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.

Propensity-matched Analysis Demonstrates Long-term Risk of Respiratory and Cardiac Mortality After Pneumonectomy Compared With Lobectomy for Lung Cancer.

OBJECTIVE: We sought to quantify and characterize long-term consequences of pneumonectomy, with particular attention to nononcologic mortality. SUMMARY OF BACKGROUND DATA: Pneumonectomy is associated with profound changes in cardiopulmonary physiology. Studies of long-term outcomes after pneumonectomy typically report generalized measures, such as disease-free and overall survival. METHODS: Patients undergoing lobectomy or pneumonectomy for lung cancer at our institution from 2000 to 2018 were reviewed. Propensity-score matching was performed for 12 clinicopathologic factors. Ninety-day complications and deaths were compared. Five-year cumulative incidence of oncologic and nononcologic mortality were compared using competing risks approaches. RESULTS: From 3339 lobectomy and 355 pneumonectomy patients identified, we derived 318 matched pairs. At 90 days, rates of overall complications were similar (46% for pneumonectomy vs 43% for lobectomy; P = 0.40), but rates of major complications (21% vs 13%; P = 0.005) and deaths (6.9% vs 1.9%; P = 0.002) were higher the pneumonectomy cohort. The cumulative incidence of oncologic mortality was not significantly different between cohorts (P = 0.9584). However, the cumulative incidence of nononcologic mortality was substantially higher in the pneumonectomy cohort for both date of surgery and 1-year landmark analyses (P < 0.0001 and P = 0.0002, respectively). Forty-five pneumonectomy patients (18%) died of nononcologic causes 1-5 years after surgery; pneumonia (n = 21) and myocardial infarction (n = 10) were the most common causes. In pneumonectomy patients, preexisting cardiac comorbidity and low diffusion capacity of the lungs for carbon monoxide were predictive of nononcologic mortality. CONCLUSIONS: Compared to lobectomy, excess mortality after pneumonectomy extends beyond 1 year and is driven primarily by nononcologic causes. Pneumonectomy patients require lifelong monitoring and may benefit from expeditious assessment and intervention at the initial signs of illness.

CT-based Radiogenomic Analysis of Clinical Stage I Lung Adenocarcinoma with Histopathologic Features and Oncologic Outcomes.

Background A preoperative predictive model is needed that can be used to identify patients with lung adenocarcinoma (LUAD) who have a higher risk of recurrence or metastasis. Purpose To investigate associations between CT-based radiomic consensus clustering of stage I LUAD and clinical-pathologic features, genomic data, and patient outcomes. Materials and Methods Patients who underwent complete surgical resection for LUAD from April 2014 to December 2017 with preoperative CT and next-generation sequencing data were retrospectively identified. Comprehensive radiomic analysis was performed on preoperative CT images; tumors were classified as solid, ground glass, or mixed. Patients were clustered into groups based on their radiomics features using consensus clustering, and clusters were compared with tumor genomic alterations, histopathologic features, and recurrence-specific survival (Kruskal-Wallis test for continuous data, χ2 or Fisher exact test for categorical data, and log-rank test for recurrence-specific survival). Cluster analysis was performed on the entire cohort and on the solid, ground-glass, and mixed lesion subgroups. Results In total, 219 patients were included in the study (median age, 68 years; interquartile range, 63-74 years; 150 [68%] women). Four radiomic clusters were identified. Cluster 1 was associated with lepidic, acinar, and papillary subtypes (76 of 90 [84%]); clusters 2 (13 of 50 [26%]) and 4 (13 of 45 [29%]) were associated with solid and micropapillary subtypes (P < .001). The EGFR alterations were highest in cluster 1 (38 of 90 [42%], P = .004). Clusters 2, 3, and 4 were associated with lymphovascular invasion (19 of 50 [38%], 14 of 34 [41%], and 28 of 45 [62%], respectively; P < .001) and tumor spread through air spaces (32 of 50 [64%], 21 of 34 [62%], and 31 of 45 [69%], respectively; P < .001). STK11 alterations (14 of 45 [31%]; P = .006), phosphoinositide 3-kinase pathway alterations (22 of 45 [49%], P < .001), and risk of recurrence (log-rank P < .001) were highest in cluster 4. Conclusion CT-based radiomic consensus clustering enabled identification of associations between radiomic features and clinicalpathologic and genomic features and outcomes in patients with clinical stage I lung adenocarcinoma. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Nishino in this issue.

Outcomes After Multidisciplinary Management of Primary Mediastinal Germ Cell Tumors.

OBJECTIVE: We examined management strategies, overall survival (OS), and progression-free survival (PFS) among patients with PMNSGCTs undergoing resection and multidisciplinary management at a high-volume institution. SUMMARY OF BACKGROUND DATA: Outcomes after resection of PMNSGCTs are not well-characterized, with limited data on factors associated with survival. METHODS: We reviewed patients with PMNSGCT who underwent resection between 1980 and 2019. Median follow-up was 3.4 years. Preoperative therapy (including use of bleomycin), surgical management, recurrence, and survival were examined. Factors associated with survival were analyzed using Cox regression. RESULTS: In total, 113 patients were included [median age, 28 years (range, 16-65)]. Preoperative serum tumor markers (STMs) normalized/decreased in 74% of patients. Pathology included necrosis only (25%), teratoma +/- necrosis (20%), viable nonteratomatous germ cell tumor +/- teratoma (41%), and secondary somatic-type malignancy +/- teratoma (20%). Bleomycin chemotherapy was not associated with pulmonary complications or 90-day mortality. Patients receiving second-line chemotherapy followed by resection had significantly worse OS and PFS than patients receiving first-line chemotherapy followed by resection. On multivariable analysis, R1/R2 resection (HR, 3.92; P < 0.001) and increasing postoperative STMs (HR, 4.98; P < 0.001) were associated with shorter PFS; necrosis on pathology (HR, 0.42, P = 0.043) was associated with longer PFS. CONCLUSIONS: In patients with PMNSGCT undergoing resection, completeness of resection, postoperative pathology, and postoperative STMs were associated with PFS. Induction bleomycin was not associated with pulmonary complications or mortality in patients undergoing resection. Patients undergoing second-line chemotherapy followed by resection have a poor prognosis, with long-term survival of 22%.

Assessment of Quality Outcomes and Learning Curve for Robot-Assisted Minimally Invasive McKeown Esophagectomy.

BACKGROUND: This study aimed to identify the results of the quality assessment and the learning curve of robot-assisted minimally invasive McKeown esophagectomy (RAMIE-MK). METHODS: The study retrospectively reviewed the data of 400 consecutive patients with esophageal cancer who underwent RAMIE-MK by a single surgeon from November 2015 to March 2019. Cumulative summation analysis of the learning curve was performed. The patients were divided into decile cohorts of 40 cases to minimize demographic deviations and to maximize the power of detecting statistically significant changes in performance. RESULTS: The 90-day mortality rate for all the patients was 0.5% (2 cases). The authors' experience was divided into the ascending phase (40 cases), the plateau phase (175 cases), and the descending phase (185 cases). After 40 cases, significant improvements in operative time (328 vs. 251 min; P = 0.019), estimated blood loss (350 vs. 200 ml; P = 0.031), and conversion rates (12.5% vs. 2.5%; P < 0.001) were observed. After 80 cases, a decrease in the rates of anastomotic leakage (22.5% vs. 8.1%; P = 0.001) and vocal cord palsy (31.3% vs. 18.4%; P = 0.024) was observed. The number of harvested lymph nodes increased after 40 cases (13 vs. 23; P < 0.001), especially for lymph nodes along the recurrent laryngeal nerve (3.0 vs. 6.0; P < 0.001). CONCLUSIONS: The learning phase of RAMIE-MK consists of 40 cases, and quality outcomes can be improved after 80 procedures. Several turning points related to the optimization of surgical outcomes can be used as benchmarks for surgeons performing RAMIE-MK.

Intraoperative opioid exposure, tumour genomic alterations, and survival differences in people with lung adenocarcinoma.

BACKGROUND: Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and intra-tumoural opioid receptor gene alterations, but no study has investigated whether the tumour genome interacts with opioid exposure to affect survival. We sought to determine whether intraoperative opioid exposure is associated with recurrence-specific survival and overall survival in early-stage lung adenocarcinoma, and whether selected tumour genomics are associated with this relationship. Associations between ketamine and dexmedetomidine and outcomes were also studied. METHODS: Surgical patients (N=740) with pathological stage I-III lung adenocarcinoma and next-generation sequencing data were retrospectively reviewed from a prospectively maintained database. RESULTS: On multivariable analysis, ketamine administration was protective for recurrence-specific survival (hazard ratio = 0.44, 95% confidence interval 0.24-0.80; P=0.007), compared with no adjunct. Higher intraoperative oral morphine milligram equivalents were significantly associated with worse overall survival (hazard ratio=1.09/10 morphine milligram equivalents, 95% confidence interval 1.02-1.17; P=0.010). Significant interaction effects were found between morphine milligram equivalents and fraction genome altered and morphine milligram equivalents and CDKN2A, such that higher fraction genome altered or CDKN2A alterations were associated with worse overall survival at higher morphine milligram equivalents (P=0.044 and P=0.052, respectively). In contrast, alterations in the Wnt (P=0.029) and Hippo (P=0.040) oncogenic pathways were associated with improved recurrence-specific survival at higher morphine milligram equivalents, compared with unaltered pathways. CONCLUSIONS: Intraoperative opioid exposure is associated with worse overall survival, whereas ketamine exposure is associated with improved recurrence-specific survival in patients with early-stage lung adenocarcinoma. This is the first study to investigate tumour-specific genomic interactions with intraoperative opioid administration to modify survival associations.

Single lumen endotracheal intubation with carbon dioxide insufflation for lung isolation in thoracic surgery.

INTRODUCTION: Double lumen tube (DLT) intubation is used for lung isolation but is not without disadvantages including increased intubation time, anesthesia expertise, risk of airway trauma, and costs over single lumen tube (SLT) intubation. SLT intubation with CO2 insufflation can be used as an alternative for lung isolation. We reviewed our experience with this technique during thoracoscopic surgery. METHODS: We performed a retrospective review of a prospectively maintained IRB-approved database from 2009 to 2018. Operations were performed with CO2 insufflation up to 15 mmHg. Indications for surgery, operative details, intraoperative complications, pathology, and postoperative complications were reviewed. RESULTS: We identified 123 patients (70 females [57%]) with a median age of 40 years (range 16-80 years) and a median BMI of 26.2 kg/m2 (range 15-59 kg/m2) that underwent minimally invasive thoracoscopic procedures with this technique. Procedures included: mediastinal mass resection or biopsy (41%), sympathectomy (37%), wedge resection (10%), first rib resection (6%), diaphragm plication (2%), segmentectomy (2%), decortication (2%), pleural biopsy (2%), and pericardial cyst resection (1%). Median operative time was 90 min (range 25-584 min) and median intraoperative blood loss was 10 mL (range 2-200 mL). Intraoperative hemodynamic parameters were obtained at procedure start, 1 h after CO2 insufflation, and at procedure completion: we observed significant changes in heart rate and systolic blood pressure (P = 0.027 and P < 0.001, respectively) although clinically inconsequential. Mean end-tidal CO2 1 h after insufflation was 36.6 ± 4.5 mmHg. There were no intraoperative complications and no conversions to a DLT. Median length of stay was 1 day (range 0-14 days). Five complications (4%) were observed and no mortalities. CONCLUSIONS: SLT intubation and CO2 insufflation is a feasible and safe alternative to DLT intubation for lung isolation. This can be a useful strategy to accomplish lung isolation for some thoracoscopic procedures, in particular when expertise for DLT placement is unavailable.

Surgical Management of Persistent or New Symptoms After Hiatal Hernia Repair.

Following a hiatal hernia repair, patients can present with recurrent or new symptoms. Symptoms can occur anywhere from weeks to years after surgery. These may include recurrent reflux, dysphagia, regurgitation, weight loss, or deteriorating quality of life. While nonoperative management can be pursued in some patients, reoperation may be the only option in select patients. A thorough preoperative workup, including a repeat esophagram, upper endoscopy, +/- chest computed tomography (CT) scan, manometry, pH probe, and/or gastric emptying study, is warranted to better understand the pathophysiology of the presenting symptoms. If a recurrent hernia, slipped, or migrated wrap is identified, surgery is considered. Pseudoachalasia must also be ruled out if obstructive symptoms are observed at the hiatus. Such an exhaustive workup is indeed necessary to ensure accurate diagnosis and optimal outcome. In addition, an understanding of the factors that may have led to the recurrence will increase the chances of a successful reoperation. Although a technically demanding procedure, redo hiatal hernia repair utilizing a minimally invasive approach is increasingly being employed with promising outcomes. Herein, the steps of a redo hiatal hernia repair via a minimally invasive approach will be outlined and detailed.

Modeling lung adenocarcinoma metastases using patient-derived organoids.

Approximately 50% of patients with surgically resected early-stage lung cancer develop distant metastasis. At present, there is no in vivo metastasis model to investigate the biology of human lung cancer metastases. Using well-characterized lung adenocarcinoma (LUAD) patient-derived organoids (PDOs), we establish an in vivo metastasis model that preserves the biologic features of human metastases. Results of whole-genome and RNA sequencing establish that our in vivo PDO metastasis model can be used to study clonality and tumor evolution and to identify biomarkers related to organotropism. Investigation of the response of KRASG12C PDOs to sotorasib demonstrates that the model can examine the efficacy of treatments to suppress metastasis and identify mechanisms of drug resistance. Finally, our PDO model cocultured with autologous peripheral blood mononuclear cells can potentially be used to determine the optimal immune-priming strategy for individual patients with LUAD.

Tumor microenvironment profoundly modifies functional status of macrophages: peritoneal and tumor-associated macrophages are two very different subpopulations.

Macrophages are key players in the inflammatory response. In this study, we tested the hypothesis that although all macrophage subpopulations in tumor hosts are affected by the disease, it is the close proximity to the tumor that induces major alterations in these cells. We compared tumor-associated macrophages (TAMs) with peritoneal macrophages from mice bearing D1-DMBA-3 mammary tumors (T-PEMs). Our results show that TAMs downregulate IL-12p70 but upregulate IL-12p40, IL-23, IL-6 and IL-10. Some NFκB and C/EBP transcription factors family members are decreased in TAMs; however NFκBp50 homodimers, STAT1/pSTAT1 and STAT3/pSTAT3 are overexpressed. Furthermore, while TAMs block T-cell proliferation and are more prone to apoptosis compared to T-PEMs, both types of macrophages have an impaired phagocytic capacity. Moreover, TAMs constitutively express iNOS and produce nitric oxide but do not express arginase and are Gr-1(high) and CD11b(low). Collectively, our analysis of two spatially distinct macrophage subpopulations in tumor-bearing mice revealed that the tumor modulates them differently into two molecularly and functionally dissimilar macrophage subpopulations.

Perioperative therapy landscape for locally advanced, resectable esophageal cancer: an updated literature review.

Background and Objective: The poor oncologic outcomes associated with esophageal cancer (EC) are primarily due to its presentation at an advanced stage and patient comorbidities. While multimodal therapy improves overall outcomes, there is a lack of uniform practice in terms of perioperative management, partly because this is a rapidly evolving field in a heterogeneous patient population. With numerous recent studies incorporating precision medicine with radiographic, pathologic, and genomic biomarkers and with emerging trials using targeted therapies, it is necessary for providers who care for these patients to be familiar with the current and evolving treatment standards to optimize patient outcomes. The objective of this paper is to perform an updated review of the main historical and recently emerging studies that impact the perioperative management of patients with locally advanced, upfront-resectable EC. Methods: We mined and reviewed PubMed and American Society of Clinical Oncology databases for pivotal works shaping the current perioperative treatment landscape in locally advanced EC. Key Content and Findings: EC are a vastly heterogeneous disease, and treatment options vary based on tumor anatomic location, histology, and patient comorbidities. Perioperative chemotherapy (CTX), chemoradiation (CRT), and, recently, immunotherapy have improved survival in patients with locally advanced disease. However, optimizing sequencing, de-escalating therapy, and incorporating novel targeted therapies in the perioperative setting are promising strategies that are under ongoing investigation to improve patient outcomes further. Conclusions: There is an ongoing need to identify predictive biomarkers and novel treatment strategies to personalize perioperative approaches and optimize outcomes of patients with EC.

Postinduction therapy pulmonary function retesting is necessary before surgical resection for non-small cell lung cancer.

OBJECTIVE: Pretreatment-predicted postoperative diffusing capacity of the lung for carbon monoxide (DLCO) has been associated with operative mortality in patients who receive induction therapy for resectable non-small cell lung cancer (NSCLC). It is unknown whether a reduction in pulmonary function after induction therapy and before surgery affects the risk of morbidity or mortality. We sought to determine the relationship between induction therapy and perioperative outcomes as a function of postinduction pulmonary status in patients who underwent surgical resection for NSCLC. METHODS: We retrospectively reviewed data for 1001 patients with pathologic stage I, II, or III NSCLC who received induction therapy before lung resection. Pulmonary function was defined according to American College of Surgeons Oncology Group major criteria: DLCO ≥50% = normal; DLCO <50% = impaired. Patients were categorized into 5 subgroups according to combined pre- and postinduction DLCO status: normal-normal, normal-impaired, impaired-normal, impaired-impaired, and preinduction only (without postinduction pulmonary function test measurements). Multivariable logistic regression was used to quantify the relationship between DLCO categories and dichotomous end points. RESULTS: In multivariable analysis, normal-impaired DLCO status was associated with an increased risk of respiratory complications (odds ratio, 2.29 [95% CI, 1.12-4.49]; P = .02) and in-hospital complications (odds ratio, 2.83 [95% CI, 1.55-5.26]; P < .001). Type of neoadjuvant therapy was not associated with an increased risk of complications, compared with conventional chemotherapy. CONCLUSIONS: Reduced postinduction DLCO might predict perioperative outcomes. The use of repeat pulmonary function testing might identify patients at higher risk of morbidity or mortality.

The Emerging Importance of Tumor Genomics in Operable Non-Small Cell Lung Cancer.

During the last two decades, next-generation sequencing (NGS) has played a key role in enhancing non-small cell lung cancer treatment paradigms through the application of "targeted therapy" in advanced and metastatic disease. The use of specific tyrosine kinase inhibitors in patients with oncogenic driver alterations, such as EGFR, ALK, ROS1, BRAF V600E, MET, and NTRK mutations, among others, has changed treatment approaches and improved outcomes in patients with late-stage disease. Although NGS technology has mostly been used in the setting of systemic therapy to identify targets, response to therapy, and mechanisms of resistance, it has multiple potential applications for patients with earlier-stage disease, as well. In this review, we discuss the emerging role of NGS technologies to better understand tumor biology in patients with non-small cell lung cancer who are undergoing surgery with curative intent. In this patient cohort, we examine tumor heterogeneity, the underlying tumor genomics associated with lung adenocarcinoma subtypes, the prediction of recurrence after complete surgical resection, the use of plasma circulating tumor DNA for detection of early cancers and monitoring for minimal residual disease, the differentiation of separate primaries from intrapulmonary metastases, and the use of NGS to guide induction and adjuvant therapies.

Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma.

While next-generation sequencing (NGS) is used to guide therapy in patients with metastatic lung adenocarcinoma (LUAD), use of NGS to determine pathologic LN metastasis prior to surgery has not been assessed. To bridge this knowledge gap, we performed NGS using MSK-IMPACT in 426 treatment-naive patients with clinical N2-negative LUAD. A multivariable logistic regression model that considered preoperative clinical and genomic variables was constructed. Most patients had cN0 disease (85%) with pN0, pN1, and pN2 rates of 80%, 11%, and 9%, respectively. Genes altered at higher rates in pN-positive than in pN-negative tumors were STK11 (p = 0.024), SMARCA4 (p = 0.006), and SMAD4 (p = 0.011). Fraction of genome altered (p = 0.037), copy number amplifications (p = 0.001), and whole-genome doubling (p = 0.028) were higher in pN-positive tumors. Multivariable analysis revealed solid tumor morphology, tumor SUVmax, clinical stage, SMARCA4 and SMAD4 alterations were independently associated with pathologic LN metastasis. Incorporation of clinical and tumor genomic features can identify patients at risk of pathologic LN metastasis; this may guide therapy decisions before surgical resection.

Management of Synchronous Extrathoracic Oligometastatic Non-Small Cell Lung Cancer.

Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of newly diagnosed cases of NSCLC. The oligometastatic state-≤5 extrathoracic metastatic lesions in ≤3 organs-is present in ~25% of patients with stage IV disease and is associated with markedly improved outcomes. We retrospectively identified patients with extrathoracic oligometastatic NSCLC who underwent primary tumor resection at our institution from 2000 to 2018. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Factors associated with EFS and OS were determined using Cox regression. In total, 111 patients with oligometastatic NSCLC underwent primary tumor resection; 87 (78%) had a single metastatic lesion. Local consolidative therapy for metastases was performed in 93 patients (84%). Seventy-seven patients experienced recurrence or progression. The five-year EFS was 19% (95% confidence interval (CI), 12-29%), and the five-year OS was 36% (95% CI, 27-50%). Factors independently associated with EFS were primary tumor size (hazard ratio (HR), 1.15 (95% CI, 1.03-1.29); p = 0.014) and lymphovascular invasion (HR, 1.73 (95% CI, 1.06-2.84); p = 0.029). Factors independently associated with OS were neoadjuvant therapy (HR, 0.43 (95% CI, 0.24-0.77); p = 0.004), primary tumor size (HR, 1.18 (95% CI, 1.02-1.35); p = 0.023), pathologic nodal disease (HR, 1.83 (95% CI, 1.05-3.20); p = 0.033), and visceral-pleural invasion (HR, 1.93 (95% CI, 1.10-3.40); p = 0.022). Primary tumor resection represents an important treatment option in the multimodal management of extrathoracic oligometastatic NSCLC. Encouraging long-term survival can be achieved in carefully selected patients, including those who received neoadjuvant therapy and those with limited intrathoracic disease.

Thoracic Metastasectomy in Germ Cell Tumor Patients Treated With First-line Versus Salvage Therapy.

BACKGROUND: Outcomes after thoracic metastasectomy in patients with testicular germ cell tumors (GCTs) who received first-line chemotherapy alone versus salvage chemotherapy remain unexplored. METHODS: We conducted a retrospective review of patients who underwent thoracic metastasectomy for residual GCT between 1997 and 2019 at a single tertiary center. Factors associated with progression-free survival (PFS) and overall survival (OS) were assessed using multivariable Cox regression. RESULTS: Of 251 patients, 191 received only first-line chemotherapy (76%) and 60 received salvage chemotherapy (24%). Median follow-up was 3.45 years (interquartile range, 1-7.93 years). Among first-line patients without teratoma in the primary tumor, with necrosis in the retroperitoneal nodes and normalized or decreasing serum tumor markers, 17 of 20 had intrathoracic necrosis (85%). Among first-line and salvage patients, respectively, 5-year OS was 93% (95% confidence interval [CI], 89%-98%) versus 63% (95% CI, 51%-78%; P < .001), and 5-year PFS was 69% (95% CI, 62%-77%) versus 40% (95% CI, 29%-56%; P < .001). On multivariable analysis, multiple lung lesions (hazard ratio [HR] = 3.01; 95% CI, 1.50-6.05; P = .002) and brain metastasis (HR = 4.51; 95% CI, 2.34-8.73; P < .001) at diagnosis, salvage chemotherapy (HR = 1.85; 95% CI, 1.10-3.13; P = .021), teratoma (HR = 2.68; 95% CI, 1.50-4.78; P = .001), and viable malignancy (HR = 4.34; 95% CI, 2.44-7.71; P < .001) were associated with worse PFS. CONCLUSIONS: Although GCT patients treated with salvage chemotherapy followed by thoracic metastasectomy have more aggressive disease and poorer PFS, they can achieve encouraging OS. Our findings highlight the integral role of aggressive thoracic metastasectomy in the treatment of GCT patients with residual thoracic disease after first line-only or salvage chemotherapy.

Intentional Segmentectomy for Clinical T1 N0 Non-small Cell Lung Cancer: Survival Differs by Segment.

BACKGROUND: Outcomes after segmentectomy compare favorably with those after lobectomy in patients with stage I non-small cell lung cancer (NSCLC). Whether long-term outcomes vary by segmentectomy location is unclear. We investigated whether disease-free survival (DFS) and overall survival (OS) differ by segmentectomy location after intentional segmentectomy for clinical T1 N0 M0 NSCLC. METHODS: Patients who received intentional segmentectomy for cT1 N0 M0 NSCLC from 2000 to 2018 were reviewed. Patients with prior lung cancer, forced expiratory volume in 1 second of less than 50%, or R1/R2 resection were excluded. Segmentectomy groups were left (L) basilar, L segment 6, L lingula, L trisegment; right (R): basilar (R_Bas), segment 6 (R_S6), and R upper. The 5- and 10-year DFS and OS were estimated using Kaplan-Meier and compared between groups using the log-rank test. Factors associated with DFS and OS were determined using Cox proportional hazards models. RESULTS: In total, 416 patients met the inclusion criteria. Segmentectomy groups differed with regard to surgical approach, mediastinal lymphadenectomy, lymphovascular invasion, tumor histology, margin distance, and adjuvant therapy. Long-term outcomes were worst after R_S6 resection (5-year DFS, 57.6% [95% confidence interval {CI}, 45.7%-72.7%]; OS, 66.3% [95% CI, 54.7%-80.3%]) and best after R_Bas resection (5-year DFS, 77.1% [95% CI, 59.2%-100%]; OS, 79.5% [95% CI, 60.9%-100%]). On multivariable analysis, R_S6 resection was independently associated with DFS vs R_Bas (hazard ratio, 2.89; 95% CI, 1.18-7.08; P = .02) and OS vs R_Bas (hazard ratio, 4.35; 95% CI, 1.61-11.76; P = .004). CONCLUSIONS: Resection of R_S6 is independently associated with worse DFS and OS in patients receiving intentional segmentectomy for cT1 N0 M0 NSCLC and may warrant more extensive resection, complete lymph node dissection, and closer postoperative surveillance.

Primary lung cancer in women after previous breast cancer.

BACKGROUND: Breast cancer is the most common malignancy among women in the USA. Improved survival has resulted in increasing incidence of second primary malignancies, of which lung cancer is the most common. The United States Preventive Services Task Force (USPSTF) guidelines for lung-cancer screening do not include previous malignancy as a high-risk feature requiring evaluation. The aim of this study was to compare women undergoing resection for lung cancer with and without a history of breast cancer and to assess whether there were differences in stage at diagnosis, survival and eligibility for lung-cancer screening between the two groups. METHODS: Women who underwent lung-cancer resection between 2000 and 2017 were identified. Demographic, clinicopathological, treatment and outcomes data were compared between patients with a history of breast cancer (BC-Lung) and patients without a history of breast cancer (P-Lung) before lung cancer. RESULTS: Of 2192 patients included, 331 (15.1 per cent) were in the BC-Lung group. The most common method of lung-cancer diagnosis in the BC-Lung group was breast-cancer surveillance or work-up imaging. Patients in the BC-Lung group had an earlier stage of lung cancer at the time of diagnosis. Five-year overall survival was not statistically significantly different between groups (73.3 per cent for both). Overall, 58.4 per cent of patients (1281 patients) had a history of smoking, and 33.3 per cent (731 patients) met the current criteria for lung-cancer screening. CONCLUSION: Differences in stage at diagnosis of lung cancer and treatment selection were observed between patients with and without a history of breast cancer. Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer. The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast-cancer history, did not meet the current USPSTF criteria for lung-cancer screening.

KRAS G12C Mutation Is Associated with Increased Risk of Recurrence in Surgically Resected Lung Adenocarcinoma.

PURPOSE: KRAS G12C is the most common KRAS mutation in primary lung adenocarcinoma. Phase I clinical trials have demonstrated encouraging clinical activity of KRAS G12C inhibitors in the metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features in patients with surgically resected KRAS G12C-mutant lung adenocarcinoma. EXPERIMENTAL DESIGN: Patients who underwent resection of stage I-III lung adenocarcinoma and next-generation sequencing (NGS) were evaluated. Exclusion criteria were receipt of induction therapy, incomplete resection, and low-quality NGS. Mutations were classified as KRAS wild-type (KRAS wt), G12C (KRAS G12C), or non-G12C (KRAS other). DFS was compared between groups using the log-rank test; factors associated with DFS were assessed using Cox regression. Mutual exclusivity and cooccurrence, tumor clonality, and mutational signatures were assessed. RESULTS: In total, 604 patients were included: 374 KRAS wt (62%), 95 KRAS G12C (16%), and 135 KRAS other (22%). Three-year DFS was not different between KRAS-mutant and KRAS wt tumors. However, 3-year DFS was worse in patients with KRAS G12C than KRAS other tumors (log-rank P = 0.029). KRAS G12C tumors had more lymphovascular invasion (51% vs. 37%; P = 0.032) and higher tumor mutation burden [median (interquartile range), 7.0 (5.3-10.8) vs. 6.1 (3.5-9.7); P = 0.021], compared with KRAS other tumors. KRAS G12C mutation was independently associated with worse DFS on multivariable analysis. Our DFS findings were externally validated in an independent The Cancer Genome Atlas cohort. CONCLUSIONS: KRAS G12C mutations are associated with worse DFS after complete resection of stage I-III lung adenocarcinoma. These tumors harbor more aggressive clinicopathologic and genomic features than other KRAS-mutant tumors. We identified a high-risk group for whom KRAS G12C inhibitors may be investigated to improve survival.