Malcolm Steel

Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

Detection of circulating tumor DNA in patients with resected stage II colon cancer provides evidence of residual disease. Footprints of persistent cancer Stage II colon cancer, which has spread through the wall of the colon but has not metastasized to the lymph nodes, can present a therapeutic dilemma. On one hand, these tumors can usually be completely removed by surgery, and the majority does not recur even without chemotherapy. On the other hand, it is difficult to determine which of these tumors will recur and to identify patients who would benefit from adjuvant chemotherapy after surgery. Tie et al. show that the presence of circulating tumor DNA in a patient’s blood after surgery is a sign of persistent tumor and a greatly increased risk of relapse, suggesting that this group of patients may require chemotherapy to prevent recurrence. Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

Extent of mesorectal invasion is a prognostic indicator in T3 rectal carcinoma

Background:  The aim of this study was to determine if local recurrence (LR) rates in patients with minimally invasive and advanced T3 rectal cancer are different. This may influence the use of adjuvant therapy.

Comparing oncological outcomes of laparoscopic versus open surgery for colon cancer: Analysis of a large prospective clinical database.

Oncological outcomes of laparoscopic colon cancer surgery have been shown to be equivalent to those of open surgery, but only in the setting of randomized controlled trials on highly selected patients. The aim of this study is to investigate whether this finding is generalizable to real world practice.

Colon trauma: Royal Melbourne Hospital experience

Background: Recent studies from the USA and South Africa suggest that primary repair or resection and primary anastomosis have become the recommended treatment for most traumatic colon injuries. The aim of the present review is to determine the applicability of these studies to the urban Australian setting.

Impact of anastomotic leak on recurrence and survival after colorectal cancer surgery: a BioGrid Australia analysis.

There is conflicting evidence regarding the oncological impact of anastomotic leak following colorectal cancer surgery. This study aims to test the hypothesis that anastomotic leak is independently associated with local recurrence and overall and cancer‐specific survival.

Impact of Surgical Complications Following Resection of Locally Advanced Rectal Adenocarcinoma on Adjuvant Chemotherapy Delivery and Survival Outcomes.

BACKGROUND: Surgical complications after resection for locally advanced rectal cancer may influence adjuvant treatment outcomes and survival. Few studies have examined this effect. OBJECTIVE: This study aimed to examine the impact of surgical complications on adjuvant therapy delivery and survival in patients with locally advanced rectal cancer treated with long-course chemoradiation followed by surgery. DESIGN: This is a retrospective analysis of a prospectively collected multicenter colorectal cancer database. SETTINGS: Data were collected from the Australian Comprehensive Cancer Outcomes and Research Database. PATIENTS: All patients who completed neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer between January 2003 and December 2014 were selected. MAIN OUTCOME MEASURES: We examined the types and frequency of surgical complications and their impact on the delivery of adjuvant chemotherapy and survival. RESULTS: Data were available for 517 patients, of whom 147 (28%) had a surgical complication. Patients with a surgical complication were less likely to commence adjuvant chemotherapy (33% vs 66%; p = 0.0005) and more likely to have adjuvant treatment commencing more than 8 weeks from surgery (71.8% vs 21.2%; p = 0.004). Wound-related complications (p = 0.001), return to operating theater (p = 0.004), and readmission within 30 days (p = 0.02) had the most significant negative impact on the delivery of adjuvant chemotherapy. Surgical complications were significantly more likely in males (31.6% vs 20.8%, p = 0.003) and laparoscopic converted cases (47.8% vs 21.8%, p = 0.03). For the entire patient population, adjuvant chemotherapy compared with surveillance was not associated with an improved recurrence-free survival (HR, 1.06; p = 0.83) but was associated with an improved overall survival (HR, 0.53; p = 0.04). LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Surgical complications in patients having surgery following neoadjuvant chemoradiotherapy for locally advanced rectal cancer were associated with significantly reduced uptake and delays to receiving adjuvant therapy. Surgical complications, however, were not associated with either significantly reduced recurrence-free or overall survival. Adjuvant chemotherapy delivery was associated with improved overall survival.

Survival Impact of Adjuvant Chemotherapy for Resected Locally Advanced Rectal Adenocarcinoma

Micro‐Abstract The benefit of adjuvant fluoropyrimidine‐containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer is uncertain. In this retrospective analysis, no significant relapse‐free or overall survival benefit was associated with adjuvant chemotherapy. However, in the subset of patients who did not achieve a pathologic complete response to preoperative chemoradiotherapy, use of adjuvant chemotherapy resulted in a significant overall survival benefit. Background: Recent data has created uncertainty regarding the benefit of adjuvant fluoropyrimidine‐containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer (LARC). In particular, patients with a pathologic complete response (pCR) may derive no benefit from adjuvant chemotherapy. Patients and Methods: This is a retrospective analysis of patients with LARC, diagnosed between January 1, 2003 and December 31, 2014 at 3 Melbourne health services. Patients were identified from the Australian Comprehensive Cancer Outcomes and Research Database, where a defined data set is prospectively collected on consecutive patients. Patient demographics, pCR rates, postoperative treatment, recurrence, and survival were analyzed. Results: A total of 717 patients with LARC were identified, of whom 555 (77%) had received preoperative long‐course chemoradiation followed by surgery. Four hundred fifty‐two of 555 patients (81%) subsequently received adjuvant fluoropyrimidine‐based chemotherapy. At a median follow‐up of 45.9 months, 95 (21%) patients in the adjuvant chemotherapy group and 20 (19%) in the surveillance group had relapsed. Five‐year relapse‐free survival was 77% in the adjuvant chemotherapy group and 71% in the surveillance group with no significant difference on univariate analysis (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.58‐1.51; P = .780). No significant impact on relapse‐free survival was seen for either pCR or non‐pCR patients. Five‐year overall survival (OS) was 85% in the adjuvant chemotherapy group and 74% in the surveillance group with a nonsignificant trend towards OS benefit (HR, 0.62; 95% CI, 0.37‐1.05; P = .074). A significant OS benefit favoring adjuvant chemotherapy was seen in the non‐pCR subset of patients (HR, 0.49; 95% CI, 0.28‐0.86; P = .014). Conclusion: A high proportion of patients in this routine practice cohort received adjuvant chemotherapy following preoperative treatment and surgery for LARC. Adjuvant chemotherapy administration was associated with a significant improvement in 5‐year OS only in the patients with a non‐pCR.

Impact of diabetes on clinicopathologic and genetic features of colorectal cancer formation.

426 Background: Diabetes mellitus is reported to increase the risk of colorectal cancer (CRC) development and has been associated with poor tumour-specific outcomes. Here we assessed the impact of diabetes on the clinicopathologic features and tumour mutation profiles of CRC. Methods: Analysis of a prospective series of patients diagnosed with CRC between January 2000 and December 2010. Fresh-frozen and formalin-fixed, paraffin-embedded tumour specimens were retrieved and genomic DNA extracted for analysis of microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and mutations in BRAF, KRAS, PIK3CA, TP53 and APC genes. Propensity-score matching and logistic regression were used to estimate the association of diabetes with tumour molecular profile, controlling for age, sex, tumour stage, body mass index (BMI), smoking and socio-economic status. Results: Of the 1,348 patients assessed, 288 (21.4%) had a history of diabetes mellitus. Compared to patients without diabetes, diabetics were mor...