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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]

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]

Background: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC).Methods: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment.Results: Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims.Conclusions: In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC. [ABSTRACT FROM AUTHOR]

BACKGROUND Surgical resection has been the standard treatment for early stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. For this report, the authors explored the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC. METHODS Patients with MPLC who received SABR (50 grays [Gy] in 4 fractions or 70 Gy in 10 fractions) for the second tumor were reviewed. Four-dimensional, computed tomography-based, planning/volumetric image-guided treatment was used for all patients. Treatment outcomes/toxicities were analyzed. RESULTS For the 101 patients who received SABR, at a median follow-up of 36 months and with a median overall survival (OS) of 46 months, the 2-year and 4-year in-field local control rates were 97.4% and 95.7%, respectively. The 2-year and 4-year OS rates were 73.2% and 47.5%, respectively; and the progression-free survival (PFS) rates were 67% and 58%, respectively. Patients who had metachronous tumors had better OS and PFS than patients who had synchronous tumors (2-year OS: 80.6% metachronous vs 61.5% synchronous; 4-year OS: 52.7% vs 39.7%, respectively; P = .047; 2-year PFS: 84.7% vs 49.4%, respectively; 4-year PFS: 75.6% vs 30.4%, respectively; P = .0001). For patients who either underwent surgery or received SABR for an index tumor, the incidence of grade ≥3 radiation pneumonitis was 3% (2 of 71 patients); however, this increased to 17% (5 of 30 patients) for those who received conventional radiotherapy for an index tumor. Other grade ≥3 toxicities included grade 3 chest wall pain (3 of 101 patients; 3%) and grade 3 skin toxicity (1 of 101 patients; 1%). CONCLUSIONS SABR achieves promising long-term tumor control and survival and may be a potential curative treatment for early stage MPLC. Cancer 2013;119:3402-10. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The optimal treatment for locally advanced superior sulcus tumors is not clear. The authors report long-term results of a trial examining the safety and efficacy of surgery followed by concurrent chemoradiation therapy for this disease. METHODS: Thirty-two patients with resectable or marginally resectable superior sulcus tumors at The University of Texas MD Anderson Cancer Center from 1994 to 2010 were enrolled in a prospective trial. Surgery involved segmentectomy or lobectomy with en bloc resection of the involved chest wall and complete nodal staging; radiation therapy (RT) began 14 to 42 days later to a dose of 60 grays (Gy) in 50 1.2-Gy fractions if surgical margins were negative or 64.8 Gy in 54 1.2-Gy fractions if margins were positive. Two cycles of etoposide (50 mg/m2) and cisplatin (50 mg/m2) were given during RT, and another 3 cycles were given after RT. Eleven patients underwent prophylactic cranial irradiation (PCI). RESULTS: The protocol completion rate was 78%. Gross total resection was accomplished in all 32 patients; 28% underwent R1 resection. Operative mortality was 0%. The most common surgical complication was postoperative pneumonia (25%). At a median follow-up time of 53.4 months (range, 2-154 months), the 2-year, 5-year, and 10-year rates of locoregional control were 84%, 76%, and 76%; distant metastasis-free survival, 52%, 48%, and 48%; disease-free survival, 49%, 45%, and 45%; and overall survival, 72%, 50%, and 45%, respectively. The brain was the most common site of distant failure (n = 5), but no patient who received PCI experienced brain metastasis. CONCLUSIONS: Surgery followed by postoperative chemoradiation is safe and effective for the treatment of marginally resectable superior sulcus tumors. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Metabolic imaging is of interest in esophageal cancer; however, the usefulness of initial standardized uptake value (SUV) in positron emission tomography (PET) is unknown in patients with esophageal or gastroesophageal carcinoma treated with definitive chemoradiotherapy. The authors hypothesized that initial SUV would correlate with patient outcome. METHODS: The authors retrospectively analyzed esophageal or gastroesophageal carcinoma patients who had baseline PET and endoscopic ultrasonography in addition to other routine staging. All patients received definitive chemoradiotherapy. Multiple statistical methods were used. RESULTS: The authors analyzed 209 consecutive esophageal or gastroesophageal carcinoma patients treated with definitive chemoradiation for outcome; of these, 180 had baseline PET for additional analyses. The median overall survival (OS) for all patients was 20.7 months (95% confidence interval, 18.8-26.3). Patients with clinical complete response (CR) lived longer than those with less than clinical CR ( P < .0001). The median initial SUV was 12.7 (range, 0-51). Higher initial SUV was associated with longer tumors ( P = .0001), higher T-stage status ( P < .0001), positive N-stage status ( P = .0001), higher overall stage ( P < .0001), lack of clinical CR ( P = .0002), and squamous cell histology ( P < .0001). In the univariate analysis, initial SUV was associated with OS (Cox model, P = .016; log-rank test, P = .002). In the multivariate analysis, initial SUV dichotomized by the median value ( P = .024) and tumor grade ( P = .016) proved to be independent OS prognosticators. Median initial SUV for clinical CR patients was 10.2, compared with 15.3 for less than clinical CR patients ( P = .0058). CONCLUSIONS: The data indicate that a higher initial SUV is associated with poorer OS in patients with esophageal or gastroesophageal carcinoma receiving definitive chemoradiation. Upon validation, baseline PET may become a useful stratification factor in randomized trials and for individualizing therapy. Cancer 2011;. © 2011 American Cancer Society. [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 pat [ABSTRACT FROM AUTHOR]

Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21 and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126 and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-β [ABSTRACT FROM AUTHOR]

The article presents information on a study which determined the value of endoscopically measured tumor length in identifying overall survival in patients with esophageal adenocarcinoma, and identifying those high-risk patients with esophageal cancer who may benefit from neoadjuvant therapy. A review of the related literature on the incidence of esophageal cancer in the U.S. is presented. Clinical data collection was done between January 1995 and December 2007. The findings of the study are discussed.

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 discusses a study which examined the role of surgery in patients with high standardized uptake value (HSUV) after receiving chemoradiation in the treatment of their localized gastroesophageal carcinoma (LGC). It says that HSUVs done through positron emission tomography (PET) after chemoradiation portends a poor prognosis. Conclusions of the study suggest that surgery may prolong overall survival and event-free survival of patients with HSUVs after chemoradiation, although further studies might be needed to confirm the conclusions.

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 presents a study which reports on the standardized uptake value (SUV) decrease percentage of positron emission tomography (PET) for the prediction of overall survival (OS) and pathologic response. It notes that the study analyzes the percentage SUV decrease both dichotomized and continuous variable in patients with gastroesophageal adenocarcinoma undergoing chemoradiation. Results show that the higher the decrease in the SUV of PET after chemoradiation, the higher is the OS.

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.

OBJECTIVE To prospectively establish objective selection criteria for metastasectomy in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS Between 1991 and 1999, 38 patients with mRCC with responsive or stable disease after initial systemic therapy, and with potentially resectable disease, were enrolled. Patients had a metastasectomy with curative intent and received consolidative adjuvant systemic therapy. RESULTS Of the patients enrolled, 79% had stable disease after initial systemic therapy and 21% had a partial or complete response. Most (84%) had metastasectomy of one organ site. There was surgically no evidence of disease (sNED) in 76%. Operative morbidity and mortality were acceptable and 90% of the patients received adjuvant systemic therapy. The median (95% confidence interval) survival was 4.7 (3.0–7.8) years, and the median time to progression was 1.8 (0.8–3.1) years. Eight of 38 patients (21%) remained free of disease by the end of the study. Significant predictors of outcome were lack of sNED after metastasectomy, and the presence of pulmonary metastases. The median overall survival for those who had sNED was 5.6 years, vs 1.4 years for those who did not ( P < 0.001). CONCLUSIONS Metastasectomy in patients with mRCC not progressing after systemic therapy is feasible, with acceptable morbidity. Predictive factors for long-term outcome include pulmonary metastases and sNED. Future work evaluating treatments that can convert patients into surgical candidates will increase the cure rate of patients with mRCC. [ABSTRACT FROM AUTHOR]

The article presents a study which explores the frequent loss of heterozygosity (LOH) of chromosome 1q in esophageal adenocarcinoma (EA). The incidence of EA in the U.S. is increasing due to increase in disease burden. The condition of chromosome 1q LOH in patients with AE was evaluated in formalin-fixed and paraffin-embedded pretreatment biopsy specimens and was identified through polymerase chain reaction analysis. The study revealed that loss of chromosome 1q was common in EA cases.

The article reports on a study assessing the prognostic significance of esophageal tumor length in the modern era. As reported, the subjects of this study had a high proportion of adenocarcinoma. It was found in the study that esophageal tumor length is a significant independent predictor of long-term survival. The study suggested that esophageal tumor length should be incorporated in the current esophageal cancer staging system to better predict the long-term survival of patients.

Background: In patients with esophageal cancer who receive chemoradiation, tools to predict/prognosticate outcome before administering therapy are lacking. The authors evaluated initial standardized unit value (iSUV) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography and its association with overall survival and the degree of pathologic response after surgery. Methods: The authors analyzed 161 patients with esophageal adenocarcinoma who had chemoradiation followed by surgery. The log-rank test, univariate Cox proportional hazards model, Kaplan-Meier survival plot, and Fisher exact test were used to analyze dichotomized iSUV and its association with overall survival and pathologic response. Results: The median age of 161 patients was 61 years (range, 26-80 years) and the majority of patients had lower esophageal or gastroesophageal junction involvement. All patients received fluoropyrimidine and, most commonly, a taxane or platinum compound with concomitant radiation. The median radiation dose was 45 grays (Gy) (range, 45 Gy-50.4 Gy). The median iSUV for all patients was 10.1 (range, 0-58). Using the Fisher exact test, iSUV was not found to be associated with the location of the primary cancer. iSUV higher than the median (10.1) was associated with a better pathologic response (P = .06). Patients with primary cancer with iSUV >10.1 had a lower risk for death (hazards ratio of 0.56) compared with those with iSUV < or = 10.1. Higher iSUV was nonsignificantly associated with improved survival (P = .07). Conclusions: Data from the current study suggest that lower iSUV is associated with poor survival and lower probability of response to chemoradiation. iSUV needs to be further evaluated because it may be used to complement other imaging or biomarker assessments to individualize therapy. [ABSTRACT FROM AUTHOR]

The article analyzes the influence of induction chemotherapy (IC) and class of cytotoxics on survival and pathologic response after preoperative chemoradiation (P-CTRT) in 180 patients with localized esophageal cancer (LEC). Accordingly, 119 patients had induction chemotherapy (IC) before P-CTRT, 57 had received a platinol, 87 had received a taxane 87, and all had received 5-fluoroacil. A detailed discussion of the results is offered.

Background: With increasing emphasis on endoscopic therapy (ET) for T1 esophageal carcinoma, the identification of low-risk patients is critical. It was hypothesized that endoscopic ultrasonography (EUS) in concert with detailed histopathologic evaluation would identify low-risk cancers for an appropriate but organ-preserving strategy. Methods: All patients who had pretreatment EUS and underwent esophagectomy as primary therapy for esophageal cancer between 1999 and 2006 were analyzed retrospectively. The accuracy of EUS in predicting the correct pathologic stage was assessed along with a histopathologic reevaluation including lymphovascular invasion (LVI). Pathologic stage and various features were incorporated into a multivariate logistic regression model. Results: A total of consecutive 87 esophageal cancer patients (81 with adenocarcinoma) were evaluable for this analysis. EUS correctly diagnosed 59 T1 cancers and 20 T2-4 cancers but understaged cancers in 2 patients and overstaged cancers in 6 patients. EUS correctly identified 8 patients with lymph node metastases but not 13 other patients. The accuracy, sensitivity, and specificity of EUS for T1 cancers were 91%, 91%, and 91%, respectively; for T1a (intramucosal) cancers, the accuracy, sensitivity, and specificity were: 82%, 67%, and 93%, respectively, and for lymph node involvement these same values were 81%, 38%, and 94%, respectively. LVI was found to be an independent predictor of lymph node metastases on the multivariate analysis (P = .02). Conclusions: Data from the current study demonstrate that EUS has excellent accuracy, sensitivity, and specificity (91% each) for identifying T1 esophageal cancers and LVI is an independent predictor of lymph node metastases. A strategy for preservation of the esophagus may be possible in patients who have EUS-designated T1 cancer without LVI after successful ET. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) using 18F-2-deoxy-D-glucose, a D-glucose analog labeled with fluorine-18, complements conventional radiologic assessment in the evaluation of patients with nonsmall-cell lung cancer (NSCLC). PET is being routinely used to improve the detection of nodal and extrathoracic metastases. PET is also currently being evaluated in the assessment of prognosis and therapeutic response and by potentially allowing an earlier assessment of response may prove invaluable in the oncologic management of patients. The article discusses the diagnosis, staging, and assessment of treatment response and prognosis with an emphasis on the appropriate clinical use of PET in management. [ABSTRACT FROM AUTHOR]