Surgery (Western Health) - Research Publications
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ItemImpact of the evolution in RAS mutation analysis in Australian patients with metastatic colorectal cancer(WILEY, 2022-10)BACKGROUND: RAS mutation testing now routinely informs the optimal management of metastatic colorectal cancer (mCRC), specifically the finding of a RAS mutation defines patients who will not benefit from treatment with an epidermal growth factor receptor inhibitor. Over time more RAS genes have been tested and more sensitive techniques used. AIMS: To review routine care RAS testing and results over time. METHODS: A retrospective analysis of the molecular data collected prospectively in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry from 2009 to 2018 was undertaken. Patients with RAS data were further analyzed. In parallel, the RAS mutation status of patients enrolled in the Test Tailor Treat (TTT) program was examined for 2011-2018. RESULTS: Of 2908 patients in the TRACC registry, 1892 (65%) were tested, with 898 (47%) of tested patients found to be RAS mutant (RASmt). RAS data were available for 5935 TTT patients. Of the tested TRACC patients diagnosed in 2009 and 2010, 38% were RASmt. For each 2-year period from 2011/2012 through to 2017/2018, the prevalence of RASmt in TRACC and TTT was 42% and 40% (2011/2012), 52% and 40% (2013/2014), 47% and 49% (2015/2016), and 47% and 49% (2017/2018). CONCLUSIONS: Based on both TRACC and TTT data, the proportion of patients reported to have a RAS mutation increased from 2009 to 2015 but has remained relatively stable in recent years. The increased proportion of RASmt patients observed over time is likely largely driven by the uptake of extended RAS testing.
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ItemPatterns of surveillance for colorectal cancer: Experience from a single large tertiary institution(WILEY, 2021-08)AIM: Colorectal cancer surveillance is an essential part of care and should include clinical review and follow-up investigations. There is limited information regarding postoperative surveillance and survivorship care in the Australian context. This study investigated patterns of colorectal cancer surveillance at a large tertiary institution. METHODS: A retrospective review of hospital records was conducted for all patients treated with curative surgery between January 2012 and June 2017. Provision of clinical surveillance, colonoscopy, computed tomography (CT), and carcinoembryonic antigen (CEA) within 24 months postoperatively were recorded. Kaplan-Meier estimates were used to evaluate time-to-surveillance review and associated investigations. RESULTS: A total of 675 patients were included in the study. Median time to first postoperative clinical review was 20 days (95% confidence interval (CI), 18-21) with only 31% of patients having their first postoperative clinic review within 2 weeks. Median time to first CEA was 100 days (95% CI, 92-109), with 47% of patients having their CEA checked within the first 3 months, increasing to 68% at 6 months. Median time to first follow-up CT scan was 262 days (95% CI, 242-278) and for colonoscopy, 560 days (95% CI, 477-625). Poor uptake of surveillance testing was more prevalent in patients from older age groups, those with multiple comorbidities, and higher stage cancers. CONCLUSION: Colorectal cancer surveillance is multi-disciplinary and involves several parallel processes, many of which lead to inconsistent follow-up. Further prospective work is required to identify the reasons for variation in care and which aspects are most important to cancer patients.
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ItemPrognostic significance of postsurgery circulating tumorDNAin nonmetastatic colorectal cancer: Individual patient pooled analysis of three cohort studies(WILEY, 2021-02-15)Studies in multiple solid tumor types have demonstrated the prognostic significance of ctDNA analysis after curative intent surgery. A combined analysis of data across completed studies could further our understanding of circulating tumor DNA (ctDNA) as a prognostic marker and inform future trial design. We combined individual patient data from three independent cohort studies of nonmetastatic colorectal cancer (CRC). Plasma samples were collected 4 to 10 weeks after surgery. Mutations in ctDNA were assayed using a massively parallel sequencing technique called SafeSeqS. We analyzed 485 CRC patients (230 Stage II colon, 96 Stage III colon, and 159 locally advanced rectum). ctDNA was detected after surgery in 59 (12%) patients overall (11.0%, 12.5% and 13.8% for samples taken at 4-6, 6-8 and 8-10 weeks; P = .740). ctDNA detection was associated with poorer 5-year recurrence-free (38.6% vs 85.5%; P < .001) and overall survival (64.6% vs 89.4%; P < .001). The predictive accuracy of postsurgery ctDNA for recurrence was higher than that of individual clinicopathologic risk features. Recurrence risk increased exponentially with increasing ctDNA mutant allele frequency (MAF) (hazard ratio, 1.2, 2.5 and 5.8 for MAF of 0.1%, 0.5% and 1%). Postsurgery ctDNA was detected in 3 of 20 (15%) patients with locoregional and 27 of 60 (45%) with distant recurrence (P = .018). This analysis demonstrates a consistent long-term impact of ctDNA as a prognostic marker across nonmetastatic CRC, where ctDNA outperforms other clinicopathologic risk factors and MAF further stratifies recurrence risk. ctDNA is a better predictor of distant vs locoregional recurrence.
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ItemThe effect of smoking, obesity and diabetes on recurrence-free and overall survival in patients with stage III colon cancer receiving adjuvant chemotherapy(WILEY, 2021-06)BACKGROUND: The association between smoking, diabetes and obesity and oncological outcomes in patients with stage III colon cancer treated with surgery and adjuvant chemotherapy is unclear. AIM: To evaluate whether smoking, obesity and diabetes are associated with the disease-free survival and overall survival rates of patients with stage III colon cancer who have received adjuvant chemotherapy. METHODS: Patients were selected from the prospectively maintained Australian Cancer Outcomes and Research Database (ACCORD). All stage III colon cancer patients who received adjuvant chemotherapy between January 2003 to December 2015 were retrospectively analyzed. The three primary exposures of interest were smoking status, body mass index (BMI) and diabetic (DM) status. The primary outcomes of interest were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 785 patients between 2003 and 2015 were included for analysis. Using Kaplan-Meier survivorship curves, there was no association between OS and smoking (P = .71), BMI (P = .3) or DM (P = .72). Similarly, DFS did not reveal an association with smoking (P = .34), BMI (P = .2) and DM (P = .34). Controlling for other covariates the results did not reach statistical significance in adjusted multiple regression models. CONCLUSION: Smoking, obesity and DM were not shown to influence DFS or OS for patients with stage III colon cancer who have received adjuvant chemotherapy.
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ItemPositive lateral pelvic lymph nodes in low rectal cancer: should we change our practice now?(WILEY, 2021-05)BACKGROUND: The role of lateral lymph node dissection (LLND) in the treatment of patients with low rectal cancer with enlarged lateral lymph nodes (LLN+) is under investigation. Enthusiasm for LLND stems from a perceived reduction in local recurrence (LR). We aimed to compare the LR rate for LLN+ patients with LLN- patients, treated with neoadjuvant chemoradiotherapy (nCRT) and surgery, in a hospital that does not perform LLND. METHODS: A retrospective study of all patients with clinical stage 3 low rectal cancer who completed nCRT and surgery between 2008 and 2017 at Western Health was performed. Outcomes for LLN+ patients were compared with LLN- patients. The primary outcome was LR. Secondary outcomes included distant metastases, disease-free survival and overall survival. RESULTS: There were 110 patients treated for stage 3 low rectal cancer over 10 years. There was no significant difference in the LR rate, with one LR from 28 LLN+ patients and one LR from 82 LLN- patients (4% versus 1.2%, P = 0.44). There were no significant differences in median disease-free survival (41 versus 52 months, P = 0.19) or mean overall survival (62 versus 60 months, P = 0.80). Of all patients studied, 21% developed distant metastases. CONCLUSION: LR after nCRT and surgery in patients with stage 3 rectal cancer is rare, irrespective of lateral pelvic node status. These data, along with the uncertain benefit and known risks of LLND, supports the continued use of standard therapy in these patients. Strategies to address distant failure in these patients should be explored.