Background
The role of tyrosine kinase inhibitors (TKI) in the neoadjuvant setting and the optimal duration of therapy remains poorly defined. As such, we aim to evaluate the impact of neoadjuvant TKI on oncological and functional outcomes in our cohort of patients with rectal GISTs.
Methods
A retrospective analysis of 36 consecutive patients who underwent treatment for rectal GIST at the National Cancer Centre Singapore from February 1996 to October 2017 was analysed. Surgical, recurrence and survival outcomes between the groups who underwent neoadjuvant therapy and those who underwent upfront surgery were compared.
Results
Patients who received neoadjuvant treatment had significantly larger tumours (median size 7.1 vs. 6.0 cm, p = 0.04) and lower mitotic count (> 10 per 50 HPF, 14 vs. 70%, p = 0.03) when compared with the non-neoadjuvant group. With TKI pre-treatment (median duration 8.8 months), majority of patients (82%) achieved at least partial response to the therapy coupled with a significant downsizing effect of up to 39% (median size of 7.1–3.6 cm), resulting in similar rates of sphincter-sparing surgery (75 vs. 76%, p = 0.94) when compared with the non-neoadjuvant group. In general, neoadjuvant group had lower rates of local recurrence (0 vs. 69%, p = 0.04) and higher overall survival (7.4 vs. 5.7 years, p = 0.03) as compared to the non-neoadjuvant group.
Conclusions
Neoadjuvant TKI has the benefit of downsizing unresectable rectal GIST to benefit from sphincter-sparing procedure and also confers protection against local recurrence and improves overall survival.
Significant factors associated with unresectability that were identified in our study could potentially create a new treatment algorithm and refine current selection process to exclude patients at risk of unresectability in planned CRS and HIPEC.
Background
Twenty to thirty percent of planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) procedures are abandoned intra-operatively. Pre-operative factors associated with unresectability identified previously were used to develop a Pre-Operative Predictive Score (PROPS), which was compared with current selection criteria—Peritoneal Surface Disease Severity Score (PSDSS), Verwaal’s Prognostic Score (PS) and Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), to determine which score provides the best prediction for unresectability.
Methods
Fifty-six patients with peritoneal metastases of colorectal origin were included. Beta-coefficient values of significant variables (
p
< 0.05) were determined from multivariate analysis to develop PROPS. PROPS, PSDSS, PS and COMPASS were compared using a receiver operating characteristic curve to calculate its accuracy, sensitivity and specificity.
Results
PROPS consisted of nine patient and tumour factors which were categorised into three groups: (i) poor tumour biology: previous inadequate resection, underwent multiple lines of chemotherapy and poorly differentiated or signet cell histology; (ii) heavy tumour burden: abdominal distension, palpable abdominal mass and computed tomography findings of ascites, small bowel disease and/or omental thickening; and (iii) active tumour proliferation: elevated tumour markers. Overall, PROPS achieved 86% accuracy with 100% sensitivity and 68% specificity, PSDSS achieved 85% accuracy with 100% sensitivity and 63% specificity, PS achieved 73% accuracy with 100% sensitivity and 68% specificity and COMPASS achieved 61% accuracy with 27% sensitivity and 100% specificity.
Conclusions
PROPS is more effective in predicting unresectability as compared to PSDSS, PS and COMPASS, and has the added advantage of using solely pre-operative factors.
Highlights
Type A aortic dissection may result in upper limb ischaemia due to progression of dissecting flap.
Despite adequate repair, residual dissecting flap may still propagate in the upper limb vasculature.
Open or endovascular techniques is the treatment of choice for salvageable cases.
Amputation is the inevitable end-point for advanced cases.
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