Neoadjuvant Therapy Vs Upfront Surgery for Clinical T2N0 Esophageal Cancer: A Systematic Review.

BACKGROUND: The optimal approach to clinical T2N0 (cT2N0) esophageal cancer is unclear. Our objective is to perform a systematic review investigating whether neoadjuvant therapy results in better outcomes compared with upfront surgery in cT2N0 esophageal cancer. METHODS: We performed a systematic review and meta-analysis of randomized and nonrandomized studies (1995 to 2017) comparing use of neoadjuvant therapy with upfront surgery in the treatment of cT2N0 esophageal cancer. Independent and duplicate assessment was used. All meta-analytical techniques were performed in RevMan 5.3. RESULTS: Nine cohort studies, including 5433 patients, were included for meta-analysis. Use of neoadjuvant therapy was associated with significantly higher complete resection rates compared with upfront surgery (risk ratio, 0.67; 95% confidence interval, 0.55 to 0.81; P < .001). There was no difference in 5-year overall or recurrence-free survival. There were no significant differences in perioperative mortality as well as perioperative complications, although meta-analysis results are limited by inconsistent reporting of such complications. Lymphovascular invasion and larger tumor size were significant predictors of upstaging. Four of the studies were at high risk of bias. The remaining 5 studies were larger and more robust but were assessed as being of uncertain risk of bias. CONCLUSIONS: Use of neoadjuvant therapy was associated with significantly higher complete resection rates compared with upfront surgery although this did not translate to differences in survival outcomes. No differences in perioperative morbidity or mortality were identified. Based on qualitative systematic review, lymphovascular invasion and larger tumor size are potential factors for helping to select those patients who may benefit from neoadjuvant therapy.

Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial.

Purpose The efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC. Patients and Methods From June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m2 intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m2 IV day 1, or 25 mg/m2 IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival. Results The pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P < .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S ( P = .212). Conclusion This trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.

The Use of Standardized Measures to Predict and Assess Quality of Life after Laparoscopic Hiatal Hernia Repair.

The literature regarding laparoscopic hiatal hernia repair is difficult to interpret because of inconsistencies in describing hernia characteristics and outcome measures. This study was performed to evaluate risk factors for an unsatisfactory outcome after repair using objective definitions of hernia size and a clinically relevant outcome instrument. A retrospective review of a prospectively maintained database was conducted over a seven-year period. Data collected included patient demographics and hernia-related variables. Outcomes were defined using a validated quality of life (QOL) instrument. Postoperatively, the mean total QOL score decreased from 22.9 to 5.8 (P < 0.001). In all, 13.8 per cent of patients had unsatisfactory QOL scores postoperatively. Multivariate analysis showed that high gastroesophageal (GE) junction position (P = 0.03) and female gender (P = 0.02) were the only significant factors associated with an unsatisfactory postoperative QOL. Laparoscopic hiatal hernia repair significantly improves QOL. With respect to predicting clinically relevant outcomes, hernias are best characterized by the position of the GE junction. Females with high GE junction position are at the highest risk for an unsatisfactory outcome.

Positron Emission Tomography in Thymic Tumors: Analysis Using a Prospective Research Database.

BACKGROUND: Positron emission tomography may have a role in the pretreatment workup of patients with thymic malignancies. This study was undertaken to determine the utility of the maximum standardized uptake value (SUVmax) in predicting histologic type and tumor stage in a large cohort of thymic epithelial tumors. METHODS: The large, multiinstitutional, prospective database of The International Thymic Malignancy Interest Group (ITMIG) was queried for the use of positron emission tomography in the pretreatment workup of patients with thymic tumors. Data analyzed included demographics, SUVmax, histologic tumor type, and tumor stage. The distribution of SUVmax according to histologic type and Masaoka-Koga pathologic stage was determined, and the ability of SUVmax to predict these two variables was calculated using analysis of receiver operating characteristic curves. RESULTS: Since 2012, data from 926 patients with thymic malignancies were entered into the ITMIG prospective database, of which 154 had a reported value for SUVmax. The area under the receiver operating characteristic curve for SUVmax in predicting histologic type and pathologic stage was 0.79 (95% confidence interval, 0.70 to 0.88; p < 0.001) and 0.81 (95% confidence interval, 0.73 to 0.88; p < 0.001), respectively. In addition, there was a significant relationship between SUVmax and histologic type (p < 0.001) as well as Masaoka-Koga pathologic stage (p < 0.001). CONCLUSIONS: Positron emission tomography has utility in predicting clinicopathologic features of thymic malignancies. These results may have clinical application in the pretreatment workup of patients with these rare tumors.

Postoperative Radiation Therapy Is Associated with Longer Overall Survival in Completely Resected Stage II and III Thymoma-An Analysis of the International Thymic Malignancies Interest Group Retrospective Database.

OBJECTIVES: The aim of this study was to determine whether postoperative radiation therapy (PORT) is associated with an overall survival (OS) benefit in patients with completely resected Masaoka or Masaoka-Koga stage II and III thymoma. METHODS: All patients with completely resected (R0) stage II or III thymoma were identified in a large database of the International Thymic Malignancy Interest Group. Clinical, pathologic, treatment, and follow-up information were extracted. OS was the primary end point. A univariate analysis using the log-rank test was performed, and a multivariate Cox model was created to identify factors associated with OS. RESULTS: Of 1263 patients meeting the selection criteria, 870 (69%) had stage II thymoma. The WHO histologic subtype was A/AB in 360 patients (30%) and B1/B2/B3 in 827 (70%). PORT was given to 55% of patients (n = 689), 15% (n = 180) received chemotherapy, and 10% (n = 122) received both. The 5- and 10-year OS rates for patients having undergone an operation plus PORT were 95% and 86%, respectively, compared with 90% and 79% for patients receiving an operation alone (p = 0.002). This OS benefit remained significant when patients with stage II (p = 0.02) and stage III thymoma (p = 0.0005) were analyzed separately. On multivariate analysis, earlier stage, younger age, absence of paraneoplastic syndrome, and PORT were significantly associated with improved OS. CONCLUSIONS: We observed an OS benefit with the use of PORT in completely resected stage II and III thymoma. In the absence of a randomized trial, this represents the most comprehensive analysis of individual patient data and strong evidence in favor of PORT in this patient population.

Successful Treatment of an Iatrogenic Tracheal Laceration With a Temporary Polyurethane-Coated Nitinol Stent.

We report the case of a 63-year-old woman who required emergent intubation after a choking episode at home. It resulted in a 5-cm tear in the membranous trachea. She was treated by placement of a temporary tracheal stent, which was successfully removed 3 months later.

AKAP4 is a circulating biomarker for non-small cell lung cancer.

Cancer testis antigens (CTAs) are widely expressed in tumor tissues, circulating tumor cells (CTCs) and in cancer derived exosomes that are frequently engulfed by lymphoid cells. To determine whether tumor derived CTA mRNAs could be detected in RNA from purified peripheral blood mononuclear cells (PBMC) of non-small cell lung cancer (NSCLC) patients, we assayed for the expression of 116 CTAs in PBMC RNA in a discovery set and identified AKAP4 as a potential NSCLC biomarker. We validated AKAP4 as a highly accurate biomarker in a cohort of 264 NSCLCs and 135 controls from 2 different sites including a subset of controls with high risk lung nodules. When all (264) lung cancers were compared with all (135) controls the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers are compared with all controls the AUC is 0.9795 and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules, a comparison of significant clinical importance, the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage, but independent of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer.

Nodal Upstaging in Robotic and Video Assisted Thoracic Surgery Lobectomy for Clinical N0 Lung Cancer.

BACKGROUND: Recent multiinstitutional published data have demonstrated increased pathologic nodal upstaging by robotic lobectomy compared with historical video-assisted thoracic surgery (VATS) lobectomy data. To eliminate potential variability from multiple surgical techniques, we compared the rate of nodal upstaging at a single institution where robotic and VATS lobectomy are both performed. METHODS: We retrospectively reviewed clinically node-negative patients with lung cancer undergoing VATS or robotic lobectomy. Clinical data were recorded in concordance with The Society of Thoracic Surgeons database elements. The rates of pathologic nodal upstaging as well as disease-free and overall survival were calculated. RESULTS: A total of 211 patients underwent anatomic lobectomy by VATS (n = 158) or robotics (n = 53) from 2009 to 2014. The two groups were statistically similar in their clinical stage, tumor size, location, and histologic evaluation. Within the VATS group, 24 patients experienced nodal upstaging (15.2%), with 13 patients having pN1 disease, and 11 patients having pN2 disease. The robotics group contained 7 patients (13.2%) with nodal upstaging, with 5 patients exhibiting pN1 disease and 2 patients with pN2 disease. When VATS and robotics were compared, there was no significant difference in pathologic upstaging (p = 0.72), 2-year overall survival (88% vs 95%, respectively; p = 0.40), or 2-year disease-free survival (83% vs 93%, respectively; p = 0.48). CONCLUSIONS: In this comparison of robotic and VATS lobectomy for clinically node-negative lung cancer that was managed with consistent surgical technique and pathologic evaluation, the rate of nodal upstaging achieved by robotics appears similar to VATS. In addition, there were no appreciable differences in disease-free or overall survival.

A practical guide from the International Thymic Malignancy Interest Group (ITMIG) regarding the radiographic assessment of treatment response of thymic epithelial tumors using modified RECIST criteria.

Measuring tumor response to chemotherapy is important for both clinical decision-making and for multi-institutional studies. Thymoma tends to spread along the pleura: a challenge for accurate tumor measurement. Inaccurate and inconsistent tumor measurements often compromise results from clinical trials that are dependent on identifying response rate and progression-free survival. In this article, we sought to provide a practical guide on how to measure thymoma by the International Thymic Malignancy Interest Group's recommendations for standard outcome measures. The aim of this article is to clarify this measuring technique, lead to consistency between institutions, and minimize intra- and interobserver variability.

Right pneumonectomy for resection of a posterior mediastinal follicular dendritic cell sarcoma arising from Castleman's disease.

Follicular dendritic cell sarcoma is a rare malignant neoplasm of immune accessory follicular dendritic cells and may be associated with Castleman's disease which is a known precursor to follicular dendritic cell sarcomas. We report a case of a follicular dendritic cell sarcoma arising in Castleman's disease in a 63-year-old man who presented with a large posterior mediastinal mass, which required a radical pneumonectomy for complete resection.

Surgical Approaches for Stage IVA Thymic Epithelial Tumors.

Thymic epithelial tumors (TET) are rare mediastinal neoplasms that can metastasize to the pleural space (stage IVA). Complete surgical resection remains the backbone of therapy for patients with early stage TET, however, the role of surgery in the management of patients with stage IVA disease is not fully defined. Published reports in this regard are mainly small, retrospective, and uncontrolled, with unclear inclusion criteria. Surgical options to manage pleural disease include metastasectomy, extrapleural pneumonectomy, and metastasectomy/pleurectomy combined with heated intrapleural chemotherapy. The choice of the most appropriate surgical strategy needs to be individualized according to the quantity and location of disease, the patient's overall condition, as well as operator and institutional expertise. In the majority of cases, metastasectomy of pleural implants will be sufficient to achieve a complete resection. The available literature suggests that in selected patients with stage IVA TET, delivery of neoadjuvant chemotherapy followed by complete resection is a viable treatment option that can be associated with long-term survival.

Transitioning from video-assisted thoracic surgical lobectomy to robotics for lung cancer: are there outcomes advantages?

OBJECTIVES: To determine if there are advantages to transitioning to robotics by a surgeon who is already proficient in performing video-assisted thoracic surgical (VATS) lobectomy. METHODS: A single surgeon proficient in VATS lobectomy initiated a robotic lobectomy program, and a retrospective review was conducted of his patients undergoing minimally invasive lobectomy (robotics or VATS) for lung cancer between 2011 and 2012. Data collected included patient/tumor characteristics, morbidity, mortality, operative times, and length of hospital stay. RESULTS: Over a 24-month period, a total of 69 patients underwent minimally invasive lobectomy (35 robotic, 34 VATS). Patients in each group were similar in age and clinical stage. Robotic upper lobectomy operative times were longer than VATS (172 vs 134 minutes; P = .001), with no significant difference in lower lobectomies noted (140 vs 123 minutes; P = .1). Median length of stay was 3 days in both groups, and the median number of lymph nodes harvested was 18 (robotic) versus 16 (VATS; P = .42). Morbidity and mortality for robotic versus VATS were 11% versus 18% (P = .46) and 0% versus 3% (P = .49), respectively. CONCLUSIONS: There does not seem to be a significant advantage for an established VATS lobectomy surgeon to transition to robotics based on clinical outcomes. The learning curve for robotic upper lobectomies seems to be more significant than that for lower lobectomies.

Neoadjuvant chemoradiotherapy for locally advanced thymic tumors: a phase II, multi-institutional clinical trial.

OBJECTIVE: To determine the response rate, toxicity, and rate of complete resection after induction chemoradiotherapy for locally advanced thymic tumors, which were defined by specific radiographic criteria. METHODS: A single-arm, pilot trial was conducted at 4 institutions. Patients with thymoma or thymic carcinoma who met specific criteria on computed tomography were accrued. Induction therapy consisted of 2 cycles of cisplatin and etoposide combined with 45 Gy of thoracic radiotherapy. Patients underwent computed tomography and positron emission tomography before and after induction therapy and then resection was attempted. Postoperative chemoradiotherapy was administered in selected patients. The primary endpoint was the pathologic response to induction therapy. The secondary endpoints were toxicity, surgical complications, radiographic response, and the rate of R0 resection. RESULTS: A total of 22 patients were accrued during a 5-year period (1 patient withdrew before starting induction therapy). Of the 22 patients, 21 completed induction therapy, and 9 (41%) experienced grade 3 or 4 toxicity. A total of 10 patients had a partial radiographic response and 11 had stable disease. Of the 21 patients, 17 (77%) underwent an R0 resection, 3 (14%) an R1 resection, and 1 (5%) underwent debulking. Eight patients sustained surgical complications (36%), and two patients (9%) died postoperatively. Of the 21 patients, 13 (62%) had either thymic carcinoma or B3 thymoma and 15 (71%) had either Masaoka stage III or IV disease. No patient had a complete pathologic response, but 5 specimens (24%) had <10% viable tumor. CONCLUSIONS: The present induction chemoradiotherapy protocol, which used specific computed tomography inclusion criteria to successfully select locally advanced thymic tumors, appeared to be tolerable and resulted in a high rate of complete surgical resection.

The effect of lung cancer on cytokine expression in peripheral blood mononuclear cells.

The purpose of this study is to evaluate cytokine expression by peripheral blood mononuclear cells (PBMC) from stage I lung cancer patients and to confirm these expression patterns by exposing PBMCs to lung cancer cells in vitro. Five altered cytokines in stage I lung cancer patients (CCL3, IL8, IL1ß, CXCL10, sIL2Rα) were identified in plasma from subjects (n = 15) before and after resection using a 30-plex panel protein assay. Gene expression studies using quantitative RT-qPCR were performed on PBMCs from stage I lung cancer patients (n = 62) before and after resection, and compared to non-cancer patients (n = 32) before and after surgery for benign disease. Co-culture experiments that exposed healthy donor PBMCs to lung cancer cells in vitro were performed to evaluate the effect on PBMC cytokine expression. PBMC gene expression of CCL3, IL8 and IL1ß was higher in lung cancer patients compared to the same patients at each of four sequential timepoints after removal of their tumors, while CXCL10 and IL2Rα were essentially unchanged. This pattern was also detected when lung cancer patients were compared to non-cancer patients. When non-cancer patients underwent surgery for benign diseases, these cytokine expression changes were not demonstrable. Lung cancer cell lines, but not benign bronchial epithelial cells, induced similar changes in cytokine gene and protein expression by healthy donor PBMCs in an in vitro co-culture system. We conclude that PBMCs from stage I lung cancer patients possess distinct cytokine expression patterns compared to both non-cancer patients, and lung cancer patients following tumor removal. These expression patterns are replicated by healthy donor PBMCs exposed to lung cancer cell lines, but not benign bronchial epithelial cells in vitro. These findings have implications for understanding the immune response to lung cancer.

Follow-up and surveillance of the patient with lung cancer after curative-intent therapy: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

BACKGROUND: These guidelines are an update of the evidence-based recommendations for follow-up and surveillance of patients after curative-intent therapy for lung cancer. Particular updates pertain to whether imaging studies, health-related quality-of-life (HRQOL) measures, tumor markers, and bronchoscopy improve outcomes after curative-intent therapy. METHODS: Meta-analysis of Observational Studies in Epidemiology guidelines were followed for this systematic review, including published studies on posttreatment outcomes in patients who received curative-intent therapy since the previous American College of Chest Physicians subject review. Four population, intervention, comparison, and outcome questions were formulated to guide the review. The MEDLINE and CINAHL databases were searched from June 1, 2005, to July 8, 2011, to ensure overlap with the search strategies used previously. RESULTS: A total of 3,412 citations from MEDLINE and 431 from CINAHL were identified. Only 303 were relevant. Seventy-six of the 303 articles were deemed eligible on the basis of predefined inclusion criteria after full-text review, but only 34 provided data pertaining directly to the subject of the questions formulated to guide this review. In patients undergoing curative-intent surgical resection of non-small cell lung cancer, chest CT imaging performed at designated time intervals after resection is suggested for detecting recurrence. It is recommended that treating physicians who are able to incorporate the patient's clinical findings into decision-making processes be included in follow-up and surveillance strategies. The use of validated HRQOL instruments at baseline and during follow-up is recommended. Biomarker testing during surveillance outside clinical trials is not suggested. Surveillance bronchoscopy is suggested for patients with early central airway squamous cell carcinoma treated by curative-intent photodynamic therapy and for patients with intraluminal bronchial carcinoid tumor who have undergone curative-intent bronchoscopic treatment with Nd:YAG laser or electrocautery. CONCLUSIONS: There is a paucity of well-designed prospective studies specifically targeting follow-up and surveillance modalities aimed at improving survival or QOL after curative-intent therapy. Additional research is warranted to clarify which curative-intent treatment modalities affect HRQOL the most and to identify patients who are at the most risk for recurrence or impaired QOL after treatment. Further evidence is needed to determine how the frequency and duration of surveillance programs that include imaging studies, QOL measurements, tumor markers, or bronchoscopy affect patient morbidity, survival, HRQOL, and health-care costs.

Systematic approach to the management of the newly found nodule on screening computed tomography: role of dedicated pulmonary nodule clinics.

Indeterminate pulmonary nodules in asymptomatic individuals are common, and their incidence is expected to increase. Although evidence-based guidelines exist for the management of these lesions, they are not in complete agreement and are often not followed, resulting in inconsistent management. A dedicated program or clinic for the management of lung nodules would allow an institution to deliver evidence-based, standardized care for patients with indeterminate nodules, and should include multidisciplinary care, state-of-the-art technology and expertise, and a patient navigation system to provide a user-friendly service for both patients and referring physicians. A dedicated pulmonary nodule clinic has many potential advantages.