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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.

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 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

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.

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.

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]

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.

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

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 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.

Thoracoscopic lobectomy is well established for the treatment of early non-small cell lung cancer (NSCLC). Its safety and efficacy for advanced-stage disease remain uncertain. Between January 1, 2002, and July 31, 2007, a total of 125 patients were evaluated for thoracoscopic lobectomy for advanced NSCLC. Thoracoscopic lobectomy was completed in 73 patients. Eleven patients were excluded for extensive chest wall involvement. Open resection was performed in 41 patients, with 19 planned thoracotomies and 22 conversions from an initial thoracoscopic approach. Median operative blood loss, operation time, major complications, and hospital length of stay were all similar for patients undergoing thoracoscopic and open resection. A higher percentage of patients who underwent thoracoscopic lobectomy were able to receive adjuvant therapy compared to the open group (37.2% vs. 5.2%; P = 0.006). The differences between the thoracoscopic and open groups in overall survival (43.7 vs. 22.9 months; P = 0.59) and disease-free survival (34.7 vs. 16.7 months; P = 0.84) were not significant. Thoracoscopic lobectomy for advanced-stage NSCLC can be performed safely, with results equivalent to open techniques. With continued experience, lower morbidity with resections performed for advanced-stage disease by video-assisted thoracoscopic surgery will be expected, similar to that observed with early-stage disease. This is particularly important given the large number of frail patients with advanced-stage disease who require multimodal therapy.

Background: Lymph node staging provides the most important prognostic information in patients with loco-regional non-small cell lung cancer. We hypothesized that gamma radiation detection using an intra-operative hand-held gamma probe following intravenous 18F-fluorodeoxyglucose (FDG) injection would identify lymph nodes containing metastases in a much more sensitive manner than standard pathological practices. We compared the accuracy of detecting thoracic lymph node metastases using positron emission tomography- computed tomography (PET-CT) versus the gamma probe. Methods: One hundred patients with resectable lung cancers had pre-operative positron emission tomography-computed tomography (PET-CT) and mediastinoscopy. 10mCi of FDG was injected on the day of surgery. A handheld gamma probe detected increased FDG uptake within thoracic lymph nodes during pulmonary resection procedures. The lymph nodes that demonstrated increased FDG uptake, but were non-malignant by conventional H&E staining underwent further serial sectioning, immunohistochemistry (IHC) and RT-PCR (reverse transcriptase - polymerase chain reaction). Sensitivity and specificity for lymph node metastasis detection by PET-CT and the gamma probe were calculated. Results: Three patients had metastatic lymphadenopathy detected at mediastinoscopy, so their procedures were aborted, while the others proceeded to lung resection and complete lymphadenectomy. Fifteen additional patients had lymph node involvement on routine pathologic analysis. IHC and RT-PCR detected micrometastatic lymph node disease in 4 and 29 patients, respectively. Using RT-PCR as the gold standard, the sensitivity and specificity of PET-CT for detection of lymph node metastasis were 11% and 98% respectively, in contrast to 38% and 50% respectively for the gamma probe. Conclusion: The intra-operative hand held gamma probe is more sensitive but less specific than PET-CT in detecting lymph node metastasis from lung cancer. Its overall accuracy was low, resulting in limited up-staging of patients. RT-PCR analysis of FDG-avid lymph nodes for epithelial markers increased the clinical utility of this probe in detecting micrometastasis. Such up-staged patients could derive a survival benefit from adjuvant chemotherapy. More specific radioisotopes are being developed to improve the clinical utility of this technique. Citation Format: Chukwumere Nwogu, Todd Demmy, Sai Yendamuri, Wei Tan, Paul Bogner, Elisabeth Dexter, Anthony Picone, Mark Hennon, Alan Hutson, Mary Reid, Richard Cheney, Alex Adjei. Radioguided detection of lymph node metastasis in non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4671. doi:10.1158/1538-7445.AM2013-4671

The last few years have witnessed an explosion of the use of minimally invasive techniques for the detection, diagnosis, and treatment of all stages of lung Cancer. The use of these techniques has improved the risk-benefit ratio of surgery and has made it more acceptable to patients considering lung surgery. They have also facilitated the delivery of multi-modality therapy to patients with advanced lung cancer. This review article summarizes current surgical techniques that represent the "cutting edge" of thoracic surgery for lung cancer.

Background. Xenograft models of non-small cell lung carcinoma (NSCLC) in immunodeficient mice have played an important role in the study of new chemotherapeutic regimens, including targeted agents. We hypothesize that the success of human tumor implantation in severe combined immune-deficient (SCID) mice will correlate with the observed clinical outcomes in patients with resected NSCLC. Such growth in mice may reflect the aggressiveness of human tumors. Methods. 196 lung cancer specimens from 193 patients who underwent surgical resection of NSCLC from June 1995 to June 2010 were implanted subcutaneously in (SCID) mice. Mice were observed for a period of six months to assess the success of tumor implantation. This was determined by the growth of tumors from 2-3 mm to 10 mm in diameter. Overall and disease free survival in patients were reviewed and were correlated with tumor growth in SCID mice. Results. Median overall and disease free survival in patients with successful tumor implantation in SCID mice was 16.3 months and 4.2 months vs. 38.6 and 20.6 months for patients whose tumor did not grow (logrank p = 0.0039 and 0.0024 respectively.) Half of all patients whose tumor successfully grew in SCID mice recurred or died within twelve months. Conclusions. Success of tumor implantation in SCID correlates with worse clinical outcome in patients with NSCLC. This model can be expanded to evaluate the predicted response of specific tumors to novel chemotherapeutic or molecularly targeted agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1610. doi:10.1158/1538-7445.AM2011-1610