Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis In Vivo Using Endobronchial Optical Coherence Tomography.

Rationale: Idiopathic pulmonary fibrosis (IPF) affects the subpleural lung but is considered to spare small airways. Micro-computed tomography (micro-CT) studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. Objectives: In this study, EB-OCT was used to evaluate small airways in early IPF and control subjects in vivo. Methods: EB-OCT was performed in 12 subjects with IPF and 5 control subjects (matched by age, sex, smoking history, height, and body mass index). Subjects with IPF had early disease with mild restriction (FVC: 83.5% predicted), which was diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for usual interstitial pneumonia present) and less affected (some but not all criteria for usual interstitial pneumonia present). Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Measurements and Main Results: Compared with the number of bronchioles in control subjects (mean = 11.2/cm3; SD = 6.2), there was significant bronchiole reduction in subjects with IPF (42% loss; mean = 6.5/cm3; SD = 3.4; P = 0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; P < 0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; P = 0.024) sites. Stereology metrics showed that IPF-affected small airways were significantly larger, more distorted, and more irregular than in IPF-less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (P = 0.36-1.0). Conclusions: EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30% and 50%), even in areas minimally affected by disease, compared with matched control subjects. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

Perioperative morbidity and 3-year survival in non-intubated thoracoscopic surgery: a propensity matched analysis.

Background: Non-intubated thoracoscopic surgery with spontaneous breathing is rarely utilized, but may have several advantages over standard intubation, especially in those with significant cardiopulmonary comorbidities. In this study we evaluate the safety, feasibility, and 3-year survival of thoracoscopic surgery without endotracheal intubation for oncologic and non-oncologic indications. Methods: All consecutive patients [2018-2022] selected for lung resection or other pleural space intervention under local anesthesia and sedation were compared to a cohort undergoing elective thoracoscopic procedures with endotracheal intubation. A propensity-score matched cohort was used to compare perioperative outcomes and 3-year overall survival. Results: A total of 72 patients underwent thoracoscopic surgery without intubation compared to 1,741 who were intubated. Non-intubated procedures included 19 lobectomies (26.4%), 9 segmentectomies (12.5%), 25 wedge resections (34.7%), and 19 pleural or mediastinal resections (26.4%). Non-intubated patients had a lower average body mass index (BMI; 24.6 vs. 27.1 kg/m2, P<0.001) and a higher comorbidity burden. Primary lung cancer was the indication in 30 (41.7%) non-intubated patients. The non-intubated cohort had no operative or 30-day mortality. After propensity-score matching, there was no significant difference in pre-operative factors. In propensity-score matched analysis, non-intubated patients had shorter median total operating room time (109 vs. 159 min, P<0.001) and procedure time (69 vs. 119 min, P<0.001). Peri-operative morbidity was rare and did not differ between intubated and non-intubated patients. There was no significant difference in 3-year survival associated with non-intubation in the propensity-score matched cohorts (95% vs. 89%, P=0.10) or in a Cox proportional hazard model [hazard ratio (HR), 1.15; 95% confidence interval (CI): 0.36-3.67; P=0.81]. Conclusions: Non-intubated thoracoscopic surgery is safe and feasible in carefully selected patients for both benign and oncologic indications.

Multimodality local ablative therapy of 23 lung metastases with surgical resection and percutaneous cryoablation in a patient with Li-Fraumeni Syndrome: A case report.

Patients with Li-Fraumeni syndrome (LFS) are prone to develop a variety of malignancies due to insufficient activity of the encoded tumor suppressor protein P53, including adrenocortical carcinoma, breast cancer, lung cancer, pancreatic cancer, and sarcoma. In the setting of LFS, local treatment options for lung metastases are limited to surgery and thermal ablation since radiotherapy and some systemic therapies predispose patients to additional future malignancies. We present the case of a 45-year-old woman with LFS with leiomyosarcoma metastases to both lungs who underwent bilateral wedge resections to treat a total of eight lung metastases followed by six percutaneous cryoablation sessions to treat 15 additional lung metastases over a period of 24 months. Our case demonstrates the option of multimodal local ablative therapies for lung metastases in patients with LFS, including percutaneous cryoablation.

The Role of Salvage Resection After Definitive Radiation Therapy for Non-small Cell Lung Cancer.

BACKGROUND: This study evaluated outcomes of patients who undergo extended delay to resection after definitive radiation therapy for non-small cell lung cancer (NSCLC). METHODS: Perioperative outcomes and 5-year overall survival of patients with NSCLC who underwent definitive radiation therapy, followed by resection, from 2004 to 2020 in the National Cancer Database were evaluated. Patients who underwent resection >180 days after the initiation of radiation therapy (including any external beam therapy at a total dose of >60 Gy) were included in the analysis. Subgroup analyses were conducted by operation type and pathologic nodal status. RESULTS: From 2004 to 2020, 293 patients had an extended delay to resection after definitive radiation therapy. The clinical stage distribution was stage I to II in 53 patients (18.1%), stage IIIA in 111 (37.9%), stage IIIB in 106 (36.2%), stage IIIC in 13 (4.4%), and stage IV in 10 (3.4%). Median dose of radiation therapy received was 64.8 Gy (interquartile range, 60.0-66.6 Gy). Median days from radiation therapy to resection were 221.0 (interquartile range, 193.0-287.0) days. Lobectomy (64.5%) was the most common operation, followed by pneumonectomy (17.1%) and wedge resection (7.5%). For wedge resection, lobectomy, and pneumonectomy, the 30-day readmission rate was 4.8%, 4.8%, and 8.3%, the 30-day mortality rate was 0%, 3.4%, and 6.4%, and the 90-day mortality rate was 0%, 6.2%, and 12.8%, respectively. Overall survival at 5 years for patients with pN0, pN1, and pN2 disease was 38.6% (95% CI, 30.0-47.2), 43.3% (95% CI, 16.3-67.9), and 24.0% (95% CI, 9.8-41.7), respectively. CONCLUSIONS: In this national analysis, extended delay to resection after definitive radiation therapy was associated with acceptable perioperative outcomes among a highly selected patient cohort.

Association Between Interstitial Lung Disease and Outcomes After Lung Cancer Resection.

BACKGROUND: Prior studies have noted that patients with interstitial lung disease (ILD) possess an increased incidence of lung cancer and risk of postoperative respiratory failure and death. We sought to understand the impact of ILD on national-scale outcomes of lung resection. METHODS: A retrospective cohort analysis using The Society of Thoracic Surgeons General Thoracic Surgery Database was conducted of patients who underwent a pulmonary resection for non-small cell lung cancer between 2009 and 2019. Baseline characteristics and postoperative outcomes were compared between patients with and without ILD (defined as interstitial fibrosis based on clinical, radiographic, or pathologic evidence). Multivariable logistic regression models identified risk factors associated with postoperative mortality, acute respiratory distress syndrome, and composite morbidity and mortality. RESULTS: ILD was documented in 1.5% (1873 of 128,723) of patients who underwent a pulmonary resection for non-small cell lung cancer. Patients with ILD were more likely to smoke (90% vs 85%, P < .001), have pulmonary hypertension (6% vs 1.7%, P < .001), impaired diffusing capacity of lung for carbon monoxide (diffusing capacity of lung for carbon monoxide 40%-75%: 64% vs 51%; diffusing capacity of lung for carbon monoxide <40%: 11% vs 4%, P < .001), and undergo more sublobar resections (34% vs 23%, P < .001) compared with patients without ILD. Patients with ILD had increased postoperative mortality (5.1% vs 1.2%, P < .001), acute respiratory distress syndrome (1.9% vs 0.5%, P < .001), and composite morbidity and mortality (13.2% vs 7.4%, P < .001). ILD remained a strong predictor of mortality (odds ratio, 3.94; 95% CI, 3.09-5.01; P < .001), even when adjusted for patient comorbidities, pulmonary function, extent of resection, and center volume effects. CONCLUSIONS: ILD is a risk factor for operative mortality and morbidity after lung cancer resection, even in patients with normal pulmonary function.

B cell-dependent subtypes and treatment-based immune correlates to survival in stage 3 and 4 lung adenocarcinomas.

Lung cancer is the leading cause of cancer-related deaths worldwide. Surgery and chemoradiation are the standard of care in early stages of non-small cell lung cancer (NSCLC), while immunotherapy is the standard of care in late-stage NSCLC. The immune composition of the tumor microenvironment (TME) is recognized as an indicator for responsiveness to immunotherapy, although much remains unknown about its role in responsiveness to surgery or chemoradiation. In this pilot study, we characterized the NSCLC TME using mass cytometry (CyTOF) and bulk RNA sequencing (RNA-Seq) with deconvolution of RNA-Seq being performed by Kassandra, a recently published deconvolution tool. Stratification of patients based on the intratumoral abundance of B cells identified that the B-cell rich patient group had increased expression of CXCL13 and greater abundance of PD1+ CD8 T cells. The presence of B cells and PD1+ CD8 T cells correlated positively with the presence of intratumoral tertiary lymphoid structures (TLS). We then assessed the predictive and prognostic utility of these cell types and TLS within publicly available stage 3 and 4 lung adenocarcinoma (LUAD) RNA-Seq datasets. As previously described by others, pre-treatment expression of intratumoral 12-chemokine TLS gene signature is associated with progression free survival (PFS) in patients who receive treatment with immune checkpoint inhibitors (ICI). Notably and unexpectedly pre-treatment percentages of intratumoral B cells are associated with PFS in patients who receive surgery, chemotherapy, or radiation. Further studies to confirm these findings would allow for more effective patient selection for both ICI and non-ICI treatments.

Safety and Effectiveness of Percutaneous Image-Guided Thermal Ablation of Juxtacardiac Lung Tumors.

PURPOSE: To evaluate the safety and effectiveness of percutaneous image-guided thermal ablation (IGTA) for juxtacardiac lung tumors. MATERIALS AND METHODS: This bi-institutional retrospective cohort study included 23 consecutive patients (13 [57%] male; mean age, 55 years ± 18) with 30 juxtacardiac lung tumors located ≤10 mm from the pericardium treated in 28 IGTA sessions (25 sessions of cryoablation and 3 sessions of microwave ablation) between April 2008 and August 2022. The primary outcome was any adverse cardiac event within 90 days after ablation. Secondary outcomes included noncardiac adverse events, local tumor progression-free survival (LT-PFS), and the cumulative incidence of local tumor progression with death as a competing risk. Two tumors treated without curative intent or follow-up imaging were considered in the safety analysis but not in the progression analysis. RESULTS: The median imaging follow-up duration was 22 months (interquartile range [IQR], 10-53 months). Primary technical success was achieved in 25 (89%) ablations. No adverse cardiac events attributable to IGTA occurred. One patient experienced a phrenic nerve injury. The median LT-PFS duration was 59 months (IQR, 32-73 months). At 1, 3, and 5 years, LT-PFS was 90% (95% CI, 78%-100%), 74% (CI, 53%-100%), and 45% (CI, 20%-97%), respectively, and the cumulative incidence of local tumor progression was 4.3% (CI, 0.29%-19%), 11% (CI, 1.6%-30%), and 26% (CI, 3.3%-58%), respectively. CONCLUSIONS: IGTA is safe and effective for lung tumors located ≤10 mm from the pericardium. No adverse cardiac events were not observed within 90 days after ablation.

Postoperative radiotherapy with modern techniques does not improve survival for operable stage IIIA-N2 non-small cell lung cancer.

OBJECTIVES: This study aims to evaluate whether postoperative radiotherapy using newer techniques (intensity-modulated radiotherapy [IMRT]) is associated with improved survival for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) who underwent complete resection. METHODS: The overall survival of patients with stage IIIA-N2 NSCLC who received postoperative IMRT versus no postoperative IMRT following induction chemotherapy and lobectomy in the National Cancer Database from 2010-2018 was assessed via Kaplan-Meier analysis, Cox proportional hazards analysis and propensity score-matched analysis. Additional survival analyses were also conducted in patients with completely resected stage IIIA-pN2 NSCLC who had upfront lobectomy (without induction therapy) followed by adjuvant chemotherapy alone or adjuvant chemotherapy with postoperative IMRT. Only patients receiving IMRT, which is a newer, more conformal radiotherapy technique, were included. Patients with positive surgical margins were excluded. RESULTS: A total of 3203 patients with stage IIA-N2 NSCLC who underwent lobectomy were included. Five hundred eighty-eight (18.4%) patients underwent induction chemotherapy followed by lobectomy, and 2615 (82%) underwent lobectomy followed by chemotherapy. In unadjusted, multivariable-adjusted, and propensity score--matched analyses, there were no significant differences in overall survival between the patients who also received postoperative IMRT versus those who did not. CONCLUSIONS: In this national analysis, the use of postoperative IMRT was not associated with improved survival in patients with completely resected stage IIIA-N2 NSCLC with or without induction chemotherapy.

Preoperative CT-guided Fiducial Marker Placement for Surgical Localization of Pulmonary Nodules.

Purpose: To assess the technical success and complication rates of CT-guided fiducial marker placement for the localization of pulmonary nodules and to assess the surgical localization failure rate. Materials and Methods: This was a single-center, retrospective analysis of consecutive patients who underwent CT-guided fiducial marker placement procedures between 2014 and 2020. End points included the technical success of the fiducial marker placement, procedural complications, and the surgical localization failure rate. A two-sample t test and a Fisher exact test were used to compare continuous and categorical variables, respectively. Multivariate logistic regression was used to identify independent risk factors for complications. Results: A total of 198 preoperative CT-guided fiducial marker placement procedures were performed in 190 patients (mean age, 64 years ± 12 [standard deviation]; 121 women) to localize 205 nodules (mean size, 10 mm ± 4; mean distance to the pleura, 10 mm ± 9). The technical success rate was 98.5% (195 of 198). There were no major complications. A total of 202 nodules were resected during 193 procedures performed 5 days ± 13 after the fiducial marker placement (range, 0-123 days). Surgical localization failure occurred in one patient (0.5%). Of the resected nodules, 146 were lung cancers, 26 nodules were metastases, two were carcinoid tumors, and 28 were benign. Conclusion: The CT-guided fiducial marker placement of pulmonary nodules was safe, effective, and resulted in a low surgical localization failure rate.Keywords: CT, Percutaneous, Thorax, Lung.

Pulmonary manifestations of chronic HPV infection in patients with recurrent respiratory papillomatosis.

Human papillomavirus (HPV) types 6 and 11 can infect the squamous epithelium of the respiratory tract. Up to 8·9% of patients with HPV-associated recurrent respiratory papillomatosis (RRP) have pulmonary involvement. Pulmonary manifestations of HPV infection are associated with considerable morbidity, in part because treatment options and management guidelines are lacking. Patients with pulmonary RRP have a 32-times increased lifetime risk of malignant transformation compared with the overall RRP population. We review the clinical and radiographic presentation, pathological features, and genetics of pulmonary RRP, and we provide management algorithms based on our clinical experience with this complex patient population. In patients with suspected pulmonary involvement, tissue-sparing procedures to address growing lesions might be warranted given the chronicity and multifocality of the disease over a patient's lifetime. However, malignant transformation of pulmonary lesion(s) warrants standard-of-care treatment for primary lung squamous cell carcinoma. Large cohort studies are needed to understand the clinical course of pulmonary RRP and to identify molecular markers of increased risk of malignant transformation in order to develop guidelines for optimal and standardised surveillance and treatment.

Risk factors for recurrent spontaneous pneumothorax: A population level analysis.

BACKGROUND: We sought to determine the rate and risk factors of recurrent spontaneous pneumothorax in a diverse population. METHODS: Cohort study using the California Public Discharge Data file (1995-2010). We identified patients with first-time spontaneous pneumothorax. The primary outcome was recurrent pneumothorax. Associations with clinical, patient, and hospital characteristics were assessed using Cox regression analysis. RESULTS: Among 14,609 patients with a first-time episode of spontaneous pneumothorax, 26.2% developed a recurrence. Risk factors included age <35 (Hazard Ratio [HR] 1.24 95%-Confidence Interval [CI] 1.14-1.36), Asian race (HR 1.24, CI 1.13-1.37), and tube thoracostomy (HR 1.2, CI 1.15-1.31). Mechancial pleurodesis (HR 0.37 CI 0.31-0.45) was superior to chemical pleurodesis (HR 0.71 CI 0.58-0.86) in reducing recurrence risk. CONCLUSIONS: The risk of recurrent pneumothorax is greatest in patients age <35, Asians, and those requiring a tube thoracostomy. The risks of operative intervention should be balanced against patient risk for recurrence.

Comparison of Percutaneous Image-Guided Microwave Ablation and Cryoablation for Sarcoma Lung Metastases: A 10-Year Experience.

BACKGROUND. To our knowledge, outcomes between percutaneous microwave ablation (MWA) and cryoablation of sarcoma lung metastases have not been compared. OBJECTIVE. The purpose of this study was to compare technical success, complications, local tumor control, and overall survival (OS) after MWA versus cryoablation of sarcoma lung metastases. METHODS. This retrospective cohort study included 27 patients (16 women, 11 men; median age, 64 years; Eastern Cooperative Oncology Group performance score, 0-2) who, from 2009 to 2021, underwent 39 percutaneous CT-guided ablation sessions (21 MWA and 18 cryoablation sessions; one to four sessions per patient) to treat 65 sarcoma lung metastases (median number of tumors per patient, one [range, one to 12]; median tumor diameter, 11.0 mm [range, 5-33 mm]; 25% of tumors were nonperipheral). We compared complications according to ablation modality by use of generalized estimating equations. We evaluated ablation modality, tumor size, and location (peripheral vs nonperipheral) in relation to local tumor progression by use of proportional Cox hazard models, with death as the competing risk. We estimated OS using the Kaplan-Meier method. RESULTS. Primary technical success was 97% for both modalities. Median follow-up was 23 months (range, one to 102 months; interquartile range, 12-44 months). A total of seven of 61 tumors (11%) showed local progression. Estimated 1-year and 2-year local control rates were, for tumors 1 cm or smaller, 97% and 95% after MWA versus 99% and 98% after cryoablation, and for tumors larger than 1 cm, 74% and 62% after MWA versus 86% and 79% after cryoablation. Tumor size of 1 cm or smaller was associated with a decreased cumulative incidence of local progression (p = .048); ablation modality and tumor location were not associated with progression (p = .86 and p = .54, respectively). Complications (Common Terminology Criteria for Adverse Events [CTCAE] grade, ≤ 3) occurred in 17 of 39 sessions (44%), prompting chest tube placement in nine (23%). There were no CTCAE grade 4 or 5 complications. OS at 1, 2, and 3 years was 100%, 89%, and 82%, respectively. CONCLUSION. High primary technical success, local control, and OS support the use of MWA and cryoablation for treating sarcoma lung metastases. Ablation modality and tumor location did not affect local progression. The rate of local tumor progression was low, especially for small tumors. No life-threatening complications occurred. CLINICAL IMPACT. Percutaneous MWA and cryoablation are both suited for the treatment of sarcoma lung metastases, especially for tumors 1 cm or smaller, whether peripheral or nonperipheral. Complications, if they occur, are not life-threatening.

Multilevel Body Composition Analysis on Chest Computed Tomography Predicts Hospital Length of Stay and Complications After Lobectomy for Lung Cancer: A Multicenter Study.

OBJECTIVE: To investigate the impact of thoracic body composition on outcomes after lobectomy for lung cancer. SUMMARY AND BACKGROUND DATA: Preoperative identification of patients at risk for adverse outcomes permits treatment modification. The impact of body composition on lung resection outcomes has not been investigated in a multicenter setting. METHODS: A total of 958 consecutive patients undergoing lobectomy for lung cancer at 3 centers from 2014 to 2017 were retrospectively analyzed. Muscle and adipose tissue cross-sectional area at the fifth, eighth, and tenth thoracic vertebral body was quantified. Prospectively collected outcomes from a national database were abstracted to characterize the association between sums of muscle and adipose tissue and hospital length of stay (LOS), number of any postoperative complications, and number of respiratory postoperative complications using multivariate regression. A priori determined covariates were forced expiratory volume in 1 second and diffusion capacity of the lungs for carbon monoxide predicted, age, sex, body mass index, race, surgical approach, smoking status, Zubrod and American Society of Anesthesiologists scores. RESULTS: Mean patient age was 67 years, body mass index 27.4 kg/m2 and 65% had stage i disease. Sixty-three percent underwent minimally invasive lobectomy. Median LOS was 4 days and 34% of patients experienced complications. Muscle (using 30 cm2 increments) was an independent predictor of LOS (adjusted coefficient 0.972; P = 0.002), any postoperative complications (odds ratio 0.897; P = 0.007) and postoperative respiratory complications (odds ratio 0.860; P = 0.010). Sarcopenic obesity was also associated with LOS and adverse outcomes. CONCLUSIONS: Body composition on preoperative chest computed tomography is an independent predictor of LOS and postoperative complications after lobectomy for lung cancer.

Racially Conscious Cancer Screening Guidelines: A Path Towards Culturally Competent Science.

OBJECTIVE: To review the racial composition of the study populations that the current USPSTF screening guidelines for lung, breast, and colorectal cancer are based on, and the effects of their application across non-white individuals. SUMMARY OF BACKGROUND DATA: USPSTF guidelines commonly become the basis for establishing standards of care, yet providers are often unaware of the racial composition of the study populations they are based on. METHODS: We accessed the USPSTF screening guidelines for lung, breast, and colorectal cancer via their website, and reviewed all referenced publications for randomized controlled trials (RCTs), focusing on the racial composition of their study populations. We then used PubMed to identify publications addressing the generalizability of such guidelines across non-white individuals. Lastly, we reviewed all guidelines published by non-USPSTF organizations to identify the availability of race-specific recommendations. RESULTS: Most RCTs used as basis for the current USPSTF guidelines either did not report race, or enrolled cohorts that were not representative of the U.S. population. Several studies were identified demonstrating the broad application of such guidelines across non-white individuals can lead to underdiagnosis and higher levels of advanced disease. Nearly all guideline-issuing bodies fail to provide race-specific recommendations, despite often acknowledging increased disease burden among non-whites. CONCLUSION: Concerted efforts to overcome limitations in the generalizability of RCTs are required to provide screening guidelines that are truly applicable to non-white populations. Broader policy changes to improve the pipeline for minority populations into science and medicine are needed to address the ongoing lack of diversity in these fields.