Cost-effective screening using a two-antibody panel for detecting mismatch repair deficiency in sporadic colorectal cancer.

BACKGROUND: The microsatellite instability (MSI) test and immunohistochemistry (IHC) are widely used to screen DNA mismatch repair (MMR) deficiency in sporadic colorectal cancer (CRC). For IHC, a two-antibody panel of MLH1 and MSH2 or four-antibody panel of MLH1, MSH2, PMS2, and MSH6 are used. In general, MSI is known as a more accurate screening test than IHC. AIM: To compare two- and four-antibody panels of IHC in terms of accuracy and cost benefit on the basis of MSI testing for detecting MMR deficiency. METHODS: We retrospectively analyzed patients with CRC who underwent curative surgery between 2015 and 2017 at a tertiary referral center. Both IHC with four antibodies and MSI tests were routinely performed. The sensitivity and specificity of a four- and two types of two-antibody panels (PMS2/MSH6 and MLH1/MSH2) were compared on the basis of MSI testing for detecting MMR deficiency. RESULTS: High-frequency MSI was found in 5.5% (n = 193) of the patients (n = 3486). The sensitivities of the four- and two types of two-antibody panels were 97.4%, 92.2%, and 87.6%, respectively. The specificities of the three types of panels did not differ significantly (99.6% for the four-antibody and PMS2/MSH6 panels, 99.7% for the MLH1/MSH2 panel). Based on Cohen's kappa statistic (κ), four- and two-antibody panels were in almost perfect agreement with the MSI test (κ > 0.9). The costs of the MSI test and the four- and two-antibody panels of IHC were approximately $200, $160, and $80, respectively. CONCLUSION: Considering the cost of the four-antibody panel IHC compared to that of the two-antibody panel IHC, a two-antibody panel of PMS2/MSH6 might be the best choice in terms of balancing cost-effectiveness and accuracy.

Improvement in the Assessment of Response to Preoperative Chemoradiotherapy for Rectal Cancer Using Magnetic Resonance Imaging and a Multigene Biomarker.

The response to preoperative chemoradiotherapy (PCRT) is correlated with oncologic outcomes in patients with locally advanced rectal cancer. Accurate prediction of PCRT response before surgery can provide crucial information to aid clinicians in further treatment planning. This study aimed to develop an evaluation tool incorporating a genetic biomarker and magnetic resonance imaging (MRI) to improve the assessment of response in post-CRT patients with locally advanced rectal cancer. A total of 198 patients who underwent PCRT followed by surgical resection for locally advanced rectal cancer between 2010 and 2016 were included in this study. Each patient's response prediction index (RPI) score, a multigene biomarker developed in our previous study, and magnetic resonance tumor regression grade (mrTRG) score were added to create a new predictive value for pathologic response after PCRT, called the combined radiation prediction value (cRPV). Based on the new value, 121 and 77 patients were predicted to be good and poor responders, respectively, showing significantly different cRPV values (p = 0.001). With an overall predictive accuracy of 84.8%, cRPV was superior to mrTRG and RPI for the prediction of pathologic chemoradiotherapy response (mrTRG, 69.2%; RPI, 77.3%). In multivariate analysis, cRPV was found to be the sole predictor of tumor response (odds ratio, 32.211; 95% confidence interval, 14.408-72.011; p = 0.001). With its good predictive value for final pathologic regression, cRPV may be a valuable tool for assessing the response to PCRT before surgery.

Intraoperative perfusion assessment of the proximal colon by a visual grading system for safe anastomosis after resection in left-sided colorectal cancer patients.

We aimed to evaluate the clinical feasibility of a new visual grading system. We included 50 patients who underwent resection of primary colorectal cancer. Before anastomosis, the marginal vessel was cut and the perfusion status was assessed by a visual grading system. The visual grading system is comprised of five grades according to the bleeding from the marginal vessel and is categorized into 4 groups: good (grade A and B), moderate (grade C), poor (grade D) and none (grade E). Colorectal anastomosis was performed only in the good and moderate groups. We compared postoperative outcomes between the good and moderate groups and analysed the factors affecting the perfusion grade. Among the patients, 48% were grade A, 12% were grade B, and 40% were grade C. There was no anastomotic leakage. Only one patient with grade C showed ischemic colitis and needed reoperation. Age was the only factor correlated with perfusion grade in multivariate analysis (OR 1.080, 95% CI 1.006-1.159, p = 0.034). The perfusion grades were significantly different between > 65 and < 65 year-old patients (> 65, A 29.2% B 12.5% C 58.3% vs. < 65, A 65.4% B 11.5% C 23.1%, p = 0.006). Our intraoperative perfusion assessment that uses a cutting method and a visual grading system is simple and useful for performing a safe anastomosis after colorectal resection. If the perfusion grade is better than grade C, an anastomosis can be performed safely. Age was found to be an important factor affecting the perfusion grade.

Assessment of the Applicability of Integrative Tumor Response Assays in Advanced Epithelial Ovarian Cancer.

AIM: To prospectively correlate clinical responses to second-line chemotherapy for recurrent epithelial ovarian cancer (EOC) with in vitro integrative tumor-response assay (ITRA) results. PATIENTS AND METHODS: Forty-four patients with advanced EOC were enrolled from 2015-2017 at the Asan Medical Center, Seoul, Korea. ITRA comprised of two sequential histoculture drug response assays (HDRAs) of the tumor tissues. The first stage was HDRA with paclitaxel-carboplatin, paclitaxel, and carboplatin chemotherapy. The second stage was performed with surviving tumor cells from the first stage using topotecan, belotecan, gemcitabine, doxorubicin, ifosfamide, vinorelbine, and etoposide. RESULTS: The median follow-up period was 23.35 (range=4-35.35) months. Eighteen patients (40.9%) completed the second-line chemotherapy, based on the ITRA results. The objective response rate was 38.9%. The clinical response rate was 50%; two patients (11.1%) had stable disease. The sensitivity of ITRA for predicting response was 85.7% (specificity=18.2%; accuracy=44.44%). CONCLUSION: ITRAs had acceptable applicability and may help choose second-line chemotherapy for patients with advanced EOC.