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Background: Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches. Methods: Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high‐volume institution from 1994 to 2015. Results: Thirty‐eight patients with median age 59 years (range 28–76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and wound infection (13%). One‐year overall survival was 84%; 1‐year locoregional disease‐free survival was 64%. Median time to locoregional recurrence was 36 months. Only esophageal invasion was associated with worse oncologic outcomes. Conclusions: Combined transcervical and transthoracic surgery for advanced thyroid cancer can be performed without mortality and with acceptable morbidity. [ABSTRACT FROM AUTHOR]

Background: Targeted kinase inhibitors have been increasingly utilized in the treatment of advanced medullary thyroid cancer (MTC) over the last decade. Recently, highly potent next generation selective RET inhibitors have been clinically validated, and selpercatinib was recently Food and Drug Administration (FDA)‐approved for advanced MTC. The advent of highly selective, potent RET inhibitors is broadening the treatment options for patients with RET‐mutated cancers. Methods: We report the first published case of neoadjuvant selpercatinib followed by surgery for a patient with initially unresectable, widely metastatic, RET‐mutated MTC who was treated on a single patient protocol. Results: After greater than 50% RECIST response, the patient underwent complete surgical resection followed by selpercatinib resumption. He remains locoregionally disease‐free 21 months after starting therapy with stable metastatic disease (after initial partial response); and calcitonin/CEA continue to decline. Conclusion: This novel treatment strategy for locoregionally advanced RET‐mutated MTC warrants further study in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Patient-derived xenograft (PDX) models increasingly are used in translational research. However, the engraftment rates of patient tumor samples in immunodeficient mice to PDX models vary greatly.Methods: Tumor tissue samples from 308 patients with non-small cell lung cancer were implanted in immunodeficient mice. The patients were followed for 1.5 to approximately 6 years. The authors performed histological analysis of PDXs and some residual tumor tissues in mice with failed PDX growth at 1 year after implantation. Quantitative polymerase chain reaction and enzyme-linked immunoadsorbent assay were performed to measure the levels of Epstein-Barr virus genes and human immunoglobulin G in PDX samples. Patient characteristics were compared for PDX growth and overall survival as outcomes using Cox regression analyses. Disease staging was based on the 7th TNM staging system.Results: The overall engraftment rate for PDXs from patients with non-small cell lung cancer was 34%. Squamous cell carcinomas had a higher engraftment rate (53%) compared with adenocarcinomas. Tumor samples from patients with stage II and stage III disease and from larger tumors were found to have relatively high engraftment rates. Patients whose tumors successfully engrafted had worse overall survival, particularly those individuals with adenocarcinoma, stage III or stage IV disease, and moderately differentiated tumors. Lymphoma formation was one of the factors associated with engraftment failure. Human CD8-positive and CD20-positive cells were detected in residual samples of tumor tissue that failed to generate a PDX at 1 year after implantation. Human immunoglobulin G was detected in the plasma of mice that did not have PDX growth at 14 months after implantation.Conclusions: The results of the current study indicate that the characteristics of cancer cells and the tumor immune microenvironment in primary tumors both can affect engraftment of a primary tumor sample. [ABSTRACT FROM AUTHOR]

Abstract: In a previous study, we determined that major pathologic response (MPR) as indicated by the percentage of residual viable tumor cells predicted overall survival (OS) in patients with non‐small‐cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. In this study, we assessed whether two genes and five protein biomarkers could predict MPR and OS in 98 patients with NSCLC receiving neoadjuvant chemotherapy. We collected formalin‐fixed, paraffin‐embedded specimens of resected NSCLC tumors from 98 patients treated with neoadjuvant chemotherapy. We identified mutations in KRAS and EGFR genes using pyrosequencing and examined the expression of protein markers VEGFR2, EZH2, ERCC1, RAD51, and PKR using immunohistochemistry. We assessed whether gene mutation status or protein expression was associated with MPR or OS. We observed that KRAS mutation tended to be associated with OS (P = .06), but EGFR mutation was not associated with OS. We found that patients with high RAD51 expression levels had a poorer prognosis than did those with low RAD51 expression. We also observed that RAD51 expression was associated with MPR. MPR and RAD51 expression were associated with OS in univariate and multivariate analyses (P = .04 and P = .02, respectively). Combination of MPR with RAD51 is a significant predictor of prognosis in patients with NSCLC who received neoadjuvant chemotherapy. We demonstrated that MPR or RAD51 expression was associated with OS in patients with NSCLC receiving neoadjuvant chemotherapy. Prediction of a patient's prognosis could be improved by combined assessment of MPR and RAD51 expression. [ABSTRACT FROM AUTHOR]

Background: Next-generation sequencing of cell-free DNA (cfDNA) has been shown to be a useful noninvasive test for detecting mutations in solid tumors.Methods: Targeted gene sequencing was performed with a panel of 263 cancer-related genes for cfDNA and genomic DNA of peripheral blood mononuclear cells (PBMCs) obtained from presurgical specimens of 6 lung cancer patients, and mutation calls in these samples were compared with those of primary tumors and corresponding patient-derived xenografts (PDXs).Results: Approximately 67% of the mutations detected in the tumor samples (primary tumors and/or PDXs) were also detected in genomic DNA from PBMCs as background mutations. These background mutations consisted of germline polymorphisms and a group of mutations with low allele frequencies, mostly <10%. These variants with a low allele frequency were repeatedly detected in all types of samples from the same patients and at similarly low allele frequency levels in PBMCs from different patients; this indicated that their detection might be derived from common causes, such as homologous sequences in the human genome. Allele frequencies of mutations detected in both primary tumors and cfDNA showed 2 patterns: 1) low allele frequencies (approximately 1%-10%) in cfDNA but high allele frequencies (usually >10% or >3-fold increase) in primary tumors and further enrichment in PDXs and 2) similar allele frequencies across samples.Conclusions: Because only a small fraction of total cfDNA might be derived from tumor cells, only mutations with the first allele frequency pattern may be regarded as tumor-specific mutations in cfDNA. Effective filtering of background mutations will be required to improve the accuracy of mutation calls in cfDNA. Cancer 2018;124:1061-9. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Reports are limited regarding clinical and pretreatment features that might predict a pathological complete response (pathCR) after treatment in patients with esophageal cancer (EC). This might allow patient selection for different strategies. This study examines the association of a pathCR with pretreatment variables, overall survival (OS), recurrence-free survival (RFS), and patterns of recurrence in a large cohort from a single institution.Methods: The baseline clinical features of 911 consecutive patients with EC who were treated with trimodality therapy from January 2000 to November 2013 were analyzed. A pathCR was defined as a surgical specimen with no residual carcinoma (primary or nodes). Logistic regressions were used to identify independent baseline features associated with a pathCR. We applied log-rank testing and Cox models to determine the association between a pathCR and the time-to-event outcomes (OS and RFS).Results: Of 911 patients, 218 (23.9%) achieved a pathCR. The pathCR rate was 23.1% for adenocarcinoma and 32.2% for squamous cell carcinoma. A lower pathCR rate was observed for 1) older patients (>60 years), 2) patients with poorly differentiated tumors, 3) patients with signet ring cells (SRCs), and 4) patients with a higher T stage. Patients with a pathCR had longer OS and RFS than those without a pathCR (P = .0021 and P = .0011, respectively). Recurrences occurred more in non-pathCR patients. Distant metastases were the most common type of recurrence. PathCR patients developed brain metastases at a marginally higher rate than non-pathCR patients (P = .051).Conclusions: In this large cohort study, a pathCR is confirmed to be associated with better OS and RFS. The presence of a poorly differentiated tumor or SRCs reduces the likelihood of a pathCR. Future research should focus on molecular classifiers. Cancer 2017;123:4106-4113. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of microscopically positive vascular margins on recurrence and cancer-specific survival ( CSS) in patients with renal cell carcinoma ( RCC) with venous thrombus, Patients and Methods We reviewed the records from the period 1993 to 2009 of consecutive patients treated surgically for RCC with venous tumour thrombus at the University of Texas MD Anderson Cancer Center., Patients with metastatic disease, positive soft tissue margins or gross residual disease at time of thrombectomy were excluded., The primary outcome measures were local or systemic disease recurrence, and CSS., Univariate and multivariate analysis were used to evaluate whether microscopically positive vascular margins were associated with RCC recurrence or CSS after nephrectomy with thrombectomy., Results A total of 256 patients with RCC were identified with a median (interquartile range) follow-up of 36.7 (18.4-63.5) months. Microscopic tumour was present at the margin of resection in 47 patients (18.4%)., The median recurrence-free interval was significantly shorter in patients with positive vascular margins: 22.1 vs 70.2 months ( P = 0.009)., The rate of local recurrence was higher in patients with positive vein margins: 12.8 vs 4.3% ( P < 0.01). Local recurrence without concomitant systemic recurrence was identified in only two of 256 (0.8%) patients., Patients with positive vascular margins had significantly worse CSS times compared with patients with negative vascular margins: 37.7 vs 93.0 months ( P = 0.004)., In multivariable analysis, positive vascular margins were found to be independently predictive of local recurrence but not of systemic recurrence or CSS., Conclusions Complete surgical excision should always be attempted because positive vascular wall margins increase local recurrence rates., Invasion of RCC into the vein wall at the resection margin is associated with aggressive tumour biology, and the majority of patients with positive vascular wall margins experience systemic recurrence. [ABSTRACT FROM AUTHOR]

Background: Treatment strategy for patients with adequately staged cT2N0M0 carcinoma of the thoracic esophagus is currently a subject of debate. This study analyzed the largest series of consecutive cT2N0M0 esophageal cancer patients treated with preoperative chemoradiotherapy.Methods: Data from all patients with cT2N0M0 (assessment included endoscopic ultrasonography and computed tomography of the chest and abdomen) thoracic esophageal cancer who were treated with preoperative chemoradiation between 1997 and 2009 were analyzed. The Cox regression model and Kaplan-Meier plots were used to analyze the data.Results: Data from 49 patients were analyzed. The median follow-up was 28.46 months. Male sex and adenocarcinoma histology predominated. Pathologic complete response was observed 19 (39%) patients. The 10-year actuarial overall survival (OS) for adenocarcinoma patients was >60%. In the univariate analysis for OS, squamous histology (P = .006), smoking (P = .015), and alcohol consumption (P = .032) were found to be associated with poor OS. In the univariate analysis for disease-free survival (DFS), squamous histology (P = .009) and smoking (P = .014) were associated with poor DFS. In the multivariate analysis for OS, smoking was an independent prognosticator (P = .02). In the multivariate analysis for DFS, advanced pathologic stage (P = .05) and lymph node metastases (P = .006) were independent prognosticators. Patients with adenocarcinoma (P = .002) and those with pathologic N0 disease had better OS and DFS. Upward stage migration occurred in only 10% of patients.Conclusions: These data suggest that smoking and alcohol influence the long-term outcome of patients with cT2N0M0 disease. Adenocarcinoma patients treated with trimodality therapy had an excellent actuarial 10-year OS and a high rate of pathologic complete response. Trimodality therapy should be prospectively compared with primary surgery in these patients. [ABSTRACT FROM AUTHOR]

This article discusses a study which examined the impact of body mass index (BMI) on survival and complications in patients with esophageal cancer (EC) who underwent surgery as their primary therapy. A brief introduction to the prevalence of high BMI in the U.S. and its association with esophageal adenocarcinoma (EAC) is included. An overview of the study population and details on the methodology are discussed. The study revealed that high BMI is common in EC patients.

The article presents a study which examines the efficacy of noncisplatin-based chemoradiotherapy to treat esophageal cancer. It poses that the study uses baseline endoscopic ultrasonography (EUS) and induction therapy to assess the organ functions and medical fitness of patients. Moreover, the study found that chemoradiotherapy is active and safe to be used for esophageal cancer.

The article reports on the findings of the study concerning the impact of age on long-term patient survival and surgical complications. The study includes an analysis with 600 consecutive patients having esophageal cancer who underwent surgery. Result shows that patients aged 60 and beyond who underwent esophageal cancer surgery achieved the best overall survival and experienced fewer complications compared with patients older than 70 years.

Background: The double-strand break (DSB) repair capacity has been implicated in the survival of patients in several cancer types. However, little is known about the prognostic importance of the key DSB repair genes-ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the Ku heterodimeric regulatory complex 86-kD subunit (Ku80)-in nonsmall cell lung cancer (NSCLC). To address this issue, the authors determined the messenger RNA (mRNA) expression of these genes in patients NSCLC and assessed their prognostic relevance.Methods: mRNA expression levels of ATM, DNA-PKcs, and Ku80 were measured in tumor and adjacent normal tissues from 140 patients with NSCLC by using quantitative real-time polymerase chain reaction analysis. Then, a Cox proportional hazards regression model and Kaplan-Meier plots were used to evaluate the association between the tumor:normal (T/N) expression ratios of the 3 genes and the overall survival rate and duration in patients with NSCLC.Results: mRNA expression of ATM and DNA-PKcs, but not of Ku80, was significantly higher in tumor tissues than in adjacent normal tissues (P=.003 and P<.001, respectively). The high T/N expression ratios of ATM and DNA-PKcs were associated significantly with a 1.82-fold increased risk of death (95% confidence interval, 1.05-2.70) and a 2.13-fold increased risk of death (95% confidence interval, 1.21-3.76), respectively. However, no significant association with risk was observed for Ku80. Kaplan-Meier analyses revealed that patients with high T/N expression ratios of ATM or DNA-PKcs had notably shorter median survival than patients with low ratios.Conclusions: The current findings suggested that the T/N expression ratios of ATM and DNA-PKcs may be useful for identifying NSCLC patients with a poor prognosis who may benefit from more aggressive therapy. [ABSTRACT FROM AUTHOR]