Valerie W. Rusch

Durvalumab With Radiation Therapy in Patients With Inoperable Locally Advanced Non–Small Cell Lung Cancer Ineligible for Concurrent Chemoradiotherapy (DART)

Minimally invasive surgical techniques for oncologic resections: A multi-specialty experience within a high-volume center

Feasibility and oncologic outcomes of minimally invasive surgery after induction chemoimmunotherapy for non–small cell lung cancer

Objective: We evaluated the feasibility and long-term outcomes of minimally invasive surgery (MIS) after neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer (NSCLC). Methods: Patients with stage IB-IIIB NSCLC who underwent induction immunotherapy followed by surgery (2015-2022) were included. Overall and event-free survival were estimated using the Kaplan-Meier approach. Cox regression was used to quantify associations between clinical and pathologic variables and survival outcomes. Conclusions: MIS after induction immunotherapy is feasible and does not compromise long-term oncologic outcomes.

The role of diagnostic laparoscopy in staging distal esophageal adenocarcinoma

Objectives: The study objectives were to determine whether diagnostic laparoscopy improves staging accuracy in selected patients with distal esophageal adenocarcinoma and to identify clinicopathologic features associated with positive diagnostic laparoscopy. Methods: Patients with distal esophageal adenocarcinoma who underwent diagnostic laparoscopy from 2000 to 2023 at a single institution were identified from a prospectively maintained surgical database. Exclusion criteria included performance of diagnostic laparoscopy after systemic therapy, absence of staging positron computed tomography/computed tomography, and M1 disease before diagnostic laparoscopy. Fisher exact test and Wilcoxon rank-sum test were used to compare categorical and continuous variables, respectively, between patients with negative and positive diagnostic laparoscopy. Clinicopathologic features were assessed using multivariable logistic regression. Results: .341) were not associated with positive diagnostic laparoscopy. Conclusions: Signet ring feature is associated with peritoneal disease. The use of diagnostic laparoscopy in these patients may lead to better staging and more appropriate treatment strategies.

Radiologist’s Guide to the Ninth Edition TNM Staging System for Quantitative and Qualitative Assessment of Pleural Mesothelioma

Resectable non−small cell lung cancer in women: A disease-specific entity?

Objective: There may be important sex-specific differences among patients with non-small cell lung cancer (NSCLC). Despite this, women are underrepresented in prospective clinical trials. We evaluated sex-specific differences in clinicopathologic and genetic factors and survival among patients with NSCLC. Methods: This is a single-center study at a high-volume dedicated cancer hospital. Patients with NSCLC who underwent complete surgical resection from 2010 to 2018 were included. Primary outcomes include cumulative incidence of recurrence and overall survival, stratified by sex. Conclusions: Clinicopathologic and genetic factors and survival among patients with NSCLC differ on the basis of sex. NSCLC in women should be considered a disease-specific entity.

Should minimally invasive surgery be the standard approach for early-stage thymoma? A 20-year experience

Background: Minimally invasive surgery (MIS) has become the prevailing technique for resecting early-stage thymoma; however, studies evaluating the oncologic impact of this evolution are lacking. This study aimed to characterize the transition from open surgery to MIS and to evaluate outcomes. Methods: This was a retrospective, single-institution review of resections performed for pathologic TNM stage I-II thymomas between January 2000 and September 2023. The relationships between factors and recurrence were quantified using competing risk regression before and after applying overlap propensity score weights. Overlap propensity score weighting revealed a cumulative incidence of recurrence at 5 years of 5.1% (95% confidence interval [CI], 0.97%-9.2%) for open surgery (n = 47) compared to 7.1% (95% CI, 2.0%-12.9%) for MIS (n = 47), a non-statistically significant difference. Conclusions: MIS has become the principal approach for resecting early-stage thymoma over the last 2 decades. MIS is associated with a lower complication rate and shorter LOS but may be associated with a higher risk of recurrence in certain situations. Larger studies to evaluate the appropriate role of MIS are warranted.

Clinical Implications of The Cancer Genome Atlas Molecular Classification System in Esophagogastric Cancer

PURPOSE: The Cancer Genome Atlas (TCGA) project defined four distinct molecular subtypes of esophagogastric adenocarcinoma: microsatellite instable (MSI), Epstein-Barr virus (EBV)-associated, genomically stable (GS), and chromosomally instable (CIN). However, an association between molecular subtypes and clinical outcomes has not been clearly demonstrated. Given few actionable biomarkers, we investigated the clinical relevance of TCGA classification system. EXPERIMENTAL DESIGN: We identified all patients with esophagogastric adenocarcinoma whose tumors underwent prospective next-generation sequencing using the Memorial Sloan Kettering-IMPACT assay from 2014 to 2023. We classified all tumors in accordance with TCGA methodology and correlated molecular subtypes with high-quality clinicopathologic data. RESULTS: Among 1,438 included patients, 941 had CIN, 344 had GS, 103 had MSI, and 50 had EBV tumors. Accounting for the clinical stage and tumor grade, molecular classification was independently associated with overall cancer-specific survival (P < 0.001) on Cox multivariable analysis. Furthermore, genomic signatures, patient demographics, pathologic responses to neoadjuvant therapy, patterns of recurrence, and metastatic organotropism differed significantly by molecular subtype. Although most distal esophageal and gastroesophageal junction tumors were CIN, up to 25% of these included GS, MSI, or EBV subtypes in contrast to TCGA. Random forest machine learning demonstrated that the molecular subtype is more influential in predicting response to treatment than tumor location. CONCLUSIONS: Molecular classification is independently prognostic and may warrant inclusion in future staging and treatment guidelines. Routine molecular profiling is clinically feasible and may play a role in the management of patients to help guide appropriate treatment selection and clinical trial enrollment in the place of tumor location.

Correlation of Histologic Features with Gene Alterations in Pleural Mesothelioma

Treatment of Pleural Mesothelioma: ASCO Guideline Update

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide evidence-based recommendations to practicing physicians and others on the management of pleural mesothelioma (PM). METHODS ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pathology, cancer genetics, and advocacy experts to conduct an updated literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2016 through 2024. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 110 additional relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Evidence-based recommendations were developed for surgical cytoreduction, immunotherapy, chemotherapy, pathology, and germline testing in patients with PM. Additional information is available at www.asco.org/thoracic-cancer-guidelines .

Remote Symptom Monitoring in Thoracic Surgery Patients After Discharge

OBJECTIVE: To evaluate an electronic platform for remote symptom monitoring to enhance postdischarge care in thoracic surgery using patient reporting of symptoms. BACKGROUND: Owing to the increased use of enhanced recovery after surgery protocols, patients are spending a larger portion of their postoperative course at home. For patients undergoing complex operations, this represents an opportunity for early identification of abnormal symptoms at home before deterioration. METHODS: An online symptom-tracking platform for thoracic surgery patients was created on the basis of opinions from stakeholders and a review of the literature. Starting in February 2021, patients were educated about the symptom tracker in preoperative clinics. After discharge, patients received a series of electronic surveys covering 23 symptom domains assessed using a Likert Scale for severity. Moderate symptoms prompted a "yellow alert," and severe symptoms prompted a "red alert," both notifying the nursing team and prompting appropriate action. Patients were considered responders if they completed at least 1 survey. RESULTS: In total, 1997 patients were enrolled; 76% (n = 1520) were responders. Responders were younger, more likely to be White, less likely to have medical comorbidities, and less likely to be readmitted [odds ratio: 0.53 (95% CI: 0.37-0.76); P < 0.001]. Responders who were readmitted had a higher percentage of red alerts (47% vs 24%; P < 0.001) and yellow alerts (74% vs 61%; P = 0.016) compared with responders who were not readmitted. CONCLUSIONS: Electronic reporting adds an additional mechanism of communication between the patient and the clinical team, with the potential to lower the odds of readmission.

Real-world Decision-making Process for Stereotactic Body Radiotherapy Versus Minimally Invasive Surgery in Early-stage Lung Cancer Patients

Objective: To generate a prediction model for selection of treatment modality for early-stage non-small cell lung cancer (NSCLC). Summary Background Data: Stereotactic body radiotherapy (SBRT) and minimally invasive surgery (MIS) are used in the local treatment of early-stage NSCLC. However, selection of patients for either SBRT or MIS remains challenging, due to the multitude of factors influencing the decision-making process. Methods: We analyzed 1291 patients with clinical stage I NSCLC treated with intended MIS or SBRT from January 2020 to July 2023. A prediction model for selection for SBRT was created based on multivariable logistic regression analysis. The receiver operating characteristic curve analysis stratified the cohort into 3 treatment-related risk categories. Post-procedural outcomes, recurrence and overall survival (OS) were investigated to assess the performance of the model. Results: In total, 1116 patients underwent MIS and 175 SBRT. The prediction model included age, performance status, previous pulmonary resection, MSK-Frailty score, FEV1 and DLCO, and demonstrated an area-under-the-curve of 0.908 (95%CI, 0.876–0.938). Based on the probability scores (n=1197), patients were stratified into a low-risk (MIS, n=970 and SBRT, n=28), intermediate-risk (MIS, n=96 and SBRT, n=53) and high-risk category (MIS, n=10 and SBRT, n=40). Treatment modality was not associated with OS (HR of SBRT, 1.67 [95%CI: 0.80-3.48]; P =0.20). Conclusion: Clinical expertise can be translated into a robust predictive model, guiding the selection of stage I NSCLC patients for MIS versus SBRT and effectively categorizing them into three distinct risk groups. Patients in the intermediate category could benefit most from multidisciplinary evaluation.

Effects of Serratus Anterior Plane Block on Early Recovery from Thoracoscopic Lung Resection: A Randomized, Blinded, Placebo-Controlled Trial

Background: The efficacy of serratus anterior plane block (SAPB) for treatment of pain after minimally invasive thoracic surgery remains unclear. This trial assesses the impact of SAPB on postoperative opioid consumption and on measures of early recovery after thoracoscopic lung resection. Methods: Patients undergoing minimally invasive anatomic lung resection at a single center were randomized to undergo SAPB with 40 mL of injectate containing bupivacaine 0.25%, clonidine 100 mcg, and dexamethasone 4 mg (SAPB group) or sham block with 40 mL of normal saline (placebo group) at the conclusion of surgery. The primary outcome was cumulative intravenous morphine equivalents during the first 24 h postoperatively. Secondary outcomes were intravenous morphine equivalents, pain scores at rest and with cough, inspiratory volume on incentive spirometry, and incidence of nausea/vomiting during the first 48 h postoperatively; Quality of Recovery–15 score on postoperative day 7; and length of stay. Results: Using the protocol-specified intention-to-treat analysis, the median (interquartile range, IQR) intravenous morphine equivalents was 10.6 (5.0 to 27.1) mg in SAPB patients (n=46) versus 18.8 (9.9 to 29.6) mg in placebo patients (n=46) (32% reduction; ratio=0.68 [95% CI, 0.44 to 1.06]; P =0.085). Of the secondary outcomes, only the composite pain with cough scores differed significantly in the SAPB group by a coefficient of -0.41 (95% CI, -0.81 to -0.01; P =0.044). A sensitivity as-treated analysis reported median (IQR) intravenous morphine equivalents of 10.0 (5.0 to 27.2) mg in SAPB patients (n=44) versus 19.9 (10.4 to 29.0) mg in placebo patients (n=48) (36% reduction; ratio=0.64 [95% CI, 0.41 to 1.00]; P =0.048). Conclusions: The protocol-specified intention-to-treat analysis demonstrated that SAPB did not result in a significant reduction in opioid consumption when added to a multimodal analgesic regimen after thoracoscopic anatomic lung resection. The sensitivity as-treated analysis showed a significant and modest clinical reduction in the primary outcome that warrants further investigation.

Robotic Resection of Spinal and Paraspinal Tumors

Robotic arm surgical systems provide minimally invasive access and are commonly used in multiple surgical fields, with limited application in neurosurgery. Our institutional experience has led us to explore the benefits of a neurosurgeon trained to perform robotic surgery as part of a multidisciplinary team. The objective of this study is to evaluate the feasibility, safety, and outcomes of robotic resection for spinal nerve sheath tumors (NST).

Ultrasensitive circulating tumor DNA (ctDNA) minimal residual disease (MRD) detection in early stage non-small cell lung cancer (NSCLC).

Feasibility and safety of neoadjuvant nivolumab and chemotherapy for resectable diffuse pleural mesotheliomas: Results of a prospective pilot study.

8003 Background: Diffuse pleural mesotheliomas (DPM) are an aggressive malignancy where even patients with potentially resectable disease have poor outcomes. With an evolving understanding of the role of pleurectomy/decortication (P/D) as the standard of care for resectable disease, the need to improve upfront therapies is more urgent. Here we report the results of our single institution prospective pilot study of nivolumab with platinum (cisplatin/carboplatin) and pemetrexed prior to P/D for patients with resectable DPM (NCT04162015). Methods: Patients deemed operable and resectable by a multidisciplinary team received 2 cycles of neoadjuvant nivolumab, pemetrexed, and platinum followed by P/D. Subsequent therapy was at the physician's discretion. Using a minimax Simon two-stage design, the primary objective was defined as attempted P/D within 30 days of the planned surgery date. Secondary objectives included evaluating safety, overall survival (OS) from diagnosis, and progression free survival (PFS). Tumor tissue and plasma were collected for exploratory analyses such as immune cell profiling and pathologic response. Using single cell RNA sequencing (scRNAseq), we explored DPM transcriptional heterogeneity and treatment-associated tumor microenvironment (TME) changes. Results: 22 patients received neoadjuvant chemo-immunotherapy and 19 underwent attempted P/D (2 progressed and 1 declined surgery). 68% were men (13/19), 89% were epithelioid (17/19; remaining 2 were biphasic), and the median age at diagnosis was 72 (range: 33-80). No patient experienced pre-operative toxicity precluding P/D. 95% (18/19) of patients underwent P/D within 30 days of the planned date; 1 patient had biopsy-proven tumor flare after cycle 2 and had surgery at day +37. As of January 2024, median OS for the 19 patients that went for attempted P/D was 41.0 mos (median follow up: 25.3mos). OS for those who underwent R1 resections (n = 12) was not reached and for R2 (n = 7) was 31.4 mos (p = 0.67; HR 1.43, 95% CI 0.28-7.30). 26% of specimens (5/19) had ≤ 10% viable tumor cells on the resection; there was no clear correlation with outcomes. scRNAseq was performed on 15 resection specimens with available material. Comparing patients with PFS greater than or less than 12mos (PFS12), we found significantly increased abundance of CD8 cytotoxic T cells, and ISG+ (interferon stimulated) T cells. Conclusions: Neoadjuvant platinum, pemetrexed, and nivolumab was reliably able to be given to patients with DPM without impacting their ability to undergo P/D. The encouraging OS of this cohort to date, and tolerance of the regimen, highlights the importance of patient selection and preoperative treatments when considering P/D. Ongoing exploratory analyses will profile the cellular and transcriptional landscape of DPM and identify correlates of response to neoadjuvant chemo-immunotherapy. Clinical trial information: NCT04162015 .

Combining a WT1 cancer vaccine (galinpepimut-S) with checkpoint inhibition (nivolumab) in patients with WT1-expressing diffuse pleural mesothelioma (DPM): A phase I study.

8083 Background: Diffuse pleural mesothelioma (DPM) is an aggressive malignancy with poor outcomes and only two FDA-approved therapeutic regimens. The Wilms’ tumor suppressor protein (WT1) is often presented on the surface of DPM and is an ideal therapeutic target. A phase I study confirmed the safety and immunogenicity of galinpepimut-S (GS), a tetravalent, non-HLA restricted, heteroclitic WT1-specific peptide vaccine, in patients with WT1-expressing cancers, and our prior randomized Phase II study of adjuvant GS in patients with DPM suggested an improvement in median overall survival. Vaccine-dependent upregulation of T cell suppressive programmed death-ligand 1 (PD-L1) has been observed in the tumor microenvironment of other malignancies. To further enhance the immunogenicity of GS by reversing the effect of T cell suppression by PD1/PD-L1, we combined GS with checkpoint inhibition using nivolumab, an anti-PD1 monoclonal antibody. This open-label, non-randomized phase I study, examined the tolerability and immunogenicity of GS in combination with nivolumab in patients with previously treated DPM. Methods: We enrolled patients with WT1-positive metastatic or recurrent and measurable DPM treated with at least one course of pemetrexed-based chemotherapy. Patients received 2 doses of GS followed by 4 dose of GS with intravenous nivolumab every 2 weeks, and up to six additional cycles until disease progression, as measured by mRECIST 1.1 on CT imaging, or unacceptable toxicity. Primary endpoint was tolerability of the combination with < 3 patients with severe toxicity. Peripheral blood mononuclear cells (PBMC) were collected every 2 weeks for immune correlative testing. Toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Eliciting of antigen-specific T cells responses was evaluated via WT1 vaccine peptide pool expansion culture of PBMC samples for 10 days in the presence of IL-2 and IL-15 followed by short-term (6 hour) peptide pool restimulation and flow cytometry evaluating CD4/CD8 T cell intracellular cytokine production. Results: Ten patients were treated; 70% experienced treatment-related adverse events which were mostly mild; 2 experienced a grade ≥3 adverse event. Four (50%) of 8 patients had T-cell responses to WT1 peptides. There were no partial responses, but three patients had prolonged stable disease with up to 17% decrease in tumor volume. Median overall survival was 13.5 months from the most recent prior line of therapy. Conclusions: Coadministration of galinpepimut-S and nivolumab demonstrated a tolerable toxicity profile and induced immune responses in a subset of patients as indicated by immunophenotyping and disease control rate of 30% at 8 weeks but initial response and survival benefit were limited which may be due to the small sample size. Clinical trial information: NCT04040231 .

A New Functional Threshold for Minimally Invasive Lobectomy

To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV 1 ) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV 1 /ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy.

Biologic versus synthetic prosthesis for chest wall reconstruction: a matched analysis

OBJECTIVES: The aim of this study was to compare postoperative outcomes between biologic and synthetic reconstructions after chest wall resection in a matched cohort. METHODS: All patients who underwent reconstruction after full-thickness chest wall resection from 2000 to 2022 were reviewed and stratified by prosthesis type (biologic or synthetic). Biologic prostheses were of biologic origin or were fully absorbable and incorporable. Integer matching was performed to reduce confounding. The study end point was surgical site complications requiring reoperation. Multivariable analysis was performed to identify associated risk factors. RESULTS: In total, 438 patients underwent prosthetic chest wall reconstruction (unmatched: biologic, n = 49; synthetic, n = 389; matched: biologic, n = 46; synthetic, n = 46). After matching, the median (interquartile range) defect size was 83 cm2 (50-142) for the biologic group and 90 cm2 (48-146) for the synthetic group (P = 0.97). Myocutaneous flaps were used in 33% of biologic reconstructions (n = 15) and 33% of synthetic reconstructions (n = 15) in the matched cohort (P = 0.99). The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic reconstructions in the unmatched (3 [6%] vs 29 [7%]; P = 0.99) and matched (2 [4%] vs 4 [9%]; P = 0.68) cohorts. On the multivariable analysis, operative time [adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI), 1.00-1.01; P = 0.006] and operative blood loss (aOR = 1.00, 95% CI, 1.00-1.00]; P = 0.012) were associated with higher rates of surgical site complications requiring reoperation; microvascular free flaps (aOR = 0.03, 95% CI, 0.00-0.42; P = 0.024) were associated with lower rates. CONCLUSIONS: The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic prostheses in chest wall reconstructions.

The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Updated Modeling of Prognostic Factors in Pleural Mesothelioma

INTRODUCTION: The International Association for the Study of Lung Cancer developed an international pleural mesothelioma database to improve staging. Data entered from 1995 to 2009 (training data set) were analyzed previously to evaluate supplemental prognostic factors. We evaluated these factors with new clinical data to determine whether the previous models could be improved. METHODS: Patients entered into the database from 2009 to 2019 (validation cohort) were assessed for the association between previous prognosticators and overall survival using Cox proportional hazards regression with bidirectional stepwise selection. Additional variables were analyzed and models were compared using Harrell's C-index. RESULTS: The training data set included 3101 patients and the validation cohort, 1733 patients. For the multivariable pathologic staging model applied to the training cohort, C-index was 0.68 (95% confidence interval [CI]: 0.656-0.705). For the validation data set (n = 497), C-index was 0.650 (95% CI: 0.614-0.685), and pathologic stage, histologic diagnosis, sex, adjuvant therapy, and platelet count were independently associated with survival. Adding anemia to the model increased the C-index to 0.652 (95% CI: 0.618-0.686). A basic presentation model including all parameters before staging yielded a C-index of 0.668 (95% CI: 0.641-0.695). In comparison, the European Organization for Research and Treatment of Cancer model yielded C-indices of 0.550 (95% CI: 0.511-0.589) and 0.577 (95% CI: 0.550-0.604) for pathologic staging and presentation models, respectively. CONCLUSIONS: Although significant predictors differed slightly, the International Association for the Study of Lung Cancer training model performed well in the validation set and better than the model of the European Organization for Research and Treatment of Cancer. International collaboration is critical to improve outcomes in this rare disease.