Sir Peter MacCallum Department of Oncology - Research Publications
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ItemThe Impact of Neoadjuvant Chemotherapy on the Surgical Management of Colorectal Peritoneal Metastases: A Systematic Review and Meta-Analysis(SPRINGER, 2022-10)BACKGROUND: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognised treatment option for the management of colorectal peritoneal metastases (CRPM). However, incorporating the routine use of neoadjuvant chemotherapy (NAC) into this management plan is controversial. METHODS: A systematic review and meta-analysis were conducted to evaluate the impact of neoadjuvant chemotherapy on perioperative morbidity and mortality, and long-term survival of patients with CRPM undergoing CRS and HIPEC. RESULTS: Twelve studies met the inclusion criteria (n = 2,463 patients). Ten were retrospective cohort, one was prospective cohort, and one was a prospective randomised by design. Patients who received NAC followed by CRS and HIPEC experienced no difference in major perioperative morbidity and mortality compared with patients who underwent surgery first (SF). There was no difference in overall survival at 3 years, but at 5 years NAC patients had superior survival (relative risk [RR] 1.31; 95% confidence interval [CI] 1.11-1.54, P < 0.001). There were no differences in 1- and 3-year, disease-free survival (DFS) between groups. Study heterogeneity was generally high across all outcome measures. CONCLUSIONS: Patients who received neoadjuvant chemotherapy did not experience any increase in perioperative morbidity or mortality. The potential improvement in 5-year overall survival in patients receiving NAC is based on limited confidence due to several limitations in the data, but not sufficiently enough to curtail its use. The practice of NAC in this setting will remain heterogeneous and guided by retrospective evidence until prospective, randomised data are reported.
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ItemPrognostic value of tumour regression grade in locally advanced rectal cancer: a systematic review and meta-analysis(WILEY, 2018-07)AIM: The current standard of care for locally advanced rectal cancer involves neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision. There is a spectrum of response to neoadjuvant therapy; however, the prognostic value of tumour regression grade (TRG) in predicting disease-free survival (DFS) or overall survival (OS) is inconsistent in the literature. METHOD: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was undertaken using Ovid MEDLINE, Embase and Google Scholar. Inclusion criteria were Stage II and III locally advanced rectal cancer treated with long-course CRT followed by radical surgery. The aim of the meta-analysis was to assess the prognostic implication of each TRG for rectal cancer following neoadjuvant CRT. Long-term prognosis was assessed. The main outcome measures were DFS and OS. A random effects model was performed to pool the hazard ratio (HR) from all included studies. RESULTS: There were 4875 patients from 17 studies, with 775 (15.9%) attaining a pathological complete response (pCR) and 719 (29.9%) with no response. A significant association with OS was identified from a pooled-estimated HR for pCR (HR = 0.47, P = 0.002) and nonresponding tumours (HR = 2.97; P < 0.001). Previously known tumour characteristics, such as ypN, lymphovascular invasion and perineural invasion, were also significantly associated with DFS and OS, with estimated pooled HRs of 2.2, 1.4 and 2.3, respectively. CONCLUSION: In conclusion, the degree of TRG was of prognostic value in predicting long-term outcomes. The current challenge is the development of a high-validity tests to predict pCR.
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ItemPrognostic factors influencing survival in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for isolated colorectal peritoneal metastases: a systematic review and meta-analysis(WILEY, 2020-11)AIM: Peritoneal metastases from colorectal cancer confer the worst survival among all metastatic sites. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with isolated colorectal peritoneal metastases (CRPM) a favourable long-term survival. There are numerous factors postulated to influence survival in patients undergoing CRS and HIPEC. The aim of this study was to identify the key perioperative prognostic factors that influence survival in patients undergoing CRS and HIPEC for isolated CRPM. METHOD: A systematic review and meta-analysis were conducted to evaluate prognostic factors influencing survival in patients undergoing CRS and HIPEC for isolated CRPM. RESULTS: Thirty-three studies fitted the inclusion criteria for the systematic review, with 25 studies included in the meta-analysis. On pooled analysis, incomplete cytoreduction, increasing peritoneal carcinoma index (PCI) and lymph node involvement were significantly associated with a worse survival. Additionally, a rectal primary [hazard ratio (HR) 1.93, 95% CI 1.10-3.37], adjuvant chemotherapy (HR 0.71, 95% CI 0.54-0.93) and perioperative grade III/IV morbidity (HR 1.59, 95% CI 1.17-2.16) were also found to significantly influence survival. Notably, tumour differentiation and signet ring cell histology did not influence survival on pooled analysis. CONCLUSION: This meta-analysis confirms that in patients undergoing CRS and HIPEC for isolated CRPM, incomplete cytoreduction, high PCI and lymph node involvement have a negative influence on survival. In addition, a rectal primary, adjuvant chemotherapy use and grade III/IV morbidity are important factors that also significantly influence survival.
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ItemNeoadjuvant therapy in rectal cancer: An ongoing conundrum(WILEY, 2021-11)
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ItemPerceptions in the management of colorectal peritoneal metastases: A bi-national survey of colorectal surgeons(SCIENDO, 2019-12)BACKGROUND: There is great variability in the uptake of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of colorectal peritoneal metastases (CRPM) in Australia and New Zealand. This study aims to provide a snapshot of perceptions among colorectal surgeons in the management of CRPM. METHODS: A structured ten-question online survey was sent to all colorectal surgeons, with three questions on clinical experience and demographics, one on health economics and six on hypothetical clinical scenarios. Scores were collated and reported based on Likert scales. RESULTS: Eighty-one respondents (36.2%) completed the survey. Most surgeons (66.7%) strongly disagreed with offering CRS and HIPEC at all hospitals. The majority (87.7%) agreed that CRS and HIPEC offered a higher survival benefit than systemic chemotherapy in pseudomyxoma peritonei (PMP), and 69.1% in CRPM (comparators: 60.5% ovarian cancer, 14.8% gastric cancer). There were mixed strategies in managing low-volume, isolated peritoneal recurrences. The majority did not recommend second-look laparoscopy, but favoured operative management of Krukenberg tumours. In the presence of incidental peritoneal metastases, only 29.6% favoured biopsy only and referring the patient to a peritoneal disease centre. CONCLUSIONS: Response rate was relatively low. In Australia and New Zealand, colorectal surgeons see a strong role for CRS and HIPEC in the management of PMP and CRPM. The role of "second look" surgery in high-risk cases is controversial and not supported. Krukenberg tumours are viewed as surgical disease. Regular updates and collaboration with peritoneal centres may help surgeons stay abreast with latest evidence in the field.