Comparing Robotic, Thoracoscopic, and Open Segmentectomy: A National Cancer Database Analysis.

INTRODUCTION: Minimally invasive approaches to lung resection have become widely acceptable and more recently, segmentectomy has demonstrated equivalent oncologic outcomes when compared to lobectomy for early-stage non-small cell lung cancer (NSCLC). However, studies comparing outcomes following segmentectomy by different surgical approaches are lacking. Our objective was to investigate the outcomes of patients undergoing robotic, video-assisted thoracoscopic surgery (VATS), or open segmentectomy for NSCLC using the National Cancer Database. METHODS: NSCLC patients with clinical stage I who underwent segmentectomy from 2010 to 2016 were identified. After propensity-score matching (1:4:1), multivariate logistic regression analyses were performed to determine predictors of 30-d readmissions, 90-d mortality, and overall survival. RESULTS: 22,792 patients met study inclusion. After matching, approaches included robotic (n = 2493; 17%), VATS (n = 9972; 66%), and open (n = 2493; 17%). An open approach was associated with higher 30-d readmissions (7% open versus 5.5% VATS versus 5.6% robot, P = 0.033) and 90-d mortality (4.4% open versus 2.2% VATS versus 2.5% robot, P < 0.001). A robotic approach was associated with improved 5-y survival (50% open versus 58% VATS versus 63% robot, P < 0.001). CONCLUSIONS: For patients with clinical stage I NSCLC undergoing segmentectomy, compared to the open approach, a VATS approach was associated with lower 30-d readmission and 90-d mortality. A robotic approach was associated with improved 5-y survival compared to open and VATS approaches when matched. Additional studies are necessary to determine if unrecognized covariates contribute to these differences.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: An Analysis of 5721 Cases.

OBJECTIVE: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). SUMMARY BACKGROUND DATA: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. RESULTS: A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS ( P < 0.0001) and OL ( P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P <0.02). Compared to VATS, RL had lower conversion rate ( P <0.0001), shorter hospital stay ( P <0.0001) and a lower postoperative transfusion rate ( P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. CONCLUSIONS: RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: Survival Analysis of 6646 Cases.

OBJECTIVE: The aim of this study was to analyze overall survival (OS) of robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VATS), and open lobectomy (OL) performed by experienced thoracic surgeons across multiple institutions. SUMMARY BACKGROUND DATA: Surgeons have increasingly adopted RL for resection of early-stage lung cancer. Comparative survival data following these approaches is largely from single-institution case series or administrative data sets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. Consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Induction therapy patients were excluded. The propensity-score method of inverse-probability of treatment weighting was used to balance baseline characteristics. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazard models were used to evaluate association among OS and relevant risk factors. RESULTS: A total of 2789 RL, 2661 VATS, and 1196 OL cases were included. The unadjusted 5-year OS rate was highest for OL (84%) followed by RL (81%) and VATS (74%); P =0.008. Similar trends were also observed after inverse-probability of treatment weighting adjustment (RL 81%; VATS 73%, OL 85%, P =0.001). Multivariable Cox regression analyses revealed that OL and RL were associated with significantly higher OS compared with VATS (OL vs. VATS: hazard ratio=0.64, P <0.001 and RL vs. VATS: hazard ratio=0.79; P =0.007). CONCLUSIONS: Our finding from this large multicenter study suggests that patients undergoing RL and OL have statistically similar OS, while the VATS group was associated with shorter OS. Further studies with longer follow-up are necessary to help evaluate these observations.

Robotic-assisted Versus Video-assisted Thoracoscopic Lobectomy: Short-term Results of a Randomized Clinical Trial (RVlob Trial).

OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

Specific complications and limitations of robotic esophagectomy.

Regardless of the approach to esophagectomy, it is an operation that may be associated with significant risk to the patient. Robotic-assisted minimally invasive esophagectomy (RAMIE) has the same potential for short- and long-term complications as does open and minimally invasive esophagectomy. These complications include among others, the risk for anastomotic leak, gastric tip necrosis, vocal cord palsy, and chylothorax. Moreover, there are additional risks that are unique to the robotic platform such as hardware or software malfunction. These risks are heavily influenced by numerous factors including the patient's comorbidities, whether neoadjuvant therapy was administered, and the extent of the surgical team's experience. The limitations of RAMIE are therefore based on the careful assessment of the patient for operability, the tumor for resectability and the team for surgical ability. This article will tackle the topic of complications and limitations of RAMIE by examining each of these issues. It will also describe the recommended terminology for reporting post-esophagectomy complications.

Surgical Management of Lung Cancer: History, Evolution, and Modern Advances.

PURPOSE OF REVIEW: Although surgery for lung cancer was not common before the early twentieth century, it has enjoyed remarkable progress since then both in type of resection and technical approach. This has been coupled with significant technological advances. Here, we will review the history and evolution of this relatively new field of surgery. RECENT FINDINGS: The gold standard of the extent of resection for lung cancer evolved from pneumonectomy to lobectomy to even sublobar resection for select situations. In addition, major advances have occurred in the technical aspect of the surgical procedure. The incisional approach has evolved from rib spreading thoracotomy to thoracoscopic surgery with the latter showing significant improvement in short-term outcomes over open thoracotomy. However, standard video-assisted thoracoscopic surgery or VATS is associated with visual and mechanical limitations, including lack of depth perception and rigid straight instruments. This makes it appropriate only for early-stage peripheral and small tumors. Most of the limitations of VATS can be overcome with the more recently introduced robotic-assisted thoracic surgery (RATS). RATS utilizes wristed instruments that are introduced in the chest through 8-mm ports and can mimic the movements of the human hand. In addition, magnified, three-dimensional and high definition imaging gives the surgeon an image of the lung unlike any other modality. This has allowed surgeons to perform advanced resections such as pneumonectomy or sleeve resection in a minimally invasive fashion. In addition, RATS has become a platform for the addition of other technical enhancements such as incorporating a near infra-red light source into the camera allowing identification of autoflourescent agents, such as indocyanin green. This has allowed localization of small nodules for resection and identification of tissue planes for sublobar resection. However, new technologies also require investments in time and money. Thoracic surgery for lung cancer has evolved to include advanced minimally invasive techniques including video-assisted and robotic-assisted thoracoscopy. RATS in particular may enable surgeons to perform more advanced procedures in a minimally invasive fashion. It is hoped that the higher costs of new surgical technology may be offset by the potential for improved patient outcomes and resultant socioeconomic benefits.

Evaluation of quality of life following placement of self-expanding plastic stents as a bridge to surgery in patients receiving neoadjuvant therapy for esophageal cancer.

PURPOSE: To determine whether self-expanding plastic stent (SEPS) placement significantly improves quality of life and maintains optimal nutrition while allowing full-dose neoadjuvant therapy (NAT) in patients with esophageal cancer. PATIENTS AND METHODS: A prospective, dual-institution, single-arm, phase II (http://ClinicalTrials.gov: NCT00727376) evaluation of esophageal cancer patients undergoing NAT prior to resection. All patients had a self-expanding polymer stent placed prior to NAT. The European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25, Functional Assessment of Cancer Therapy-Anorexia, and Functional Assessment of Cancer Therapy-General surveys were administered prior to stenting, within 1 week post-stent placement, and at the completion of neoadjuvant therapy. RESULTS: Fifty-two patients were enrolled; 3 (5.8%) had stent migrations requiring replacement. There were no instances of esophageal erosion or perforation. All patients received some form of neoadjuvant therapy. Thirty-six (69%) received chemoradiation; 34 (93%) of these patients received the planned dose of chemotherapy, and 27 (75%) received the full planned dose of radiotherapy. There were 16 (31%) patients receiving chemotherapy alone; 12 (74%) of patients in the chemotherapy-alone group completed the planned dose of therapy. CONCLUSION: Placement of SEPS appears to provide significant improvement in quality of life related to dysphagia and eating restriction in patients with esophageal cancer undergoing neoadjuvant therapy. Consideration of SEPS instead of percutaneous feeding tube should be initiated as a first line in dysphagia palliation and NAT nutritional support.

Laparoscopic versus robot-assisted surgery for median arcuate ligament syndrome.

BACKGROUND: Median arcuate ligament syndrome (MALS) is an uncommon disorder characterized by postprandial abdominal pain, weight loss, and vomiting related to the compression of the celiac artery by the median arcuate ligament. This syndrome has been classically treated with an open surgical approach. More recently, laparoscopic and robotic approaches have been used. We present our outcomes with laparoscopic and robot-assisted treatment of MALS. METHODS: We performed a retrospective review of all patients treated for MALS from March 2006 to August 2012 at a single institution. RESULTS: A total of 16 patients with MALS were treated: 12 patients via a laparoscopic approach and 4 patients via a robot-assisted approach. Patient characteristics and comorbidities were similar between groups. We experienced no intraoperative or perioperative conversions, complications, or deaths. The mean operative time for the laparoscopic approach was significantly shorter than for the robotic approach (101.7 vs. 145.8 min; P = 0.02). However, we found no significant difference in length of hospital stay (1.7 vs. 1.3 days, P = 0.23). The mean length of follow-up for laparoscopically treated patients was 22.2 months and for robotically treated patients it was 20 months. Eight patients (67 %) in the laparoscopic group and two patients (50 %) in the robotic group had full resolution of their abdominal pain. Three patients in the laparoscopic group and two patients in the robotic group ceased chronic narcotic use after surgery. CONCLUSIONS: Both laparoscopic and robotic approaches to MALS treatment can be performed with minimal morbidity and mortality. The laparoscopic approach was associated with a significantly shorter operative time. While innovative, the true advantages to robot-assisted MALS surgery are yet to be seen.

Robotic Belsey Mark IV Repair of the Paraesophageal Hernia.

OBJECTIVE: Surgical repair of paraesophageal hernias in patients with hostile abdomen is challenging. Despite its utility as an open procedure, the adoption of the minimally invasive Belsey Mark IV procedure has been limited because of the complexity of using traditional video-assisted thoracoscopic instrumentation. The robotic platform offers additional degrees of freedom, which enables minimally invasive transthoracic approach despite challenging anatomy. The purpose of this article is to describe a technique of robotic approach for the Belsey Mark IV operation. METHODS: We retrospectively reviewed 5 cases of the robotic Belsey Mark IV procedure completed at a single institution between June 2018 and November 2021. Data were collected from a review of the medical records, including operative reports, anesthesia records, imaging, and clinical notes. The operative technique is described in the present article. There were 4 men and 1 woman. The average age of the patients was 64.4 ± 13.6 years, with an average body mass index of 24.5 kg/m2. Three patients had undergone previous transabdominal hiatal hernia repair, and 2 of them had 2 prior repairs. One patient underwent simultaneous pulmonary left lower lobectomy for cancer with the Belsey Mark IV procedure. RESULTS: The average operative time was 209 ± 95 min (110 to 360 min). The average postoperative length of stay was 4.2 days, and 2 patients experienced complications including bleeding and persistent air leak (after lobectomy). The average blood loss was 67 ± 25 mL. CONCLUSIONS: The robotic platform enables a transthoracic minimally invasive approach to the Belsey Mark IV operation.

Transsternal Approach for Broncho-Pleural Fistula Closure After Right Pneumonectomy.

Broncho-pleural fistula (BPF) is an abnormal communication between the bronchial lumen and the pleural space that typically occurs postoperatively. Surgical intervention is typically needed to patch the fistula; however, current literature lacks a gold standard for which treatment to use. With a high mortality rate, there is a clear urgency for quick and successful intervention. This case examines a 59-year-old patient presenting with a BPF 14 years after incidental pneumonectomy during upper lobectomy for invasive aspergillus. A fistula was appreciated during bronchoscopy with contrast injection. The fistula was closed via the transsternal approach through median sternotomy and pericardiotomy. This case report aims to provide a viable option to successfully repair a BPF via the transsternal approach.

Health-Related Quality of Life Following Robotic-Assisted or Video-Assisted Lobectomy in Patients With Non-Small Cell Lung Cancer: Results From the RVlob Randomized Clinical Trial.

BACKGROUND: Robot-assisted lobectomy (RAL) is increasingly used as an alternative to video-assisted lobectomy (VAL) for resectable non-small cell lung cancer (NSCLC). However, there is little evidence of any difference in postoperative health-related quality of life (HRQoL) between these two approaches. RESEARCH QUESTION: Is RAL superior to VAL in improving quality of life in patients with resectable NSCLC? STUDY DESIGN AND METHODS: We performed a single-center, open-label randomized clinical trial from May 2017 to May 2020 with 320 enrolled patients undergoing RAL or VAL for resectable NSCLC (RVlob trial; NCT03134534). Postoperative pain was evaluated by visual analog score or numeric rating score on postoperative day 1 and at weeks 4, 24, and 48. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), and the European Quality of Life 5 Dimensions (EQ-5D) questionnaire were also administered at weeks 4, 24, and 48 after surgery. RESULTS: One hundred and fifty-seven patients underwent RAL and 163 underwent VAL. The mean pain score of patients after RAL was significantly lower at week 4 (2.097 ± 0.111 vs 2.431 ± 0.108; P = .032). QLQ-C30 and QLQ-LC13 summary scores (P > .05) were similar for both RAL and VAL during the first 48 weeks of follow-up. HRQoL scores assessed with the EQ-5D questionnaire were also comparable between the two groups (P > .05) during the whole study period. INTERPRETATION: Both RAL and VAL showed satisfactory and comparable HRQoL and postoperative pain up to 48 weeks after surgery, despite some minor statistical differences at week 4. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03134534; URL: www. CLINICALTRIALS: gov.

Understanding the Challenges Faced by Esophageal and Gastroesophageal Junction Cancer Survivors.

The primary aim of this study is to characterize long-term quality of life (QOL) in patients with esophageal and gastroesophageal junction (EGEJ) cancers who underwent curative intent treatment. EGEJ survivors were recruited to participate in a one-time cross-sectional survey study using validated questionnaires assessing QOL. Chart review was conducted for patient demographics and clinical characteristics. Spearman correlation coefficients, Wilcoxon signed-rank test, and Fisher's exact test were used to assess relationships between patient characteristics and long-term outcomes. QOL was relatively high in this sample, as evidenced by high median scores on the functional scales and low median scores in the symptom domains of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, with an overall median global health score of 75.0 (range 66.7-83.3). Patients using opiates at the time of survey reported lower role functioning (P = .004), social functioning (P = .052), and overall global health (P = .041). Younger patients had significantly higher rates of reflux (P = .019), odynophagia (P = .045), choking (P = .005), and cough (P = .007). Patients using opiates or of younger age had lower QOL and higher symptoms in this cohort of long-term EGEJ survivors.

Preclinical Synergistic Combination Therapy of Lurbinectedin with Irinotecan and 5-Fluorouracil in Pancreatic Cancer.

Pancreatic cancer is a devastating disease with a poor prognosis. Novel chemotherapeutics in pancreatic cancer have shown limited success, illustrating the urgent need for new treatments. Lurbinectedin (PM01183; LY-01017) received FDA approval in 2020 for metastatic small cell lung cancer on or after platinum-based chemotherapy and is currently undergoing clinical trials in a variety of tumor types. Lurbinectedin stalls and degrades RNA Polymerase II and introduces breaks in DNA, causing subsequent apoptosis. We now demonstrate lurbinectedin's highly efficient killing of human-derived pancreatic tumor cell lines PANC-1, BxPC-3, and HPAF-II as a single agent. We further demonstrate that a combination of lurbinectedin and irinotecan, a topoisomerase I inhibitor with FDA approval for advanced pancreatic cancer, results in the synergistic killing of pancreatic tumor cells. Western blot analysis of combination therapy indicates an upregulation of γH2AX, a DNA damage marker, and the Chk1/ATR pathway, which is involved in replicative stress and DNA damage response. We further demonstrate that the triple combination between lurbinectedin, irinotecan, and 5-fluorouracil (5-FU) results in a highly efficient killing of tumor cells. Our results are developing insights regarding molecular mechanisms underlying the therapeutic efficacy of a novel combination drug treatment for pancreatic cancer.

Defining the learning curve of robotic portal segmentectomy in small pulmonary lesions: a prospective observational study.

Although robotic segmentectomy has been applied for the treatment of small pulmonary lesions for many years, studies on the learning curve of robotic segmentectomy are quite limited. Thus, we aim to investigate the learning curve of robotic portal segmentectomy with 4 arms (RPS-4) using prospectively collected data in patients with small pulmonary lesions. One hundred consecutive patients with small pulmonary lesions who underwent RPS-4 between June 2018 and April 2021 were included in the study. Da Vinci Si/Xi systems were used to perform RPS-4. The mean operative time, console time, and docking time for the entire cohort were 119.2 ± 41.6, 85.0 ± 39.6, and 6.6 ± 2.8 min, respectively. The learning curve of RPS-4 can be divided into three different phases: 1-37 cases (learning phase), 38-78 cases (plateau phase), and > 78 cases (mastery phase). Moreover, 64 cases were required to ensure acceptable surgical outcomes. The total operative time (P < 0.001), console time (P < 0.001), blood loss (P < 0.001), and chest tube duration (P = 0.014) were reduced as experience increased. In conclusion, the learning curve of RPS-4 could be divided into three phases. 37 cases were required to pass the learning phase, and 78 cases were needed to truly master this technique.

Minimally Invasive Diaphragm Plication for Acquired Unilateral Diaphragm Paralysis: A Systematic Review.

Objective: Diaphragm paralysis is a relatively uncommon entity that can be both congenital and acquired in nature. While commonly asymptomatic, it can also cause a significant decrease in pulmonary function and reserve, particularly in patients with underlying pulmonary diseases. Our aim was to summarize the current literature regarding the minimally invasive techniques used in the surgical correction of acquired diaphragm paralysis via traditional and robotic minimally invasive approaches. Methods: We conducted a systematic review of available literature using the Cochrane methodology and reported findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Results: A total of 6,561 citations were identified through initial database and reference searches, of which 90 articles met the inclusion criteria for review. After further assessment, 33 appropriate full-text studies were selected for the review. Of the selected publications, the majority represented case reports and single-center retrospective studies with level of evidence 4. Only 1 level 2b study (individual cohort study) was identified, comparing minimally invasive and open approaches. Conclusions: Each of the minimally invasive approaches has its unique benefits and disadvantages, which are summarized and delineated in this article. Ultimately, no preferred method of diaphragm plication for diaphragm paralysis can be recommended at this time based on clinical data. The choice of procedure and surgical approach continues to be selected based on the surgeon's experience and preference.

Tracheobronchoplasty for tracheobronchomalacia.

Tracheobronchoplasty (TBP) consists of splinting of the posterior membranous wall of the central airways with the goal of restoring a normal configuration and preventing excessive collapse in patients with tracheobronchomalacia (TBM). Despite some variation in technique, it consists of sewing a mesh on the posterior membranous wall of the trachea and both main stem bronchi. Traditionally performed through a right posterolateral thoracotomy, it should be reserved for cases of severe TBM. Surgical exposure necessitates dissection of the trachea from the thoracic inlet to the carina, as well the right main stem bronchus, bronchus intermedius and left main stem bronchus. Airway management in the operating room requires manipulation of the endotracheal tube (ETT) to allow safe placement of the sutures without puncturing the balloon. Other key technical considerations include downsizing of the airway with the mesh, and appropriate spacing of the sutures to ensure a plicating effect of the posterior membranous wall. More recently the robotic platform was used to perform TBP surgery. Its fine precise wristed motion and excellent visualization offer potential advantages over a thoracotomy and early outcomes of robotic-assisted TBP are encouraging. Longitudinal follow-up is still necessary to ensure the durability of repair in a patient population with significant underlying respiratory co-morbidities.

Robotic Transgastric Reconstruction of the Double Lumen Esophagus.

Double lumen esophagus is an extremely rare condition, developing in most cases as a complication of antireflux procedures or gastroesophageal reflux itself secondary to the severe inflammatory process in and around the lower esophagus. We describe a case of iatrogenic double lumen esophagus after multiple previous Nissen fundoplications for chronic gastroesophageal reflux disease. There is no standard surgical intervention for the management of this complication. We present a first report of successful robot-assisted surgical reconstruction of a double lumen esophagus.

A Rare Complication of Esophageal Exclusion: Esophageal Mucocele.

Bipolar esophageal exclusion is a "Hail Mary" procedure for control of leak and persistent mediastinal soilage from esophageal injury. Usually, the esophageal remnant scars down without negative consequences. Esophageal mucocele is a rare complication of bipolar esophageal exclusion. This is a case report of an iatrogenic esophageal transection and the subsequent treatment course. A retrospective chart review of the patient's medical and surgical history was performed. After a robotic hiatal hernia repair at an outside institution, the patient suffered an esophageal leak and was surgically treated with esophageal exclusion, wide drainage of the mediastinum, and decortication of the resulting empyema. She subsequently underwent retrosternal gastric conduit for esophageal reconstruction 4 months later. Three years after this, she developed a rare complication of esophageal exclusion, a symptomatic esophageal mucocele that required resection.

The Scan, the Needle, or the Knife? National Trends in Diagnosing Stage I Lung Cancer.

OBJECTIVE: Indeterminate lung nodules have been increasingly discovered since the expansion of lung cancer screening programs. The diagnostic approach for suspicious nodules varies based on institutional resources and preferences. The aim of this study is to analyze factors associated with diagnostic modalities used for early-stage non-small cell lung cancer (NSCLC). METHODS: The National Cancer Database was queried for all patients with stage I NSCLC from 2004 to 2015. Four diagnostic modalities were identified, including clinical radiography alone (CRA), bronchial cytology (BC), procedural biopsy (PB), and surgical biopsy (SB). A multivariable multinomial logistic regression was used to assess associations of patient demographics, cancer characteristics, and facility characteristics with these modalities. RESULTS: Of 250,614 patients, 4,233 (1.7%) had CRA, 5,226 (2.1%) had BC, 147,621 (59.9%) had PB, and 93,534 (37.3%) had SB. Older patients were more likely to receive CRA (adjusted odds ratio [ORadj] = 5.3) and less likely to receive SB (ORadj = 0.73). Black patients were less likely to receive SB (ORadj = 0.83) and more likely to receive BC (ORadj = 1.31). Private insurance was associated with SB (ORadj = 1.11), whereas Medicaid was associated with BC (ORadj = 1.21). Patients more than 50 miles from the facility were more likely to undergo SB (ORadj = 1.25 vs PB; ORadj = 1.30 vs CRA; ORadj = 1.38 vs BC). Patients receiving SB had shorter days from diagnosis to treatment (23.0 vs 53.5 to 64.7 for other modalities, P < 0.001). CONCLUSIONS: Diagnostic SB to confirm early-stage NSCLC was associated with younger age, greater travel distance, and shorter time to treatment in comparison with other modalities. Black race and non-private insurance were less likely to be associated with SB.

Preclinical studies with ONC201/TIC10 and lurbinectedin as a novel combination therapy in small cell lung cancer (SCLC).

The American Cancer Society estimates that ~15% of all lung cancers are categorized as small cell lung cancer (SCLC) with an overall five-year survival rate of less than 7%. Due to disease aggressiveness, more other malignancies, the standard of care is based on clinical efficacy rather than helpful biomarkers. Lurbinectedin is a small molecule RNA polymerase II inhibitor that binds the minor groove of DNA to induce double-strand breaks. Lurbinectedin has efficacy towards SCLC cells at sub-nM concentration and received accelerated FDA approval in 2020 for metastatic SCLC that progressed on platinum-based therapy. ONC201/TIC10 is a TRAIL pathway-inducing compound that with demonstrated clinical efficacy in H3K27M-mutated diffuse midline glioma and neuroendocrine tumors, in early phase clinical trials. We hypothesized that combining ONC201 and lurbinectedin may yield synergistic and targeted killing of SCLC cells. SCLC cell lines H1048, H1105, H1882, and H1417 were treated with ONC201 and lurbinectedin and cell viability was determined using a CellTiter-Glo assay using varying drug concentrations. Synergistic growth inhibition of SCLC cells was noted with combination of ONC201 and lurbinectedin. Induction of the integrated stress response mediator ATF4 and CHOP was observed with ONC201 and lurbinectedin along with induction of PARP cleavage indicative of apoptosis in response to cellular stress. Additionally, SCLC lines treated with the combination therapy displayed increased DNA breakage-related proteins such as phosphorylated Chk-1, Wee1 and γ-H2AX. Combination index revealed the most potent synergy occurred at the concentrations of 0.16 µM ONC201 and 0.05 nM lurbinectedin in the H1048 cell line, demonstrating highly efficient and selective killing of these tumor cells in vitro. While these therapies showed potency against the cell lines derived from SCLC patients, it is noteworthy that the combination showed significantly less toxicity to healthy human lung epithelial cells. Future studies could explore the combination of ONC201 and lurbinectedin in SCLC cell lines, SCLC patient-derived organoids, other tumor types, including in vivo studies and clinical translation.