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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 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

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

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.

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.

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.

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.

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.

An 86-year-old man was evaluated for asymptomatic persistent right upper lung (RUL) consolidation measuring 4×5 cm. He had worked as a welder in an automobile plant for 40 years and had, without protective gear, been exposed to smoke and dust from combustion of fuels. He had quit smoking 15 years prior to the work up for lung consolidation, with a previous 10 pack-year cigarette smoking history. He denied travelling to endemic areas of tuberculosis and sick contact exposure. His medications included hydrochlorothiazide and lisinopril for blood pressure control. Physical examination and laboratory work up were unremarkable. RUL consolidation …

Reversal of heparin anticoagulation with protamine may be associated with acute pulmonary vasoconstriction. The specific site of pulmonary vasoconstriction has not been determined. This study was designed to determine the site of protamine-induced pulmonary vasoconstriction and the role of nitric oxide (NO) after protamine injection. Pigs were anesthetized and instrumented with catheters for monitoring pulmonary arterial, systemic arterial, and central venous pressures. Pulmonary capillary pressure was estimated using the arterial occlusion concept, while left atrial pressure was estimated from the equilibrium wedge pressure. Hemodynamic measurements were made during baseline, before and after heparin (200 U/kg), at peak pressure response after protamine injection (2 mg/kg), and 10 and 30 min thereafter. In the control group, pulmonary vascular resistance (PVR) values during baseline and after heparin were identical (2.7 ± 0.4 mm Hg.L -1 .min -1 ). At peak protamine response (1-2 min) PVR increased to 8.0 ± 1.6, but returned to baseline value after 10 min (2.8 ± 0.3) and remained stable for 30 min (2.2 ± 0.3). The increase in PVR after protamine was primarily due to an increase in venous resistance from 1.0 ± 0.2 to 4.9 ± 1.4 mm Hg.L -1 .min -1 , and a much smaller increase in arterial resistance from 1.7 ± 0.3 to 3.4 ± 0.6 mm Hg.L -1 .min -1 . A second group was treated with nitro w -L-arginine (LNA, 20 mg/kg) to inhibit NO release, and then heparin and protamine were administered as in the first group. Heparin had no effect on pressures, but protamine increased PVR by the same magnitude as in Group 1. At peak response, venous resistance increased from 2.4 ± 0.5 to 6.2 ± 0.9 mm Hg.L -1 .min -1 and arterial resistance increased from 3.1 ± 0.4 to 5.7 ± 0.8 mm Hg.L -1 .min -1 . These results suggest that in this animal model, pulmonary hypertension after protamine is due to marked pulmonary venoconstriction with minimal change in systemic vascular resistance. Furthermore, inhibition of NO release did not play a major role in the heparin-protamine hemodynamic responses.

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