A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Patients With Esophageal Adenocarcinoma.

OBJECTIVE: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC). BACKGROUND: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC. METHODS: Serum SMRP and tumoral mesothelin expression from 101 patients with locally advanced esophageal ADC were analyzed before induction chemoradiation (pretreatment) and at the time of resection (posttreatment), as a biomarker for treatment response, disease recurrence, and overall survival (OS). RESULTS: Pre and posttreatment serum SMRP was ≥1 nM in 49% and 53%, and pre and post-treatment tumor mesothelin expression was >25% in 35% and 46% of patients, respectively. Pretreatment serum SMRP was not significantly associated with tumor stage ( P = 0.9), treatment response (radiologic response, P = 0.4; pathologic response, P = 0.7), or recurrence ( P =0.229). Pretreatment tumor mesothelin expression was associated with OS (hazard ratio: 2.08; 95% CI: 1.14-3.79; P = 0.017) but had no statistically significant association with recurrence ( P = 0.9). Three-year OS of patients with pretreatment tumor mesothelin expression of ≤25% was 78% (95% CI: 68%-89%), compared with 49% (95% CI: 35%-70%) among those with >25%. CONCLUSIONS: Pretreatment tumor mesothelin expression is prognostic of OS for patients with locally advanced esophageal ADC, whereas serum SMRP is not a reliable biomarker for monitoring treatment response or recurrence.

The Case of the Vanishing Vessel Loop: Unrecognized Removal Via Laparoscopic Suction Device.

Although the incidence rate of retained surgical items is low, it remains an important cause of patient injury and can lead to harm, death, and waste of time and resources when looking for the missing item. Perioperative counting of equipment is a common method to identify missing surgical items. We present a rare case report of a missing vessel loop that was suctioned by a suction irrigator device. The diagnosis of a retained surgical item is extremely important; special attention should be paid when suctioning body liquids with small surgical items nearby, to prevent incidences of missing items after the surgery.

Major modifications to minimize thoracic esophago-gastric leak and eradicate esophageal stricture after Ivor Lewis esophagectomy.

BACKGROUND: The Ivor Lewis esophagectomy (ILE) remains the procedure of choice for localized middle or lower esophageal carcinoma. Nevertheless, anastomotic leak remains a common complication with rates from 3% to 25% and a stricture rate as high as 40%. The frequency of these complications suggests that the procedure itself may have inherent limitations including the use of potentially ischemic tissue for the esophagogastric anastomosis. We introduce a modified technique that reduces operative steps, preserves blood supply, and uses a modified esophagogastric anastomosis. METHODS: All consecutive patients undergoing ILE with the described modified technique were identified. An esophagram was performed on postoperative day six or seven. To ensure that all cases were identified, anastomotic leaks were defined as any radiographic evidence of contrast extravasation. RESULTS: A total of 110 patients underwent the modified esophagectomy with 2 anastomotic leaks (1.82%) and zero strictures. There was 1 late death but no early deaths (<30 or 90 days) or early re-admissions (<30 days). The average number of risk factors was 2.12, and 98 patients (90%) had at least 1 risk factor in their medical history. CONCLUSIONS: The modifications proposed simplify procedural steps, limit unnecessary dissection and introduce a technique that ends the practice of connecting ischemic tissue. We believe this technique contributes to surgical durability and reduces the rate of postoperative leak and eliminates stricture.

Two-Year Quality of Life Outcomes After Robotic-Assisted Minimally Invasive and Open Esophagectomy.

BACKGROUND: Robotic-assisted minimally invasive esophagectomy (RAMIE) is a safe alternative to open esophagectomy (OE). However, differences in quality of life (QOL) after these procedures remain unclear. We previously reported short-term QOL outcomes after RAMIE and OE and describe here our results from 2 years of follow-up. METHODS: We conducted a prospective, nonrandomized trial of patients with esophageal cancer undergoing transthoracic resection by RAMIE or OE at a single institution. The primary outcomes were patient-reported QOL, measured by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E), and pain, measured by the Brief Pain Inventory (BPI). Generalized linear models were used to assess the relationship between QOL outcomes and surgery cohort. P values were adjusted (P-adj) within each model using the false discovery rate correction. RESULTS: Esophagectomy was performed in 170 patients (106 OE and 64 RAMIE). The groups did not differ significantly by any measured clinicopathologic variables. After covariates were controlled for, FACT-E scores were higher in the RAMIE cohort than in the OE cohort (parameter estimate [PE], 6.13; P-adj = .051). RAMIE was associated with higher esophageal cancer subscale (PE, 2.72; P-adj = .022) and emotional well-being (PE, 1.25; P-adj = .016) scores. BPI pain severity scores were lower in the RAMIE cohort than in the OE cohort (PE, -0.56; P-adj = .005), but pain interference scores did not differ significantly between groups (P-adj = .11). CONCLUSIONS: During 2 years of follow-up, RAMIE was associated with improved patient-reported QOL, including esophageal symptoms, emotional well-being, and decreased pain, compared with OE.

Lean Lobectomy: Streamlining Video-Assisted Lobectomy to Increase the Value of Lung Cancer Care.

PURPOSE: A review of the outcomes of patients who received our video-assisted thoracic surgery (VATS) lung lobectomy in 2015 revealed long lengths of stay, inefficient care transitions, and overuse of resources. Focused process redesign offers a proven method for instituting improvement and changes in health care. We sought to use systems process improvement to streamline VATS lobectomies at our institution, and we targeted cost drivers to optimize quality of care and minimize overuse of resources. METHODS: We performed a retrospective review of perioperative practices between January 2015 and March 2016 for patients undergoing VATS lobectomy that helped establish a value stream map, used a granular cost database, and performed real-time analysis. We used an outcomes database, which allowed us to identify cost drivers, practice variability, and rent seeking. We implemented process redesign with constant review and formal value stream reanalysis at 6-month intervals over a 2-year period. RESULTS: We ultimately experienced an overall 187% reduction of time in the operating room (297 v 159 minutes). Our process redesign also resulted in significantly fewer chest x-rays per patient (mean, 6.7 v 2), laboratory draws (100% v 5.7%), and consultations (100% v 5.7%), which resulted in a 234% reduction in mean length of stay (4.4 v 1.88 days) and an overall cost reduction of 40%. These changes did not have a detrimental effect on patient outcomes: pulmonary complications (16.9% v 8.6%), cardiac complications (13.2% v 8.6%), and readmission rates (13.6% v 2.9%) all decreased. CONCLUSION: By using value stream analysis and process redesign methodologies, closely paired with highly granular cost and outcomes data, we were able to achieve significant improvements in patient outcomes and use of resources.

A prospective trial of intraoperative tissue oxygenation measurement and its association with anastomotic leak rate after Ivor Lewis esophagectomy.

BACKGROUND: Anastomotic leak following Ivor Lewis esophagectomy is associated with increased morbidity/mortality and decreased survival. Tissue oxygenation at the anastomotic site may influence anastomotic leak. Methods for establishing tissue oxygenation at the anastomotic site are lacking. METHODS: Over a 2-year study period, 185 Ivor Lewis esophagectomies were performed. Study participants underwent measurement of gastric conduit tissue oxygenation at the planned anastomotic site using the wireless pulse oximetry device. Associations between anastomotic leaks or strictures and tissue oxygenation levels were analyzed using Wilcoxon rank sum test or Fisher's exact test. RESULTS: Among study participants (n=114), median gastric conduit tissue oxygenation level was 92% (range, 62-100%). There were 8 (7.0%) anastomotic leaks and 3 (2.6%) strictures. Analysis of tissue oxygenation as a continuous variable showed no difference in median tissue oxygenation in patients with and without leaks (98% and 92%; P=0.2) and stricture formation (89% and 92%; P=0.6). Analysis of tissue oxygenation as a dichotomous variable found no difference in anastomotic leak rates [7.5% (n=93) in >80% vs. 0% (n=20) in ≤80%; P=0.3]. There were no significant differences in leak rates in concurrent study nonparticipants. CONCLUSIONS: No significant association was observed between intraoperative tissue oxygenation at the anastomotic site and subsequent anastomotic leak or stricture formation among patients undergoing Ivor Lewis esophagectomy.

Early Quality of Life Outcomes After Robotic-Assisted Minimally Invasive and Open Esophagectomy.

BACKGROUND: Minimally invasive esophagectomy may improve some perioperative outcomes over open approaches; effects on quality of life are less clear. METHODS: A prospective trial of robotic-assisted minimally invasive esophagectomy (RAMIE) and open esophagectomy was initiated, measuring quality of life via the Functional Assessment of Cancer Therapy-Esophageal and Brief Pain Inventory. Mixed generalized linear models assessed associations between quality of life scores over time and by surgery type. RESULTS: In total, 106 patients underwent open esophagectomy; 64 underwent minimally invasive esophagectomy (98% RAMIE). The groups did not differ in age, sex, comorbidities, histologic subtype, stage, or induction treatment (P = .42 to P > .95). Total Functional Assessment of Cancer Therapy-Esophageal scores were lower at 1 month (P < .001), returned to near baseline by 4 months, and did not differ between groups (P = .83). Brief Pain Inventory average pain severity (P = .007) and interference (P = .004) were lower for RAMIE. RAMIE had lower estimated blood loss (250 vs 350 cm3; P < .001), shorter length of stay (9 vs 11 days; P < .001), fewer intensive care unit admissions (8% vs 20%; P = .033), more lymph nodes harvested (25 vs 22; P = .05), and longer surgical time (6.4 vs 5.4 hours; P < .001). Major complications (39% for RAMIE vs 52% for open esophagectomy; P > .95), anastomotic leak (3% vs 9%; P = .41), and 90-day mortality (2% vs 4%; P = .85) did not differ between groups. Pulmonary (14% vs 34%; P = .014) and infectious (17% vs 36%; P = .029) complications were lower for RAMIE. CONCLUSIONS: RAMIE is associated with lower immediate postoperative pain severity and interference and decreased pulmonary and infectious complications. Ongoing data accrual will assess mid-term and long-term outcomes in this cohort.

Multi-dimensional analysis of oral cavity and oropharyngeal defects following cancer extirpation surgery, a cadaveric study.

BACKGROUND: Defects following resection of tumors in the head and neck region are complex; more detailed and defect-specific reconstruction would likely result in better functional and cosmetic outcomes. The objectives of our study were: 1) to improve the understanding of the two- and three-dimensional nature of oral cavity and oropharyngeal defects following oncological resection and 2) to assess the geometric dimensions and the shapes of fasciocutaneous free flaps and locoregional tissue flaps required for reconstruction of these defects. METHODS: This study was an anatomic cadaveric study which involved creating defects in the oral cavity and oropharynx in two cadaveric specimens. Specifically, partial and total glossectomies, floor of mouth excisions, and base of tongue excisions were carried out. These subsites were subsequently geometrically analyzed and their volumes measured. The two-dimensional (2D) assessment of these three-dimensional (3D) structures included measures of surface area and assessment of tissue contours and shapes. RESULTS: The resected specimens all demonstrated unique dimensional geometry for the various anatomic sites. Using 2D analysis, hemiglossectomy defects revealed right triangle geometry, whereas total glossectomy geometry was a square. Finally, the base of tongue defects exhibited a trapezoid shape. CONCLUSIONS: Customizing the geometry and dimensions of fasciocutaneous free flaps so that they are specific to the confronted head and neck defects will likely result in better functional and cosmetic outcomes.

Post-Treatment/Pre-operative PET Response Is Not an Independent Predictor of Outcomes for Patients With Gastric and GEJ Adenocarcinoma.

OBJECTIVE: To determine whether changes in positron emission tomography (PET) avidity correlated with histologic response and were independently associated with outcome. BACKGROUND: The implications of metabolic response to neoadjuvant therapy as measured by repeat PET imaging remain ill-defined for patients with gastric and gastroesophageal junction (GEJ) cancers. METHODS: We identified patients with gastric and GEJ adenocarcinoma who were evaluated with PET imaging before and following neoadjuvant treatment, and subsequently underwent curative resections. Spearman rank correlation and Cox proportional hazards regression were used to evaluate standardized uptake value (SUV) and histologic response, pathologic parameters, and disease-specific survival (DSS). RESULTS: From 2002 to 2013, 192 patients met our inclusion criteria. The median SUVmax response was 57.3% (range: -110% to 100%) for patients with GEJ cancers, with a corresponding median pathologic treatment response of 80% (range: 0% to 100%). The median SUVmax response was 32.5% (-230% to 100%) for patients with gastric cancers, with a corresponding median pathologic treatment response of 35% (range: 0% to 100%). The Spearman correlation between SUVmax response and histologic response was significant for patients with GEJ (rho = 0.19, P = 0.04) and gastric (rho = 0.44, P < 0.0001) cancers. For patients with GEJ (P <0.0001 to 0.046) and gastric cancers (P = 0.0003 to 0.016), histopathologic response and tumor staging predicted DSS. SUVmax response failed to demonstrate a relationship with DSS when entered into multivariable models containing conventional pathologic variables. CONCLUSION: Following completion of neoadjuvant therapy for gastric and GEJ adenocarcinoma, histopathologic staging remains the best predictor of outcome. Repeat post-treatment/preoperative PET imaging for the purpose of prognostication is of limited value.

Preservation of replaced left hepatic artery during robotic-assisted minimally invasive esophagectomy: A case series.

OBJECTIVE: Finding of a significant replaced left hepatic artery (RLHA) during esophagectomy is relatively rare, with an incidence of approximately 5%. Sparing of the artery may be required to avoid complications of liver ischemia. Robotic assistance during esophagectomy may provide a technically superior method of artery preservation with minimally invasive approaches. METHODS: This is a retrospective case series of patients undergoing robotic-assisted minimally invasive esophagectomy (RAMIE) identified to have a significant RLHA at time of surgery. RESULTS: Five patients with a significant RLHA were identified from a series of over 100 RAMIE operations. Preservation of RLHA was accomplished in all cases without need for conversion, no intra-operative complications, and no post-operative liver dysfunction. The stomach was suitable and used for conduit reconstruction in all patients. CONCLUSIONS: Sparing of the RLHA during RAMIE is feasible and effective. The robotic assisted approach may obviate the need for open conversion during these complex minimally invasive operations.

Incidence of occult pN2 disease following resection and mediastinal lymph node dissection in clinical stage I lung cancer patients.

Objectives: Early clinical stage (T1 and T2) non-small cell lung cancer (NSCLC) is commonly treated with anatomic lung resection and lymph node sampling or dissection. The aims of this study were to evaluate the incidence and the distribution of occult N2 disease according to tumour location and the short- and long-term outcomes. Methods: We performed a retrospective review of patients with clinical stage I NSCLC who underwent anatomic lung resection and lymphadenectomy. Mediastinal lymphadenectomy (ML) was defined as resection of at least 2 mediastinal stations, always including station 7 lymph nodes. Patients who had a lobe-specific lymphadenectomy were excluded. Results: One thousand six hundred and sixty-seven consecutive patients met inclusion criteria and were included. Overall, 9% (146/1667) of the patients had occult pN2 disease. At multivariable analysis, adenocarcinoma histology and vascular invasion were independently associated with greater risk of occult pN2 disease. In left and right upper lobe tumours, station 7 nodes were involved in 5 and 13% of pN2 positive cases, respectively. Station 5 and station 2/4 nodes were involved in 29 and 18% of left and right lower lobe pN2 tumours, respectively. There was no postoperative mortality, and postoperative morbidity was 28%. The median overall survival was 77.4 months. N0 patients had a median overall survival of 83.7 months vs 48.0 months and 37.9 months in N1 and N2 populations, respectively ( P < 0.001). Conclusions: Sixteen percent of pN2 patients had mediastinal lymph node metastasis beyond the lobe-specific lymphatic drainage. We recommend a complete lymphadenectomy be performed, even in clinical stage I NSCLC.

Long-term Survival Based on the Surgical Approach to Lobectomy For Clinical Stage I Nonsmall Cell Lung Cancer: Comparison of Robotic, Video-assisted Thoracic Surgery, and Thoracotomy Lobectomy.

OBJECTIVE: To compare the long-term outcomes among robotic, video-assisted thoracic surgery (VATS), and open lobectomy in stage I nonsmall cell lung cancer (NSCLC). BACKGROUND: Survival comparisons between robotic, VATS, and open lobectomy in NSCLC have not yet been reported. Some studies have suggested that survival after VATS is superior, for unclear reasons. METHODS: Three cohorts (robotic, VATS, and open) of clinical stage I NSCLC patients were matched by propensity score and compared to assess overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed to identify factors associated with the outcomes. RESULTS: From January 2002 to December 2012, 470 unique patients (172 robotic, 141 VATS, and 157 open) were included in the analysis. The robotic approach harvested a higher number of median stations of lymph nodes (5 for robotic vs 3 for VATS vs 4 for open; P < 0.001). Patients undergoing minimally invasive approaches had shorter median length of hospital stay (4 d for robotic vs 4 d for VATS vs 5 d for open; P < 0.001). The 5-year OS for the robotic, VATS, and open matched groups were 77.6%, 73.5%, and 77.9%, respectively, without a statistically significant difference; corresponding 5-year DFS were 72.7%, 65.5%, and 69.0%, respectively, with a statistically significant difference between the robotic and VATS groups (P = 0.047). However, multivariate analysis found that surgical approach was not independently associated with shorter OS and DFS. CONCLUSIONS: Minimally invasive approaches to lobectomy for clinical stage I NSCLC result in similar long-term survival as thoracotomy. Use of VATS and robotics is associated with shorter length of stay, and the robotic approach resulted in greater lymph node assessment.

Early operative outcomes and learning curve of robotic assisted giant paraesophageal hernia repair.

BACKGROUND: We have previously described our technique of robotic-assisted giant paraesophageal hernia repair (RA-GPEHR). The purpose of this study was to report our initial experience, early outcomes and learning curve with RA-GPEHR using a four-arm robotic platform. METHODS: 24 consecutive patients presenting with symptomatic giant paraesophageal hernias (GPEH) underwent RA-GPEHR from April 2011 to February 2014. Peri-operative data and short-term patient outcomes were assessed by retrospective review of a prospectively maintained database. RESULTS: Median age was 62 years (range 44-84). 15 (63%) patients underwent fundoplication and 9 (37%) gastropexy. Median procedure time was 277 min (range: 185-485) and decreased steadily over the experience. There were no intra-operative complications or surgical mortality. No patients experienced dysphagia in the early post-operative period. CONCLUSIONS: RA-GPEHR is safe, with reported short-term operative and functional outcomes similar to conventional laparoscopic approaches. The initial learning curve appears relatively short for experienced minimally invasive esophageal surgeons. Copyright © 2016 John Wiley & Sons, Ltd.

Unusual late presentation of metastatic extrathoracic thymoma to gastrohepatic lymph node treated by surgical resection.

In advanced stages, thymic tumors tend to spread locally. Distant metastatic disease is rare. We present the first report of single metastatic abdominal lymph node in a 37-year-old female patient and 5 years after an extrapleural pneumonectomy for stage IV thymoma followed by radiotherapy with no other evidence of abdominal disease successfully treated by robotic surgical resection.

Attaining Proficiency in Robotic-Assisted Minimally Invasive Esophagectomy While Maximizing Safety During Procedure Development.

OBJECTIVE: Robotic-assisted minimally invasive esophagectomy (RAMIE) is an emerging complex operation with limited reports detailing morbidity, mortality, and requirements for attaining proficiency. Our objective was to develop a standardized RAMIE technique, evaluate procedure safety, and assess outcomes using a dedicated operative team and 2-surgeon approach. METHODS: We conducted a study of sequential patients undergoing RAMIE from January 25, 2011, to May 5, 2014. Intermedian demographics and perioperative data were compared between sequential halves of the experience using the Wilcoxon rank sum test and the Fischer exact test. Median operative time was tracked over successive 15-patient cohorts. RESULTS: One hundred of 313 esophageal resections performed at our institution underwent RAMIE during the study period. A dedicated team including 2 attending surgeons and uniform anesthesia and OR staff was established. There were no significant differences in age, sex, histology, stage, induction therapy, or risk class between the 2 halves of the study. Estimated blood loss, conversions, operative times, and overall complications significantly decreased. The median resected lymph nodes increased but was not statistically significant. Median operative time decreased to approximately 370 minutes between the 30th and the 45th cases. There were no emergent intraoperative complications, and the anastomotic leak rate was 6% (6/100). The 30-day mortality was 0% (0/100), and the 90-day mortality was 1% (1/100). CONCLUSIONS: Excellent perioperative and short-term patient outcomes with minimal mortality can be achieved using a standardized RAMIE procedure and a dedicated team approach. The structured process described may serve as a model to maximize patients' safety during development and assessment of complex novel procedures.

Use of positron emission tomography scan response to guide treatment change for locally advanced gastric cancer: the Memorial Sloan Kettering Cancer Center experience.

BACKGROUND: Early metabolic response on 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) during neoadjuvant chemotherapy is PET non-responders have poor outcomes whether continuing chemotherapy or proceeding directly to surgery. Use of PET may identify early treatment failure, sparing patients from inactive therapy and allowing for crossover to alternative therapies. We examined the effectiveness of PET directed switching to salvage chemotherapy in the PET non-responders. METHODS: Patients with locally advanced resectable FDG-avid gastric or gastroesophageal junction (GEJ) adenocarcinoma received bevacizumab 15 mg/kg, epirubicin 50 mg/m(2), cisplatin 60 mg/m(2) day 1, and capecitabine 625 mg/m(2) bid (ECX) every 21 days. PET scan was obtained at baseline and after cycle 1. PET responders, (i.e., ≥35% reduction in FDG uptake at the primary tumor) continued ECX + bev. Non-responders switched to docetaxel 30 mg/m(2), irinotecan 50 mg/mg(2) day 1 and 8 plus bevacizumab every 21 days for 2 cycles. Patients then underwent surgery. The primary objective was to improve the 2-year disease free survival (DFS) from 30% (historical control) to 53% in the non-responders. RESULTS: Twenty evaluable patients enrolled before the study closed for poor accrual. Eleven were PET responders and the 9 non-responders switched to the salvage regimen. With a median follow-up of 38.2 months, the 2-year DFS was 55% [95% confidence interval (CI), 30-85%] in responders compared with 56% in the non-responder group (95% CI, 20-80%, P=0.93). CONCLUSIONS: The results suggest that changing chemotherapy regimens in PET non-responding patients may improve outcomes. Results from this pilot trial are hypothesis generating and suggest that PET directed neoadjuvant therapy merits evaluation in a larger trial.

Detection of Recurrence Patterns After Wedge Resection for Early Stage Lung Cancer: Rationale for Radiologic Follow-Up.

BACKGROUND: Wedge resection for selected patients with early stage non-small cell lung cancer is considered to be a valid treatment option. The aim of this study was to evaluate the recurrence patterns after wedge resection, to analyze the survival of patients under routine follow-up, and to recommend a follow-up regimen. METHODS: A retrospective analysis was done of 446 consecutive patients between May 2000 and December 2012 who underwent a wedge resection for clinical stage I non-small cell lung cancer. All patients were followed up with a computed tomography scan with or without contrast. The recurrence was recorded as local (involving the same lobe of wedge resection), regional (involving mediastinal or hilar lymph nodes or a different lobe), or distant (including distant metastasis and pleural disease). RESULTS: Median follow-up for survivors (n = 283) was 44.6 months. In all, 163 patients died; median overall survival was 82.6 months. Thirty-six patients were diagnosed with new primary non-small cell lung cancer, and 152 with recurrence (79 local, 45 regional, and 28 distant). There was no difference in the incidence of recurrence detection detected by computed tomography scans with versus without contrast (p = 0.18). The cumulative incidence of local recurrences at 1, 2, and 3 years was higher than the cumulative incidence for local, regional, and distant recurrences: 5.2%, 11.1%, and 14.9% versus 3.7%, 6.6%, and 9.5% versus 2.3%, 4.7%, and 6.4%, respectively. Primary tumor diameter was associated with local recurrence in univariate analysis. CONCLUSIONS: Wedge resection for early stage non-small cell lung cancer is associated with a significant risk for local and regional recurrence. Long-term follow-up using noncontrast computed tomography scans at consistent intervals is appropriate to monitor for these recurrences.

Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma.

BACKGROUND: A standard-of-care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is pre-operative chemoradiation. Elevated levels of vascular endothelial growth factor (VEGF) have been associated with worse outcomes following chemoradiation and anti-VEGF therapies can potentiate radiation efficacy. METHODS: In this single-arm phase II study, we added bevacizumab to induction chemotherapy and concurrent chemoradiation with cisplatin/irinotecan for locally advanced esophageal and GEJ adenocarcinomas. RESULTS: Thirty-three patients were enrolled, with all evaluable. All tumors involved the GEJ and 67% were node-positive by endoscopic ultrasound (EUS) and imaging. Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic complete response (pCR) rate was 15%. Median progression-free survival (PFS) and overall survival (OS) were 15.1 and 30.5 months respectively. Higher baseline VEGF-A levels were associated with a trend toward improved OS (not reached vs. 21.0 months, P=0.11). Response on positron emission tomography (PET) scan after induction chemotherapy was predictive of PFS and showed trends toward improved OS and pCR rate. CONCLUSIONS: The addition of bevacizumab to chemoradiation was not associated with clear worsening of toxicities but also led to no improvement in outcomes, when compared to a prior phase II study of 55 patients. Higher baseline VEGF-A levels correlated with a trend toward improved survival and might be used to stratify or select patients for future studies incorporating this or similar agents. PET scan to assess response following induction chemotherapy and change chemotherapy in non-responders during chemoradiation is the subject of a fully-accrued national trial (NCT01333033).

Postinduction positron emission tomography assessment of N2 nodes is not associated with ypN2 disease or overall survival in stage IIIA non-small cell lung cancer.

OBJECTIVE: Induction therapy is often recommended for patients with clinical stage IIIA-N2 (cIIIA/pN2) lung cancer. We examined whether postinduction positron emission tomography (PET) scans were associated with ypN2 disease and survival of patients with cIIIA/pN2 disease. METHODS: We performed a retrospective review of a prospectively maintained database to identify patients with cIIIA/pN2 non-small cell lung cancer treated with induction chemotherapy followed by surgery between January 2007 and December 2012. The primary aim was the association between postinduction PET avidity and ypN2 status; the secondary aims were overall survival, disease-free survival, and recurrence. RESULTS: Persistent pathologic N2 disease was present in 61% of patients (61 out of 100). PET N2-negative disease increased from 7% (6 out of 92) before induction therapy to 47% (36 out of 77) afterward. The sensitivity, specificity, and accuracy of postinduction PET for identification of ypN2 disease were 59%, 55%, and 57%, respectively. Logistic regression analysis indicated that postinduction PET N2 status was not associated with ypN2 disease. Of the 39 patients with both pre- and postinduction PET N2-avidity, 25 (64%) had ypN2 disease. The 5-year overall survival was 40% for ypN2 disease versus 38% for N2-persistent disease (P = .936); the 5-year overall survival was 43% for postinduction PET N2-negative disease versus 39% for N2-avid disease (P = .251). The 5-year disease-free survival was 34% for ypN2-negative disease versus 9% for N2-persistent disease (P = .079). CONCLUSIONS: Postinduction PET avidity for N2 nodes is not associated with ypN2 disease, overall survival, or disease-free survival in patients undergoing induction chemotherapy for stage IIIA/pN2 disease.