Factors associated with access and approach to esophagectomy for cancer: a National Cancer Database study.

BACKGROUND: Minimally invasive esophagectomy (MIE) for esophageal cancer has been associated with decreased pain, less blood loss, and shorter hospital stay with comparable survival to open surgery. To date, there is minimal information regarding what factors are associated with access to MIE. METHODS: The National Cancer Database (NCDB) was used to compare rates of MIE (either robotic or laparoscopic) and open esophagectomy (OE) by demographic and clinical factors. Continuous variables were compared using a linear trend test, and categorical variables were compared using Mantel-Haenszel tests. Binomial regression was performed to examine significant factors after adjusting for confounding variables. RESULTS: There were 18,366 patients included in the analysis. Of all esophagectomies performed in the US, 49% were performed by OE and 51% were performed by MIE. Patients who had undergone MIE were more likely to live in the Eastern US as compared with the Midwest [odds ratio (OR) 1.72; 95% confidence interval (CI) 1.58, 1.88] or the South (OR 1.31; 95% CI 1.19, 1.44). They were also more likely to be treated at an academic center (OR 1.64; 95% CI 1.53, 1.75) rather than a community hospital, and to be of White race as compared with Asian race (OR 1.46; 95% CI 1.10, 1.92). There was not a significant difference in the rates of MIE between White and Black patients (OR 1.12; 95% CI 0.96, 1.32). MIE was more likely with each passing year, and higher TNM stages of cancer were less likely to be treated with MIE (P < 0.001 for all). CONCLUSION: While MIE is evolving, OE is still considered standard of care with robotic approaches representing a minority of MIE. While there are several factors associated with access to MIE, including race, facility type and geographic location, these factors should be further explored to help increase access to MIE.

Smoking Cessation, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.

Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.

Racial and Ethnic Differences in Lung Cancer Surgical Stage: An STS Database Study.

BACKGROUND: Racial and ethnic differences in lung cancer care have been previously documented. These differences may be related to access to care, cultural differences, or fewer patients presenting with operable lung cancer. The relationship between race and pathologic stage of patients who undergo lung cancer resection has not been defined. This study estimates racial disparities in lung cancer stage among patients who undergo surgical resection. METHODS: The Society of Thoracic Surgeons (STS) database was queried for patients who underwent resection of non-small cell lung cancer and had complete pathologic staging and racial identification. Univariate and multivariate analyses were performed. Study end point was the pathologic stage and we evaluated its association with the racial and ethnic origins of the patients. RESULTS: Of 19,173 eligible patients with non-small cell lung cancer of known pathological stage who underwent surgery between 2002 and 2008, the majority were Caucasian (17,148, 89.4%), 1,502 (7.8%) were African-American, 273 (1.4%) were Asian, and 250 (1.3%) were Hispanic. In univariate analysis, significantly more Caucasian and African-American patients underwent resection of stage I/II lung cancer (13,929, 81.2% and 1,217, 81%, respectively) as compared with the Asian (207, 75.2%) and Hispanic (188, 75.8%) patients (p = 0.007). Stage at operation did not differ between Caucasians and African-Americans. Multivariate analysis confirmed these findings (p = 0.03) after adjustment for age, gender, tobacco use, diabetes, and year of surgery. CONCLUSION: Within the STS database, patients identified as Asian or Hispanic had a significantly higher pathologic stage at the time of resection than Caucasian or African-American patients. The causes of these differences in the treatment of potentially curable lung cancer are unknown and require further investigation.

Robot-Assisted Bronchoscopy for Identification of Lung Nodules During Minimally Invasive Pulmonary Resection.

OBJECTIVE: Small pulmonary nodules can be difficult to identify during minimally invasive surgical (MIS) resection. Previous investigators have reported using standard bronchoscopy with electromagnetic navigation to identify small pulmonary nodules. Robot-assisted bronchoscopy has been introduced into clinical practice and has shown utility for the biopsy of small lesions. We report our experience using robot-assisted bronchoscopy with dye marking to aid in minimally invasive pulmonary resection. METHODS: Patients with peripheral pulmonary nodules underwent robot-assisted bronchoscopy before a planned minimally invasive resection. Indocyanine green or methylene blue was injected directly into the targeted lesion. Surgical resection was then immediately performed. Success was defined as dye visualization leading to sublobar resection of the target nodule without the need for lobectomy or thoracotomy. RESULTS: Thirty patients with a single targeted nodule underwent robot-assisted bronchoscopy followed by MIS resection. The median lesion size was 9 mm (4 to 25 mm), and the median distance from the pleura was 5 mm (1 to 32 mm). The success rate was 83.3% (25 of 30). There were 3 cases in which the dye was not visualized, and in 2 cases there was free extravasation of dye. The targeted nodule was identified in these 5 patients without the need for thoracotomy or lobectomy. Pathology revealed non-small cell lung cancer (n = 13, 43.3%), metastatic disease (n = 11, 36.7%), and benign disease (n = 6, 20%). There were no complications related to the use of robot-assisted bronchoscopy. CONCLUSIONS: Robot-assisted bronchoscopy with dye marking is safe and effective for guiding minimally invasive resection of small peripheral pulmonary nodules.

Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer.

PURPOSE: Although immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect-especially in the setting of stable disease-calls for the development of molecularly informed real-time minimally invasive approaches. In addition to capturing tumor regression, liquid biopsies may be informative in capturing immune-related adverse events (irAE). EXPERIMENTAL DESIGN: We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles. RESULTS: Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank P = 0.0003) and overall survival (log-rank P = 0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, on-treatment peripheral blood T-cell repertoire reshaping, assessed by significant T-cell receptor (TCR) clonotypic expansions and regressions, was identified on average 5 months prior to clinical diagnosis of an irAE. CONCLUSIONS: Molecular responses assist with the interpretation of heterogeneous clinical responses, especially for patients with stable disease. Our complementary assessment of the peripheral tumor and immune compartments provides an approach for monitoring of clinical benefits and irAEs during immunotherapy.

Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses.

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 .

Major perioperative morbidity does not affect long-term survival in patients undergoing esophagectomy for cancer of the esophagus or gastroesophageal junction.

INTRODUCTION: The incidence of cancer of the esophagus/GE junction is dramatically increasing but continues to have a dismal prognosis. Esophagectomy provides the best opportunity for long-term cure but is hampered by increased rates of perioperative morbidity. We reviewed our large institutional experience to evaluate the impact of postoperative complications on the long-term survival of patients undergoing resection for curative intent. METHODS: We identified 237 patients who underwent esophagogastrectomy, with curative intent, for cancer between 1994 and 2008. Complications were graded using the previously published Clavien scale. Survival was calculated using Kaplan-Meier methodology and survival curves were compared using log-rank tests. Multivariate analysis was performed with continuous and categorical variables as predictors of survival, and examined with logistic regression and odds ratio confidence intervals. RESULTS: There were 12 (5 %) perioperative deaths. The average age of all patients was 62 years, and the majority (82 %) was male. Complication grade did not significantly affect long-term survival, although patients with grade IV (serious) complications did have a decreased survival (p = 0.15). Predictors of survival showed that the minimally invasive type esophagectomy (p = 0.0004) and pathologic stage (p = 0.0007) were determining factors. There was a significant difference in overall survival among patients who experienced pneumonia (p = 0.00016) and respiratory complications (p = 0.0004), but this was not significant on multivariate analysis. CONCLUSIONS: In this single-institution series, we found that major perioperative morbidity did not have a negative impact on long-term survival which is different than previous series. The impact of tumor characteristics at time of resection on long-term survival is of most importance.

Intercostal Cryoablation During Video-Assisted Lung Resection Can Decrease Postoperative Opioid Use.

OBJECTIVE: Pain requiring opioid use remains an issue even with minimally invasive thoracic surgery. The objective of this study was to investigate the effectiveness of intercostal nerve cryoablation (CRYO) for pain control in adult patients undergoing pulmonary resection. METHODS: A retrospective analysis of patients undergoing pulmonary resection by uniportal video-assisted thoracic (uVATS) approach was undertaken. Patients treated with our usual pain regimen (STANDARD) were compared with those who additionally received CRYO. STANDARD includes intercostal bupivacaine, patient-controlled analgesia (24 h), ketorolac (48 to 72 h), and tramadol. Intraoperative CRYO was performed on 5 intercostal levels. The primary aim was to compare pain scores (range, 0 to 10) and morphine equivalent dosages (MED). Secondary outcomes included length of stay, chest tube duration, presence of an air leak, and adverse events. A p value <0.05 was considered significant. RESULTS: There were 49 patients (34 female, 15 male). The median age was 74 (37 to 90) years. Procedures included lobectomy (n = 32), segmentectomy (n = 7), and wedge resections (n = 10). There were 23 (46.9%) CRYO and 26 (53.1%) STANDARD patients. Baseline characteristics were similar. Mean length of stay (2.9 vs 3.5 days), chest tube duration (2.2 vs 1.8 days), and adverse events (9 of 23 vs 7 of 26) were similar. There were no complications attributable to CRYO. Pain scores were not significantly different on postoperative days (POD) 1 to 4. MED was significantly reduced after CRYO on POD 1 (5 vs 47.24), POD 2 (10.93 vs 25.04), POD 3 (8.13 vs 21.7), and POD 4 (7.08 vs 19.17). CONCLUSIONS: CRYO can be performed safely during pulmonary resection and can decrease in-hospital opioid use. The results from this retrospective study will need to be validated in future prospective studies.

Safety of adjuvant atezolizumab after pneumonectomy/bilobectomy in stage II-IIIA non-small cell lung cancer in the randomized phase III IMpower010 trial.

OBJECTIVE: Adjuvant atezolizumab is a standard of care after chemotherapy in completely resected stage II-IIIA programmed death ligand-1 tumor cell 1% or greater non-small cell lung cancer based on results from the phase III IMpower010 study. We explored the safety and tolerability of adjuvant atezolizumab by surgery type in IMpower010. METHODS: Patients had completely resected stage IB-IIIA non-small cell lung cancer (Union Internationale Contre le Cancer/American Joint Committee on Cancer, 7th Ed), received up to four 21-day cycles of cisplatin-based chemotherapy, and were randomized 1:1 to receive atezolizumab 1200 mg every 3 weeks (≤16 cycles or 1 year) or best supportive care. Adverse events and clinical characteristics were investigated by surgery type (pneumonectomy/bilobectomy or lobectomy/sleeve lobectomy) in the randomized stage II-IIIA population who received 1 or more atezolizumab dose or with 1 or more postbaseline assessment (safety evaluable) for best supportive care. RESULTS: Overall, 871 patients comprised the safety-evaluable randomized stage II-IIIA population. In the atezolizumab arm, 23% (100/433) received pneumonectomy/bilobectomy and 77% (332/433) received lobectomy/sleeve lobectomy. Atezolizumab discontinuation occurred in 32% (n = 32) and 35% (n = 115) of the pneumonectomy/bilobectomy and lobectomy/sleeve lobectomy groups, respectively. Grade 3/4 adverse events were reported in 21% (n = 21) and 23% (n = 76) of patients in the atezolizumab arms in the pneumonectomy/bilobectomy and lobectomy/sleeve lobectomy groups, respectively. In the atezolizumab arms of the surgery groups, 13% (n = 13) and 17% (n = 55) had an adverse event leading to hospitalization. Atezolizumab-related adverse events leading to hospitalization occurred in 5% (n = 5) and 7% (n = 23) of the surgery groups. CONCLUSIONS: These exploratory findings support use of adjuvant atezolizumab after platinum-based chemotherapy in patients with completely resected stage II-IIIA programmed death ligand-1 tumor cell 1% or more non-small cell lung cancer, regardless of surgery type.

Profibrotic role of miR-154 in pulmonary fibrosis.

In this study, we explored the regulation and the role of up-regulated microRNAs in idiopathic pulmonary fibrosis (IPF), a progressive interstitial lung disease of unknown origin. We analyzed the expression of microRNAs in IPF lungs and identified 43 significantly up-regulated microRNAs. Twenty-four of the 43 increased microRNAs were localized to the chromosome 14q32 microRNA cluster. We validated the increased expression of miR-154, miR-134, miR-299-5p, miR-410, miR-382, miR-409-3p, miR-487b, miR-31, and miR-127 by quantitative RT-PCR and determined that they were similarly expressed in embryonic lungs. We did not find evidence for differential methylation in this region, but analysis of transcription factor binding sites identified multiple SMAD3-binding elements in the 14q32 microRNA cluster. TGF-ß1 stimulation of normal human lung fibroblasts (NHLF) caused up-regulation of microRNAs on chr14q32 that were also increased in IPF lungs. Chromatin immunoprecipitation confirmed binding of SMAD3 to the putative promoter of miR-154. Mir-154 was increased in IPF fibroblasts, and transfection of NHLF with miR-154 caused significant increases in cell proliferation and migration. The increase in proliferation induced by TGF-ß was not observed when NHLF or IPF fibroblasts were transfected with a mir-154 inhibitor. Transfection with miR-154 caused activation of the WNT pathway in NHLF. ICG-001 and XAV939, inhibitors of the WNT/ß-catenin pathway, reduced the proliferative effect of miR-154. The potential role of miR-154, one of multiple chr14q32 microRNA cluster members up-regulated in IPF and a regulator of fibroblast migration and proliferation, should be further explored in IPF.

Outcomes after minimally invasive esophagectomy: review of over 1000 patients.

BACKGROUND: Esophagectomy is a complex operation and is associated with significant morbidity and mortality. In an attempt to lower morbidity, we have adopted a minimally invasive approach to esophagectomy. OBJECTIVES: Our primary objective was to evaluate the outcomes of minimally invasive esophagectomy (MIE) in a large group of patients. Our secondary objective was to compare the modified McKeown minimally invasive approach (videothoracoscopic surgery, laparoscopy, neck anastomosis [MIE-neck]) with our current approach, a modified Ivor Lewis approach (laparoscopy, videothoracoscopic surgery, chest anastomosis [MIE-chest]). METHODS: We reviewed 1033 consecutive patients undergoing MIE. Elective operation was performed on 1011 patients; 22 patients with nonelective operations were excluded. Patients were stratified by surgical approach and perioperative outcomes analyzed. The primary endpoint studied was 30-day mortality. RESULTS: The MIE-neck was performed in 481 (48%) and MIE-Ivor Lewis in 530 (52%). Patients undergoing MIE-Ivor Lewis were operated in the current era. The median number of lymph nodes resected was 21. The operative mortality was 1.68%. Median length of stay (8 days) and ICU stay (2 days) were similar between the 2 approaches. Mortality rate was 0.9%, and recurrent nerve injury was less frequent in the Ivor Lewis MIE group (P < 0.001). CONCLUSIONS: MIE in our center resulted in acceptable lymph node resection, postoperative outcomes, and low mortality using either an MIE-neck or an MIE-chest approach. The MIE Ivor Lewis approach was associated with reduced recurrent laryngeal nerve injury and mortality of 0.9% and is now our preferred approach. Minimally invasive esophagectomy can be performed safely, with good results in an experienced center.

Robot-assisted thymectomy is superior to transsternal thymectomy.

BACKGROUND: Complete thymectomy is the procedure of choice in the treatment of thymomas and in treating selected patients with myasthenia gravis. Transsternal thymectomy is the gold standard for most patients. Robot-assisted thymectomy has emerged as an alternative to open transsternal surgery. The goal of this study was to compare perioperative outcomes in patients who underwent transsternal or robot-assisted thymectomy. METHODS: We performed a retrospective review of all patients who underwent robot-assisted or transsternal thymectomy at our institution from February 2001 to February 2010. Data are presented as mean ± SD. Significance was set as P < 0.05. RESULTS: Fifty patients underwent either transsternal (n = 35) or robot-assisted (n = 15) thymectomy. Patient demographics and the incidence of myasthenia gravis were similar between groups. There were no intraoperative complications or conversions to open surgery in the robot-assisted group. Intraoperative blood loss was significantly higher in the transsternal group (151.43 vs. 41.67 ml, P = 0.01). There were 20 postoperative complications and 1 postoperative death in the transsternal group and 1 postoperative complication in the robot-assisted group (P = 0.001). Hospital length of stay was 4 days (range 2-27 days) in the transsternal group and 1 day (range 1-7 days) in the robot-assisted group (P = 0.002). CONCLUSIONS: Robot-assisted thymectomy is superior to transsternal thymectomy, reducing intraoperative blood loss, postoperative complications, and hospital length of stay. Further investigation of the long-term oncologic results in thymoma patients and long-term remission rates in patients with myasthenia gravis who underwent robot-assisted thymectomy is warranted.

Randomized trial of bupivacaine with epinephrine versus bupivacaine liposome suspension in patients undergoing minimally invasive lung resection.

OBJECTIVES: Thoracic surgery can cause significant pain, and multiple strategies have been developed to control pain after surgery. We compared 2 bupivacaine formulations given intraoperatively: bupivacaine with epinephrine (1,200,000) or liposomal bupivacaine. METHODS: This was a randomized, open-label study (NCT03560362). Eligible patients were adults scheduled for a minimally invasive lung procedure. Incision sites were injected with bupivacaine with epinephrine or liposomal bupivacaine before incision, and each intercostal space was injected with 1 mL of bupivacaine with epinephrine or liposomal bupivacaine entering the thoracic cavity. Patient-controlled analgesia was initiated in the recovery room. Pain was recorded using a visual analog scale. The primary outcome was the amount of narcotics taken during the postoperative hospital stay. RESULTS: We recruited 50 patients; 25 received bupivacaine with epinephrine, and 25 received liposomal bupivacaine. The treatment groups were similar in age, histology, and procedure performed. There were no statistical differences between the treatment groups in the amount of narcotics required during the hospital stay (36.3 mg for bupivacaine and 38 mg for liposomal bupivacaine) or in pain assessed the day of surgery (5 and 5), the first day (3.5 and 2.3), second day (3 and 2.6), 2 weeks (0 and 1), or 3 months (0 and 0) postoperatively. Hospital length of stay and complications were also similar. CONCLUSIONS: In a small, randomized study, we did not find significant differences between bupivacaine with epinephrine or liposomal bupivacaine in mitigating pain after minimally invasive lung resection. We currently favor using the less expensive nonliposomal bupivacaine preparations until additional data are available.

Surgical resection versus stereotactic body radiation therapy in early stage bronchopulmonary large cell neuroendocrine carcinoma.

BACKGROUND: Surgery is the standard of care for early stage non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is another definitive treatment option for those patients who have not been treated surgically. Comparison of approaches is being explored in NSCLC, but has yet to be compared exclusively in large cell neuroendocrine carcinoma (LCNEC) of the lung. We used the National Cancer Database (NCDB) to conduct such a comparison. METHODS: We accessed the NCDB for patients with LCNEC who were recorded as having lung stage T1-2N0M0 treated with lobectomy/pneumonectomy or SBRT. Multivariable logistic regression identified predictors of SBRT. Multivariable Cox regression was used to identify predictors of survival propensity matching and account for indication bias. RESULTS: A total of 3209 patients met the criteria, of which 238 (7%) received SBRT. The median SBRT dose was 50 Gy (48-60) in four fractions (3-5). Predictors of SBRT were age >68, T1 disease, and most recent year of treatment. Predictors of survival were younger age, surgical treatment, female sex, and T1 disease. After propensity matching, median survival was 57 months versus 35 months in favor of surgical resection, P < 0.0001. CONCLUSION: Surgical resection in comparison to SBRT has improved survival for patients with early stage LCNEC of the lung. SBRT represents a viable treatment alternative for those patients who do not meet the criteria for surgery.

Drivers of 30- and 90-day Postoperative Death After Neoadjuvant Chemoradiation for Esophageal Cancer.

BACKGROUND: Neoadjuvant chemoradiation, followed by esophagectomy, is a standard of care for locally advanced esophageal cancers. The ChemoRadiOtherapy plus Surgery versus Surgery alone (CROSS) trial reported a 30-day mortality rate of 6%. We sought to evaluate 30- and 90-day mortality in similar patients in the United States and identify predictors of higher mortality rates. METHODS: The National Cancer Database was used to identify patients with cT3-4/N+ esophageal cancers treated with neoadjuvant chemoradiation followed by esophagectomy. Bivariate univariable and multivariable regression analysis was used to identify predictors of 30- and 90-day mortality. RESULTS: We identified 7691 patients. Readmission within 30 days of surgery occurred in 6.0% of patients. Mortality was 2.9% at 30 days and 7.2% at 90 days. Positive surgical margins conferred a more than doubled risk of 30- and 90-day mortality, 5.5% vs 2.7% and 14.6% vs 6.8% (both P < .001). Facility surgical volume impacted 30-day mortality, whereas readmission was associated with 90-day mortality, both exceeding 10% (P = .004 and P = .001, respectively). In patients undergoing minimally invasive surgery converted to open, 90-day mortality was 12.1% (P < .01). For patients 69 years and older, 90-day mortality was also 12.1% (P < .001). Patients who underwent esophagectomy more than 45 days from completion of chemoradiation also had higher 90-day mortality at 8.3% vs 6.2% (P < .001). CONCLUSIONS: Postoperative death at 30 and 90 days after neoadjuvant chemoradiation and esophagectomy appears to be on par with randomized data. Positive surgical margins, squamous cell carcinomas, age 69 and older, readmission within 30 days, and conversion from a minimally invasive operation to an open operation all carry a 90-day mortality risk exceeding 10%.

Transection of more than one sympathetic chain ganglion for hyperhidrosis increases the severity of compensatory hyperhidrosis and decreases patient satisfaction.

Sympathectomy (ETS) is an effective treatment for hyperhidrosis (HH), but compensatory hyperhidrosis (CH) is a common side effect. We reviewed our experience with 200 patients. Two hundred patients were retrospectively analyzed. Patients completed a questionnaire regarding their postoperative symptoms [% improvement score (IS), CH score], and their level of dissatisfaction, which was assessed as a function of regretting the choice to undergo ETS. Significance set at P< or =0.05. There were 123 (61.5%) females. Mean age was 28.2+/-7.4. Follow-up (mo) was 20.9+/-12.1. One ganglion was transected in 112 (56%) patients (G1), and more than one in 88 (G2). Overall, 157 (78.5%) patients had CH, 88 (74.1%) patients in G1 and 74 (84.1%) in G2, P=0.06. Patients in G2 had a higher CH score (4.1+/-2.7 versus 3.0+/-2.5, P<0.01), and a higher number of patients regretting surgery (11.4% versus 3.6%, P=0.05). Multivariate analysis showed age, high CH score, and surgery on T2 as independent predictors of patient's dissatisfaction (P<0.05). Patients with more than one ganglion transected demonstrate a trend toward a higher incidence of CH, a significantly higher CH score, and are more dissatisfied with ETS. Age, surgery on T2, and high CH score are independent predictors of patient's dissatisfaction.

Adjuvant chemotherapy is associated with improved survival in patients with nodal metastases after neoadjuvant therapy and esophagectomy.

BACKGROUND: Studies supporting adjuvant chemotherapy after complete resection of esophageal cancer are scarce, and current clinical guidelines recommend either adjuvant chemotherapy or observation. We aimed to clarify the role of adjuvant chemotherapy in patients found to have persistent nodal metastases after neoadjuvant chemoradiation and complete resection of esophageal adenocarcinoma. METHODS: We queried the National Cancer Database (NCDB) for all patients from 2006 to 2012 with esophageal adenocarcinoma who received neoadjuvant chemoradiotherapy, underwent esophagectomy with complete resection, and were found to have lymph node metastases on final pathology. We compared patients who received adjuvant chemotherapy with patients followed by observation only. After performing propensity-score matching to create a well-balanced cohort, we compared survival using the Kaplan-Meier method. RESULTS: We identified 2,046 patients with lymph node metastases after neoadjuvant chemoradiotherapy and esophagectomy; 295 received adjuvant chemotherapy, and 1,751 did not. The median survival in the unmatched cohort was 2.6 years with adjuvant chemotherapy and 2.1 years with observation only (P=0.0185). Five-year survival was 27.9% with adjuvant chemotherapy and 21.5% with observation only. When we examined survival in a balanced cohort of 295 propensity-matched pairs, median survival was 2.6 years with adjuvant chemotherapy and 2.0 years with observation only (P=0.031). Five-year survival was 27.9% with adjuvant chemotherapy and 20.2% with observation only. CONCLUSIONS: In a large, propensity-matched cohort, adjuvant chemotherapy was associated with significantly improved survival for patients with node-positive esophageal adenocarcinoma after neoadjuvant therapy and complete resection. This finding supports the use of adjuvant therapy for patients with node-positive adenocarcinoma after neoadjuvant therapy and surgery.

Establishing a histology-specific biologically effective dose threshold for lung stereotactic ablative radiotherapy (SABR): Is ≥100 Gy10 enough?

OBJECTIVES: Squamous cell carcinoma (SCC) is associated with worse local control and overall survival (OS) compared to adenocarcinoma (ADC) in patients with early stage non-small cell lung cancer (ES-NSCLC). Biological effective dose (BED) escalation above 100 Gy10 improves tumor control, yet SCC and ADC may respond differentially to BED beyond 100 Gy10. MATERIALS AND METHODS: We queried the National Cancer Database for ES-NSCLC (T1-2N0, Stage I-IIA) patients with SCC or ADC treated with stereotactic ablative radiotherapy (SABR). Receiver operator characteristic (ROC) curve analysis was used to identify the optimal dose threshold for SCC and ADC. Patients were stratified by histology and BED (≥122 Gy10 vs <122 Gy10). Univariable and multivariable analyses identified characteristics predictive of OS. Cox proportional hazard ratios with inverse probability weighting (IPW) were used to mitigate indication bias between the two dose arms. RESULTS: Ultimately 11,084 ES-NSCLC patients with either ADC (n = 6476) or SCC (n = 4608) were eligible for analysis. Calculated optimal BED threshold for both SCC and ADC was 122 Gy10. Univariable analysis demonstrated a median (36 months vs 32 months), 3-year (51% vs 43%), and 5-year (27% vs 22%) OS advantage in SCC patients receiving BED escalation ≥122 Gy10 (p = 0.002). No survival difference was observed in the ADC dose escalation arm (p = 0.650). BED escalation ≥122 Gy10 remained an independent predictor of improved survival on IPW multivariable comparison (p < 0.0001). CONCLUSION: Escalation of BED ≥ 122 Gy10 was an independent prognosticator of improved survival in patients with SCC of the lung post-SABR. No survival benefit was observed for ADC, suggesting a differential response to BED escalation.

The role of adjuvant therapy for atypical bronchopulmonary carcinoids.

BACKGROUND: Atypical bronchopulmonary carcinoid tumors are rare but carry high recurrence rates following resection. The role of adjuvant therapy remains unclear owing to a lack of high-volume data. To address this knowledge gap, we examined predictors of adjuvant therapy and effects on outcome. METHODS: We queried the National Cancer Database for patients with resected stage I-III atypical carcinoid. Adjuvant therapy was defined as chest radiation, chemotherapy, or a combination thereof. Multivariable logistic regression identified predictors of adjuvant therapy. Multivariable Cox regression evaluated predictors of survival. Propensity matching accounted for indication biases. RESULTS: Overall, 533 stage I/II and 129 stage III patients were identified. Predictors for adjuvant therapy in stage I/II disease were stage II, positive margins, lymph node ratio (LNR) of 1-25%, and more remote year of treatment. Predictors for adjuvant therapy in stage III were female gender and LNR of 26-50%. Median overall survival in stage I/II and III was 116 months and 61 months, respectively. Predictors for survival in stage I/II were age, margins, comorbidity score, and LNR; factors for stage III disease were LNR and more remote year of treatment. Delivery of adjuvant therapy was not independently associated with survival in either stage I/II or III patients. Furthermore, propensity matched analysis did not reveal a benefit to adjuvant therapy. CONCLUSIONS: This study shows no clear survival benefit with adjuvant radiotherapy and/or chemotherapy, even in stage III disease. Although this implies that adjuvant therapy should not be routinely delivered, individualized judgment is still recommended.