Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma.

BACKGROUND: Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets. METHODS: Bisulfite-treated DNA samples from 73 eligible patients were amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9 [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D-aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated. RESULTS: Two-gene methylation combinations among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional recurrence-free survival, recurrence-free survival, and overall survival. The methylated gene combination of EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor locoregional recurrence-free survival (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.30-8.46; P = .012) independent of standard histologic factors. In addition, methylation of both EDNRB and HOXA9 indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95% CI, 0.90-8.33; P = .075) and reduced OS (HR, 5.78; 95% CI, 0.75-44.7; P = .093) in multivariable analysis. CONCLUSIONS: A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of postoperative locoregional recurrence. Intraoperative use of molecular margin imprint analysis may assist surgeons in obtaining rigorously negative surgical margins and improve the outcome of head and neck surgery.

Utility of a Clinical Decision Support System in Weight Loss Prediction After Head and Neck Cancer Radiotherapy.

PURPOSE: To evaluate the utility of a clinical decision support system (CDSS) using a weight loss prediction model. METHODS: A prediction model for significant weight loss (loss of greater than or equal to 7.5% of body mass at 3-month post radiotherapy) was created with clinical, dosimetric, and radiomics predictors from 63 patients in an independent training data set (accuracy, 0.78; area under the curve [AUC], 0.81) using least absolute shrinkage and selection operator logistic regression. Four physicians with varying experience levels were then recruited to evaluate 100 patients in an independent validation data set of head and neck cancer twice (ie, a pre-post design): first without and then with the aid of a CDSS derived from the prediction model. At both evaluations, physicians were asked to predict the development (yes/no) and probability of significant weight loss for each patient on the basis of patient characteristics, including pretreatment dysphagia and weight loss and information from the treatment plan. At the second evaluation, physicians were also provided with the prediction model's results for weight loss probability. Physicians' predictions were compared with actual weight loss, and accuracy and AUC were investigated between the two evaluations. RESULTS: The mean accuracy of the physicians' ability to identify patients who will experience significant weight loss (yes/no) increased from 0.58 (range, 0.47 to 0.63) to 0.63 (range, 0.58 to 0.72) with the CDSS ( P = .06). The AUC of weight loss probability predicted by physicians significantly increased from 0.56 (range, 0.46 to 0.64) to 0.69 (range, 0.63 to 0.73) with the aid of the CDSS ( P < .05). Specifically, more improvement was observed among less-experienced physicians ( P < .01). CONCLUSION: Our preliminary results demonstrate that physicians' decisions may be improved by a weight loss CDSS model, especially among less-experienced physicians. Additional study with a larger cohort of patients and more participating physicians is thus warranted for understanding the usefulness of CDSSs.

Neutrophil-to-lymphocyte ratio: Prognostic indicator for head and neck squamous cell carcinoma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has prognostic significance for many cancers, with higher values correlating with poor outcomes. The purpose of this study was to determine the prognostic significance of this inflammatory marker for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Univariate logistic regression and multivariate Cox regression analyses were performed on a retrospective cohort of 123 patients treated with primary chemoradiotherapy. RESULTS: The NLR is an indicator of both recurrence-free and overall survival, but the NLR does not have independent prognostic significance when the favorable prognostic influence of human papillomavirus (HPV) status is incorporated into multivariate models. CONCLUSION: The interaction between NLR and HPV status suggests that HPV status may be a determining factor in the favorable prognosis associated with a decreased NLR in HNSCC; these findings also suggest that HPV status may interact with the prognostic associations of indicators of systemic inflammation in HNSCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 662-667, 2017.

Reduction of Pharyngocutaneous Fistulae in Laryngectomy Patients by a Comprehensive Performance Improvement Intervention.

OBJECTIVE: Pharyngocutaneous fistula is a common complication in laryngectomy patients, particularly in previously irradiated cases. We initiated a comprehensive performance improvement intervention in all head and neck surgery patients intended to reduce postoperative infection and fistulae rates. We report our review of outcomes within laryngectomy patients. STUDY DESIGN: Case series with chart review. SETTING: Academic tertiary referral center. SUBJECTS: Nineteen laryngectomy patients at risk of postoperative fistula formation. METHODS: We reviewed the medical records of all patients who had undergone laryngectomy procedures between January 2013 and April 2014. Clinicodemographic data were obtained, including history of diabetes, prior radiation therapy, type of reconstruction performed for closure of the pharyngeal defect, and the presence or absence of postoperative fistula. RESULTS: The study population comprised 19 laryngectomy patients. Prior to implementation of our performance improvement intervention, 8 of 11 (73%) patients undergoing laryngectomy developed postoperative fistulae. After intervention, 0 of 8 patients developed fistulae (P = .002). Prior radiation, diabetes mellitus, and overall stage were not associated with a reduction in fistula rate (P > .05). CONCLUSION: Comprehensive uniform application of a standard antibiotic prophylaxis, surgical technique, perioperative care, and treatment of comorbid conditions can significantly reduce and potentially eliminate fistulae in laryngectomy patients who are especially at risk.

Resected pancreatic ductal adenocarcinomas with recurrence limited in lung have a significantly better prognosis than those with other recurrence patterns.

The majority of patients with curative resection of pancreatic ductal adenocarcinoma recur within 5 years of resection. However, the prognosis associated with different patterns of recurrence has not been well studied. A retrospective review of patients who underwent curative surgical resection of pancreatic cancer was performed. Of the 209 patients, 174 patients developed recurrent disease. Of these 174, 28(16.1%) had recurrent disease limited to lung metastases, 20(11.5%) had recurrence in the lung plus one or more other sites excluding the liver, 73(42.0%) had liver metastasis alone or liver metastasis with any other site except lung, 28(16.1%) local recurrence only, and 25(14.3%) peritoneal recurrence alone or together with local recurrence. Patients with recurrence limited to lung had a 8.5 months(Mo) median survival from recurrence to death, which was significantly better than the survival associated with recurrence in the liver(5.1Mo), in the peritoneum(2.3Mo) or locally(5.1Mo) in multivariable analyses. Among all groups, the time from surgery to the diagnosis of recurrence in patients who recurred in only in the lung was also the longest. However, 75% of patients were found to have indeterminate lung nodules on their surveillance CT scans prior to the diagnosis of recurrence in lung. This delayed diagnosis of lung recurrence may have a negative impact on survival after recurrence. In conclusion, pancreatic cancer with lung recurrence has a significantly better prognosis than recurrence in other sites. Further studies are needed to investigate how different diagnostic and treatment modalities affect the survival of this unique subpopulation of pancreatic cancer patients.

EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions.

PURPOSE: Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy. EXPERIMENTAL DESIGN: Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR. RESULTS: HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with a similar area under curve [AUC; 0.61, 95% confidence interval (CI) = 0.60-0.81] when compared to EDNRB and DCC combined AUC (0.60, 95% CI = 0.51-0.69), sensitivity of 46% and specificity of 72%. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95% CI = 0.58-0.76). CONCLUSIONS: EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.