RAS Mutation Status Should Not Be Used to Predict Outcome from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases.

BACKGROUND: Genetic biomarkers guide systemic anti-cancer treatment (SACT) in metastatic colorectal cancer. It has been suggested they have a role in selecting patients with colorectal peritoneal metastases (CRPM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). This study aims to quantify the effect of mutation status on overall survival (OS), adjusting for confounders such as pre-operative systemic anticancer treatment (SACT). PATIENTS AND METHODS: Retrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004-2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan-Meier curves were used to determine overall survival. RESULTS: One hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4-184.9 months) and median OS was 38.7 months (95% CI 32.4-44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402-16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995-2.843, p = 0.052). CONCLUSIONS: RAS mutation status should not in isolation be used to select patients for CRS/HIPEC.

Development and internal validation of a clinical prediction model for 90-day mortality after lung resection: the RESECT-90 score.

OBJECTIVES: The ability to accurately estimate the risk of peri-operative mortality after lung resection is important. There are concerns about the performance and validity of existing models developed for this purpose, especially when predicting mortality within 90 days of surgery. The aim of this study was therefore to develop a clinical prediction model for mortality within 90 days of undergoing lung resection. METHODS: A retrospective database of patients undergoing lung resection in two UK centres between 2012 and 2018 was used to develop a multivariable logistic risk prediction model, with bootstrap sampling used for internal validation. Apparent and adjusted measures of discrimination (area under receiving operator characteristic curve) and calibration (calibration-in-the-large and calibration slope) were assessed as measures of model performance. RESULTS: Data were available for 6600 lung resections for model development. Predictors included in the final model were age, sex, performance status, percentage predicted diffusion capacity of the lung for carbon monoxide, anaemia, serum creatinine, pre-operative arrhythmia, right-sided resection, number of resected bronchopulmonary segments, open approach and malignant diagnosis. Good model performance was demonstrated, with adjusted area under receiving operator characteristic curve, calibration-in-the-large and calibration slope values (95% confidence intervals) of 0.741 (0.700, 0.782), 0.006 (-0.143, 0.156) and 0.870 (0.679, 1.060), respectively. CONCLUSIONS: The RESECT-90 model demonstrates good statistical performance for the prediction of 90-day mortality after lung resection. A project to facilitate large-scale external validation of the model to ensure that the model retains accuracy and is transferable to other centres in different geographical locations is currently underway.

Local flaps vs. free flaps for complex lower limb fractures: Effect of flap choice on patient-reported outcomes.

The optimal flap cover for managing open lower limb fractures is debated. Most studies have reported on surgical outcome but clinical outcome is not well recognised. We aimed to determine whether there are differences in patient-reported quality of life (QoL) outcome between local flap versus free flap. All patients admitted with lower limb open fractures were retrospectively reviewed. Patient notes were assessed for demographics, time to fracture union, wound healing and patient-reported QoL with EQ-5D-5L alongside a novel flap assessment tool. A total of 40 patients had flap reconstruction of their lower limb injury; 23 local flap (Group I) and 17 free flap (Group II). Average length of follow-up was 33.8 months. Group I - 10 revisions of flaps (43.5%) and 14 surgical complications (60.9%). Fracture union was 171 days and wound healing 130 days. EQ-5D index and EQ-VAS scores were 0.709 and 79.3, respectively. Group II - 8 revision of flaps (47.1%) and 12 surgical complications (70.6%). Fracture union was 273 days and wound healing 213 days. EQ-5D index and EQ-VAS scores were 0.525 and 57.2, respectively. Aesthetic appeal - 48% Group I vs. 66% Group II. Significant differences were found between the two flap groups with higher scores for daily living in Group I (p = 0.007) compared to higher overall flap ratings in Group II (p = 0.049). Both groups were comparable in terms of complications; while flap congestion and dehiscence were more common with free flaps statistical interrogation did not elicit significance (p > 0.05). Local flap and free flap techniques offer distinct advantages. Local flaps have better surgical outcome and patient-reported QoL in the first few years post soft tissue reconstruction. Differences between local and free reconstructive techniques in terms of patient health and function are ameliorated in the longer term.