adverse consequences of rectal cancer surgery are becoming increasingly recognised. Low anterior resection syndrome (LARS) is one such consequence and describes a constellation of bowel symptoms after rectal cancer surgery which includes urgency, faecal incontinence, stool clustering and incomplete evacuation. LARS has a significant adverse impact on quality of life (QoL) and symptoms are present in up to 75% of patients in the first year after surgery. Despite this, little is known about the natural history and there is poor evidence to support current treatment options.Methods and analysis The objectives of POLARiS are to explore the natural history of LARS and to evaluate the clinical and cost-effectiveness of transanal irrigation (TAI) or sacral neuromodulation (SNM) compared with optimised conservative management (OCM) for people with major LARS.POLARiS is a prospective, international, open-label, multi-arm, phase 3 randomised superiority trial within a cohort design, with internal pilot phase, qualitative sub-study, process evaluation and economic evaluation. Approximately 1500 adult participants from UK hospitals and 500 from Australian hospitals who have undergone a high or low anterior resection for colorectal cancer in the last 10 years will be recruited into the cohort. Six-hundred participants from the UK and 200 participants from Australia, with major LARS symptoms, defined as a LARS score of ≥30, will be recruited to the randomised controlled trial (RCT) element. Participants entering the RCT will be randomised between OCM, TAI or SNM, all with equal allocation ratios.Cohort and RCT participants will be followed up for a 24-month period, completing a series of questionnaires measuring LARS symptoms and QoL, as well as clinical review for those in the RCT. A process evaluation, qualitative sub-study and economic evaluation will also be conducted.The primary outcome measure of the POLARiS cohort and RCT is the LARS score up to 24 months post-registration/randomisation. Analyses of the RCT will be conducted on an intention-to-treat basis. Comparative effectiveness analyses for each endpoint will consist of two pairwise treatment comparisons: TAI versus OCM and SNM versus OCM. Secondary outcomes include health-related QoL, adverse events, treatment compliance and cost-effectiveness (up to 24 months post-registration/randomisation).Ethics and dissemination Ethical approval has been granted by Wales REC 4 (reference: 23/WA/0171) in the UK and Sydney Local Health District HREC (reference: 2023/ETH00749) in Australia. The results of this trial will be disseminated to participants on request and published on completion of the trial in a peer-reviewed journal and at international conferences.Trial registration number ISRCTN12834598; ACTRN12623001166662.

BACKGROUND AND OBJECTIVES:Inhaled corticosteroids have been proposed as treatment for acute COVID-19 infection in the community. We sought to determine the efficacy and safety of inhaled ciclesonide 320 mcg daily for 14 days compared to placebo in reducing the time to first recovery from all symptoms within 28 days of randomisation. METHODS:We conducted a two-arm, double blind, placebo-controlled, community-based randomised trial. Participants received inhaled ciclesonide 320 mcg daily or matching placebo for 14 days. The primary outcome was time to recovery of symptoms to day 28. An updated systematic review of all controlled trials of inhaled corticosteroids for acute COVID-19 was then undertaken. RESULTS:There were 189 people randomised and 185 completed treatment; 96% were COVID-19 vaccinated. No difference was seen in the time to first recovery using a proportional hazards analysis, recovery rate ratio 1.04 (95% CI; 0.77, 1.40). The median time to recovery with ciclesonide was 7 days (95% CI 6-9), compared with placebo of 7 days (95% CI 6-9), p = 0.84. There were no significant differences in secondary outcomes, including time to sustained recovery and respiratory symptoms. The treatment was safe and well tolerated. CONCLUSION:In a highly vaccinated (> 90%) population exposed to Omicron variants of SARS-CoV-2, the addition of inhaled ciclesonide had no effect on accelerating recovery from acute symptoms. These trial results and updated combined evidence of placebo-controlled trials do not support the use of inhaled corticosteroids for the treatment of COVID-19. TRIAL REGISTRATION:ACTRN12620000566932.

Background The efficacy and safety of avatrombopag, a second generation thrombopoietin-receptor agonist, in the treatment of newly diagnosed severe aplastic anemia (sAA) is being evaluated in the DIAAMOND-Ava-FIRST trial. Herein, we report somatic and germline molecular findings of this study in which treatment-naïve patients received avatrombopag in combination with immunosuppressive therapy (IST; equine ATG and ciclosporin). Methods Enrolled patients (pts) received IST plus oral avatrombopag at a maximum dose of 60mg for an initial six months (mths; standard), with those achieving a partial response eligible to receive a further six mths of avatrombopag (extended). At baseline, occult germline disease was screened for with use of a 37-gene inherited bone marrow failure (IBMF) NGS hybridisation-based capture panel. Cellular (bone marrow aspirate) and cell free (peripheral blood) DNA samples were obtained at baseline, 6, 12, 18 and 24 mths and were analysed using a targeted unique molecular index-corrected hematological malignancy NGS panel. Whole genome NGS copy number variation (CNV) analysis was performed by comparing read counts from on and off target reads to a pooled reference comprising normal samples to correct for enrichment and sequencing biases. Avatrombopag therapy has now been completed for enrolled pts, with a median follow up of 20.4 mths (IQR (8.9, 23.4)). Results 56 eligible pts (male:female 1.33:1) with a median age 58 years (yrs) (range 18-78 yrs) were enrolled. IBMF testing did not reveal occult germline disease in any pt (two pts had non-suspicious variants of uncertain significance (in GATA2 and RTEL1)). Somatic profiling at baseline (excluding PIGA), demonstrated that 15 pts (27%) had somatic mutations; 9 (16%) had 1 mutation, 5 (9%) had 2 mutations, and 1 pt (2%) had more than 2 mutations. Patients with detectable somatic mutations were typically older compared to those with no detectable mutations (median age 65 v 50 yrs). DNMT3A was the most frequently mutated gene at baseline, followed by PIGA, ASXL1, and TET2. 47 pts had both baseline and 6 mth somatic data available, with mutations present in 21 (45%) of these pts at 6 mths. Newly emergent mutations at 6 mths were most frequent in ASXL1, DNMT3A, PIGA and U2AF1. The presence of mutations at baseline did not correlate with complete response (p=0.49) or overall response (p=0.31) at 6 mths. 13 pts received extended avatrombopag therapy for a total of 12 mths, with this extended therapy group demonstrating enrichment of somatic mutations at baseline (≥1 mutation 58% vs 20% standard, ≥2 mutations 42% vs 0% standard) and at 12 mths (≥1 mutation 83% v 48% standard, ≥2 mutations 67% v 20% standard) and a trend to higher median variant allele frequencies compared with the standard therapy arm (14.2% v 8% at 12 mths and 24.2% v 12.1% at 24 mths, p=0.08). 2 pts developed myelodysplastic syndrome (MDS); at 12 mths and 18 mths, with both pts harbouring ASXL1 mutations at the time of MDS development. One of the pts who developed MDS had received extended avatrombopag therapy to 12 mths. 22/53 pts (42%) had a PNH clone by flow cytometry reported at baseline; of these 8 (36%) had a PIGA mutation detected. There were no PIGA mutations detected in the absence of a PNH clone. Baseline NGS CNV analysis was performed in 52 pts and detected trisomy 8 in 1 pt (concordant with conventional cytogenetics (CG) result), acquired loss of heterozygosity in 1p, 6p and 13q in 1 ptBCOR duplication in 1 pt and a duplication of Xq21.33 involving DIAPH2 in 1 pt. CG at baseline failed in 23/56 pts (41%), with no detectable chromosomal aberrations from NGS CNV analysis in this group. Finally, we analysed cell-free DNA from the cohort which showed broad concordance between mutations detected in the cellular and cell free compartments, however the cell free DNA compartment samples did reveal further clonal complexity at baseline in 5/46 (11%) pt samples with mutations detected that were not detected in the cellular compartment (in TP53, BRAF, MAP2K1 and DNMT3A). Conclusion Molecular profiling of pts with sAA treated with avatrombopag demonstrated that clonal hematopoiesis is common at baseline, with an increase in pts with clonal hematopoiesis observed at 6 and 12 months after commencing therapy, with enrichment of somatic mutations in those who received extended duration of avatrombopag. Moreover, further genomic complexity may be revealed in this subgroup from cell-free DNA analysis.

Background: The PRIORITY-CONNECT 2 pilot trial will establish the feasibility and acceptability of a virtual multimodal programme following gastrointestinal cancer surgery. The secondary aims are to obtain pilot data on the likely difference in key outcomes, data elements that will guide future implementation studies, and to identify barriers and facilitators that inform the development and execution of a substantive randomised clinical effectiveness trial of teleprehabilitation/rehabilitation. Methods: This is a multicentre, assessor-blinded, pilot, randomised controlled trial utilising a Hybrid Type I effectiveness-implementation design. 20 participants undergoing major gastrointestinal cancer surgery will be randomised (1:1 allocation) to attend a virtual multimodal prehabilitation-rehabilitation hub (intervention group), delivered before (1-6 weeks) and after (up to 3 months) surgery plus usual care, or to usual care alone (control group). An individualised intervention will be delivered by an experienced multidisciplinary team including a physiotherapist, psychologist, dietitian, nurse, social worker, and a geriatrician. Outcomes will be collected at baseline, 1-2 days before surgery, during the hospital stay, day of discharge from hospital, and 3 months postoperatively. The primary outcomes will be feasibility and acceptability of the virtual multimodal hub. Secondary outcomes assess the rate of postoperative complications within 30 days after surgery, quality of life, the number of days at home within 30 and 90 days after surgery, healthcare use, and implementation outcomes. Discussion: The PRIORITY-CONNECT 2 pilot trial will generate findings about the feasibility and acceptability of delivering an evidence-based virtual multimodal preoperative (prehabilitation) and postoperative (rehabilita-tion) intervention targeting patients having major gastrointestinal cancer surgery. Trial registration: This trial was registered prospectively with the National Library of Medicine ClinicalTrials.gov Registry (NCT06212700) on 8th January 2024.

Introduction Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and ciclosporin is standard of care for patients with severe aplastic anaemia (sAA) not eligible or suitable for allogeneic stem cell transplant. While patients respond to IST, few achieve complete responses and a significant proportion are refractory or relapse. The addition of eltrombopag, a thrombopoietin-receptor agonist (TPO-A), to IST has been shown to improve haematological responses in sAA. Avatrombopag is a second-generation TPO-A with potential advantages over eltrombopag. However, to date avatrombopag has not been studied in sAA.Methods and analysis Investigator-initiated, single-arm registry-based Bayesian Optimal Phase II trial of avatrombopag conducted in two cohorts, patients with untreated sAA (FIRST cohort) and in patients with sAA that has relapsed or is refractory to IST (NEXT cohort). In the FIRST cohort, participants receive IST (equine ATG and ciclosporin) plus avatrombopag from day 1 until day 180 at 60 mg oral daily, with dose adjusted according to platelet count. Participants in the NEXT cohort receive avatrombopag at 60 mg oral daily from day 1 until day 180, with or without additional IST at the discretion of the treating clinician.For each cohort, two primary endpoints (haematological response and acquired clonal evolution) are jointly monitored and the trial reviewed at each interim analysis where a ‘go/no-go’ decision is made by evaluating the posterior probability of the events of interests.Ethics and dissemination The trial has received ethics approval (Monash Health RES-18-0000707A). The trial conduct will comply with ICH-GCP and all applicable regulatory requirements. The results of the trial will be submitted to a peer-review journal for publication.Trial registration number ACTRN12619001042134, ACTRN12619001043123.

Laparoscopic-assisted surgery for rectal cancer is widely used, however the healthcare costs are thought to be higher than for open resection. This secondary endpoint analysis of a randomized controlled trial aimed to evaluate total healthcare costs of laparoscopic-assisted surgery compared with open resection for rectal cancer over a 12-month period. Patients in the Australasian Laparoscopic Cancer of the Rectum Trial (ALaCaRT) were included in a prospective costing analysis. All healthcare use for the index surgery and hospital admission, readmissions, and follow-up care over 12 months were included. Unit costs were valued in Australian dollars (AUD$) using scheduled Medicare fees and hospital cost weights. The primary outcome was mean per patient cost. Non-parametric bootstrapping with 10,000 replications was undertaken for robustness checks. Data from 468 patients indicated that the laparoscopic-assisted surgical procedure incurred a mean cost of AUD$4542 (standard deviation [SD] AUD$1050)—AUD$521 higher than the open procedure mean cost of AUD$4021 (SD AUD$804) due to longer operative time and involvement of more costly equipment (95% confidence interval [CI] AUD$354–AUD$692). At 12 months, the average cost for the laparoscopic-assisted and open groups was AUD$43,288 (SD AUD$40,883) and AUD$45,384 (SD AUD$38,659), respectively, due to the shorter subsequent hospital stays. No overall significant cost difference between groups was found (95% CI −AUD$9358 to AUD$5003). One-way sensitivity analyses confirmed the robustness of the results. While initially higher, the costs of laparoscopic-assisted surgery for rectal cancer were similar to open resection at 12 months. Clinicians may choose a surgical approach based on clinical need. The Australasian Gastro-Intestinal Trials Group (AGITG) was the legal sponsor and trial coordination was performed by the NHMRC Clinical Trials Centre. The trial was registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12609000663257)

Objective: The aim of this study was to compare patient-reported urinary, bowel, and sexual functioning of ALaCaRT Trial participants randomized to open or laparoscopic surgery for rectal cancer. Summary Background Data: The primary endpoint, noninferiority of laparoscopic surgical resection adequacy, was not established. Methods: Participants completed QLQ-CR29 at baseline, 3, and 12 months post-surgery. Additionally, women completed Rosen’s Female Sexual Functioning Index (FSFI). Men completed the International Index of Erectile Function (IIEF) and QLQ-PR25. We compared the proportions of participants in each group who experienced moderate/severe symptoms/dysfunction at each time-point and compared mean difference scores from baseline to 12 months between groups. All analyses were intention-to-treat. Sexual functioning analyses included only the participants who expressed sexual interest at baseline. Results: Baseline PRO compliance of 475 randomized participants was 88%. At 12 months, a lower proportion of open surgery participants experienced moderate–severe fecal incontinence and sore skin, compared to Laparoscopic participants, and a lower proportion of men randomized to open surgery experienced moderate–severe urinary symptoms. There were no differences at 3 months for bowel or urinary symptoms. Sexual functioning among sexually interested participants was similar between groups at 3 and 12 months; however, a lower proportion of women reported moderate to severe sexual dissatisfaction at 3 months in the open as compared to the laparoscopic group, (Rebecca.mercieca@sydney.edu.au., 95% CI 0.03–0.39). Discussion: Despite the slightly lower proportions of open surgery participants self-reporting moderate-severe symptoms for 3 of 16 urinary/bowel domains, and lack of differences in sexual domains, it remains difficult to recommend one surgical approach over another for rectal resection.

Advanced biliary tract cancer (ABTC) is a highly aggressive malignancy, with a 5‐year overall survival of < 10%. Although preliminary evidence suggests a role of targeted treatments or immunotherapy in a subset of patients, chemotherapy remains the standard second‐line treatment in the majority. We conducted a pilot study of second‐line chemotherapy with capecitabine and nab‐paclitaxel after failure of gemcitabine and platinum.

Abstract Background Among patients with non-metastatic pancreatic cancer, 80% have high-risk, borderline resectable or locally advanced cancer, with a 5-year overall survival of 12%. MASTERPLAN evaluates the safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in these patients. Methods and design MASTERPLAN is a multi-centre randomised phase II trial of 120 patients with histologically confirmed potentially operable pancreatic cancer (POPC) or inoperable pancreatic cancer (IPC). POPC includes patients with borderline resectable or high-risk tumours; IPC is defined as locally advanced or medically inoperable pancreatic cancer. Randomisation is 2:1 to chemotherapy + SBRT (investigational arm) or chemotherapy alone (control arm) by minimisation and stratified by patient cohort (POPC v IPC), planned induction chemotherapy and institution. Chemotherapy can have been commenced ≤28 days prior to randomisation. Both arms receive 6 × 2 weekly cycles of modified FOLFIRINOX (oxaliplatin (85 mg/m2 IV), irinotecan (150 mg/m2), 5-fluorouracil (2400 mg/m2 CIV), leucovorin (50 mg IV bolus)) plus SBRT in the investigational arm. Gemcitabine+nab-paclitaxel is permitted for patients unsuitable for mFOLFIRINOX. SBRT is 40Gy in five fractions with planning quality assurance to occur in real time. Following initial chemotherapy ± SBRT, resectability will be evaluated. For resected patients, adjuvant chemotherapy is six cycles of mFOLFIRINOX. Where gemcitabine+nab-paclitaxel was used initially, the adjuvant treatment is 12 weeks of gemcitabine and capecitabine or mFOLFIRINOX. Unresectable or medically inoperable patients with stable/responding disease will continue with a further six cycles of mFOLFIRINOX or three cycles of gemcitabine+nab-paclitaxel, whatever was used initially. The primary endpoint is 12-month locoregional control. Secondary endpoints are safety, surgical morbidity and mortality, radiological response rates, progression-free survival, pathological response rates, surgical resection rates, R0 resection rate, quality of life, deterioration-free survival and overall survival. Tertiary/correlative objectives are radiological measures of nutrition and sarcopenia, and serial tissue, blood and microbiome samples to be assessed for associations between clinical endpoints and potential predictive/prognostic biomarkers. Interim analysis will review rates of locoregional recurrence, distant failure and death after 40 patients complete 12 months follow-up. Fifteen Australian and New Zealand sites will recruit over a 4-year period, with minimum follow-up period of 12 months. Discussion MASTERPLAN evaluates SBRT in both resectable and unresectable patients with pancreatic ductal adenocarcinoma. Trial registration Australia New Zealand Clinical Trials Registry ACTRN12619000409178 , 13/03/2019. Protocol version: 2.0, 19 May 2019

Background Doublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a “lighter” treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer; however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population. Methods/design MONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS / BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies. Discussion MONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer. Trial registration Australia New Zealand Clinical Trials Registry: ACTRN12618000233224 , prospectively registered 14 February 2018.

AbstractBackgroundMaintaining employment for adults with cancer is important, however, little is known about the impact of surgery for rectal cancer on an individual's capacity to return to work (RTW). This study aimed to determine the impact of laparoscopic vs. open resection on RTW at 12 months.MethodsAnalyses were undertaken among participants randomized in the Australian Laparoscopic Cancer of the Rectum Trial (ALaCaRT), with work status available at baseline (presurgery), and 12 months. Multivariable logistic regression, adjusted for sociodemographic and clinical characteristics estimated the effect of surgery on RTW in any capacity, or return to preoperative work status at 12 months.ResultsAbout 228 of 449 (51%) surviving trial participants at 12 months completed work status questionnaires; mean age was 62 years, 66% males, 117 of these received laparoscopic resection (51%). Of 228, 120 were employed at baseline (90 full‐time, 30 part‐time). Overall RTW in 120 participants in paid work at baseline was 78% (84% laparoscopic, 70% open surgery). Those employed full‐time were more likely to RTW at 12 months (OR, 3.55; 95% CI, 1.02–12.31). Those with distant metastases at baseline were less likely to RTW (OR, 0.07; 95% CI, <0.01–0.83). Laparoscopic surgery was associated with a higher rate of RTW but did not reach statistical significance (OR 2.88; 95% CI, 0.95–8.76).ConclusionsFull‐time work presurgery and the presence of metastatic disease predicts RTW status at 12 months. A laparoscopic‐assisted surgical approach to rectal cancer may facilitate more patients to RTW, however, larger sample sizes are likely needed to confirm this result.