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The public is placing increased emphasis on specialty specific rankings, thereby affecting patients' choices of clinical care programs. In the spirit of transparency, public reporting initiatives are underway or being considered by various surgical specialties whose databases rank programs based on short-term outcomes. Of concern, short-term risk avoidance excludes important comparative cases from surgical database participation and may adversely affect overall long-term oncologic treatment team results. To assess the validity of comparing short-term perioperative and long-term survival outcomes of all patients treated at major centers, we studied the correlations between these variables.The National Cancer Database was queried for patients diagnosed with non-small cell lung carcinoma (NSCLC) between 2008 and 2012, yielding 5-year follow-up data for all patients at centers treating at least 100 patients annually. Mortality (30- and 90-day), unplanned 30-day readmissions, and hospital length of stay were modeled using logistic regression with sex, race, age, Charlson-Deyo combined comorbidity, extent of surgery, income, insurance status, histology, grade, and analytic stage as predictors, all with 2-way interaction terms. The differences between the predicted rates and observed rates were calculated for each short-term outcome, and the average of these was used to create a short-term metric (STM). A similar approach was used to create a long-term metric (LTM) that used overall survival as a single dependent variable. Centers were ranked into deciles based on these metrics. Visual plotting as well as correlation coefficients were used to judge correlation between STM and LTM.A total of 298,175 patients from 541 centers were included in this analysis, of whom 102,860 underwent surgical resection for NSCLC. The correlation between STM and LTM was negative using parametric estimates (Pearson correlation coefficient = -0.09 [P = .03] and -0.22 [P .01]) and nonparametric estimates (Spearman rank correlation coefficient = -0.09 [P = .02] and -0.22 [P .01]) for squamous cell carcinoma and adenocarcinoma, respectively.Short-term perioperative outcome rankings correlate poorly with long-term survival outcome rankings when cancer treatment centers are compared. Factors explaining this discrepancy merit further study. Rankings based on short-term outcomes alone may be incomplete for public reporting.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

ImportanceChanges in postsurgical opioid prescribing practices may help reduce chronic opioid use in surgical patients.ObjectiveTo investigate whether postsurgical acute pain across different surgical subspecialties can be managed effectively after hospital discharge with an opioid supply of 3 or fewer days and whether this reduction in prescribed opioids is associated with reduced new, persistent opioid use.Design, Setting, and ParticipantsIn this prospective cohort study with a case-control design, a restrictive opioid prescription protocol (ROPP) specifying an opioid supply of 3 or fewer days after discharge from surgery along with standardized patient education was implemented across all surgical services at a tertiary-care comprehensive cancer center. Participants were all patients who underwent surgery from August 1, 2018, to July 31, 2019.Main Outcomes and MeasuresMain outcomes were the rate of compliance with the ROPP in each surgical service, the mean number of prescription days and refill requests, type of opioid prescribed, and rate of conversion to chronic opioid use determined via a state-run opioid prescription program. Postsurgical complications were also measured.ResultsA total of 4068 patients (mean [SD] age, 61.0 [13.8] years; 2528 women [62.1%]) were included, with 2017 in the pre-ROPP group (August 1, 2018, to January 31, 2019) and 2051 in the post-ROPP group (February 1, 2019, to July 31, 2019). The rate of compliance with the protocol was 95%. After implementation of the ROPP, mean opioid prescription days decreased from a mean (SD) of 3.9 (4.5) days in the pre-ROPP group to 1.9 (3.6) days in the post-ROPP group (P P P = .02). There was no statistically significant difference in surgical complications. The conversion rate to chronic opioid use decreased following ROPP implementation among both opioid-naive patients with cancer (11.3% [143 of 1267] to 4.5% [118 of 2645]; P P = .02).Conclusions and RelevanceIn this cohort study, prescribing an opioid supply of 3 or fewer days to surgical patients after hospital discharge was feasible for most patients, led to a significant decrease in the number of opioids prescribed after surgery, and was associated with a significantly decreased conversion to long-term opioid use without concomitant increases in refill requests or significant compromises in surgical recovery.

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as “preferred interventions,” whereas others are categorized as either “other recommended interventions” or “useful under certain circumstances.”

Simple Summary The optimal way to treat central (CLT) and ultracentral (UCLT) lung tumors with curative radiation is unclear. We evaluated 83 patients with CLT and UCLT who underwent a curative radiotherapy technique called stereotactic body radiation therapy (SBRT). On statistical analysis, patients with UCLT had worse overall survival. Using a cohort of patients matched for relevant variables such as gender and performance status, we evaluated radiation doses to critical central structures such as the airway and heart. In this group, patients with UCLT were more likely to exceed dose constraints as compared CLT, particularly constraints regarding the airway. Additionally, patients had worse non-cancer associated survival when radiation doses were higher than 18 Gy to 4cc’s of either the trachea or proximal bronchial tree. Based on these findings, patients with UCLT have worse outcomes which could be secondary to higher radiation doses to the trachea and proximal bronchial tree. Abstract The preferred radiotherapeutic approach for central (CLT) and ultracentral (UCLT) lung tumors is unclear. We assessed the toxicity and outcomes of patients with CLT and UCLT who underwent definitive five-fraction stereotactic body radiation therapy (SBRT). We reviewed the charts of patients with either CLT or UCLT managed with SBRT from June 2010–April 2019. CLT were defined as gross tumor volume (GTV) within 2 cm of either the proximal bronchial tree, trachea, mediastinum, aorta, or spinal cord. UCLT were defined as GTV abutting any of these structures. Propensity score matching was performed for gender, performance status, and history of prior lung cancer. Within this cohort of 83 patients, 43 (51.8%) patients had UCLT. The median patient age was 73.1 years with a median follow up of 29.9 months. The two most common dose fractionation schemes were 5000 cGy (44.6%) and 5500 cGy (42.2%) in five fractions. Multivariate analysis revealed UCLT to be associated with worse overall survival (OS) (HR = 1.9, p = 0.02) but not time to progression (TTP). Using propensity score match pairing, UCLT correlated with reduced non-cancer associated survival (p = 0.049) and OS (p = 0.03), but not TTP. Within the matched cohort, dosimetric study found exceeding a D4cc of 18 Gy to either the proximal bronchus (HR = 3.9, p = 0.007) or trachea (HR = 4.0, p = 0.02) was correlated with worse non-cancer associated survival. In patients undergoing five fraction SBRT, UCLT location was associated with worse non-cancer associated survival and OS, which could be secondary to excessive D4cc dose to the proximal airways.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Background: Bronchial pre-malignant lesions (PMLs) are the putative precursors for bronchial squamous cell carcinoma. PMLs represent a spectrum of histologies, from low-grade lesions (hyperplasia, metaplasia) to high-grade lesions (dysplasia, carcinoma in situ). The majority of these lesions will regress or remain stable without clinical intervention while a subset of lesions will progress to invasive carcinoma. We performed single-cell RNA sequencing (scRNAseq) of these lesions to elucidate the cross-talk between epithelial, stromal, and immune populations in lesions of increasing histological grade. Methods: Thirty lesions from seventeen participants were biopsied via bronchoscopy. Cells were sorted by CD45+/- FACS gating and sequenced with the Cel-Seq2 protocol. Celda was used to bi-cluster genes into modules and cells into clusters. Cells were filtered by mitochondrial percentage (%mito < 50%), minimum UMI counts (nUMI > 300), and doublet detection. Cell types were labeled by marker gene expression. Results: After filtering low quality cells, we analyzed 4,382 cells. We observed expected smoking related shifts in epithelial cell type proportions, including an increase in secretory cells (χ2 = 31.39, p = 2.11 X 10-8) and a decrease in ciliated cells (χ2 = 4.83, p = 0.028) among current smokers. Distinct differences in expression of transcriptional modules were observed between KRT5+ (basal) cells from different histologic grades. Basal cells from high grade lesions expressed smoking detoxification and cell cycle gene programs, while low grade lesion basal cells expressed differentiation gene programs. We also identified a group of cells from CIS lesions involved in an epithelial-to-mesenchymal transition, marked by an increase in SPARC and COL4A1 expression and a decrease in CDH1 expression. Subpopulations of immune cells identified include macrophages, CD4/8+ T, B, dendritic cells, and natural killer cells. Several clusters of CD4+ and CD8+ T cells displayed an exhausted phenotype, marked by the expression of PD-1, CTLA4, LAG3, and TIGIT. Samples with high grade histology (dysplasia, carcinoma in situ) were enriched in CD4+ Tregs and myeloid cells compared to low grade histology samples (hyperplasia, metaplasia), which were enriched in Natural Killer and cytotoxic CD8+ T cells (χ2 = 298.95, p = 0.001). Discussion: Our results suggest that changes in specific transcriptional programs are associated with the transition of epithelial cells to more invasive states and that changes in immune populations are associated with increasing histological grade. These signatures can suggest novel avenues for chemoprevention and cancer interception. Citation Format: Conor Shea, Lukas Kalinke, Kitty De Jong, Kate Gowers, Diane Ding, Sherry Zhang, Gang Liu, Jack Cunningham, Ipsita Dey-Guha, Mark Hennon, Sai Yendamuri, Christopher Stevenson, Avrum Spira, Mary E. Reid, Marc E. Lenburg, Sam M. Janes, Jennifer E. Beane, Sarah A. Mazzilli, Joshua D. Campbell. Epithelial, stromal, and immune changes associated with lung squamous premalignant lesion severity identified by single-cell RNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2201.

Background In patients with clinical N1 disease, minimally invasive surgery (MIS) has potentially better perioperative outcome compared to open thoracotomy. Additionally, whether adjuvant or neoadjuvant chemotherapy produces the best long-term survival is still debatable. Methods We queried The National Cancer Database for patients with clinical N1 NSCLC who underwent surgical resection between 2010 and 2014. Comparison between patients receiving MIS and patients who underwent open thoracotomy was done using an intention-to-treat analysis. Comparison was also done among neoadjuvant, adjuvant chemotherapy, and only surgery. Proportional hazard models were used to evaluate the effects of surgical approach and timing of chemotherapy on overall survival. Results A total of 1440 and 3942 patients underwent MIS and open thoracotomy respectively. MIS achieved better surgical margins (90.0% versus 88.6%) and shorter length of stay (6.5 ± 6.5 versus 7.3 ± 6.4 d, P ≤ 0.01) compared to open thoracotomy. There were no differences in 30-day and 90-day mortality, nor readmission rates. Neoadjuvant and adjuvant chemotherapy were administered to 13.5% and 57.2% of patients respectively. There was no significant difference in the 5-year overall survival between MIS and open thoracotomy (46% versus 46% P = 0.08). There was significantly better 5-year overall survival in neoadjuvant and adjuvant chemotherapy versus only surgery, but no difference between neoadjuvant and adjuvant chemotherapy (48% versus 47% versus 44%, P Conclusions In clinical N1 NSCLC, MIS does not compromise oncological quality or overall survival when compared to open thoracotomy. Overall survival improved in patients treated with chemotherapy but there is no difference when given as neoadjuvant versus adjuvant chemotherapy.

BACKGROUND Despite occurring commonly, the prognoses of second early-stage non-small cell lung cancers (NSCLC) are not well known. METHODS The authors retrospectively reviewed the charts of inoperable patients who underwent thoracic stereotactic body radiation therapy (SBRT) from February 2007 to April 2019. Those with previous small cell lung cancers or SBRT treatments for tumors other than NSCLC were excluded. Multivariate Cox regression and a matched pair cohort analyses evaluated the prognoses of patients undergoing definitive SBRT for a new second primary. RESULTS Of 438 patients who underwent definitive SBRT for NSCLC, 84 had previously treated NSCLC. Univariate log-rank tests identified gender, Karnofksy performance status (KPS), prior lung cancer, anticoagulation use, and history of heart disease to correlate with overall survival (OS) (P

With the complexity of cancer treatment rising, the role of multidisciplinary conferences (MDCs) in making diagnostic and treatment decisions has become critical. This study evaluated the impact of a thoracic MDC (T-MDC) on lung cancer care quality and survival.Lung cancer cases over 7 years were identified from the Roswell Park cancer registry system. The survival rates and treatment plans of 300 patients presented at the MDC were compared with 300 matched patients. The National Comprehensive Cancer Network (NCCN) guidelines were used to define the standard of care. The compliance of care plans with NCCN guidelines was summarized using counts and percentages, with comparisons made using the Fisher exact test. Survival outcomes were summarized using Kaplan-Meier methods.There was improvement in median overall survival (36.9 vs 19.3 months; P.001) and cancer-specific survival (48 vs 28.1 months; P.001) for lung cancer patients discussed at the T-MDC compared with controls. These differences were statistically significant in patients with stages III/IV disease but not in patients with stages I/II disease. The NCCN guidelines compliance rate of treatment plans improved from 80% to 94% (P.001) after MDC discussion. MDC recommendations resulted in treatment plan changes in 123 of 300 patients (41%).Our results suggest that lung cancer patients have a survival benefit from MDC discussion compared with controls. Patients with advanced disease (stages III and IV) benefited the most. Further research is necessary to understand the precise mechanisms that drive these results.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

Mediastinoscopy is considered the gold standard for preresectional staging of lung cancer. We sought to examine the effect of concomitant mediastinoscopy on postoperative pneumonia (POP) in patients undergoing lobectomy. All patients in our institutional database (2008–2015) undergoing lobectomy who did not receive neoadjuvant therapy were included in our study. The relationship between mediastinoscopy and POP was examined using univariate (Chi square) and multivariate analyses (binary logistic regression). In order to validate our institutional findings, lobectomy data in the National Surgical Quality Improvement Program (NSQIP) from 2005 to 2014 were analyzed for these associations. Of 810 patients who underwent a lobectomy at our institution, 741 (91.5%) surgeries were performed by video-assisted thoracic surgery (VATS) and 487 (60.1%) patients underwent concomitant mediastinoscopy. Univariate analysis demonstrated an association between mediastinoscopy and POP in patients undergoing VATS [odds ratio (OR) 1.80; p = 0.003], but not open lobectomy. Multivariate analysis retained mediastinoscopy as a variable, although the relationship showed only a trend (OR 1.64; p = 0.1). In the NSQIP cohort (N = 12,562), concomitant mediastinoscopy was performed in 9.0% of patients, with 44.5% of all the lobectomies performed by VATS. Mediastinoscopy was associated with POP in patients having both open (OR1.69; p

Background: Sampling the bronchial airway during bronchoscopies in screening populations at high risk for lung cancer has increased detection of squamous bronchial pre-malignant lesions (PML). The majority of these lesions will regress or remain stable without any clinical intervention. However, a subset of lesions will progress to invasive malignancy. In this work, we investigate the gene expression changes in epithelial cell states and immune cell proportion shifts associated with premalignant histologic stage using single-cell RNA sequencing to begin to identify molecular features associated with PML regression or progression. Methods: Cells (n=3,325) were isolated from 11 endobronchial biopsies from 9 patients, where biopsy histology range from normal, dysplasia, carcinoma in situ (CIS) and squamous cell carcinoma. Immune cells (CD45+) and epithelial cells (CD45− EPCAM+) were sorted into separate 96-well plates using fluorescence activated cell sorting (FACS) and sequenced using CEL-Seq2 single cell RNA seq protocol. Results: After filtering low quality cells, we profiled 2,998 cells (1,052 CD45+ and 1,946 CD45−) with an average of 1,190 genes per cell. Within the epithelial cells, we focused on basal cells as they are the airway progenitor cells. We observed distinct differences in expression of KRT5+ (basal) cells between different histologic grades, where KRT5+ cells present in a hyperplasic lesion expressed multiple secretory cell markers suggesting they were transitioning to a secretory cell phenotype and KRT5+ cells from a CIS lesion from a current smoker expressed higher levels of smoking inducible genes, such as GSTM1 and CYP1A1. Lastly, KRT5+ cells from a lung squamous carcinoma tumor expressed higher levels of many genes related to cell cycle progression. Among the immune populations, low-grade PMLs with non-dysplastic histology were enriched for CD8+ T cells, whereas higher-grade PMLs and an invasive tumor were enriched for myeloid cells. Conclusions: To date, we have begun to identify histology-associated cellular and molecular profiles in bronchial premalignancy and early-stage carcinoma. Future resampling of these patients and expansion of cases will allow us to discover biomarkers associated with lesion progression and molecular targets for lung cancer interception. Citation Format: Conor Shea, Lukas Kalinke, Kitty De Jong, Kate Gowers, Diane Ding, Sherry Zhang, Gang Liu, Jack Cunningham, Ipsita Dey-Guha, Mark Hennon, Sai Yendumuri, Christopher Stevenson, Steven Dubinett, Avrum Spira, Marc Lenburg, Samuel Janes, Mary Reid, Jennifer Beane, Sarah Mazzilli, Joshua D. Campbell. Cellular and molecular changes associated with lung squamous premalignant lesion severity identified by single-cell RNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2212.

Accurate staging of the mediastinum is a critical element of therapeutic decision making in non-small cell lung cancer. We sought to determine the utility of transcervical extended mediastinal lymphadenectomy (TEMLA) in staging non-small cell lung cancer for large central tumors and after induction therapy.A retrospective record review was performed of all patients who underwent TEMLA at our institution from 2010 to 2015. Clinical stage as assessed by positron emission tomography integrated with computed tomography (PET-CT), stage as assessed by TEMLA, final pathologic stage, lymph node yield, and clinical characteristics of tumors were assessed along with TEMLA-related perioperative morbidity. Accuracy of staging by TEMLA for restaging the mediastinum after neoadjuvant therapy was compared with that of PET-CT.Of 164 patients who underwent TEMLA, 157 (95.7%) were completed successfully. Combined surgical resection along with TEMLA was performed in 138 of these patients, with 131 (94.2%) undergoing a video-assisted thoracoscopic resection. The recurrent laryngeal nerve injury rate was 6.7%. TEMLA was performed in 118 of 164 patients for restaging after neoadjuvant therapy, and 101 of these patients were also restaged by PET-CT. Based on TEMLA, 7 patients did not go on to have resection. Of the 101 patients who did have a resection, TEMLA was more accurate than PET-CT in staging the mediastinum (95% vs 73%, p0.0001). However, the pneumonia rate in this subgroup of patients was 13%.TEMLA is a safe procedure and superior to PET-CT for restaging of the mediastinum after neoadjuvant therapy for non-small cell lung cancer. However, this increased accuracy comes with a high postoperative pneumonia rate.

Video-assisted thoracoscopic surgery (VATS) has been widely accepted as a standard approach for early stage non-small cell lung cancer resection, along with increased application for more complex tumor pathology. With advancing techniques and technology, more complex cases are being performed with acceptable results. We reviewed recent advances in how VATS techniques are increasingly being used to successfully and safely replicate open thoracic surgical procedures. We reviewed current literature on VATS for complex cases. VATS is feasible and can be safely performed for complex cases in experienced hands. Further prospective studies are needed to validate its utility for complex cases.

This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

Standard treatment for early-stage non–small cell lung cancer has traditionally involved lobectomy. Historical data that demonstrates suboptimal results for sublobar resection compared to lobectomy have been challenged in recent years with retrospective data for patients with T1a disease. For patients who are not candidates for lobectomy, options for sublobar resection include wedge resection or anatomic segmentectomy. Segmentectomy has long been held to be a better cancer operation than wedge resection, and its role in treating early-stage lung cancer remains controversial in patients who are candidates for lobectomy. A review of available literature involving segmentectomy and possible predictors of failure for segmentectomy was performed in an attempt to clarify the role of segmentectomy for early-stage lung cancer. Current evidence is conflicting regarding the optimal scenario for sublobar resection with segmentectomy. Two large-scale randomized trials are currently addressing the question. In the meantime, certain preoperative and intraoperative considerations should be taken into account when considering segmentectomy for the treatment of early-stage non–small cell lung cancer.

OBJECTIVES Proponents of open thoracotomy (OPEN) and robot-assisted thoracic surgery (RATS) claim its oncological superiority over video-assisted thoracic surgery (VATS) in terms of the accuracy of lymph node staging. METHODS The National Cancer Database was queried for patients with non-small-cell lung cancer (NSCLC) undergoing lobectomy without neoadjuvant therapy from 2010 to 2014. Nodal upstaging rates were compared using a surgical approach. Overall survival adjusted for confounding variables was examined using the Cox proportional hazards model. RESULTS A total of 64 676 patients fulfilled the selection criteria. The number of patients who underwent lobectomy by RATS, VATS and OPEN approaches was 5470 (8.5%), 17 545 (27.1%) and 41 661 (64.4%), respectively. The mean number of lymph nodes examined for each of these approaches was 10.9, 11.3 and 10 (P CONCLUSIONS RATS lobectomy is not superior to VATS lobectomy with respect to lymph node yield or upstaging of NSCLC. Increased nodal upstaging by the OPEN approach does not confer a survival advantage in any stage of NSCLC and may be associated with decreased overall survival.

BACKGROUND: Minimally invasive foregut surgery is increasingly performed for both benign and malignant diseases. We present a retrospective series of patients who underwent minimally invasive Ivor Lewis esophagectomy (MIE) with linear stapled anastomosis performed at two centers in the United States, with a focus on evaluating leak and stricture rates. METHODS: Patients treated from 2007 to 2018 were included, and data on demographics, oncologic treatment, pathology, and outcomes were analyzed. The surgical technique utilized laparoscopic and thoracoscopic access, with an intrathoracic esophagogastric anastomosis using a 6-cm linear stapled side-to-side technique. RESULTS: A total of 124 patients were included and 114 resections (91.9%) were completed in a minimally invasive fashion with a 6-cm linear stapled side-to-side anastomosis. Patients were predominantly male (90.7%) with a median age of 66.0 years and body mass index of 28.8 kg/m(2). Of 121 patients with malignancy, negative margins were obtained in 94.3% and median lymph node yield was 15 (IQR 12–22). In the intention to treat analysis, median operative time was 463 minutes (IQR 403–515), blood loss was 150 mL (IQR 100–200), and length of stay was 8 days (IQR 7–11). Postoperative complications were experienced by 64 patients (51.6%) including respiratory failure in 14 (11.3%) and pneumonia in 12 (9.7%). In patients who successfully underwent a 6-cm stapled side-to-side anastomosis, anastomotic leaks occurred in 6 patients (5.1%) without need for operative intervention, and anastomotic strictures occurred in 6 patients (5.1%) requiring endoscopic management. CONCLUSIONS: Ivor Lewis MIE with a 6-cm linear stapled anastomosis can be completed with a high technical success rate, and low rates of anastomotic leak and stricture.

103 Background: Opioids are routinely given for postoperative pain management with limited evidence on the amount needed to be dispensed. Prescribed opioids increase the risk of chronic use, abuse, and diversion, which contribute to the opioid epidemic. We sought to demonstrate that postsurgical acute pain can be effectively managed across different surgical specialties with a markedly reduced number of opioids. Methods: A prospective case-control study of restrictive opioid prescription protocol (ROPP) was implemented in all surgical services from February 2019 through July 2019 at a tertiary comprehensive cancer center for all patients undergoing a surgery for which opioids would be routinely prescribed at discharge (n = 2,015). Data from surgeries performed by the same services from August 2018 through January 2019 were used for comparison (n = 2,051). At discharge, patients did not routinely receive opioids unless they had a maximally invasive procedure or if they required multiple doses of opioids during hospitalization (maximum 3-day supply). Compliance with the protocol was tracked by pharmacists daily. Patient demographics and surgical details were collected. State-run opioid prescription database was used to determine the number of opioids prescribed to all surgical patients within a 120-day surgical window. Validated patient satisfaction surveys were used at postoperative visits to assess patient experience. Results: After implementation of the ROPP, 45% less opioids were prescribed after surgery for all participating patients (323,674 morphine milligram equivalents (MME) vs 179,458 MME, p < 0.001). The majority of services complied with the ROPP in more than 95% of cases. There was no difference in postsurgical pain intensity between cohorts. Patients in the ROPP cohort had less refill requests compared to the control group (20.9% vs 17.9%, p value = 0.016). Surveys were completed by 338 patients in the control group (16.5%) and 360 in the ROPP group (17.9%). There was no significant difference in patient reported satisfaction with postoperative pain control or on the impact of pain on daily activities between the cohorts. Conclusions: Implementation of a ROPP by multiple surgical services at a tertiary cancer center was feasible and resulted in substantial decrease in the number of opioids prescribed while not compromising patient experience. Patients did not require more prescription refills despite being provided no opioids or a limited supply. This study provides evidence to support reducing the number of opioids routinely prescribed after surgery.[Table: see text]

Primary tracheobronchial neoplasms represent approximately 0.1% of all pulmonary tumors (1). They have been a topic of interest for many decades due to the challenge in their diagnosis and management. Many of tracheobronchial tumors are found incidentally. They are sometimes misdiagnosed as asthma or chronic obstructive pulmonary disease.

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

Background Standard therapy for stage III non-small cell lung cancer with chemotherapy and conventional radiation has suboptimal outcomes. We hypothesized that a combination of surgery followed by stereotactic body radiation therapy (SBRT) would be a safe alternative. Methods Patients with stage IIIA (multistation N2) or IIIB non-small cell lung cancer were enrolled from March 2013 to December 2015. The protocol included transcervical extended mediastinal lymphadenectomy (TEMLA) followed by surgical resection, 10 Gy SBRT directed to the involved mediastinum/hilar stations and/or positive surgical margins, and adjuvant systemic therapy. Patients not suitable for anatomic lung resection were treated with 30 Gy to the primary tumor. The primary efficacy end-point was the proportion of patients with grade 3 or higher adverse events (AE) or toxicities. Results Of 10 patients, 7 patients underwent neoadjuvant chemotherapy. All patients had TEMLA. Nine of 10 patients underwent surgical resection. The remaining patient had an unresectable tumor and received 30 Gy SBRT to the primary lesion. All patients had post-operative SBRT. Median follow-up was 18 months. There were no perioperative mortalities. Six patients had any grade 3 AEs with no grade 4–5 AEs. Of these, 4 were not attributable to radiation. Pulmonary-related grade 3 AEs were experienced by 2 patients. There were no failures within the 10 Gy volume. Overall survival and progression-free survival rates at 2 years were 68% (90% CI 36–86) and 40% (90% CI 16–63), respectively. Conclusions In carefully selected patients with locally advanced non-small cell lung cancer, combining surgery with SBRT was well tolerated with no local failure. Trial registration ClinicalTrials.gov identifying number NCT01781741. Registered February 1, 2013.

Introduction Minimally invasive approaches are increasingly being used for the conduct of complex surgical procedures. Whether the benefits of minimally invasive approaches compared to thoracotomy for sublobar and lobar lung resection for NSCLC are realized for patients undergoing pneumonectomy is not clear. Methods The National Cancer Database was queried for patients who underwent pneumonectomy for NSCLC from 2010 to 2014. Case data from patients who underwent resection by minimally invasive surgery (MIS) were compared with those from patients who received thoracotomy (open) in an intention-to-treat analysis. Associations between potential covariates and treatment were analyzed using the Pearson chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables. Univariable and multivariable logistic models and proportional hazards model were used to assess the effect of surgical approach on 30-day and 90-day mortality and overall survival. Relative prognosis was summarized using odds ratios and hazards ratios estimates and 95% confidence limits. Results A total of 4,938 patients underwent pneumonectomy during the study period, of which 755 (15.3%) were completed by MIS. No difference was noted in 30- and 90-day mortality rates for MIS compared to open approaches (6.8% and 12.3% versus 6.7% and 11.9%, respectively; p = 0.9 and 0.86, respectively). Tumor histology and stage characteristics were similar between the two groups. The mean number of lymph nodes examined was higher in the MIS group compared to the open thoracotomy group (17.1 ± 0.4 versus 16.1 ± 0.2, p = 0.034). The conversion rate for the MIS cohort was 36.7%. Surgical approach was not associated with any difference in perioperative mortality with univariable or multivariable analysis. MIS was associated with improved overall survival on univariable analysis, but this was not evident with multivariable analysis. Conclusions Pneumonectomy performed by minimally invasive approaches does not compromise perioperative mortality or long-term outcomes. Further investigation into the impact of minimally invasive approaches on perioperative outcomes for whole-lung resection is warranted.

Aim Although tumor depth of invasion is strongly associated with risk of lymph node metastasis and long-term survival in patients with esophageal adenocarcinoma, the significance of differential T2 invasion (inner circular layer versus outer longitudinal layer) is unknown. The current study was undertaken to explore the hypothesis that greater T2-specific depth of invasion is associated with inferior long-term outcomes in patients with esophageal adenocarcinoma treated with esophagectomy. Patients and methods Demographic, treatment, and outcome data were collected for patients with resected pT2N0-3M0 esophageal adenocarcinoma treated between 2005 and 2015 pooled from four U.S. academic medical centers. Two blinded pathologists evaluated depth of muscularis propria tumor invasion. Univariate and Cox proportional hazard regression analyses were performed to identify prognostic factors for overall (OS) and disease-free (DFS) survival, and Kaplan-Meier analysis to compare survival differences specific to prognostic factors. Results A total of 84 patients were identified for analysis (53 with circular invasion; 31 with longitudinal invasion), with a median age of 66 years. Sixty percent of patients (50/84) received induction therapy prior to esophagectomy. The median OS and DFS was 58 months (95% confidence interval(CI)=42 months-not reached) and 27 months (95% CI=13.7-66 months) respectively. Depth of muscularis propria invasion did not correlate with OS or DFS on univariate (p=0.42; and p=0.34, respectively) or multivariate (p=0.15 and p=0.21, respectively) analysis after adjustment for age, nodal status, perineural invasion, and tumor grade. These findings did not vary by induction therapy status. Conclusion Depth of muscularis propria invasion does not appear to correlate with survival in patients with esophageal adenocarcinoma.

Background Neoadjuvant treatment improves survival for patients undergoing esophagectomy for esophageal cancer. Recent evidence suggests that neoadjuvant chemoradiation offers no advantage over chemotherapy alone before surgical resection for adenocarcinoma histology. We sought to examine if this applies to patients with squamous cell histology. Materials and methods The National Cancer Database was queried for patients who underwent treatment for squamous cell carcinoma of the esophagus from 2004 to 2012. Patients who underwent neoadjuvant chemotherapy before esophagectomy were compared with those undergoing chemotherapy and radiation before surgical resection. Associations between potential covariates and treatment were analyzed using the Pearson chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables. Univariate and multivariate proportional hazards modeling results were used to assess the effect of treatment on overall survival. Relative prognosis was summarized using estimates and 95% confidence limits for the hazard ratio. Unadjusted differences in overall survival and disease-specific survival between the treatment are shown using Kaplan-Meier methods. Results A total of 902 patients underwent neoadjuvant therapy before surgical resection during the study period, with 827 receiving chemotherapy and radiation, and 75 receiving chemotherapy alone preoperatively. The 30- and 90-d mortality for patients undergoing neoadjuvant chemotherapy and radiation followed by surgery were 5.4% and 10.4% compared to 5.5% and 11.1% for patients who received chemotherapy alone preoperatively (P = 0.963 and P = 0.856), respectively. Median overall survival for patients receiving chemotherapy and radiation was 36.0 mo versus 40.8 mo for chemotherapy alone. The 5-y survival was 39% for the chemotherapy and radiation group and 43% for the chemotherapy group (logrank P = 0.7212). Conclusions For patients undergoing neoadjuvant treatment before planned surgical resection of squamous cell carcinoma of the esophagus, the addition of radiation to neoadjuvant chemotherapy did not improve long-term survival and did not appear to impact short-term outcomes postoperatively. Further study with a randomized phase III trial is needed.

Although tumor depth of invasion is strongly associated with risk of lymph node metastasis and long-term survival in patients with esophageal adenocarcinoma, the significance of differential T2 invasion (inner circular layer versus outer longitudinal layer) is unknown. The current study was undertaken to explore the hypothesis that greater T2-specific depth of invasion is associated with inferior long-term outcomes in patients with esophageal adenocarcinoma treated with esophagectomy.Demographic, treatment, and outcome data were collected for patients with resected pT2N0-3M0 esophageal adenocarcinoma treated between 2005 and 2015 pooled from four U.S. academic medical centers. Two blinded pathologists evaluated depth of muscularis propria tumor invasion. Univariate and Cox proportional hazard regression analyses were performed to identify prognostic factors for overall (OS) and disease-free (DFS) survival, and Kaplan-Meier analysis to compare survival differences specific to prognostic factors.A total of 84 patients were identified for analysis (53 with circular invasion; 31 with longitudinal invasion), with a median age of 66 years. Sixty percent of patients (50/84) received induction therapy prior to esophagectomy. The median OS and DFS was 58 months (95% confidence interval(CI)=42 months-not reached) and 27 months (95% CI=13.7-66 months) respectively. Depth of muscularis propria invasion did not correlate with OS or DFS on univariate (p=0.42; and p=0.34, respectively) or multivariate (p=0.15 and p=0.21, respectively) analysis after adjustment for age, nodal status, perineural invasion, and tumor grade. These findings did not vary by induction therapy status.Depth of muscularis propria invasion does not appear to correlate with survival in patients with esophageal adenocarcinoma.

The case of a 56-year-old male who developed bronchopulmonary hemorrhage after a course of stereotactic body radiation therapy (SBRT) for centrally located squamous cell lung carcinoma is presented. The patient was previously treated with concurrent chemoradiation for stage IVA squamous cell carcinoma of the base of tongue. He showed no evidence of disease for 4 years until he developed a solitary metastasis of squamous cell carcinoma in the right hilum. He underwent a single fraction of 26 Gy with heterogeneity correction. He showed no evidence of disease for 13 months until he developed a sudden grade 4 bronchopulmonary hemorrhage. He underwent an urgent right pneumonectomy and later died of a post-operative complication. Pathologic analysis of the specimen revealed no evidence of tumor. Single-fraction SBRT of 26 Gy was sufficient to achieve complete response of his large central lung tumor. However, when treating patients with central lung tumors, some risk of mortality may be unavoidable with either SBRT or pneumonectomy.

Background: As screening for lung cancer rises, an increase in the diagnosis of early stage lung cancers is expected. Lobectomy remains the standard treatment, but there are alternatives, consideration of which requires an estimation of the risk of surgery. Sarcopenia, irrespective of body mass index, confers a worse prognosis in many groups of patients including those undergoing surgery. Here we examine the association of muscle mass with outcomes for patients undergoing lobectomy. Methods: Consecutive patients undergoing lobectomy were retrospectively reviewed. Preoperative computed tomography scans were reviewed, and cross-sectional area of the erector spinae muscles and pectoralis muscles was determined and normalized for height. Univariate and multivariate analyses were then done to examine for an association of muscle mass with morbidity and short- and long-term mortality. Results: During the study period, there were 299 lobectomies, 278 of which were done by video assisted thoracoscopic surgery. The average age of the patients was 67.5±10.6 years. Overall complication rate was 52.2%, pneumonia rate was 8.7%, and the 30-day mortality rate was 1.3%. Mean height adjusted-erector spinae muscle cross-sectional area was 10.6±2.6 cm 2 /m 2 , and mean height adjusted-pectoralis muscle cross sectional area was 13.3±3.8 cm 2 /m 2 . The height adjusted cross sectional areas of the erector spinae and pectoralis muscles were not associated with overall complication rate, rate of pneumonia, readmission, or intensive care unit length of stay. The height adjusted-erector spinae muscle cross sectional area was inversely correlated with 30-day mortality risk, odds ratio 0.77 (95% CI, 0.60–0.98, P=0.036). Mean length of stay was 7.0 days (95% CI, 5.5–8.4 days). Multivariate analysis demonstrated a significant inverse association of the height adjusted-erector spinae muscle cross sectional area with length of stay (P=0.019). Conclusions: The height adjusted-erector spinae muscle cross sectional area was significantly associated with 30-day mortality and length of stay in the hospital. Measurement of muscle mass on preoperative computed tomography imaging may have a role to help predict risk of morbidity and mortality prior to lobectomy.

Recently published results from Semenkovich et al. in the March 2019 edition of the Annals of Thoracic Surgery reporting on the impact of induction radiation dosing on outcomes after esophageal resection in patients undergoing tri-modality therapy offer an answer to an important question regarding the treatment of patients with operable esophageal cancer (1).

Recently published results from Long et al . in the February 2018 edition of the Annals of Thoracic Surgery report on a completed surgical trial that many thoracic surgeons may have deemed mission impossible: a trial comparing results for patients undergoing lobectomy for early stage non-small cell lung cancer (NSCLC) who were randomized by approach to resection by video assisted thoracoscopic surgery (VATS) versus axillary thoracotomy (1).

Background Because the traditional open lung approach with en bloc chest wall resection carries substantial risk for complications and death, we studied our thoracoscopic approach for this operation. Methods From 2007 to 2013, all consecutive video-assisted thoracoscopic (VATS) and open chest wall resections at a comprehensive cancer center were tabulated retrospectively. Data were analyzed by approach, type, and cause of early major morbidity and mortality. Lung cancer cases (the largest subset, T3) were analyzed separately. Statistical tests included the Kruskal-Wallis test for continuous variables and the χ 2 for categoric variables. Survival data were analyzed by the Kaplan-Meier method and log-rank tests. Results Of 47 chest wall resections performed, 17 (36%) were performed by VATS with no conversions. Resections were performed for primary non-small cell lung cancer (15 VATS and 16 thoracotomy), sarcoma (11), metastatic disease from a separate primary (2), and benign conditions (3). Patients undergoing a VATS approach were older (76 vs 56 years, p = 0.003), and the operative times, blood loss, and ribs resected were similar between groups. Patients undergoing VATS had shorter intensive care unit and hospital lengths of stay, but both groups had high hospital morbidity and mortality, largely resulting from postoperative pneumonia or respiratory systemic inflammatory response syndrome (n = 5), stroke (n = 2), and postoperative colon ischemia (n = 1). Groups had a 90-day mortality of 26.7% and 25% respectively. Stage-matched survival curves for both approaches were superimposable ( p =0.88). Conclusions Thoracoscopic chest wall resection was feasible, expanded our case selection, and reduced prosthetic reconstruction. It did not, however, protect frail, elderly patients reliably. Briefer, less traumatic operations may be needed for this cohort.

OBJECTIVES: Neoadjuvant therapy has emerged as a favoured treatment paradigm for patients with clinical N2 disease undergoing surgical resection for non-small-cell lung cancer. It is unclear whether such a treatment paradigm affects perioperative outcomes. We sought to examine the National Cancer Database (NCDB) to assess the impact of neoadjuvant therapy on perioperative outcomes and long-term survival in these patients. METHODS: All patients with a history of non-small-cell lung cancer undergoing anatomical resection between 2004 and 2014 were included. Thirty-day and 90-day mortality of all patients having neoadjuvant therapy versus those who did not were compared. In addition, the impact of neoadjuvant therapy on the overall survival of patients with clinical N2 disease was examined. RESULTS: Of the 134 428 selected patients, 9896 (7.4%) patients had neoadjuvant chemotherapy. Patients undergoing neoadjuvant therapy had a higher 30-day (3% vs 2.6%; P

Early stage lung cancer is being detected at a higher frequency with the implementation of screening programs. At the same time, medically complex patients with multiple comorbidities are presenting for surgery, with a concomitant rise in rates of sublobar resection. We sought to examine the effect of sampling lymph nodes on the outcomes of patients who undergo sublobar resection for small (2 cm) stage I non-small cell lung cancer (NSCLC).All patients in the Surveillance, Epidemiology, and End Results database from 2004 to 2013 with small (2 cm) stage I NSCLC who underwent sublobar resection (wedge/segmentectomy) and no other cancer history were included. The association of the number of lymph nodes examined (LNE; categories none, 1-3, 4-6, 7-9,9) with the overall survival as well as disease-specific survival were examined using univariate as well as multivariate analyses while controlling for covariates such as age, size (1 cm,1 cm), grade, histology (adenocarcinoma vs others), and extent of resection (wedge/segmentectomy).Data from 3916 eligible patients were analyzed. Seven hundred fifteen patients (18.3%) had segmentectomy. No lymph nodes were examined in 49% and 23% of wedge resection and segmentectomy patients, respectively. Among all eligible patients, 1132 (29%), 474 (12%), 228 (6%), and 328 (8%) patients had 1 to 3, 4 to 6, 7 to 9 and 9 LNE, respectively. Univariate analyses showed significant associations between overall and disease-specific survivals with age, grade, histology, sex, extent of surgery, and LNE. The association between the number of LNE and survival remained significant even after adjusting for significant covariates including extent of sublobar resection (hazard ratio for groups with LNE 1-3, 4-6, 7-9, and9 compared with 0 LNE were 0.79, 0.77, 0.68, and 0.45 for overall survival; P .001) and 0.85, 0.77, 0.71, and 0.44 for disease-specific survival (P .05), respectively. In multivariate modeling, LNE was retained as a significant variable and extent of resection was not. In patients in whom at least 1 lymph node was examined, extent of resection was not predictive of outcome.Many patients having sublobar resection for early stage NSCLC in the United States do not have a single lymph node removed for pathologic examination. The number of LNE is associated with improved survival, presumably due to avoidance of mis-staging. This association seems greater than the association with extent of resection (segmentectomy vs wedge resection). Appropriate lymph node examination remains an important part of resection for lung cancer even if the resection is sublobar.

Current published information of adenosquamous carcinoma (ASC) of the esophagus in the United States is limited to isolated case reports. We sought to study the clinical characteristics of this tumor using the Surveillance, Epidemiology and End Results (SEER) database.Relevant data of all patients with esophageal cancer in the SEER database diagnosed from 1998-2010 was obtained. Demographic, grade, stage, treatment and survival characteristics of patients with ASC were summarized and compared to those patients with adenocarcinoma (ACA) and squamous cell carcinoma (SqCC). Univariate analyses across comparison groups were performed using Wilcoxon rank sum test for continuous covariates and the Pearson Chi-square test for categorical covariates. To evaluate the association of selected covariates to survival by histology, unadjusted and adjusted proportional hazards models were generated for the entire study population. To further control for the difference in covariates among the histology groups, propensity weighted Cox regression modeling was performed using the inverse propensity to treat weighting (IPTW) approach.Of 29,890 patients with the histological subgroups, only 284 patients had ASC (1%). Patients with ACA had a higher grade (72.9% with grade III/IV) and presented with advanced stage (48.2% distant disease) than their comparison group. Patients with ASC had worse overall survival compared to ACA but not SqCC in both univariate and multivariate analyses (OR =0.76; P0.05 and OR =0.86; P0.05 respectively). These results were further confirmed by the propensity weighted Cox regression analysis. Analysis of the ASC population alone demonstrated that decreasing stage, radiation therapy (OR =0.59; P0.001) and surgery (OR =0.86; P0.001) were associated with better overall survival, but grade was not.ASC of the esophagus is a rare histological variant comprising 1% of esophageal ACA in the Unites States. This histological subtype presents in later stages, at a higher grade and portends a poorer survival than the more common ACA. Radiation therapy and surgical resection of appropriate stage patients provide the best chance of survival.

BACKGROUND It is unclear whether thoracoscopic (video-assisted thoracoscopic surgery [VATS]) pneumonectomy improves outcomes compared with open approaches. METHODS One hundred seven consecutive pneumonectomies performed at an experienced center from January 2002 to December 2012 were studied retrospectively. Forty cases were open, and 50 successful VATS and 17 conversions were combined (intent-to-treat [ITT] analysis). RESULTS The VATS cohort had more preoperative comorbidities (three vs two, P = .003), women (57% vs 30%, P = .009), and older ages (65 years vs 63 years, P = .07). Although advanced clinical stage was less for VATS (26% vs 50% stage III, P = .035), final pathologic staging was similar (25% vs 38%, P = .77). Pursuing a VATS approach yielded similar complications (two vs two, median, P = .73) with no catastrophic intraoperative events like bleeding. Successful VATS pneumonectomy rates rose from 50%-82% by the second half of the series ( P P = .03). Conversions resulted in longer ICU stays (4 days vs 2 days, P = .01). Advanced clinical stage (III-IV) ITT VATS had longer median overall survival (OS) (42 months vs 13 months, log-rank P = .042). Successful VATS cases with early pathologic stage (0-II) had a median OS of 80 vs 16 months for converted and 28 months for open (log rank = 0.083). CONCLUSIONS Attempting thoracoscopic pneumonectomy at an experienced center appears safe but does not yield the early pain/complication reductions observed for VATS lobectomy. There may be long-term pain/survival advantages for certain stages that warrant further study and refinement of this approach.

Video-assisted thoracoscopic surgery (VATS) approaches to lobectomy for treatment of early stage non-small cell lung cancer (NSCLC) have generally been accepted to be beneficial. Experience and results for more extensive resections, including thoracoscopic pneumonectomy are limited. Here we report a case with attached videos describing key technical aspects of performing a thoracoscopic left pneumonectomy. This demonstrates the adoption of VATS for tumor pathology requiring pneumonectomy is feasible and can be done safely. Further study is needed to clarify potential advantages or drawbacks to approaching more complex tumor pathology by VATS.

Background By avoiding chest wall resection, iridium-192 (Ir-192) high-dose-rate (HDR) intraoperative brachytherapy (IOBT) and video-assisted thoracoscopic surgery (VATS) might improve outcomes for high-risk patients requiring surgical resection for pulmonary malignancy with limited pleura and/or chest wall involvement. Methods and materials Seven patients with non-small cell lung cancer involving the pleura or chest wall underwent VATS pulmonary resections combined with HDR IOBT. After tumor extraction, an Ir-192 source was delivered via a Freiburg applicator to intrathoracic sites with potential for R1-positive surgical margins. The number of catheters, dwell position along each catheter, prescription depth, and dose were customized based on clinical needs. Results Six patients had pT3N0M0 non-small cell lung cancers. A seventh case was a recurrent sarcomatoid carcinoma. One case required conversion to open thoracotomy for pneumonectomy with en bloc chest wall resection. There were no intraoperative complications and average operative time was 5.8 hours. Five of seven patients without transmural chest wall involvement underwent rib-sparing resection. Four of the 6 patients treated with VATS and IORT remain alive in follow-up without evidence of local recurrence (median follow-up, 25 months). Noted toxicities were recurrent postoperative pneumothorax, pleural effusion with persistent chest wall pain, avid fibrosis at 2 years of follow-up, and a late traumatic rib fracture. Conclusions HDR IOBT with Ir-192 via VATS is technically feasible and safe for intrathoracic disease with pleural and/or limited chest wall involvement. Short-term morbidity associated with chest wall resection may be reduced. Additional study is required to define long-term benefits.