Saturday, May 6, 2023: 8:00 AM - Tuesday, May 9, 2023: 11:45 AM
Los Angeles Convention Center
Posted Room Name: Outside of Room 408
Track
Thoracic
103rd Annual Meeting
Presentations
Objective: Our preclinical studies have demonstrated that loss of secretory Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3) results in immune evasion and that restoring tumoral DKK3 can sensitize the tumor microenvironment of malignant pleural mesothelioma (MPM) to checkpoint immunotherapy. Here, we present the results of phase 2 study of Ad-SGE-DKK3 gene therapy, a replication-incompetent adenovirus containing the DKK3 gene, in combination with nivolumab in patients with chemotherapy-refractory epithelioid MPM (NCT04013334).
Methods: Patients with epithelioid MPM refractory to pemetrexed-platin-based chemotherapy were treated with CT-guided intratumoral injections of Ad-SGE-DKK3 on Days 1, 8, 22, and 50 and 480mg nivolumab intravenously every 4 weeks until disease progression (Fig.1A). The primary objective was to determine objective response rate (ORR). Secondary and exploratory objectives included safety, rate of durable clinical benefit (DCB), survival, and alteration of tumor and serum biomarkers.
Results: Sixteen patients were screened for eligibility and 12 patients were enrolled between 2019 and 2022. Nine patients (75%) completed four injections of Ad-SGE-DKK3. Three patients received at least one injection of Ad-SGE-DKK3 but discontinued treatment due to disease progression (n=2) or COVID-19 infection (n=1). Two patients (16.6%) had a partial response (PR) and five (41.7%) had stable disease (SD), as the best response within the 6-month treatment timeframe (Fig.1B-C), with a DCB (PR+SD) rate of 58.3%. At 17.8 months follow-up, median overall survival and median progression-free survival were 14.5 months and 4.5 months, respectively (Fig.1D). Grade 3 adverse events developed in 5 patients (41.7%). Imaging mass cytometry on serial tumor biopsy samples (Fig.1E-F) revealed that tumor-infiltrating CD8 T cells significantly increased after treatment (Fig.1G) and that activated and memory CD8 T cells were abundant in on-treatment tumors (Fig.1H). Immunoassays in serum showed that DCB patients had lower pre-treatment levels of IL-6 and M-CSF than patients with progressive disease and sustained lower concentrations of soluble PD-L1 and M-CSF than progressors. Soluble PD-1 was significantly decreased after treatment in both groups (Fig.1I).
Conclusions: Intratumoral administration of Ad-SGE-DKK3 combined with immune checkpoint blockade showed a favorable safety profile and promising efficacy in patients with chemotherapy-refractory epithelioid MPM.
View Submission
Poster Presenter(s)
*Bryan Burt, University of California Los Angeles
-
Contact Me
Los Angeles, CA
United States
Hee-Jin Jang, Baylor College of Medicine
-
Contact Me
Houston, TX
United States
Objective: Sublobar resection is oncologically effective for small peripheral Ia non-small cell lung cancer (NSCLC), but the role of non-anatomic wedge resection for tumors with high-risk histologic features remains controversial. This study compares the long-term prognosis of patients with non-lepidic variants of adenocarcinoma treated with anatomic vs. non-anatomic lung resection for small (<2cm) pathologically node negative tumors.
Methods: The National Cancer Database (2004-2017) was queried for patients with invasive mucinous (MA), predominantly papillary (PA) and solid type (SA) lung adenocarcinoma who were staged pT1N0 after surgery and with tumor size <2 cm on surgical pathology. Overall survival was compared between non-anatomic (wedge) versus anatomic resection (segmentectomy/lobectomy) using inverse probability of treatment weight (IPTW) adjusted Kaplan-Meier and Cox regression analyses.
Results: A total of 2,766 patients (64.2% MA, 29.0% PA, 6.7% SA) were analyzed, accounting for 5.7% of all patients with invasive stage IA1-2 adenocarcinoma who underwent surgery in the study period. The comparison groups comprised of 2,138 (77.3%) patients who underwent anatomic lobectomy or segmentectomy and 628 (22.7%) patients treated with wedge resection. Demographics and clinical characteristics were well balanced after IPTW. The complete R0 resection rate was similarly high (anatomic 99.3% vs. wedge 98.2%; p=0.12), but anatomic resection was associated with a higher number of lymph nodes removed (>10 nodes, 38.1% vs. 13.1%; p<0.001). Ninety-day mortality was 1.9% in both groups. IPTW adjusted survival was significantly longer after anatomic resection for MA (5-year OS, 85.4% vs. 75.2%; p=0.010) and PA adenocarcinoma patients (5-year OS, 81.3% vs. 72.3%, p=0.018), but not for the SA type (Figure). On multivariable analysis, adjusting for IPTW, demographics, comorbidities, margin status and number of lymph nodes removed, anatomic resection remained independently associated with improved survival for patients with MA (HR 0.76 (95% CI:0.59-0.98; p=0.034) or PA (HR 0.62 (95% CI: 0.42-0.89; p=0.009).
Conclusions: Invasive mucinous and predominantly papillary adenocarcinoma represent a small portion of small stage I lung adenocarcinoma patients. Anatomic resection is associated with better lymph node harvest and improved long-term survival compared with wedge resection for these adenocarcinoma histologic types.
View Submission
Poster Presenter
Jane Zhao, University of Tennessee Health Science Center College of Medicine
-
Contact Me
Memphis, TN
United States
Objective: A recent report from the Extracorporeal Life Support in Lung Transplant (ECLS) Registry showed that lung transplantation (LT) using extracorporeal membrane oxygenation (ECMO) was associated with a greater incidence of primary graft dysfunction (PGD) compared to LT performed off-pump. We examined the association between cannulation strategy and the incidence of both PGD and cannulation-related vascular complications.
Methods: The ECLS registry includes entries from 7 US and 2 European centers each performing >40 LT per year. We retrospectively reviewed this registry to identify our study cohort, which included double LT performed on patients >13 years of age using intraoperative veno-arterial (VA) ECMO between January 1, 2016 and May 31, 2022. We excluded entries with multi-organ transplants and preoperative ECMO use. Our primary outcome was PGD defined as Grade 3 PGD at 48-72 hours after LT. Secondary outcomes included incidence of aortic dissection, femoral artery dissection, limb ischemia requiring surgical intervention, and stroke. We divided the study cohort into two groups based on intraoperative ECMO cannulation strategy: (1) central, defined as using aortic arterial inflow, and (2) peripheral, defined as using a peripheral arterial inflow. To evaluate the association between cannulation strategy and PGD, we used both a multivariate regression model, as well as optimal pair propensity score matching (PSM). We compared secondary outcomes using chi-square and Fisher's exact test.
Results: We identified 201 patients in the central group and 111 patients in the peripheral group. The incidence of PGD was 41 (20.4%) in the central group and 42 (37.8%) in the peripheral group (P<0.001). After adjusting for clinical differences (Table 1) using a multivariate regression model, the probability of developing PGD in the central group was 13% lower than in the peripheral group [odds ratio 0.87 (95% CI: 0.78-0.98, P=0.033)]. PSM analysis was consistent showing PGD incidence of 19 (20.7%) in the central group compared to 35 (38.0%) in the peripheral group (P=0.009). The peripheral group showed significantly greater incidence of femoral artery dissection and limb ischemia. There was no significant difference in aortic dissection and stroke incidence (Table 1).
Conclusions: This analysis of the ECLS registry suggests that a central aortic cannulation strategy may be preferred over peripheral arterial cannulation when VA ECMO is used during LT.
View Submission
Poster Presenter
Ethan D'Silva, Baylor College of Medicine
-
Contact Me
Houston, TX
United States
Objective: To develop a computer vision-based approach to reliably identify the pulmonary artery during robotic right lower lobectomy.
Methods: Four patients with biopsy-proven Stage I non-small-cell lung cancer (NSCLC) of the right lower lobe underwent robotic lobectomy with mediastinal lymph node dissection. Complete videos of each operation were obtained, and video fragments of the pulmonary artery were identified by two board-certified thoracic surgeons. Annotation masks of the pulmonary artery were then created using Computer Vision Annotation Tool (CVAT), an open-source web-based annotation tool. The labeled data was next used to train a state-of-the-art instance segmentation algorithm (Figure 1) called Mask Regional-Convolutional Neural Network (Mask R-CNN) using an 80:20 random sample split from three cases for training and validation, respectively. A fourth case was utilized for generalization testing. Three custom performance metrics commonly utilized in deep learning-based instance segmentation were used to evaluate our approach: Intersection over Union (IoU), Average Precision at IoU threshold of 50% (AP50) and at 75% (AP75).
Results: Annotation masks of the pulmonary artery were created in 1,883 images across four cases of robotic right lower lobectomy. 1,312 and 310 annotated images across three (75%) cases were used for training and validation, respectively; and 261 annotated images from one (25%) case were used for generalization testing. A mean IoU of 94.2% was achieved in the validation dataset. The AP50 attained by our model was 96.0% and AP75 was 89.1%. In generalizability testing, when the model was tested on data never exposed to it, it was able to partially generalize with a mean IoU of 22.0%.
Conclusions: Our study shows that our Mask R-CNN model was able to identify surgical anatomy during robotic lobectomy with high accuracy in the validation dataset. While still at an early stage, more variable labeled data and collaborative efforts are needed to improve the generalizability of our model. We envision such a computer vision system to be valuable in resident and early surgeon training. Future real-time augmentation of thoracic surgery video feedback can potentially be utilized to prevent major complications and improve surgical outcomes.
View Submission
Poster Presenter
Arian Mansur, Harvard Medical School
-
Contact Me
Boston, MA
United States
Objective: No evidence currently supports specific air leak resolution criteria when using digital pleural drainage devices after lung resection. The aim of this study was to determine an optimal air leak resolution criteria where duration of chest tube drainage is minimized while avoiding potential complications from premature chest tube removal.
Methods: Airflow data was collected prospectively in 400 patients from September 2015 to April 2019 at 10-minute intervals using a digital pleural drainage device (Thopaz-TM Medela, Bar, Switzerland). All air leak resolution criteria permutations were created by combining airflow thresholds ranging from 10-100 mL/min at 5 mL/min increments, and time periods ranging from 4-12 hours at 1-hour increments. To determine the duration of the postoperative air leak, alongside the frequency and volume of any air leak recurrence, all air leak resolution criteria were retrospectively applied to the digital pleural drainage data of each patient. An air leak recurred if transpleural airflow exceeded threshold after the air leak was deemed resolved according to the criteria being tested. Descriptive statistics were used to identify an optimal air leak resolution criteria in terms of safety (lowest frequency and volume of recurrent air leaks), and efficiency (minimizing hospital stay).
Results: The majority of the 400 patients underwent lobectomies (57% [226/400]), wedge resections (29% [116/400]), or segmentectomies (8% [32/400]) for lung cancer (86% [342/400]). A total of 171 air leak resolution criteria were used to analyze 1808 patient-days of digital pleural drainage data. Most patients (67% [266/400]) experienced an air leak recurrence for at least one of the air leak resolution criteria evaluated. The air leak resolution criteria with the most recurrences (48% [192/400]) was 10 mL/min for 4 hours of fluid drainage and the criteria with the least recurrences (24% [94/400]) was 80 mL/min for 12 hours of fluid drainage. An air leak resolution criteria of 60 mL/min for 8 hours of fluid drainage was associated with the shortest initial drainage, combined with the lowest air leak recurrence frequency and volume.
Conclusion: A postoperative air leak that remains less than 60 mL/min for 8 consecutive hours can be deemed resolved and carries minimal risk of recurrence after chest tube removal. This criteria should be prospectively evaluated in future studies.
View Submission
Poster Presenter
Mohsen Alayche, University of Ottawa
-
Contact Me
Objective: Chylothorax following esophagectomy can lead to significant sequelae. Low volume leaks often respond to non-operative measures, while high output (>1 liter over 24 hours) leaks (HOL) may require invasive interventions. Our objective was to investigate various therapeutic approaches and their effect on length of stay (LOS) and overall survival (OS).
Methods: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001-2021 who underwent esophagectomy for esophageal cancer and manifested a HOL. Clinicopathologic and operative characteristics were collected, as were hospital LOS and OS data. Early intervention was defined as receiving a procedure within 72 hours of HOL diagnosis. Late intervention occurred beyond 72 hours, and conservative management encompassed patients managed without intervention. A Cox multivariate model, and a multivariate linear regression were built to investigate the effect of HOL management on OS, and LOS, respectively. The Kaplan Meier method was used to compare length of stay based on timing and type of treatment for chylothorax.
Results: A total of 53/2299 patients, most of whom were male (77%) with a median age of 62 years, manifested a HOL. Most resections were performed in an open manner (n=51, 96.2%). Of this group, 15 patients received non-operative management, 15 and 23 patients received early interventional management and late interventional management, respectively. The median overall survival in patients with HOL was 40.3 months (IQR: 12.0-51.7). Late intervention (Hazard Ratio (HR) 4.772, CI: 1.384 to 16.460) and non-operative management (HR 4.731, CI: 1.294 to 17.305) were associated with increased mortality compared to early intervention. The median length of stay in patients with HOL was 19 days (IQR: 13-29). Patients in the late intervention group had longer length of stay compared to early intervention (Regression Coefficient=9.849, 95% Confidence Interval [CI] 3.431 to 16.267). Patients with early intervention for HOL had an OS similar to patients without chyle leaks in Kaplan Meier analysis (Figure).
Conclusions: Development of chylothorax following esophagectomy is associated with high morbidity. Patients with HOL should receive early operative intervention within the first 72 hours in order to combat the potential deleterious outcomes of delayed treatment and their associated prognostic implications, including prolonged LOS and decreased OS.
View Submission
Poster Presenter
Nathaniel Deboever, University of Texas MD Anderson Cancer Center
-
Contact Me
houston, TX
United States
Background:
Pulmonary metastasectomy for colorectal cancer has been shown to provide respite from systemic therapy as well as to provide some patients with prolonged disease-free intervals. However, patients with lung-limited metastatic colorectal cancer may not receive equitable access to pulmonary resection. We sought to identify factors associated with pulmonary metastasectomy as well as to characterize the differential impact on survival outcomes for those offered lung resection.
Methods:
The National Cancer Database (NCDB) was queried for all patients with stage IV colorectal cancer and lung-limited metastatic disease between 2010-2016. Patients who underwent resection of the primary tumor only were compared to those who underwent both resection of the primary tumor and their pulmonary metastatic disease. Penalized regression with the least absolute selection and shrinkage operator (LASSO) was used to determine factors associated with receiving metastasectomy as well as those associated with overall survival in multivariate models.
Results:
5731 patients met inclusion criteria, including 867 (15.1%) who underwent resection of both the primary tumor and pulmonary metastases and 4864 (84.8%) who had surgery for the primary tumor only. In unadjusted analyses, metastasectomy patents were younger (median age 60 vs 63 years, p<0.001), more often privately insured (49.1% vs 37.7%, p<0.001), more educated (p=0.001), and often traveled farther to receive their care (p<0.001) compared to those not receiving metastasectomy. In multivariable analyses, younger age, traveling > 25 miles, and care at high-volume hospitals were associated with pulmonary metastasectomy (p<0.01). In adjusted analyses within the entire cohort, primary site surgery without metastasectomy was associated with worse overall survival (hazard ratio [HR] 1.35, confidence interval [CI] 1.23-1.49), even after adjusting for patient, tumor, and hospital-related factors, highlighting the importance of providing pulmonary metastasectomy (Figure).
Conclusions:
Patients who were older, received care closer to home, and those treated at low-volume hospitals were less likely to receive pulmonary metastasectomy for lung-limited colorectal cancer after undergoing definitive resection of their primary tumor. Moreover, failure to receive pulmonary metastasectomy resulted in worse overall survival, emphasizing the strong need for efforts to provide uniform, equitable care to all patients.
View Submission
Poster Presenter
*Mara Antonoff, MD Anderson Cancer Center
-
Contact Me
Bellaire, TX
United States
Objective: Pneumonia, both in the community and hospital setting, represents a significant cause of morbidity and mortality in the cardiothoracic patient population. Diagnosis of pneumonia can be masked by other disease processes, and is often diagnosed after the patient is already suffering from the disease. A non-invasive, sensitive test for pneumonia, which would allow for treatment before clinical deterioration, would decrease hospitalizations and length of stay for patients. We have developed a porcine model of pneumonia, and evaluated the exhaled breath of infected pigs for biomarkers of infection.
Methods: 60kg adult pigs were intubated and a bronchoscope was used to instill either a solution containing 12 x 10^8 cfu of methicillin sensitive staph aureus (MSSA), or a control solution without bacteria (SHAM), into the distal airways. The pigs were then re-intubated on POD#3, #6, and #9, with bronchoscopic bronchial lavages taken at each time point. At each time point, a 500cc breath was captured from each pig. The breath was evacuated over a silicon microchip, with the contents of the breath captured via oximation reaction, and the results of this capture were analyzed by mass spectroscopy.
Results: The pigs infected with MSSA demonstrated clinical signs of infection (initial fever and persistent cough), demonstrated consolidation on CXR, and showed increasing counts of MSSA in the bronchial lavages over the span of the experiment. Analysis of the exhaled breath demonstrated one carbonyl compound (Unsaturated 2-pentanal) that increased 10-fold over the span of the experiment, from an average of 0.0294 nmols/L before infection to an average of 0.3836 nmol/L on POD#9. The sham infected pigs showed no significant change in this compound over the same time frame.
Conclusions: We were able to successfully develop a clinical pneumonia in adult 60kg pigs. Unsaturated 2-pentanal functions as a biomarker for MSSA infection in pigs, demonstrating the potential utility of this technology for early diagnosis of pneumonia.
View Submission
Poster Presenter
Gianna Katsaros, University of Louisville School of Medicine
-
Contact Me
Louisville, KY
United States
Objective: Donors with characteristics that increase risk of HBV, HCV, and HIV transmission are deemed increased-risk donors (IRD) per 2013 Public Health Service guidelines. Compared to organs from standard-risk donors (SRDs), IRD organs are often declined and used at much lower rates. Concerns due to the IRD label may result in underutilization of viable organs and worsened waitlist mortality. In this study, we sought to investigate the outcomes of lung transplant recipients who received IRD allografts following the PHS guideline change.
Methods: We retrospectively identified lung transplant recipients from the United Network of Organ Sharing registry (February 2014 to March 2020). Patients were divided into 2 cohorts, based on CDC blood-borne pathogen risk status of the donor: SRD or IRD. Demographics and clinical parameters were compared across donor age groups. Survival was compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazard model was performed to identify variables associated with survival outcome. P-values <0.05 were considered significant.
Results: We identified 13,890 lung transplant recipients, 10,506 who received allografts from SRDs and 3,384 who received allografts from IRDs. IRDs showed a notable young age distribution, with 2663 (79%) being under 40 and only 244 (7.2%) over 50. Comparatively, 6197 SRDs (60%) were under 40 and 2410 SRDs (23%) were over 50. IRDs also demonstrated a lower median BMI and higher median height. IRDs were associated with increased alcohol, cigarette, cocaine, and other drug use, while SRDs had an increased history of cancer, hypertension, myocardial infarction, and diabetes. There was no significant difference in type of transplant (single versus double lung), lung allocation score, or length of stay between SRD and IRD transplantations. Survival analysis showed no significant difference in 90 day, 1-year, 3-year, or 5-year survival (p=0.410, 0=0.681, p=0.395, p=0.469, respectively). Cox regression demonstrated that single-lung transplants were associated with 18% increased mortality risk compared to double-lung (p<0.0001).
Conclusions: Recipients of SRD and IRD organs showed equivalent survival outcomes following lung transplantation. Compared to SRDs, IRDs were generally younger and had fewer underlying conditions. Our findings suggest that IRD lung transplantation may offer a safe and valuable option for improving organ shortages.
View Submission
Poster Presenter
Meredith Brown, Temple University
-
Contact Me
Philadelphia
United States
Objective: Lung volume reduction surgery (LVRS) has been shown to improve exercise capacity and survival in patients with upper lobe predominant emphysema. Bronchoscopic lung volume reduction (BLVR) has supplanted surgery, with LVRS often being reserved for patients who are either not candidates for or who have failed BLVR. Our study aims to investigate the outcomes of LVRS among patients who either failed BLVR or were not candidates for it.
Methods: We conducted a retrospective analysis of patients who underwent LVRS for upper lobe predominant emphysema in a single tertiary center between March 2018 and June 2022. The main outcomes measured were pre- and post-operative respiratory parameters, peri-operative morbidity and mortality.
Results: A total of 50 LVRS were performed, of which 10 had prior failed valve placement. The rest were found to have collateral flow on bronchoscopy (n=11) or had preoperative imaging that demonstrated fissure integrity (n=29) precluding BLVR. The mean age of patients was 68 ± 6, and 22 (44%) were female. The mean pre-operative FEV1 was 0.85 L ± 0.27, DLCO 34.2% ± 9.3 and VO2 max of 10.5 ± 2.4 (peak, ml/kg/min). All procedures were performed thoracoscopically (VATS), with 30 patients (60%) undergoing bilateral LVRS. Average specimen weight was 63 g for right sided procedures, and 67 g for the left. Post operatively, only 2 patients remained intubated, and 14 (28%) patients required ICU admission. The median length of hospital stay was 8 days (IQR=6). Prolonged air leak (>7 days) occurred in 20 (40%) patients, of which 3 required successful surgical re-exploration via VATS; 13 patients (26%) were discharged home with a Heimlich valve. Other complications included DVT/PE (n=2), pneumonia (n=4), re-intubation (n=4). There was only one 90-day mortality from a nosocomial pneumonia (non-Covid related). Mean parameter improvements were as follows: FEV1 38.3% from 31% (p=0.01), DLCO 39.2% from 34.2% (p=0.07), and residual volume 3.3 L from 4.6 (p<0.01). On the 6-minute walk test, traveled distance increased to 272 m from 254 (p=0.3) and the reported dyspnea improved from 4.9 to 2.9 (p=0.03).
Conclusion: LVRS can be safely performed in patients who are either not candidates for BLVR or those who did not respond favorably. It is associated with acceptable morbidity, low mortality, and significant functional improvement. LVRS remains an important tool in the treatment of patients with upper lobe predominant emphysema.
View Submission
Poster Presenter
Jessica Magarinos, Temple University Hospital
-
Contact Me
Objective: The lymph node metastasis (LNM) site may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether ESCC patients with LNM around the respiratory system and digestive system have difference survival outcomes. This study aimed to investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count.
Methods: ESCC patients with LNM between January 2014 and December 2019 at three institutes were retrospectively reviewed and set in training (two institutes) and external validation (one institute) cohorts. Pararespiratory LN stations were defined as the site in cervical (station 1) and thoracic (stations 2, 3, 4, 5, 6, 7, 9, 10) regions, while paradigestive LN stations were defined as the thoracic and abdomen regions (stations 8, 15, 16, 17, 18, 19, 20). Kaplan-Meier and Cox proportional hazards models were used to analyze overall survival (OS) and prognosis. FactorMerger method with factor merge tree and survival plot was performed to determine the nN staging system. The performance of nN staging system was evaluated by the area under the receiver operating characteristic curve (AUC).
Results: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site, sex, postoperative complications and T stage were independent prognostic factors (all P < 0.001). Age, surgical approach and tumor location were independent risk factors for paradigestive LNM (all P < 0.001). A nN staging system with four subsets that integrated both the site and count of LNM was developed. Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems.
Conclusions: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems.
View Submission
Poster Presenter
Dong Tian, West China Hospital, Sichuan University
-
Contact Me
Chengdu, Sichuan
China
Objectives: The prognosis of advanced esophageal cancer is poor. The advent of the neoadjuvant regimen has brought new hope for these patients. The present study aims to further demonstrate the efficacy of neoadjuvant chemoimmunotherapy. Materials and Methods: A real-world observational study was conducted concerning patients who received neoadjuvant pembrolizumab, camrelizumab, tislelizumab and sintilimab combined with chemotherapy between January 2019 and January 2022 in Tandu Hospital. The primary endpoint was major pathologic response (MPR), pathologic complete response (pCR) and the secondary endpoints were objective response rate (ORR), pathologic complete response (pCR), disease-free survival (DFS), overall survival (OS) and toxicity. Results: A total of 177 patients were analyzed with a median follow-up time of 14.0 months. Most patients (42.4%) had stage II disease, while 109 (61.6%) and 37 (20.9%) patients initially diagnosed clinical T3 and T2, respectively. Thirty-seven (20.9%), 37 (61.6%) and 20 (11.3%) patients received two, three and four cycles of neoadjuvant treatment, separately, achieving an ORR of 73.4%. None of them needed a reduced initial dose or delay due to intolerable adverse events. Ninety-six (58.1%) and 57 (32.3%) patients achieved MPR and pCR, respectively. Mean PFS was 12.6 months and mOS was 12.8 months. Postoperative complication rate is 34.6% according to Clavien-Dindo classification. One-hundred patients occurred treatment‐related adverse event (TRAE), 18.1% are more than grade 2. Conclusion: The feasibility of neoadjuvant chemoimmunotherapy for resectable esophageal cancer was further validated, with a high MPR rate and manageable adverse events.
View Submission
Poster Presenter
Lan Ke, Peking University People's Hospital
-
Contact Me
Bei jing, Bei jing
China
Representation of Women in Lung Cancer Randomized Trials – A Systematic Review
Vaishnavi Krishnan, MD, MPH, Lucsa Fass, MD, Talib Chaudhry, MD, Justin Karush, DO, Nicole Geissen DO, Michael Liptay, MD, Christopher W. Seder, MD, Gillian Alex, MD
Rush University Medical Center
Objective: To perform a systematic review of randomized trials examining non-small cell lung cancer to better understand the equity afforded to women in the study of lung cancer.
Methods: An electronic search was conducted for all non-small cell lung cancer randomized trials published between 2010 and 2020 with included words "carcinoma, non-small cell lung" and "non-small cell lung cancer". Studies from PubMed, Cochrane and SCOPUS were included, and 2049 studies were initially uploaded into Covidence to assist with systematic review. A two-person screening of all studies was performed, and 269 articles were identified as eligible for this study. All articles were reviewed for data regarding location, study type, cancer stage, field of study of the research team and number of males and females included in analysis. A two-sample T-test comparing the overall means of males and females was calculated.
Results: Across all studies, 38.7% of patients were female. Compared to studies from 2010-2015, those from 2016-2020 had an increase in the representation of females from 36.7% to 41.4% (p=0.0081). Published studies from non-surgical groups enrolled 38.1% female patients compared to their surgical counterparts at 43.1% (p=0.0005). RCTs and clinical trials had similar breakdowns of sex with 37.4% and 39.1% of females, respectively. When stratified by geographical location, all regions had a higher percentage of male patients enrolled except for South America, which only had two studies included. Trials from the United States had the least difference between sexes with 46.7% females. Studies examining stage I-IIIA patients enrolled 37.6% females and studies examining stage IIIB-IV enrolled 37.6% females. Comparing the overall representation of female to males patients enrolled in these trials yielded a significant difference (p<0.0001).
Conclusions: There is a difference in representation between males and females in randomized trials. Future trials should include more females as they currently do not reflect the high incidence of lung cancer in women, which in 2022 was approximately 50.2%.
View Submission
Poster Presenter
Gillian Alex, Rush
-
Contact Me
Chicago, IL
United States
Objective:
To evaluate the likelihood of developing a COVID-19 infection while undergoing treatment for lung cancer during the first year of the pandemic, as well as the additional risk of death associated with COVID-19 infection in this time period.
Methods:
Patients diagnosed with non-small cell lung cancer (NSCLC) in 2020 were evaluated in the National Cancer Database (NCDB). Three data fields were added in 2020 by the NCDB: 1) was a COVID-19 test performed, 2) did the patient test positive for COVID-19, and 3) the date of the patient's first positive COVID-19 test. The 90-day survival (from treatment initiation) for patients with a first COVID-19 diagnosis within 90 days following treatment initiation was assessed by calculating relative risks and by using Kaplan-Meier analysis among 1:2 propensity score-matched cohorts.
Results:
A total of 80,471 patients underwent treatment for NSCLC in 2020, of which 37,599 (46.7%) were tested for COVID-19. Overall, 525 (1.5%) patients tested positive for COVID-19 within the first 90 days of initiating treatment. This included 0.9% (n=89) of surgically managed patients, 1.5% (n=269) of patients who received chemotherapy, and 1.6% (n=327) of patients who received radiotherapy. The relative risk of 90-day mortality (COVID-19 positive vs. negative) was 4.75 (95% CI: 2.66-8.46) after surgery, 2.55 (95% CI: 2.03-3.19) after chemotherapy, and 2.25 (95% CI: 1.86-2.72) after radiotherapy. For each treatment modality, Kaplan-Meier analysis demonstrated significantly worse 90-day survival among patients testing positive for COVID-19 (Figure).
Conclusions:
In the first year of the COVID-19 pandemic, the risk of developing a COVID-19 infection while undergoing surgery, chemotherapy, and radiotherapy for non-small cell lung cancer appeared to be low. However, a COVID-19 infection during the time frame in which patients were undergoing treatment was associated with increased 90-day mortality, particularly in surgically managed patients.
View Submission
Poster Presenter
Peter Zhan, Department of Surgery, Yale University School of Medicine
-
Contact Me
New Haven, CT
United States
Objective: To report the world first pediatric Robotic Tracheal resection using V-V ECMO
Case Video Summary: This surgical video demonstrates the history and surgical technique of a young child with primary tracheal tumor that undergoes tracheal resection with end-to-end anastomosis using a completely robotic portal platform and V-V ECMO
Conclusions:
A completely portal robotic approach is safe and effective for patients with primary tracheal tumor using ECMO without heparin
View Submission
Poster Presenter
Mohamed El Zaeedi, NYU Langone hospital
-
Contact Me
New York, NY
United States
Objective: The benefits of segmentectomy for non-small cell lung cancer (NSCLC) >2 cm were demonstrated in the JCOG0802 and CALGB140503 trial results. However, for clinical T1c NSCLC, its benefits remain unclear. This study aimed to investigate the outcome of segmentectomy for clinical T1c NSCLC.
Methods: A total of 257 patients who underwent anatomical resection and lymph node dissection for clinical T1c NSCLC from January 2006 to April 2020 were enrolled. All patients were divided into two groups: segmentectomy and lobectomy, and a retrospective analysis was conducted. Kaplan–Meier method was used to estimate relapse-free survival (RFS) curves, and significance was assessed using log-rank test.
Results: The median age of all patients was 70 years (164 males and 93 females); 224 patients underwent lobectomy, and 33 patients underwent segmentectomy. Only the pathological T factor was significantly more advanced in the segmentectomy group than in the lobectomy group. There were no significant differences in age (median 74 years vs. 70 years), sex (24 males and 9 females vs. 140 males and 84 females), pulmonary function, carcinoembryonic antigen (CEA) (median 3.2 ng/mL vs. 3.2 ng/mL), maximum standardized uptake value (SUVmax) (median 4.7 vs. 7.8), and clinical stage between the segmentectomy and lobectomy groups. The median observation period was 47 months. In the RFS curve analysis, the 5-year RFS rate was significantly higher in the lobectomy group (69.8%) than the segmentectomy group (59.6%) (p = 0.24). Conversely, as the figure shows, in the RFS curve analysis of pure-solid NSCLC, the 5-year RFS rate was significantly higher in the lobectomy group (68.8%) than the segmentectomy group (46.2%) (p < 0.01). Among the pure-solid NSCLC, univariable analysis identified age (hazard ratio [HR] = 1.03, p = 0.02), %FVC (<80%; HR = 2.99, p = 0.01), CEA (>5.0 ng/mL; HR = 2.45, p < 0.01), SUVmax (>5.0; HR = 2.38, p < 0.01), and segmentectomy (HR = 2.04, p = 0.03) as significant prognostic factors for RFS. Multivariable analysis identified CEA (>5.0 ng/mL; HR = 2.14, p < 0.01), SUVmax (>5.0; HR = 1.95, p = 0.04), and segmentectomy (HR = 2.14, p = 0.02) as significant independent prognostic factors for RFS.
Conclusions: There is no significant difference in survival outcome between the segmentectomy and lobectomy groups in clinical T1c NSCLC; however, in clinical T1c pure-solid NSCLC, the segmentectomy group has a worse prognosis than the lobectomy group.
View Submission
Poster Presenter
Kenta Nakahashi, Toronto General Hospital, UHN
-
Contact Me
Toronto, ON
Canada
Objective: Serious mental illness (SMI) is associated with increased complications and worse outcomes in a variety of diseases; however, SMI as a risk factor in thoracic surgery patients is incompletely understood. We hypothesized that comorbid SMI would impact mortality and morbidity following lung cancer resection.
Methods: We identified 501 patients at our institution who underwent anatomic lung cancer resection, including segmentectomy, lobectomy, bilobectomy, and pneumonectomy. Patients with comorbid SMI were identified using natural language processing (NLP)-assisted chart review and stratified into mood, anxiety and psychosis disorders. The primary outcome was a composite of postoperative complications. We analyzed the risk-adjusted impact of SMI on composite morbidity and mortality and LOS using multivariable logistic regression and Poisson regression analysis, respectively.
Results: Patients with SMI were younger, more frequently female and more likely to have a smoking history (p < 0.05, Table 1). Among identified patients, 186 (37.1%) had comorbid serious mental illness which were predominantly mood disorders (168/186, 90.3%). Overall, 116 patients (23.1%) had the primary outcome of composite postoperative mortality or morbidity. Following multivariable risk adjustment, patients with and without SMI did not have significantly different morbidity and mortality [odds ratio (OR) 1.36, 95% confidence interval (CI) 0.86-2.15]. Individually, mood disorders (OR 1.23, 95% CI 0.70-2.14), anxiety disorders (OR 1.11, 95% CI 0.58-2.10) and psychosis disorders (OR 1.70, 95% CI 0.60-4.54) did not significantly contribute to postoperative morbidity or mortality. Mean length of stay was longer in patients with SMI (7.16 days) than in patients without SMI (5.91 days). After adjusting for type of procedure and other covariates, LOS was significantly longer among patients with SMI (risk ratio 1.22, 95% CI 1.13-1.31). SMI was not associated with the extent of resection performed.
Conclusions: SMI is a risk factor for poor postoperative outcomes. In a 7.5-year period from a single academic institution, patients undergoing lung cancer resection had high rates of SMI and patients with SMI had significantly longer admissions. Future work should design and test interventions to optimize perioperative and post-discharge care for patients with SMI.
View Submission
Poster Presenter
John Diehl, UNC at Chapel Hill
-
Contact Me
United States
Objectives: Donation after Circulatory Death (DCD) donors for lung continues to be underutilized in the United States. Through a meta-analysis of comparative studies, we investigated the impact of procurement strategy donation after brain death (DBD) versus DCD on the short- and long-term outcomes of lung transplantation.
Methods: We performed a systematic literature search using the items “lung transplantation” AND “donation after circulatory death” from inception till July 2022 for studies comparing outcomes of lung transplantation from DCD versus DBD. Variables extracted included recipient & donor characteristics, short- and long-term outcomes. Primary endpoints were early mortality, primary graft dysfunction (PGD), acute rejection, and long-term survival. A pooled Odds ratio (OR) and mean differences with inverse variance weighting using random effect models were computed to account for between-trial variance (τ2). Heterogeneity among the trials was quantified by I2-index and Cochran's Q test.
Results: Of the 2937 total studies, 48 manuscripts were assessed for full text review. Nine studies comparatively reported data on the short-term outcomes and 18 studies reported long-term survival for both groups. We included 70,784 patients, of whom 68,280 were transplanted after DBD and 2,504 after DCD. They were mostly male (57%) and their mean age was 50.8 years. No publication bias was observed by funnel plot. The estimated pooled odds ratio (OR) of early mortality resulting from 9 studies favored DBD with a total of 1,291 events over 28,912 patients (4.46%) versus 55 events over 1,060 patients (5.18%) in the DCD group (OR 0.73 CI 0.55-0.98 with a 0% heterogeneity). No statistically significant difference was observed regarding the risk of acute rejection (OR 1.19 CI 0.94-1.68) and PGD grade 2-3 (OR 0.91 CI 0.72-1.14). The estimated pooled odds ratio of 1-year mortality cumulative incidence resulting from 18 studies with a total of 40,148 patients was 1.02 (CI 0.86-1.21), at 3 years was 0.89 (0.66-1.20) and at 5 years was 0.97 (CI 0.81-1.16).
Conclusions: This is the first meta-analysis of comparative studies between DCD and DBD demonstrating increased early mortality in DCD lung transplant. However, there was no difference in PGD, acute rejection and long-term survival at 1,3 and 5 years. While the long-term survival supports the continued implementation of DCD lungs, further studies are required to elucidate the mechanism of increased early mortal
View Submission
Poster Presenter
Kukbin Choi, Mayo clinic
-
Contact Me
rochester, MN
Background:
We have previously demonstrated that patients with oligometastatic non-small cell lung cancer (NSCLC) treated with local consolidative therapy (LCT) have improved survival outcomes compared to patients treated with systemic therapy alone, and that oligometastatic patients with EGFR mutations derive a more substantial benefit from LCT. A phase 2 randomized, multicenter study to evaluate the efficacy of osimertinib with or without LCT for patients with EGFR-mutant stage IV NSCLC (NORTHSTAR) was undertaken, including patients with oligo- as well as polymetastatic disease. We sought to assess feasibility and safety of lung resection in this patient population.
Methods:
Previously untreated patients with EGFR-mutant NSCLC (L858R, Ex19 deletion) or acquired EGFR T790M were enrolled in the NORTHSTAR trial. Patients with non-progressive disease after 6-12 weeks of osimertinib were randomized 1:1 to continue osimertinib alone or to undergo LCT + osimertinib. LCT patients underwent either surgery or radiation, and surgical patients were reviewed for details of intraoperative and 30-day postoperative courses. All procedures occurred between 06/2018-09/2022.
Results:
20 NORTHSTAR patients underwent lung resection, including 11 (55%) women, with median age of 65.1 years. 18 (90%) and 2 (10%) patients presented with poly- and oligometastatic disease, respectively. Procedures were performed by thoracotomy in 19 (95%) patients, and included 17 (85%) lobectomies, 1 (5%) wedge, and 2 (10%) segmentectomies. 3 (15%) had evidence of pretreatment malignant effusions. Surgeons reported operations as severely difficult in 17 (85%, Figure), with severe adhesions in 7 (35%) and severe hilar fibrosis in 13 (65%). Median operative duration and blood loss were 234 min (interquartile range [IQR] 154-271) and 175 mL (IQR 100-219), respectively, with 2 (10%) receiving intraoperative transfusion. There were no perioperative mortalities or ICU admissions. Median postoperative chest tube duration was 2.2 days (IQR: 1.4-2.7). Typical postoperative events occurred with prolonged airleak in 1 (5%) and atrial arrhythmias in 2 (10%).
Conclusions:
Patients with metastatic EGFR-mutated NSCLC who were randomized to LCT and underwent lung resection successfully achieved outcomes similar to historical standards for early-stage disease. These operations are feasible and safe, emphasizing the importance of including surgical resection in ongoing clinical trials for stage IV NSCLC.
View Submission
Poster Presenter
*Mara Antonoff, MD Anderson Cancer Center
-
Contact Me
Bellaire, TX
United States
Objective: Covid-19 is still an ongoing entity and every day we face new sequelae of the disease. It's association with thrombosis is a well-known fact. We hereby present surgical results of patients who are treated with post-Covid CTEPH.
Methods: Data were collected prospectively among patients who underwent pulmonary endarterectomy (PEA) and had a diagnosis of Post-Covid CTEPH. Between July 2021 and July 2022, 108 consecutive patients underwent PEA at our institution. Patients who had pulmonary emboli during or after infection with Covid-19 were followed up at least 6 months with anticoagulants and the ones who developed CTEPH were treated with pulmonary endarterectomy. All data were retrospectively reviewed from database in terms of demographics, clinical features, complications, short and long-term results, length of hospital stay, morbidity and mortality. The ethical application for this study was approved by the ethics committee of our center.
Results: Eleven patients (seven male, four female, median age 52 (22–63) years) were identified. Patients who had a past medical history of pulmonary emboli, any kind of coagulopathy or major risk factors were excluded from the study. Mortality was observed in one patient due to sepsis on the 5th postoperative day. One patient needed two-vessel CABG in addition to PEA. Pulmonary vascular resistance improved significantly from 572 dyn/s/cm-5 (240–1192) to 240 (195–377) dyn/s/cm-5 (p<0.005). Significant difference was also detected in median mPAP as decline from 40 mmHg (24-54) to 24 mmHg (15-36) (p<0.005). following surgery. Median time from Covid-19 disease to surgery was 12 months (6 -24). Median length of hospital stay of the survivors was 10 days (8-14). Median follow-up after PEA was 8 (2-14) months for all the survivors.
Conclusions: Patients who had Covid-19 may develop pulmonary emboli and CTEPH. Pulmonary endarterectomy is the only therapeutic option for the treatment of those patients as in the other CTEPH patients. We hereby report the first series of post-Covid CTEPH patients who were surgically treated. As we see a lot of symptoms and clinical manifestations in patients who had Covid-19, we should always remember CTEPH in the differential diagnosis.
View Submission
Poster Presenter
bedrettin yildizeli, Marmara University, Istanbul
-
Contact Me
ISTANBUL
Turkey
Objective: Previous studies suggest that SGLT2, a sodium-dependent glucose transporter, may play a role in the metabolism of lung adenocarcinomas. Our goal is to characterize SGLT2 expression with a large number of human tumor samples representing multiple lung cancer types.
Methods: Tissue microarray analysis (TMA), previously described (Yanagawa J, et. al, Clin Cancer Res, 2009), was constructed using University of California at Los Angeles Department of Pathology archival paraffin-embedded human lung cancer specimens from consecutively accrued cases that were obtained under Institutional Review Board (IRB02-07-011). SGLT2 expression of the TMA was validated by performing immunohistochemistry using a polyclonal antibody at 1:250. Specificity of the antibody was confirmed using a blocking peptide specific for SGLT2 with the SGLT2 antibody in separate slides. Two pathologists reviewed the SGLT2 stained slides and scored SGLT2 expression only on the tumor cells, based on the intensity of the immunohistochemistry staining (0 = absent, 1 = weak, 2 = moderate, 3 = strong). We took the average of SGLT2 staining for each patient and analyzed it with the corresponding clinical database (grade, sex, race, histology, and stage). Using STATA 13, we performed descriptive statistics, and ANOVA test to characterize SGLT2 expression in lung cancer.
Results: The TMA included 578 tumors with corresponding histology and SGLT2 expression. 544 (94%) tumors demonstrated some degree of SGLT2 expression (weak n=156 [27%], moderate n=262 [45%], strong n=126 [22%]). When stratified by histology, strong SGLT2 expression was present in 29% (97/340) adenocarcinomas, 7% (10/135) squamous cell carcinomas, 32% (8/25) adenosquamous carcinomas, 50% (3/6) carcinoids, 12% (7/59) large cell carcinoma cases, and 8% (1/13) small cell carcinomas. The degree of average SGLT2 expression varied significantly by sex, histology, and grade (Table 1). When comparing by tumor grade for lung adenocarcinomas only, the average SGLT2 expression in grade 1 is 2.26, in grade 2 is 2.24, and in grade 3 is 1.89 (p-value = 0.0001).
Conclusions: SGLT2 expression is widely present in multiple lung cancer types, with the strongest expression in lung adenocarcinomas, adenosquamous carcinomas, and carcinoids. For lung adenocarcinomas, SGLT2 expression is correlated with grade, with the highest expression in low grade tumors and lowest expression in high grade tumors.
View Submission
Poster Presenter
John Deng, UCLA Health
-
Contact Me
Los Angeles, CA
United States
Objective: To analyze the effects of smoking on perioperative and postoperative outcomes of robotic-assisted lobectomy and segmentectomy in an NCI-designated cancer center.
Methods: Data was analyzed from 1,420 consecutive patients who underwent robotic-assisted segmentectomy (n=1,370) and lobectomy (n=50) performed by three different surgeons over a 12-year period. The perioperative, postoperative, and overall survival outcomes were compared between smoking patients (n=297) and non-smoking patients (n=1,123). The perioperative outcomes that were compared include estimated blood loss (cc), surgical duration (min), chest tube days, and hospital length of stay (LOS). Postoperative complications, 30-day mortality, and overall survival (OS) were also compared. Perioperative outcomes were compared between smoking and non-smoking groups using the student t-test. 5-year OS was compared using the log-rank test.
Results: There was a significant difference in preoperative FEV1% (p<0.0001) between smoking and non-smoking groups. Non-smoking patients had a greater mean FEV.1%. The smoking group had a significantly larger proportion of patients with chronic obstructive pulmonary disease compared to the non-smoking group (p<0.0001). The most significant differences in perioperative outcomes were chest tube duration (p<0.001) and total surgical duration (p=0.047), in which smoking patients experienced both longer chest tube duration and surgical duration. The remaining perioperative outcomes, 30-day mortality, and overall survival did not show any significant differences between both groups. The most significant differences in postoperative complications were prolonged air leak (p=0.025) and pneumonia (p=0.02), with smoking patients having a higher rate of incidence for both. Prolonged air leak was the most common complication in both smoking (67/297, 22.6%) and non-smoking patients (184/1,123, 16.4%). Pneumonia was the second most common complication in smoking patients (21/297, 7.1%).
Conclusion: The results indicate that smoking not only has a negative impact on preoperative FEV1%, but also on perioperative outcomes and postoperative complications in patients undergoing robotic-assisted pulmonary resections.
View Submission
Poster Presenter
Emma Wong, University of South Florida Morsani College of Medicine
-
Contact Me
Tampa, FL
United States
Objective: To evaluate the clinical significance of sampling station 9 nodes during lobectomy for primary NSCLC and its association with oncologic outcome.
Methods: A single center retrospective analysis of patients who underwent a lobectomy for primary NSCLC from 8/2020 – 9/2022. Patients with fewer than 3 N2 stations sampled, secondary pulmonary metastasis, and diagnosis other than NSCLC were excluded. PET-avidity and final pathology results were documented for station 9 nodes along with the associated lobe of the primary tumor. Median follow-up was 12 months.
Results: 419 lobectomies were performed from 8/2020 – 9/2022 of which Station 9 was sampled in 126 cases. 37 cases with less than 3 N2 stations sampled and 1 case of pulmonary metastasis were excluded. 89 lobectomies with R0 resection for primary NSCLC with station 9 nodes sampled were analyzed (46 upper lobe, 3 middle lobe, 40 lower lobe). There were 46 females (52%) and 73 cases of adenocarcinoma (82%), 14 squamous cell carcinoma (16%) and 2 large cell cancers (2%). Station 9 nodes were pathologically positive in 5 cases (6%), negative in 79 cases (89%), and non-diagnostic in 5 cases (6%). The non-diagnostic results demonstrated fibroadipose tissue without lymphoid tissue. There was 1 case (1%) of PET-avid station 9 node. The 5 cases of positive station 9 nodes were only associated with tumors in the middle and lower lobes and none in the upper lobes. 68 patients (76%) were included in follow-up analysis. After excluding non-diagnostic nodes, 26 patients with middle and lower lobe tumors were included. 3 patients (12%) had locoregional recurrence (pathologic stages IA, IIIA), 2 (8%) had distant recurrence (IIA, IIB), and 1 patient (4%) had both (IIB). 2 of the patients who recurred (IIIA) had multi-station N2 disease. One had a positive station 9 node and one negative. Relationship among station 9 disease, pathologic stage, and number of recurrences is shown in table 1.
Conclusions: Occult metastasis to station 9 nodes associated with middle and lower lobe cancers is surprisingly common (4 of 43, 9%) and is not seen in primary NSCLC of upper lobes. Station 9 lymph nodes should be sampled for primary NSCLC of middle and lower lobes.
View Submission
Poster Presenter
Anupama Singh, Brigham And Women's Hospital
-
Contact Me
Boston, MA
United States
Objective: We previously demonstrated that lung subjected to a mild thermal preconditioning (TP) of 41.5°C during ex vivo lung perfusion (EVLP) had improved function and decreased inflammatory and cell death markers. How TP affects the populations of immune cells in the lung airways and the perfusion solution after EVLP is the purpose of this study.
Methods: Male rats were randomly assigned into 2 groups: controls (Ctl, n=7) or TP (n=9). Lungs were kept in situ for 1h at room temperature and flushed with cold Perfadex. The heart-lung block was harvested, kept at 4°C for 1h and mounted on the EVLP system. In the Ctl group, the temperature of the perfusion solution was kept at 37°C. In the TP group, a heat shock was done after 1h of EVLP by heating the perfusion solution to 41.5°C for 30 minutes. At the end of EVLP, we sampled and centrifuged the bronchoalveolar lavage fluid (BALF) and the perfusion solution to collect cells. The BALF and perfusion solution contents of B lymphocytes, CD4+ and CD8+ T lymphocytes as well as contents in macrophages, monocytes and granulocytes were analyzed by flow cytometry and expressed as the percentages of live cells.
Results: We did not observe significant differences in total live cell counts in the perfusate and the BALF between the Ctl and TP groups. In the BALF, the proportions of immune cells were unchanged by TP as compared to Ctl. In the perfusate, we observed a significant reduction in T cells populations in TP group as compared to Ctl. CD4+ T cells were 40.5 ± 8.7% of viable cells in Ctl group and 26.9±4.5% (p=0.001) in the TP group. CD8+ were 25.8 ± 3.8% in Ctl and 19.6 ± 3.8% in TP (p=0.005). B lymphocytes were not changed (15.6 ± 5.2% in Ctl vs 18.8 ± 6.2% in TP). The proportion of myeloid cells were increased in TP with 14.0 ± 5.1% in Ctl and 23.7 ± 5.0% in TP (p=0.002). Myeloid cells were predominantly monocytes (13.3 ± 4.9% in Ctl and 21.5± 4.9% in TP (p=0.003)) and neutrophils (0.4 ± 0.3% in Ctl and 1.7± 1.0% in TP (p=0.005)).
Conclusion: TP during EVLP reduces T lymphocytes and augments monocytes and neutrophils proportions in the perfusion solution. Whether this results from changes in endothelium adhesion capability or permeability in responses to TP and/or immune cell type specific responses to TP will need more investigations. This underlines the profound effects of TP on immune responses and opens an exciting field of research.
View Submission
Poster Presenter
Thorsten Krueger
-
Contact Me
Lausanne
Switzerland
Tyrosine kinase inhibitor therapy has been demonstrated to significantly improve disease-free survival for completely resected stage IB to IIIA EGFR-mutant non-small cell lung cancer. Although trials are underway, it is unknown whether these drugs will be effective as neoadjuvant therapy for patients with resectable NSCLC. Neoadjuvant therapy can potentially reduce tumor size, improve resectability, and provide earlier systemic control. However, TKIs are sometimes considered cytostatic rather than cytotoxic, and there is no data on how tumors will respond to short courses of treatment.
We present the case of a 52-year-old never-smoker Hispanic female who presented with cT4N2 EGFR-mutated (exon 21 L858R) stage IIIB NSCLC. On workup of a chronic cough and hemoptysis, she was found to have a 9.6 x 6.4 x 5.8 cm left lower lobe mass with SUVmax 15.0 and bulky FDG-avid subcarinal lymphadenopathy. The tumor appeared resectable only by sleeve resection or pneumonectomy. We therefore elected to treat with upfront osimertinib and reassess for local therapy. She tolerated induction TKI therapy well and without toxicity. After eight weeks of treatment, the patient was found to have a major radiographic response. Repeat imaging demonstrated a reduction in the size of the primary lesion as well as improvement of subcarinal adenopathy. Given the favorable response to treatment, the tumor now appeared to be resectable by lobectomy. The patient was taken to the operating room, where we performed a thoracoscopic left lower lobe lobectomy and extensive lymphadenectomy. Intraoperatively, we encountered only mild to moderate evidence of post-induction treatment firborsis. Pathology revealed a significant response with an estimated viable tumor size of 0.9 cm and residual disease in only one of 24 lymph nodes. This 3.3cm subcarinal node harbored only 10% viable tumor with a significant treatment effect. The patient did have visceral pleural invasion and was pathologically staged as ypT2aN2. We highlight this case to demonstrate the importance of early molecular testing and of the successful use of neoadjuvant TKI and subsequent minimally invasive lung resection.
View Submission
Poster Presenter
Roger Zhu, Staten Island University Hospital - Northwell Health
-
Contact Me
Staten Island, NY
United States