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Background: In the development of anticancer agents for solid tumours, body surface area continues to be used to personalise dosing despite minimal evidence for its use over other dosing strategies. With the development of tyrosine kinase inhibitors and other oral targeted anticancer agents, dosing using therapeutic drug monitoring (TDM) is now utilised in many health systems but has had limited uptake in Australia. Aim: To determine attitudes and barriers to the implementation of TDM among Australian oncologists. Methods: A comprehensive questionnaire was developed by the Dutch Pharmacology Oncology Group from semistructured interviews of stakeholders. Seventy‐nine questions across seven domains were developed with three free‐text responses. This was rationalised to 17 questions with three free‐text responses for Australian medical oncologists who identified limited experience with TDM. Results: Fifty‐seven responses were received, with 49 clinicians (86%) identifying limited experience of performing TDM in daily practice. Clinicians were positive (62–91% agree/strongly agree across seven questions) about the advantages of TDM. There was a mixed response for cost‐effectiveness and scientific evidence being a barrier to implementation, but strong agreement that prospective studies were needed (75% agreed or strongly agreed); that national treatment guidelines would enable practice (80%) and that a 'pharmacology of oncolytics' education programme would be useful (96%) to provide knowledge for dose individualisation. Conclusion: Despite the limited experience of TDM in oncology in Australia, medical oncologists appear positive about the potential benefit to their patients. We have identified three barriers to implementation that could be targeted for increased adoption of TDM in oncology in Australia. [ABSTRACT FROM AUTHOR]

The article reports that Clinical Pharmacogenetics Implementation Consortium updated best practice guidelines in 2018 for 5-FU and capecitabine dose optimization. Topics include examines CPIC recommended that the four common DPYD genetic variants known to affect DPD enzyme activity should be incorporated as part of a DPD screening program.

Background: Rectal Cancer is a common malignancy. The current treatment approach for patients with locally advanced rectal cancer involves neoadjuvant chemoradiotherapy followed by surgical resection of the rectum. The resection can lead to complications and long-term consequences. A clinical complete response is observed in some patients after chemoradiotherapy. A number of recent studies have shown that patients can be observed safely after completing chemoradiotherapy (without surgery), provided clinical complete response has been achieved. In this approach, resection is reserved for cases of regrowth. This is called the watch and wait approach. This approach potentially avoids unnecessary surgical resection of the rectum and the resulting complications. In this study, we will prospectively investigate this approach.Methods: Adult patients with a diagnosis of rectal cancer planned to receive neoadjuvant long course chemoradiotherapy (± subsequent combination chemotherapy) will be consented into the study prior to commencing treatment. After completing the chemoradiotherapy (± subsequent combination chemotherapy), based on the clinical response, subjects will be allocated to one of the following arms: subjects who achieved a clinical complete response will be allocated to the watch and wait arm and others to the standard management arm (which includes resection). The aim of the study is to determine the rate of local failure and other safety and efficacy outcomes in the watch and wait arm. Patient reported outcome measures and the use of biomarkers as part of the clinical monitoring will be studied in both arms of the study.Discussion: This study will prospectively investigate the safety of the watch and wait approach. We will investigate predictive biomarkers (molecular biomarkers and imaging biomarkers) and patient reported outcome measures in the study population and the cost effectiveness of the watch and wait approach. This study will also help evaluate a defined monitoring schedule for patients managed with the watch and wait approach. This protocol covers the first two years of follow up, we are planning a subsequent study which covers year 3-5 follow up for the study population.Trial Registration: Name of the registry: Australia and New Zealand Clinical Trials Registry (ANZCTR).Trial Registration Number: Trial ID: ACTRN12619000207112 Registered 13 February 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376810. [ABSTRACT FROM AUTHOR]

Purpose: Irinotecan (IR) displays significant PK/PD variability. This study evaluated functional hepatic imaging (HNI) and extensive pharmacogenomics (PGs) to explore associations with IR PK and PD (toxicity and response).Methods: Eligible patients (pts) suitable for Irinotecan-based therapy. At baseline: (i) PGs: blood analyzed by the Affymetrix-DMET™-Plus-Array (1936 variants: 1931 single nucleotide polymorphisms [SNPs] and 5 copy number variants in 225 genes, including 47 phase I, 80 phase II enzymes, and membrane transporters) and Sanger sequencing (variants in HNF1A, Topo-1, XRCC1, PARP1, TDP, CDC45L, NKFB1, and MTHFR), (ii) HNI: pts given IV 250 MBq-99mTc-IDA, data derived for hepatic extraction/excretion parameters (CLHNI, T1/2-HNI, 1hRET, HEF, Td1/2). In cycle 1, blood was taken for IR analysis and PK parameters were derived by non-compartmental methods. Associations were evaluated between HNI and PGs, with IR PK, toxicity, objective response rate (ORR) and progression-free survival (PFS).Results: N = 31 pts. The two most significant associations between PK and PD with gene variants or HNI parameters (P < 0.05) included: (1) PK: SN38-Metabolic Ratio with CLHNI, 1hRET, (2) Grade 3+ diarrhea with SLC22A2 (rs 316019), GSTM5 (rs 1296954), (3) Grade 3+ neutropenia with CLHNI, 1hRET, SLC22A2 (rs 316019), CYP4F2 (rs2074900) (4) ORR with ALDH2 (rs 886205), MTHFR (rs 1801133). (5) PFS with T1/2-HNI, XDH (rs 207440), and ABCB11 (rs 4148777).Conclusions: Exploratory associations were observed between Irinotecan PK/PD with hepatic functional imaging and extensive pharmacogenomics. Further work is required to confirm and validate these findings in a larger cohort of patients.Australian New Zealand Clinical Trials Registry (anzctr) Number: ACTRN12610000897066, Date registered: 21/10/2010. [ABSTRACT FROM AUTHOR]

The increased prevalence of location based services has raised a number of socio-technical issues, especially in respect of the privacy expectations of individuals. Although there have been assessments of the regulatory environment regarding location based services, the research presented in this article engaged key government agency stakeholders, rather than end-users. In doing so, it provides a contribution that complements the work with end users provided by others. The article also considers the policy context for location based services regulation. It does this by describing the policy-making processes in Australia in order to provide a context for the views of government agency stakeholders. The article analyses official statements received from privacy-related and emergency-related government agencies in Australia in order to assess stakeholder views. [ABSTRACT FROM AUTHOR]

First-line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head phase III randomised controlled trials (RCT). Data on optimum first-line treatment and subsequent sequencing is lacking. To compare overall survival (OS) between first-line treatment regimens in a real-world population to determine if an optimal therapeutic sequence is associated with survival benefit. A retrospective analysis of prospectively collated data from the Australasian PURPLE pancreatic cancer registry was undertaken. From 2016 to 2020, of 1551 pancreatic cancer patients, 615 received palliative-intent chemotherapy. Patients with early-stage resected disease without recurrence (n = 369), radiotherapy alone (n = 43), received supportive care alone (n = 458) or had less than 3 months follow-up (n = 66) were excluded. Median OS was comparable between patients receiving first-line Gemcitabine/Nab-Paclitaxel (n = 376) and those receiving FOLFIRINOX (n = 73) (11.3 versus 12.3 months, P = 0.37), with 38% proceeding to second-line chemotherapy which was associated with longer mOS compared to first-line treatment alone (17.4 versus 8.2 months, P < 0.001). With second-line treatment following prior FOLFIRINOX (n = 29) or Gemcitabine/Nab-Paclitaxel (n = 101), mOS did not differ significantly (17.3 versus 15.9 months, P = 0.92), respectively, whilst median progression-free survival was longer with prior FOLFIRINOX (5.2 versus 2.9 months, P = 0.03). There was no significant difference in overall survival between either first-line chemotherapy choice, despite patients receiving FOLFIRINOX being younger, fitter, and more likely to have localised disease. However, FOLFIRINOX was associated with delayed progression. In the absence of phase III RCT data, clinicians should be comfortable using either Gemcitabine/Nab-Paclitaxel or FOLFIRINOX as first-line therapy in advanced PDAC. • Analysis of optimal therapeutic sequencing in advanced pancreatic cancer (n = 615). • 1st-line FFX efficacy comparable to GEM-P (mOS 11.3 versus 12.3 months P = 0.37). • Longer mOS with 2nd-line chemotherapy versus 1st-line only (17.4 versus 8.2 months P < 0.001). • 2nd-line 5FU versus GEM-based treatment mOS similar (17.3 versus 15.9 months P = 0.92). [ABSTRACT FROM AUTHOR]

PACIFIC-PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype-guided dosing on severe fluoropyrimidine (FP) and irinotecan-related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis). DPYD genotyping identified 96% (n = 443/462) Wild-Type, 4% (n = 19/462) Intermediate Metabolizers (50% dose reduction), and 0% Poor Metabolizers. UGT1A1 genotyping identified 52% (n = 26/50) Wild-Type, 40% (n = 20/50) heterozygous, and 8% (n = 4/50) homozygous (30% dose reduction). Key demographics for the FP/irinotecan safety cohorts included: age range 23-89/34-74 years, male 56%/73%, Caucasian 83%/73%, lower gastrointestinal cancer 50%/57%. Genotype results were reported prior to cycle-1 (96%), average 5-7 days from sample collection. PGx-dosing for DPYD variant allele carriers reduced high-grade toxicities compared to historic controls (7% vs. 39%; OR = 0.11, 95% CI 0.01-0.97, p = 0.024). High-grade toxicities among Wild-Type were similar (14% vs. 14%; OR = 0.99, 95% CI 0.64-1.54, p = 0.490). PGx-dosing reduced FP-related hospitalizations (-22%) and deaths (-3.7%) compared to controls. There were no high-grade toxicities or hospitalizations for UGT1A1*28 homozygotes. PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Hormonal crises are a rare but increasingly recognized phenomenon following peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine neoplasms (NENs). Due to the paucity of published studies, approaches to the identification, prevention, and management of risk factors are inconsistent between different institutions. This consensus statement aimed to provide guidance for NEN patients undergoing PRRT. Our statement has been created on the basis of clinical demand and concerns regarding the precipitation of hormonal crises. A formal literature review was conducted to identify available studies. A total of 19 Australian and New Zealand experts in the fields of medical oncology, nuclear medicine, anaesthetics, and endocrinology collaborated on this consensus statement. The main focus is on carcinoid crises. Other hormonal crises seen in patients with functional pancreatic NENs are addressed briefly. These recommendations are relevant to PRRT centres internationally and should be tailored to local experience and available resources., (© 2022 S. Karger AG, Basel.)

Background: Oesophageal and gastrooesophageal junction (GOJ) carcinoma frequently present with dysphagia and de novo metastatic disease. There is scope to improve treatment paradigms to both address symptoms and improve survival. One method is integrating immune checkpoint inhibition with novel treatment combinations., Methods: PALEO is a single arm, phase II clinical trial in patients with previously untreated, oligometastatic or locoregionally advanced oesophageal or GOJ carcinoma and dysphagia. PALEO is sponsored by the Australasian Gastro-Intestinal Trials Group (AGITG). Participants receive 2 weeks of therapy with concurrent hypofractionated radiotherapy of 30Gy in 10 fractions to the primary tumour, weekly carboplatin AUC2, weekly paclitaxel 50 mg/m 2 and durvalumab 1500 mg q4 weekly, followed by durvalumab monotherapy continuing at 1500 mg q4weekly until disease progression, unacceptable toxicity or 24 months of therapy. A single metastasis is treated with stereotactic radiotherapy of 24Gy in 3 fractions in week 7. The trial primary endpoint is the progression free survival rate at 6 months. Secondary endpoints include duration of dysphagia relief, nutritional status change, quality of life, response rate, toxicity, progression free survival and overall survival. The tertiary endpoint is prediction of outcome based on biomarkers identified from patient serial blood samples collected pre- and post-radiotherapy., Discussion: This unique investigator-initiated clinical trial is designed to simultaneously address the clinically relevant problems of dysphagia and distant disease control. The overarching aims are to improve patient nutrition, quality of life and survival with low toxicity therapy. AGITG PALEO is a multidisciplinary collaboration and will add to the understanding of the relationship between radiotherapy and the anti-tumour immune response., Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12619001371189 , registered 8 October 2019., (© 2022. The Author(s).)

Background: Computed tomography (CT) is the first-line staging imaging modality for pancreatic ductal adenocarcinoma (PDAC) which determines resectability and treatment pathways., Methods: Between January 2016 and December 2019, prospectively collated data from two Australian cancer centres was extracted from the PURPLE Pancreatic Cancer registry. Real-world staging CTs and corresponding reports were blindly reviewed by a sub-specialist radiologist and compared to initial reports., Results: Of 131 patients assessed, 117 (89.3%) presented with symptoms, 74 (56.5%) CTs included slices ≤3 mm thickness and CT pancreas protocol was applied in 69 (52.7%) patients. Initial reports lacked synoptic reporting in 131 (100%), tumour identification in 2 (1.6%) and tumour measurement in 13 (9.9%) cases. Tumour-vascular relationship reporting was missing in 69-109 (52.7-83.2%) for regarding the key arterial and venous structures that is required to assess resectability. Initial reports had no comment on venous thrombus or venous collaterals in 80 (61.1%) and 109 (83.2%) and lacked locoregional lymphadenopathy interpretation in 13 (9.9%) cases. Complete initial staging report was present in 72 (55.0%) patients. Sub-specialist radiological review resulted in down-staging in 16 (22.2%) and up-staging in 1 (1.4%) patient. Staging discrepancies were mainly regarding metastatic disease (12, 70.6%) and tumour-vascular relationship (5, 29.4%)., Conclusion: Real-world staging imaging in PDAC patients show low proportion of dedicated CT pancreas protocol, high proportion of incomplete staging reports and no synoptic reporting. The most common discrepancy between initial and sub-specialist reporting was regarding metastases and tumour-vascular relationship assessment resulting in sub-specialist down-staging in almost every fifth case., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Aim: Carcinoid heart disease (CHD) is a well-documented complication of neuroendocrine tumors (NETs) due to secreted hormones causing fibrosis. Somatostatin analogues (SSAs) can decrease hormonal secretion and inhibit tumor growth. The reported incidence of CHD has decreased as SSA use has increased. We describe a series of patients who have developed CHD even though they were treated with SSA therapy., Methods: Nine patients were seen in four centers in Australia and New Zealand. The average duration of follow-up from diagnosis was 39 months., Results: Three patients had Grade 1 and six Grade 2 disease by World Health Organization 2010 criteria. All patients had no CHD symptoms at baseline and started SSA therapy soon after diagnosis, yet developed significant, symptomatic cardiac dysfunction in their disease course. The median time from NET diagnosis to SSA initiation was 1 month, and median time from NET diagnosis to CHD diagnosis was 23 months (range 4-52). All patients who were tested had persistently increased hormonal levels (chromogranin A, urinary 5-hydroxyindolacetic acid)., Conclusions: The good symptomatic control afforded by SSAs should not lead to reduced vigilance in screening for CHD, especially in patients with persistently elevated hormonal assays. Clinicians should consider regular echocardiographic screening in patients with a secretory syndrome., (© 2021 John Wiley & Sons Australia, Ltd.)

Background: Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization., Methods: Patients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) by Sanger sequencing. For HNI, patients underwent 99m Tc-IDA hepatic imaging, and data was analysed for hepatic extraction/excretion parameters. Blood was taken for IR and metabolite (SN38, SN38G) analysis on day 1 cycle 1. Population modelling utilised NONMEM version 7.2.0, with structural PK models developed for each moiety. Covariates include patient demographics, HNI parameters and pharmacogenomic variants., Results: Analysis included (i) PK data: 32 patients; (ii) pharmacogenomic data: 31 patients: 750 DMET and 22 PD variants; and (iii) HNI data: 32 patients. On initial analysis, overall five SNPs were identified as significant covariates for CL SN38 . Only UGT1A3&#95;c.31 T > C and ABCB1&#95;c.3435C > T were included in the final model, whereby CL SN38 reduced from 76.8 to 55.1%., Conclusion: The identified UGT1A3&#95;c.31 T > C and ABCB1&#95;c.3435C > T variants, from wild type to homozygous, were included in the final model for SN38 clearance., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown., Experimental Design: CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing., Results: Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for two patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications., Conclusions: Our approach is feasible, reproducible, and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies., (©2020 American Association for Cancer Research.)

Background and Objective: Little is known about the economic burden to patients and families with neuroendocrine tumours (NETs) for medical out-of-pocket expenses and employment decisions. This study was performed to determine the extent and factors influencing the financial consequences of living with NETs and their effect on quality of life., Methods: We undertook an online cross-sectional survey using a targeted approach and collected Australian Medicare claims data. Validated surveys measured health-related quality of life (EuroQol 5-dimension 5-level [EuroQol-5D-5L]) and financial toxicity (COmprehenSive Financial Toxicity [COST]), supplemented with questions on employment and retirement, insurance and out-of-pocket medical expenses. Generalised linear models were performed to assess determinants of quality of life and out-of-pocket expenses recorded by Medicare., Results: The survey was answered by 204 patients with a mean age of 59 years who were diagnosed on average 5.2 years ago. Self-reported mean costs were 1698 Australian dollars ($A) (standard deviation [SD] $A2132) over 3 months (median $A877) and were highest for medical tests (mean $A376 [17% of total costs], SD $A722), travel-related expenses (mean $A289 [13%], SD $A559), and specialist visits (mean $A225 [10%], SD $A342) ($A1 = $US0.69). Imaging scans, surgery and travel expenses were the most common cost burdens reported by patients. Having private health insurance was the key determinant of higher out-of-pocket costs. Poorer quality of life was significantly associated with higher financial toxicity, not working due to cancer, nausea/diarrhoea, two or more co-morbidities and younger age., Conclusions: Medical expenses are substantial for some patients with NETs. Quality of life is adversely affected for patients experiencing financial toxicity and avoiding early retirement is an important issue for supportive care services.

Background: Data, particularly 'big' data are increasingly being used for research in health. Using data from electronic medical records optimally requires coded data, but not all systems produce coded data., Objective: To design a suitable, accurate method for converting large volumes of narrative diagnoses from Australian general practice records to codify them into SNOMED-CT-AU. Such codification will make them clinically useful for aggregation for population health and research purposes., Method: The developed method consisted of using natural language processing to automatically code the texts, followed by a manual process to correct codes and subsequent natural language processing re-computation. These steps were repeated for four iterations until 95% of the records were coded. The coded data were then aggregated into classes considered to be useful for population health analytics., Results: Coding the data effectively covered 95% of the corpus. Problems with the use of SNOMED CT-AU were identified and protocols for creating consistent coding were created. These protocols can be used to guide further development of SNOMED CT-AU (SCT). The coded values will be immensely useful for the development of population health analytics for Australia, and the lessons learnt applicable elsewhere., Competing Interests: Competing interests: CP, AM, NR, JF and AF are the employees of Outcome health, the not for profit organisation that performed this study. JP is an employee of HLA analytics that provided the machine learning tool., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia., Participants: It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation., Findings to Date: The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile., Future Plans: The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Appendiceal epithelial neoplasms are rare cancers. Management of peritoneal disease from appendiceal neoplasms has historically been with debulking surgery. In recent decades, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care. Here, we report our single institution 10-year experience with CRS and HIPEC for appendiceal neoplasms., Methods: This is a retrospective review from 1 January 2008 to 1 June 2017 of all patients undergoing CRS and HIPEC for appendiceal neoplasms. Institutional ethics approval was granted for this project., Results: One hundred and seventy-two patients underwent 208 CRSs during this time. Overall, 83.72% of patients had one CRS and HIPEC procedure. Pseudomyxoma peritonei from a perforated appendiceal mucinous neoplasm accounted for 67.9% of cases. The median peritoneal carcinomatosis index (PCI) was 14, with complete cytoreduction achieved in 74.2% of patients. Fifty-four percent of patients had at least one complication, with one (0.5%) peri-operative mortality in our cohort. For the entire cohort, the median overall survival was 104 months and a 5-year survival of 75%. In those having a complete cytoreduction, 5-year survival was 90%, with a median disease free interval of 63 months. PCI and completeness of cytoreduction were independent predictors of overall survival., Conclusion: Our results demonstrate that CRS and HIPEC for appendiceal neoplasms are safe and effective. Despite carrying some morbidity, it offers patients an excellent disease free and overall survival., (© 2019 Royal Australasian College of Surgeons.)

Background: Mismatch repair deficiency (dMMR) has been shown to confer a superior prognosis and is possibly predictive of a lack of benefit from fluoropyrimidine adjuvant chemotherapy (AC) for early-stage colon cancer (ESCC). We conducted a survey to assess medical oncologists' views regarding ESCC AC, with an emphasis on the use of MMR status to guide their recommendations., Materials and Methods: The survey was distributed to all members of the Medical Oncology Group of Australia. Their demographic data, practice information, and views on the use of MMR status in ESCC and in 3 case scenarios were collected. The 3 case scenarios were a 68-year-old woman with moderate-risk stage II disease, who was eager to undergo AC (case 1); a 43-year-old woman with high-risk stage II disease, who was ambivalent regarding AC (case 2); and a 78-year-old woman with multiple comorbidities and high-risk stage II disease, who was eager to undergo AC., Results: The survey response rate was 35% (190 of 550). Of the 190 responders, 152 (80%) routinely treated patients with colon cancer (CC) and completed the survey. For patients with stage II CC, 112 of 141 (79%) would use MMR status to assist AC recommendations, and 97 (69%) thought it changed their practice. In the case scenarios, 81% (case 1, 110 of 136), 67% (case 2, 92 of 137), and 43% (case 3, 57 of 133) used MMR status to assist AC recommendations. If dMMR was present, 78% (case 1, 86 of 110), 53% (case 2, 49 of 92), and 53% (case 3, 30 of 57) changed their initial recommendations by advising against AC., Conclusion: The use of MMR status to assist AC recommendations for patients with stage II CC is an accepted practice for most Australian medical oncologists who responded to our survey., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery., Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined, multiple-field, three-dimensional conformal techniques., Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%., Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate the impact of FDG-PET following chemoradiotherapy (CRT) on treatment planning and survival in patients with oesophageal cancer (OC)., Methods: Fifty-three consecutive OC patients had a post-treatment PET scan to evaluate tumour response to CRT prior to possible surgery. Baseline pre-CRT PET was performed in 33 patients. Prospectively recorded post-CRT management plans were compared with post-PET treatment. High impact was defined as a change in treatment intent or modality. Survival was analysed using the Kaplan-Meier product limit method and Cox proportional hazards regression model., Results: After completion of CRT, 23/53 patients (43%) achieved complete metabolic response (CMR), as compared with only four (8%) with complete response on computed tomography. High PET impact was observed in 19 patients (36%). CMR was strongly predictive of survival (p<0.008) on multivariate analysis. CMR patients in whom resection was not performed had comparable survival to those (CMR and non-CMR) who underwent resection., Conclusion: The use of post-treatment FDG-PET for assessment of tumour response after CRT changed the clinical management of more than one-third of OC patients. CMR status as assessed by PET powerfully stratified prognosis. Even in the absence of a baseline study, normalisation of uptake at all sites of known tumoral involvement carries a good medium-term prognosis.