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1.
J Surg Oncol ; 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004940

ABSTRACT

BACKGROUND AND METHODS: Although signet ring cell (SRC) histology is associated with resistance to neoadjuvant chemoradiotherapy and worse overall survival (OS) in esophageal adenocarcinoma (EAC), its prognostic relationship among patients who survive the early period following resection is unknown. EAC patients who underwent trimodality therapy at a single institution (2006-2018) were identified. Bayesian multivariable regression (BMR) analyses of OS and additional OS from a 3-year landmark were performed. RESULTS: Of 631 patients, SRCs were present in 16.0% (N = 101). SRC was associated with shorter median OS (45.8 [95% confidence interval: 31.0-96.7] vs. 79.8 [63.0-107.2] months; p = 0.014). In BMR analysis, the absence of an SRC component was moderately associated with improved OS (probability of beneficial effect, PBE = 0.879). Three-year conditional BMR analysis of additional OS (N = 357) showed that SRC status no longer had a prognostic effect (PBE = 0.546); higher pathological stage was strongly associated with worse additional OS (PBE < 0.001). CONCLUSIONS: The presence of SRC portends worse OS following trimodality therapy for EAC. However, this prognostic impact is dynamic and abates by 3 years postoperatively. In contrast, a higher pathological stage is strongly associated with poor overall and 3-year conditional survival. DISCUSSION: These findings may inform postoperative patient counseling and surveillance protocols.

2.
J Surg Oncol ; 124(4): 699-703, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34057733

ABSTRACT

BACKGROUND AND OBJECTIVES: Adoptive T-cell therapies (ACTs) using expansion of tumor-infiltrating lymphocyte (TIL) populations are of great interest for advanced malignancies, with promising response rates in trial settings. However, postoperative outcomes following pulmonary TIL harvest have not been widely documented, and surgeons may be hesitant to operate in the setting of widespread disease. METHODS: Patients who underwent pulmonary TIL harvest were identified, and postoperative outcomes were studied, including pulmonary, cardiovascular, infectious, and wound complications. RESULTS: 83 patients met inclusion criteria. Pulmonary TIL harvest was undertaken primarily via a thoracoscopy with a median operative blood loss and duration of 30 ml and 65 min, respectively. The median length of stay was 2 days. Postoperative events were rare, occurring in only five (6%) patients, including two discharged with a chest tube, one discharged with oxygen, one episode of urinary retention, and one blood transfusion. No reoperations occurred. The median time from TIL harvest to ACT infusion was 37 days. CONCLUSIONS: Pulmonary TIL harvest is safe and feasible, without major postoperative events in our cohort. All patients were able to receive intended ACT infusion without delays. Therefore, thoracic surgeons should actively participate in ongoing ACT trials and aggressively seek to enroll patients on these protocols.


Subject(s)
Immunotherapy, Adoptive/methods , Lung Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating/immunology , Melanoma/therapy , Pulmonary Surgical Procedures/methods , Adult , Feasibility Studies , Female , Follow-Up Studies , Humans , Lung Neoplasms/immunology , Lung Neoplasms/secondary , Male , Melanoma/immunology , Melanoma/pathology , Middle Aged , Postoperative Care , Prognosis , Prospective Studies
3.
Cancer Immunol Immunother ; 69(8): 1519-1534, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32300858

ABSTRACT

Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor 18F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) 18F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUVMax, SUVTotal, SUVMean, TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each 18F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated 18F-FDG SUVMax was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other 18F-FDG PET parameters. Increased SUVMax was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57+ cell density, and increased T cell exhaustion gene signature. Elevated SUVMax identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that 18F-FDG SUVMax has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/metabolism , Fluorodeoxyglucose F18/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Positron-Emission Tomography/methods , Tumor Microenvironment/immunology , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/surgery , Glycolysis , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Lung Neoplasms/surgery , Prognosis , Radiopharmaceuticals/metabolism , Retrospective Studies , Survival Rate , Transcriptome
4.
J Surg Oncol ; 122(3): 515-522, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32468580

ABSTRACT

BACKGROUND AND OBJECTIVES: It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes. METHODS: Records of patients who presented with stage IVA thymic neoplasms from 2000 to 2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival. RESULTS: Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%). CONCLUSIONS: Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed.


Subject(s)
Pleural Neoplasms/secondary , Pleural Neoplasms/surgery , Thymus Neoplasms/pathology , Thymus Neoplasms/surgery , Adult , Aged , Disease Progression , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Proportional Hazards Models , Thoracic Surgical Procedures , Thymectomy
5.
J Surg Oncol ; 121(6): 984-989, 2020 May.
Article in English | MEDLINE | ID: mdl-32077113

ABSTRACT

BACKGROUND AND OBJECTIVES: Precision medicine has altered the management of colorectal cancer (CRC). However, the concordance of mutational findings between primary CRC tumors and associated pulmonary metastases (PM) is not well-described. This study aims to determine the concordance of genomic profiles between primary CRC and PM. METHODS: Patients treated for colorectal PM at a single institution from 2000 to 2017 were identified. Mutational concordance was defined as either both wild-type or both mutant alleles in lung and colorectal lesion; genes with opposing mutational profiles were reported as discordant. RESULTS: Thirty-eight patients met inclusion criteria, among whom KRAS, BRAF, NRAS, MET, RET, and PIK3CA were examined for concordance. High concordance was demonstrated among all evaluated genes, ranging from 86% (KRAS) to 100% concordance (NRAS, RET, and MET). De novo KRAS mutations were detected in the PM of 4 from 35 (11%) patients, 3 of whom had previously received anti-epidermal growth factor receptor (EGFR) therapy. Evaluation of Cohen's κ statistic demonstrated moderate to perfect correlation among evaluated genes. CONCLUSIONS: Because high intertumoral genomic homogeneity exists, it may be reasonable to use primary CRC mutational profiles to guide prognostication and targeted therapy for PM. However, the possibility of de novo KRAS-mutant PM should be considered, particularly among patients previously treated with anti-EGFR therapy.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Cetuximab/therapeutic use , Colorectal Neoplasms/drug therapy , DNA Mutational Analysis , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Humans , Lung Neoplasms/drug therapy , Molecular Targeted Therapy , Precision Medicine , Proto-Oncogene Proteins p21(ras)/genetics
6.
J Surg Oncol ; 120(4): 729-735, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31290159

ABSTRACT

BACKGROUND AND OBJECTIVES: While knowledge has grown extensively regarding the impact of mutations on colorectal cancer prognosis, their role in outcomes after pulmonary metastasectomy (PM) remains minimally understood. We sought to determine the prognostic role of mutant disease on survival and recurrence after metastasectomy. METHODS: Patients with available tumor sequencing profiles who underwent PM for colorectal cancer at a single institution from 2011 to 2017 were reviewed. Various demographic and clinicopathologic factors, as well as mutational status, were tested in the Cox regression analyses to identify predictors of survival and disease-free survival (DFS). RESULTS: A total of 130 patients met inclusion criteria, among whom 78 (60%) were male and the mean age was 57 years. The median survival time and 5-year survival rate were 58.2 months and 47%, respectively. A single pulmonary nodule was present in 54%. Disease recurrence occurred for 87 (67%) patients, including 75 (58%) who had at least one lung recurrence after metastasectomy at a median time to recurrence of 19.4 months. Upon multivariable analysis, RAS and TP53 mutations were associated with shorter survival DFS, while APC is associated with prolonged survival. CONCLUSIONS: After metastasectomy for colorectal cancer, mutations in RAS, TP53, and APC play an important role in survival and recurrence.


Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/mortality , Lung Neoplasms/mortality , Metastasectomy/mortality , Mutation , Neoplasm Recurrence, Local/mortality , Pneumonectomy/mortality , Adult , Aged , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies , Survival Rate
7.
Dis Esophagus ; 32(10): 1-6, 2019 Dec 13.
Article in English | MEDLINE | ID: mdl-30888418

ABSTRACT

Endoscopic mucosal resection (EMR) can be an effective therapy for superficial esophageal cancer. Many patients with cT2 invasion by endoscopic ultrasound (EUS) receive surgery but are subsequently found to have superficial disease. The purpose of this study was to investigate the safety profile and the added value of attempting EMR for EUS-staged cT2N0 esophageal cancer. A retrospective review was performed at a single institution from 2008 to 2017. Patients who were staged cT2N0 by EUS were identified from a prospectively maintained surgical database. Among 75 patients identified for analysis, 30 underwent an attempt at EMR. No perforations or other immediate complications occurred. EMR was more likely to be attempted among older patients (P = 0.001) with smaller tumor size (P < 0.001) and diminished SUVmax (P = 0.001). At the time of treatment, EMR was successful in clearing all known disease among 17/30 patients, with 12 representing pT1a or less and 5 representing pT1b with negative margins. Among the 17 patients for whom EMR was able to clear all known disease, there were no recurrences or cancer-related deaths. Although all the patients were staged as cT2N0 by EUS, many patients were identified by EMR to have superficial disease. There were no perforations or other adverse events related to EMR. Furthermore, EMR cleared all known disease among 17 patients with no known recurrences or cancer-related deaths. The results indicate that EMR for cT2N0 esophageal cancer is a safe diagnostic option that is therapeutic for some.


Subject(s)
Endoscopic Mucosal Resection/statistics & numerical data , Esophageal Neoplasms/surgery , Esophagectomy/statistics & numerical data , Patient Selection , Aged , Aged, 80 and over , Databases, Factual , Endoscopic Mucosal Resection/methods , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/pathology , Esophagectomy/methods , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Retrospective Studies , Treatment Outcome , Ultrasonography
8.
Surg Today ; 49(11): 927-935, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31144105

ABSTRACT

PURPOSE: Several studies have assessed the physician-nurse relationship, particularly between females working together. While the surgeon workforce is increasingly represented by females, gendered relationships and biases in the operating room remain largely unstudied. METHODS: We performed a prospective randomized study in which operative support staff, including nurses, surgical technologists, and surgical assistants, assessed scenarios describing questionable surgeon behaviors. Respondents were randomized to a survey that either discussed a female or male surgeon. For each scenario, one of the four standardized responses was selected. The respondents' assessments of surgeon behaviors were analyzed. RESULTS: The response rate was 4.4% (3128/71143). Females were more likely than males to deem the surgeon's behavior inappropriate regardless of surgeon sex (p = 0.001). The likelihood of writing up the surgeon was predicted by role, with technologists, nurses, and assistants reporting surgeons at frequencies of 65.5%, 53.2%, and 48.8%, respectively (p = 0.008). While the overall respondents did not show a propensity to write-up either sex differentially (p = 0.070), technologists were significantly more likely to report female surgeons than male surgeons (p = 0.006). CONCLUSION: Characteristics of operative personnel were correlated with varying tolerance of surgeon behaviors, with specific subgroups more critical of female surgeons than males. Further exploration of these perceptions will serve to improve interactions in a diverse workplace.


Subject(s)
Behavior , Health Personnel/psychology , Operating Rooms , Patient Care Team , Surgeons/psychology , Female , Humans , Male , Prospective Studies , Random Allocation , Sexism , Surveys and Questionnaires
9.
J Surg Oncol ; 118(3): 518-524, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30109699

ABSTRACT

BACKGROUND AND OBJECTIVES: Chest wall sarcomas are rare and may demonstrate heterogeneous features. Surgery remains the mainstay of treatment with chemotherapy and radiotherapy used as adjuncts. Herein, we report outcomes of a large cohort of patients with primary chest wall sarcoma who underwent resection. METHODS: Records of 121 patients who underwent resection for primary chest wall sarcoma between 1998 and 2013 were reviewed. A thoracic pathologist reexamined all tumors and categorized them according to grade. Univariable and multivariable Cox analyses were conducted to identify predictors of overall survival (OS). RESULTS: The median age was 45.0 (range, 11-81) years, and most tumors (63.6%, 77) were high grade. The median tumor size was 7 cm (range, 1-21 cm). Fifty-nine (48.8%) patients received neoadjuvant chemotherapy and 12 (9.9%) received neoadjuvant radiotherapy. A complete resection was achieved in 103 (85.1%) patients. Neoadjuvant chemotherapy (P = 0.532) and radiation ( P = 1.000) were not associated with a complete resection. Five-year OS among patients undergoing R0 and R1 resections was 61.9% and 27.8%, respectively. Multivariable analysis identified high grade (HR, 15.21; CI, 3.57-64.87; P < 0.001), R1 (HR, 3.10; CI, 1.40-6.86; P = 0.005), R2 resection (HR, 5.18; CI, 1.91-14.01; P = 0.001), and age (HR, 1.02; CI, 1.01-1.03; P = 0.002) as predictors of OS. CONCLUSIONS: In this series of resected chest wall sarcomas, complete resection and tumor grade remain the most important survival predictors. Individual decisions are required for the utilization of neoadjuvant therapy.


Subject(s)
Sarcoma/mortality , Thoracic Neoplasms/mortality , Thoracic Surgical Procedures/mortality , Thoracic Wall/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Middle Aged , Prognosis , Prospective Studies , Retrospective Studies , Sarcoma/pathology , Sarcoma/surgery , Survival Rate , Thoracic Neoplasms/pathology , Thoracic Neoplasms/surgery , Thoracic Wall/surgery , Young Adult
11.
Ann Thorac Surg ; 117(2): 320-326, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37080372

ABSTRACT

BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Peritoneal Neoplasms , Stomach Neoplasms , Humans , Retrospective Studies , Peritoneal Neoplasms/therapy , Gastrectomy , Adenocarcinoma/surgery , Stomach Neoplasms/surgery , Esophagogastric Junction/surgery , Esophageal Neoplasms/surgery , Neoplasm Staging
12.
Innovations (Phila) ; 18(1): 100-102, 2023.
Article in English | MEDLINE | ID: mdl-36782085

ABSTRACT

The application of robot-assisted thoracoscopy to cardiac surgery affords an opportunity to leverage the exceptional intraoperative exposure, visualization, and dexterity of the robotic platform. Here, we report the case of a 72-year-old woman who presented to our institution for evaluation of a left ventricular mass that was identified following workup for an embolic event. We present an intraoperative video that provides technical details of the robot-assisted resection of the lesion, which was found to be a left ventricular papillary fibroelastoma arising from the mitral chordal apparatus. This case highlights the advantages provided by the robotic platform, which permitted complete, minimally invasive surgical excision of the lesion while minimizing the burden of surgical trauma.


Subject(s)
Cardiac Papillary Fibroelastoma , Heart Neoplasms , Robotics , Female , Humans , Aged , Heart Neoplasms/diagnostic imaging , Heart Neoplasms/surgery , Heart Neoplasms/pathology , Heart Ventricles/diagnostic imaging , Heart Ventricles/surgery , Heart Ventricles/pathology , Thoracoscopy
13.
World J Pediatr Congenit Heart Surg ; 14(6): 754-756, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37697743

ABSTRACT

Aortic arch obstruction is often present with complex concomitant congenital heart defects (CHDs). The use of nonvalved femoral vein homograft (FVH) to reconstruct the aortic arch has distinct surgical advantages, including simplified reconstruction. We present an intraoperative video of a Yasui procedure utilizing FVH for aortic reconstruction in a 12-day-old (2.2 kg) neonate with right ventricular outflow tract obstruction, malalignment ventricular septal defect, aortic valve atresia, aortic arch hypoplasia, atrial septal defect, and ductal dependent systemic circulation. Further, we report outcomes for a series of three additional neonatal patients with complex CHD and aortic arch obstruction who underwent FVH arch reconstruction.


Subject(s)
Aortic Coarctation , Heart Defects, Congenital , Ventricular Outflow Obstruction , Infant, Newborn , Humans , Aorta, Thoracic/surgery , Femoral Vein , Ventricular Outflow Obstruction/surgery , Aortic Coarctation/surgery , Heart Defects, Congenital/surgery , Allografts
14.
Article in English | MEDLINE | ID: mdl-37619884

ABSTRACT

OBJECTIVES: Recent randomized trials have demonstrated a survival advantage with the use of local consolidative therapy in oligometastatic non-small cell lung cancer; however, the indications for and outcomes after pulmonary resection as a component of local consolidative therapy remain ill defined. We sought to characterize the perioperative and long-term survival outcomes among patients with resected oligometastatic non-small cell lung cancer. METHODS: Patients presenting to a single center (2000-2017) with oligometastatic non-small cell lung cancer (≤3 synchronous metastases, intrathoracic nodal disease counted as a single site) who underwent resection of the primary tumor were retrospectively identified. Charts were reviewed, and demographic, clinical, pathologic, oncologic, and survival outcomes were recorded. Survival outcomes were analyzed from the date of surgery. RESULTS: A total of 52 patients met inclusion criteria, among whom most (38, 73.1%) were ever smokers, had nonsquamous tumors (48, 92.3%), had no intrathoracic nodal disease (33, 63.5%), and had 1 to 2 sites of metastases (49, 94.2%). The majority (41, 78.9%) received systemic therapy, predominantly in the neoadjuvant setting (24/41, 58.5%). After resection, there were no 30- or 90-day deaths. After a median follow-up of 94.6 months (95% CI, 69.0-139.1), 37 patients (71.2%) progressed and 38 patients (73.1%) died. Median postoperative progression-free survival and overall survival were 9.4 (5.5-11.6) months and 51.7 (22.3-65.3) months, respectively. CONCLUSIONS: Pulmonary resection as a means of maximum locoregional control in oligometastatic non-small cell lung cancer is feasible and safe, and may be associated with durable long-term survival benefits. The frequency of systemic postoperative progression highlights an urgent need to characterize perioperative and oncologic outcomes after pulmonary resection in the current era of novel systemic therapies.

15.
JCO Precis Oncol ; 7: e2200540, 2023 01.
Article in English | MEDLINE | ID: mdl-36716413

ABSTRACT

PURPOSE: Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients. METHODS: We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis. RESULTS: Of 194 included patients, 121 received comprehensive LCT to all sites of disease with either surgery or radiation. TP53 mutations were identified in 40 of 78 (55%), KRAS in 32 of 95 (34%), EGFR in 24 of 109 (22%), and STK11 in nine of 77 (12%). At median follow-up of 96 months, median OS and PFS were 26 (95% CI, 23 to 31) months and 11 (95% CI, 9 to 13) months, respectively. On multivariable analysis, patients with EGFR mutations had lower mortality risk (hazard ratio [HR], 0.53; 95% CI, 0.29 to 0.98; P = .044) compared with wild-type patients, and patients with STK11 mutations had higher risk of progression or mortality (HR, 2.32; 95% CI, 1.12 to 4.79; P = .023) compared with wild-type patients. TP53 and KRAS mutations were not associated with OS or PFS. Among 71 patients with known EGFR mutational status who received comprehensive LCT, EGFR mutations were associated with lower mortality compared with wild-type (HR, 0.45; 95% CI, 0.22 to 0.94; P = .032). CONCLUSION: When compared with wild-type patients, those with EGFR and STK11 mutations had longer OS and shorter PFS, respectively. EGFR mutations were associated with longer OS among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Benchmarking , Proto-Oncogene Proteins p21(ras)/genetics , Mutation , ErbB Receptors/genetics
16.
J Thorac Dis ; 15(11): 6362-6372, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38090303

ABSTRACT

Background: The accurate clinical staging of esophageal squamous cell carcinoma (ESCC) is pivotal for guiding treatment strategies. However, the current precision in staging for clinical T (cT)2 and cT3 stages remains unsatisfactory. This article discusses the role of multidisciplinary teams (MDTs) in the clinical staging and formulation of neoadjuvant treatment strategies for locally advanced operable ESCC. These challenges underscore the importance of precise staging in the decision-making process for appropriate therapeutic interventions. Case Description: Through the lens of two patient case studies with locally advanced resectable ESCC, the article showcases the intricate process of treatment planning undertaken by MDTs. It captures a range of expert perspectives from Japan, China, Hong Kong (China), Korea, the USA, and Europe, focusing on the challenges of differentiating between cT2 and cT3 stages of the disease, which is a critical determinant in the management and therapeutic approach for patients. Conclusions: The article concludes that the accurate staging of ESCC is a cornerstone in determining the most suitable treatment strategies. It underscores the vital role that MDTs play in both clinical staging and the decision-making process for treatment. Highlighting the limitations in current diagnostic methods, the article emphasizes the urgent need for advanced research and the refinement of diagnostic tools to improve the precision of staging, particularly between the cT2 and cT3 stages. It suggests that future research should consider whether a reclassification of these stages could be warranted to enhance treatment planning and outcomes for patients with ESCC.

17.
Thorac Surg Clin ; 32(1): 83-90, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34801199

ABSTRACT

A complex relationship exists between health care disparities and large databases among the thoracic surgical patient population. Using the example of thoracic malignancies, the ability of investigations leveraging large databases and novel analytical approaches to highlight disparate access to care and discordant outcomes following treatment is illustrated. Large, widely used databases may not be representative of the thoracic surgical patient population as a whole, and caution must be used when interpreting and generalizing results gleaned from such database analyses. Ensuring appropriate representation of all relevant patient subgroups in research databases will improve external generalizability and scientific validity of future investigations.


Subject(s)
Thoracic Neoplasms , Thoracic Surgery , Thoracic Surgical Procedures , Databases, Factual , Humans
18.
Cancers (Basel) ; 14(5)2022 Feb 28.
Article in English | MEDLINE | ID: mdl-35267572

ABSTRACT

With recent strides made within the field of thoracic oncology, the management of NSCLC is evolving rapidly. Careful patient selection and timing of multi-modality therapy to permit the optimization of therapeutic benefit must be pursued. While chemotherapy and radiotherapy continue to have a role in the management of lung cancer, surgical therapy remains an essential component of lung cancer treatment in early, locally and regionally advanced, as well as in selected, cases of metastatic disease. Recent and most impactful advances in the treatment of lung cancer relate to the advent of immunotherapy and targeted therapy, molecular profiling, and predictive biomarker discovery. Many of these systemic therapies are a part of the standard of care in metastatic NSCLC, and their indications are expanding towards surgically operable lung cancer to improve survival outcomes. Numerous completed and ongoing clinical trials in the surgically operable NSCLC speak to the interest and importance of the multi-modality therapy even in earlier stages of NSCLC. In this review, we focus on the current standard of care indications for surgical therapy in stage I-IV NSCLC as well as on the anticipated future direction of multi-disciplinary lung cancer therapy.

19.
J Matern Fetal Neonatal Med ; 35(25): 6823-6829, 2022 Dec.
Article in English | MEDLINE | ID: mdl-33998394

ABSTRACT

PURPOSE: The purpose of this study was to analyze the clinical characteristics and outcomes of low birthweight (LBW) infants with congenital diaphragmatic hernia (CDH) compared to normal birthweight (NBW) infants with CDH. We hypothesized that LBW was associated with increased mortality, decreased extracorporeal life support (ECLS) utilization, and increased pulmonary morbidity in CDH patients. METHODS: Patients in the CDH Study Group from 2007 to 2018 were included. LBW was defined as <2.5 kg. Clinical characteristics and outcomes for LBW patients were compared to normal birthweight (NBW) patients using univariate and multivariable analyses. RESULTS: Of 5,586 patients, 1,157 (21%) were LBW. LBW infants had more congenital anomalies and larger diaphragmatic defects than NBW infants. ECLS utilization was decreased, and overall mortality was increased among LBW infants compared to NBW infants. A 1 kg increase in birthweight was associated with 34% higher odds of survival after repair (adjusted Odds Ratio 1.34, 95% CI 1.03-1.76; p = .03). LBW infants had longer durations of mechanical ventilation and were more likely to require supplemental oxygen at 30 days and at the time of discharge. CONCLUSION: LBW is a risk factor for mortality and pulmonary morbidity in CDH. Prolonged oxygen requirement and increased length of stay are important considerations when managing this population.


Subject(s)
Extracorporeal Membrane Oxygenation , Hernias, Diaphragmatic, Congenital , Infant , Humans , Hernias, Diaphragmatic, Congenital/surgery , Birth Weight , Herniorrhaphy , Oxygen , Retrospective Studies
20.
Ann Thorac Surg ; 113(1): 209-216, 2022 01.
Article in English | MEDLINE | ID: mdl-33524359

ABSTRACT

BACKGROUND: The objective of this study was to determine how thoracic surgeons manage intraoperative esophagectomy positive margins and how these decisions may relate to overall survival and progression-free survival in esophageal cancer. METHODS: A survey was sent to thoracic surgeons to understand the management of intraoperative positive esophagectomy margins. Primary data at two high-volume esophageal cancer institutions from 1994 to 2017 were retrospectively reviewed to identify patients who had intraoperative positive frozen section margins during esophagectomy. Patient characteristics and survival data were collected and analyzed. Overall survival and progression-free survival were assessed using a Cox model. RESULTS: Eighty-five percent of thoracic surgeons responding to a survey reported the utilization of frozen pathologic evaluation during esophagectomy with attempts at re-resection to achieve negative margin. Our esophagectomy database identified 94 patients with intraoperative positive margins. Of those re-resected (n = 67, 63%), 44 patients (46.8%) were converted to R0 resections. overall survival was improved for patients in the R0 group (13 months) vs R+ group (3.4 months, P = .04). Progression-free survival was also improved between the R0 group (8.6 months) and the R+ group (2.2 months, P = .03). In a multivariable analysis for progression-free survival, margin status was an independent predictor of survival (hazard ratio 3.13, P = .03). CONCLUSIONS: From a thoracic surgery survey, 85% of surgeons use intraoperative frozen section margin analysis to guide surgical decision making during an esophagectomy. Analyzing patients with a positive margin discovered during esophagectomy suggests that esophageal cancer patients who can undergo re-resection to a negative margin have increased progression-free survival. The final margin appears to be related to progression-free survival.


Subject(s)
Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagectomy , Margins of Excision , Esophageal Neoplasms/surgery , Female , Humans , Male , Middle Aged , Progression-Free Survival , Retrospective Studies , Survival Rate
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