Surgery For Non-small Cell Lung Cancer Research Articles

Persistent racial disparities in refusal of resection in non-small cell lung cancer patients at high-volume and Black-serving institutions

BackgroundSurgical resection is the standard of care for early-stage non-small cell lung cancer. Black patients have higher surgical refusal rates than White patients. We evaluated factors associated with the refusal of resection and subsequent non-small cell lung cancer outcomes. MethodsWe identified patients with non-small cell lung cancer stages IA to IIIA eligible for surgical resection (lobectomy or pneumonectomy) listed between 2004 and 2017 in the National Cancer Database. We stratified hospitals by the proportion of Black patients served and lung cancer resection volume. We used multivariable regression models to identify factors associated with refusal of resection and assessed 5-year mortality using Kaplan–Meier analysis and Cox proportional hazard modeling. ResultsOf 221,396 patients identified, 7,753 (3.5%) refused surgery. Black race was associated with increased refusal (adjusted odds ratio 2.06, 95% confidence interval 1.90–2.22). Compared to White race, Black race was associated with increased refusal across the highest (adjusted odds ratio 2.29, 95% confidence interval 1.94–2.54), intermediate (adjusted odds ratio 2.05, 95% confidence interval 1.78–2.37), and lowest (adjusted odds ratio 1.77, 95% confidence interval 1.58–1.99) volume tertiles. Similarly, Black race was associated with increased refusal across the highest (adjusted odds ratio 1.97, 95% confidence interval 1.78–2.17), intermediate (adjusted odds ratio 2.08, 95% confidence interval 1.80–2.40), and lowest (adjusted odds ratio 1.53, 95% confidence interval 1.13–2.06) Black-serving tertiles. However, surgical resection yielded similar 5-year survival for Black and White patients. ConclusionRacial disparities in non-small cell lung cancer surgery refusal persist regardless of hospital volume or proportion of Black patients served. These findings suggest that a better understanding of patient and patient–provider level interventions could facilitate a better understanding of treatment decision-making.

Association of Wildfire Exposure While Recovering From Lung Cancer Surgery With Overall Survival

With a changing climate, wildfire activity in the US has increased dramatically, presenting multifaceted and compounding health hazards. Individuals discharged from the hospital following surgical resection of non-small cell lung cancer (NSCLC) are potentially at higher risk from wildfires' health hazards. To assess the association between wildfire exposure and postoperative long-term overall survival among patients with lung cancer in the US. In this cohort study, individuals who underwent curative-intent NSCLC resection between January 1, 2004, and December 31, 2019, were selected from the National Cancer Database. Daily wildfire information was aggregated at the zip code level from the National Aeronautics and Space Administration Fire Information for Resource Management System. The data analysis was performed between July 19, 2022, and April 14, 2023. An active wildfire detected at the zip code of residence between 0 and 3, 4 and 6, or 7 and 12 months after NSCLC surgery. Overall survival was defined as the interval between age at hospital discharge and age at death, last contact, or study end, whichever came first. Cox proportional hazards were used for estimating hazard ratios (HRs) adjusted for sex, region, metropolitan category, health insurance type, comorbidities, tumor size, lymph node involvement, era, and facility type. A total of 466 912 individuals included in the study (249 303 female and [53.4] and 217 609 male [46.6%]; mean [SD] age at diagnosis, 67.3 [9.9] years), with 48 582 (10.4%) first exposed to a wildfire between 0 and 3 months, 48 328 (10.6%) between 4 and 6 months, and 71 735 (15.3%) between 7 and 12 months following NSCLC surgery. Individuals exposed to a wildfire within 3 months (adjusted HR [AHR], 1.43; 95% CI, 1.41-1.45), between 4 and 6 months (AHR, 1.39; 95% CI, 1.37-1.41), and between 7 and 12 months (AHR, 1.17; 95% CI, 1.15-1.19) after discharge from the hospital following stage I to III NSCLC resection had worse overall survival than unexposed individuals. In this cohort study, wildfire exposure was associated with worse overall survival following NSCLC surgical resection, suggesting that patients with lung cancer are at greater risk from the health hazards of wildfires and need to be prioritized in climate adaptation efforts.

Salvage surgery for advanced non-small cell lung cancer following previous immunotherapy: a retrospective study

BackgroundThe development of systemic chemotherapy including immune checkpoint inhibitors (ICIs) has provided patients with unresectable advanced non-small cell lung cancer (NSCLC) an opportunity to undergo surgical intervention after initial treatment. However, no consensus regarding the indication for salvage surgery in these patients has been reached.MethodsWe conducted a retrospective study of patients who underwent salvage surgery for advanced NSCLC (cStage IIIA–IVB) after treatment with ICIs from January 2018 to December 2022 at Aizu Medical Center and Fukushima Medical University Hospital. We evaluated the patients’ clinical data, calculated disease-free survival (DFS) and overall survival (OS), and assessed the survival benefit using the Kaplan–Meier method.ResultsThirteen patients underwent salvage surgery after immunotherapy. All patients achieved downstaging after initial chemotherapy. Eleven patients underwent lobectomy, and one patient underwent extirpation of intra-abdominal lymph nodes. The mean surgery time and intraoperative blood loss were 242.2 min and 415.1 g, respectively. The mean drainage period was 4.2 days (range, 2–9 days). Grade ≥ 3 postoperative complications were confirmed in three patients. The 2-year DFS rate was 71.2%, and the 2-year OS rate was 76.2%. A pathological complete response compatible with ypStage 0 was achieved in four (30.8%) patients. Patients with ypStage 0 and I achieved significantly better OS than those with ypStage ≥ II (p = 0.044), and patients without severe complications achieved significantly better DFS and OS than those with severe complications (p = 0.001 and p < 0.001, respectively).ConclusionsSalvage surgery after chemotherapy including ICIs is a feasible and effective treatment option for patients with advanced NSCLC, especially those who acquire downstaging to pathological stage 0 or I. However, severe perioperative complications might affect patient survival. A prospective study is urgently needed to evaluate the efficacy of salvage surgery.

Multimodal prehabilitation in patients with non-small cell lung cancer undergoing anatomical resection: protocol of a non-randomised feasibility study

BackgroundThe preoperative period can be used to enhance a patient’s functional capacity with multimodal prehabilitation and consequently improve and fasten postoperative recovery. Especially, non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is challenging, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to NSCLC surgery and aimed to conduct a study to assess feasibility and indicative evidence of efficacy of this programme. Publication of this protocol may help other healthcare facilities to implement such a programme.MethodsThe multimodal prehabilitation programme consists of an exercise programme, nutritional support, psychological support, smoking cessation, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme, and 20 will be assessed in the control group, according to patient preference. Assessments will take place at four time points: baseline, the week before surgery, 6 weeks postoperatively and 3 months postoperatively. Feasibility and indicative evidence of efficacy of the prehabilitation programme will be assessed as primary outcomes.DiscussionSince the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible, and evidence of efficacy can be found. The non-randomised fashion of the study might result in a selection and confounding bias. However, the control group may help putting the results of the prehabilitation group in perspective. By publishing this protocol, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical NSCLC patients.Trial registrationThe current study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080. Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045.

Interpretable prediction of cardiopulmonary complications after non-small cell lung cancer surgery based on machine learning and SHapley additive exPlanations

IntroductionLung cancer is a prevalent malignancy globally, with approximately 20% of patients developing cardiopulmonary complications after lobectomy. In order to prevent complications, an accurate and personalized method based on machine learning (ML) is required. MethodsDuring the period of 2017–2021, a retrospective analysis was conducted on the medical records of patients who had undergone lobectomy for non-small cell lung cancer (NSCLC). We performed logical regression, decision tree (DT), random forest (RF), gradient boost DT, and eXtreme gradient boosting analyses to establish an ML model. The ten-fold cross-validation was used to evaluate the performance of multiple ML models based on various evaluation metrics, including accuracy, precision, recall, F1 score, and area under the receiver operating (AUC). Additionally, we also calculated the Kappa value of these model. Each model used grid search to optimize hyper-parameters and then used the interpretability method to provide explanations for the model's Decisions. ResultsThe study included 718 eligible patients, among whom the incidence of postoperative cardiopulmonary complications was 20.89%. The RF model showed the best comprehensive performance among all models, and its ten-fold cross-validation accuracy, precision, recall, F1 score, and AUC were (OR and 95% confidence interval [CI]) 0.786 (0.738–0.834), 0.803 (0.735–0.872), 0.738 (0.678–0.797), 0.766 (0.714–0.818), 0.856 (0.815–0.898), respectively. The kappa value of the RF model was 0.696 (0.617–0.768). The SHAP method showed that gender, age, and intraoperative blood loss were closely associated with postoperative cardiopulmonary complications. ConclusionThe application of ML methods for predicting postoperative cardiopulmonary complications based on clinical data of patients with NSCLC showed a good performance. The results indicate that ML combined with the SHAP individualized interpretation method has practical clinical value.

Association between Mortality and Lung Low Attenuation Areas in NSCLC Treated by Surgery.

to test the association with overall survival (OS) of low attenuation areas (LAAs) quantified by staging computed tomography (CT) of patients who underwent radical surgery for nonsmall-cell lung cancer (NSCLC). patients who underwent radical surgery for NSCLC at our institution between 1 January 2017 and 30 November 2021 were retrospectively evaluated. Patients who performed staging or follow-up CTs in other institutions, who received lung radiotherapy or chemotherapy, and who underwent previous lung surgery were excluded. At staging and 12-months follow-up CT, LAAs defined as voxels <-950 Hounsfield units, were extracted by software. The percent of LAAs relative to whole-lung volume (%LAAs) and the ratio between LAAs in the lobe to resect and whole-lung LAAs (%LAAs lobe ratio) were calculated. Cox proportional hazards regression analysis was used to test the association between OS and LAAs. the final sample included 75 patients (median age 70 years, IQR 63-75 years; females 29/75, 39%). It identified a significant association with OS for pathological stage III (HR, 6.50; 95%CI, 1.11-37.92; p = 0.038), staging CT %LAAs ≥ 5% (HR, 7.27; 95%CI, 1.60-32.96; p = 0.010), and staging CT %LAA lobe ratio > 10% (HR, 0.24; 95%CI 0.05-0.94; p = 0.046). in patients with NSCLC who underwent radical surgery, a %LAAs ≥ 5% and a %LAA lobe ratio > 10% at staging CT are predictors, respectively, of shorter and longer OS. The LAA ratio to the whole lung at staging CT could be a critical factor to predict the overall survival of the NSCLC patients treated by surgery.

Salvage Surgery in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Abstract Background In patients with stage IIIB, stage IIIC and stage IV non-small cell lung cancer (NSCLC), guidelines generally recommend systemic therapy with or without radiotherapy. Despite this treatment, complete response remains rare. However, in a selected group of patients with either residual disease after partial response to first-line systemic treatment, or oligo-recurrence, surgical resection within a salvage concept is under evaluation as an additional treatment option. Currently, clinical data on the outcome of this approach are scarce. Aims We aimed to assess short- and long-term outcomes of salvage surgery in advanced NSCLC. Methods We retrospectively identified 35 patients with initial stage IIIB, IIIC, or IV NSCLC who underwent anatomical lung resection to treat local relapse or residual disease. All patients had initially received systemic treatment with or without radiotherapy. Patients were only included if surgical resection had not been part of the first-line treatment approach. Results Among 35 patients (54% male, mean age 60.2±10.9 years), the initial clinical UICC stage was IIIB in 4, IIIC in 4, IVA in 22, and IVB in 5 cases. The indication for salvage resection was residual disease after first-line treatment in 21 cases and local relapse in 14 cases. Anatomical lung resections included 22 lobectomies, 11 pneumonectomies, 1 bilobectomy and 1 segmentectomy. R0-resection was achieved in 94.3% and pathological complete response was found in 22.9% of all resections. 30-and 90-day mortality were 0% and 11.4%, respectively. mOS and progression-free-survival (calculated from the date of salvage surgery) of the entire cohort were 69 months [95% CI 37–101 months] and 22 months [95% CI: 0–45 months] respectively. Conclusions In selected patients with advanced stage NSCLC presenting with local relapse or residual disease after systemic treatment, anatomical salvage lung resections are associated with a favorable short- and long-term outcome. However, further prospective evaluation of this treatment approach is required.

Correlation analysis of MRD positivity after non-small cell lung cancer surgery.

e20590 Background: To explore the relationship between postoperative molecular residual disease (MRD) status in patients with non-small cell lung cancer (NSCLC) and clinicopathological features, gene mutations, the tumour immune microenvironment and treatment effects. Methods: The clinical data of 90 patients with stage I-IIIA NSCLC who underwent radical resection of lung cancer from January 2021 to March 2022 in our hospital were retrospectively collected, and demographic data, clinicopathological characteristics, genetic test results, MRD status, and treatment effects were analysed. Results: Sex, age, smoking status, pathological type, and gene mutations were not associated with postoperative MRD status. T (tumour diameter &gt; 3 cm) and N (lymph node metastasis) were statistically correlated with MRD positivity ( p values of 0.004 and 0.003, respectively). The higher the proportion of micropapillary and solid pathological subtypes of lung adenocarcinoma, the higher was the MRD-positivity rate after surgery ( p = 0.005). MRD positivity was correlated with vascular invasion ( p = 0.0002). For the expression of programmed cell death ligand 1 (PD-L1), tumour positive score (TPS) ≥ 1% and combined positive score (CPS) ≥ 5 were correlated with postoperative MRD status ( p value distribution was 0.0391 and 0.0153). For ctDNA clearance, among postoperative MRD-positive patients, postoperative adjuvant targeted therapy was superior to chemotherapy for patients without gene mutations. Conclusions: Postoperative ctDNA-MRD status in NSCLC patients is associated with primary tumour size, lymph node metastasis, lung adenocarcinoma pathological subtype, vascular invasion, TPS and CPS for PD-L1 expression; for postoperative MRD-positive patients, clearance of ctDNA by adjuvant EGFR-TKI target treatment is superior to chemotherapy.

Benefit of post-operative radiation therapy for incompletely resected stage I-IIIA non-small cell lung cancer: An analysis of the National Cancer Database.

8558 Background: The presence of micro-residual (R1) or macro-residual (R2) disease in non-small cell lung cancer (NSCLC) is associated with a higher risk of recurrence. The benefits of post-operative radiation therapy (PORT) in incompletely resected NSCLC is not clear. The purpose of this study is to compare median overall survival (mOS) of treatment modalities in the post-operative setting for resected stage I-IIIA NSCLC with residual disease (R1/R2) and to determine if PORT provides benefit in this patient population using the National Cancer Database (NCDB). Methods: From the NCDB dataset for the years of 2006-2016, we extracted patients diagnosed with stage I-IIIA NSCLC and who had incomplete resection with residual disease (R1/R2). Kaplan-Meier analysis was performed to differentiate the effect of different post-operative treatment modalities, concurrent chemo-radiotherapy (CCRT), sequential chemo-radiotherapy (SCRT) and chemotherapy (CT) alone on mOS. Subsequently, univariate Cox regression was used to identify statistically significant variables, then multivariate Cox regression was performed to establish variables that contributed to the survival. Lastly, multinomial logistic regression was utilized to establish association of the independent factors. SAS version 9.4 was used to analyze the data. Results: Among the 2701 patients who met inclusion criteria, the average age was 64.1, 64.8 and 65.9 year old for CCRT, SCRT and CT, respectively. Male's constituted 53.6% and white's were 88.1%, and patient's were distributed equally across clinical stages. The majority of patients received SCRT (51.7%) followed by CT alone (39%), and CCRT (9.2%). There were no statistically significant differences in mOS between the different treatment modalities (p=0.220). Patients with R2 were 177% more likely to receive CCRT than CT compared to R1 (OR 2.77, CI 1.86-4.13 and p&lt;0.001). Male's were 28% more likely to receive SCRT than CT compared to females (OR 1.28, CI 1.08-1.52 and p=0.0041). Nodal involvement was associated with decreased mOS with N2/N3 having 37% lower mOS compared to N0 (HR=1.37, CI 1.19-1.57 and p&lt;0.0001). Patients who had R2 disease had a 38% lower mOS compared to those R1 (HR 1.38%, CI 1.19-1.62, p&lt;0.0001). Conclusions: Despite the risk of unfavorable outcomes for patients with residual disease after surgery for NSCLC, the addition of radiotherapy, either concurrently or sequentially, to CT did not offer statistically significant mOS benefit compared to CT alone. Given the known toxicities of radiation, and the lack of impact on survival, the benefit of post-operative radiation is questionable among patients with residual disease after resection.

Associations of frailty with overall survival (OS) and functional decline among older adults with non–small-cell lung cancer (NSCLC) receiving chemotherapy, immunotherapy, and/or targeted therapy.

12040 Background: Among older adults with cancer receiving chemotherapy, frailty indices can predict poor outcomes including survival and toxicity. Given the increasing use of immunotherapy and targeted therapy to treat NSCLC, we assessed the prognostic importance of frailty among older adults with NSCLC receiving systemic therapy. Methods: This multi-site prospective cohort study enrolled adults age ≥65 with advanced NSCLC starting chemotherapy, immunotherapy, and/or targeted therapy with non-curative intent. Patients completed geriatric assessments pretreatment and at 1, 2, 4, and 6 months. We constructed a 47-item deficit-accumulation frailty index including pretreatment demographic, geriatric assessment, and clinical factors using established methodology. Frailty scores ranged from 0 (no frailty deficits) to 1 (all frailty deficits present). We categorized patients as robust ( &lt; 0.2), pre-frail (0.2-0.34), or frail (≥0.35). The primary outcome was OS. Secondary outcomes included treatment-related grade ≥3 adverse events (AE), unplanned hospitalization, and functional decline in instrumental activities of daily living (IADL). We conducted a Kaplan-Meier survival analysis to estimate OS by frailty group and Cox proportional hazards models adjusting for treatment type. We used logistic regression models to evaluate the association of frailty with secondary outcomes adjusting for treatment type. Results: Among 149 patients, median age was 73 (range 65-94). During the study, 32% received targeted therapy, 29% immunotherapy, 27% chemoimmunotherapy, and 12% chemotherapy. Overall 43% of patients were robust, 38% pre-frail, and 19% frail. Frailty was associated with Asian race, lower education, Medicaid insurance, and no prior NSCLC surgery. Notably, frailty was not associated with age or treatment type. Median OS was 18.7 months overall: not reached for robust patients, 8.9 months for pre-frail, and 5.6 months for frail patients. Adjusting for treatment type, pre-frail (HR 2.11, 95% CI 1.24-3.60; p = 0.006) and frail (HR 2.86, 95% CI 1.52-5.39; p = 0.001) patients had worse OS compared to robust patients. During treatment, 29% developed a grade ≥3 AE, 31% had an unplanned hospitalization, and 41% developed IADL decline. Pre-frail/frail patients were more likely to develop IADL decline (HR 2.18, 95% CI 1.02-4.68; p = 0.04) than robust patients, but there were no differences in toxicity or hospitalization. Conclusions: Frailty is prognostic for OS among older adults with advanced NSCLC receiving systemic therapy across treatment types and predicted IADL decline. Frailty assessment before initiation of systemic therapy may help identify older adults with advanced NSCLC at higher risk of poor outcomes to inform decision making, individualize anticipatory guidance, and optimize supportive care.

Identification of Factors Related to the Quality of Lymphadenectomy for Lung Cancer: Secondary Analysis of Prospective Randomized Trial Data.

The outcomes of non-small cell lung cancer surgery are influenced by the quality of lymphadenectomy. This study aimed to evaluate the impact of different energy devices on lymphadenectomy quality and identify additional influencing factors. This secondary analysis of the prospective randomized trial data (clinicaltrials.gov: NCT03125798) compared patients who underwent thoracoscopic lobectomy with the LigaSure device (study group, n = 96) and monopolar device (control group, n = 94). The primary endpoint was the lobe-specific mediastinal lymphadenectomy. Lobe-specific mediastinal lymphadenectomy criteria were met in 60.4% and 38.3% of patients in the study and control groups, respectively (p = 0.002). In addition, in the study group, the median number of mediastinal lymph node stations removed was higher (4 vs. 3, p = 0.017), and complete resection was more often achieved (91.7% vs. 80.9%, p = 0.030). Logistic regression analysis indicated that lymphadenectomy quality was positively associated with the use of the LigaSure device (OR, 2.729; 95% CI, 1.446 to 5.152; p = 0.002) and female sex (OR, 2.012; 95% CI, 1.058 to 3.829; p = 0.033), but negatively associated with a higher Charlson Comorbidity Index (OR, 0.781; 95% CI, 0.620 to 0.986; p = 0.037), left lower lobectomy (OR, 0.263; 95% CI, 0.096 to 0.726; p = 0.010) and middle lobectomy (OR, 0.136; 95% CI, 0.031 to 0.606, p = 0.009). This study found that using the LigaSure device can improve the quality of lymphadenectomy in lung cancer patients and also identified other factors that affect the quality of lymphadenectomy. These findings contribute to improving lung cancer surgical treatment outcomes and provide valuable insights for clinical practice.

Lung Segmentectomy in NSCLC Surgery.

Current guidelines recommend surgery for early-stage non-small cell lung cancer (NSCLC). The standard treatment for patients with cT1N0 NSCLC has been lobectomy with lymph-node dissection, with sublobar resection used only in patients with inadequate cardio-respiratory reserve, with poor performance status, or who are elderly. In 1995, the Lung Cancer Study Group published the results of a randomized, prospective trial demonstrating the superiority of lobectomy compared with sublobar resection. From then on, wedge resection and segmentectomy were reserved exclusively for patients with poor functional reserve who could not tolerate lobectomy. Therefore, the exact role of segmentectomy has been controversial over the past 20 years. Recently, the randomized controlled trial JCOG0802/WJOG4607L demonstrated that segmentectomy was superior to lobectomy in patients with stage IA NSCLC (<2 cm and CTR < 0.5) in terms of both overall-survival and post-operative lung function. Based on these results, segmentectomy should be considered the standard surgical procedure for this patient group. In 2023, the randomized phase III CALGB 140503 (Alliance) trial demonstrated the efficacy and non-inferiority of sublobar resection, including wedge resection, for clinical stage IA NSCLC with tumor diameter of < 2 cm. This article is a narrative review of the current role of segmentectomy in lung cancer treatment and summarizes the most relevant studies in this context.

109 - Impact and causes of readmission within 90-days of non-small cell lung cancer surgery

109 - Impact and causes of readmission within 90-days of non-small cell lung cancer surgery

Elevation of the Neutrophil-to-Lymphocyte Ratio Is a Significant Postoperative Poor Prognostic Factor in Patients With Clinical T3-4 Centrally Located Primary Lung Cancer.

In centrally located non-small cell lung cancer (CLNSCLC) surgery, large tumors and extension to neighboring structures prevent the attainment of adequate surgical fields and make operations more difficult, and some patients have extremely poor outcomes. This study aimed to identify novel postoperative prognostic factors in patients with advanced CLNSCLC. CLNSCLC was defined as a tumor requiring pneumonectomy or sleeve lobectomy for complete removal. We retrospectively investigated the clinical courses of 35 patients with cT3-4 CLNSCLC. This study included 21 patients with cT3 and 14 with cT4 lung cancer. Nine patients underwent pneumonectomy and 26 underwent sleeve lobectomy. Univariate analysis revealed that a high neutrophil-to-lymphocyte ratio (NLR, p=0.005) and carcinoembryonic antigen (CEA) positivity (p=0.028) were significant poor prognostic factors. Only high NLR (p=0.020) was a significant independent predictor in multivariate analysis. Nine of 16 patients with high NLR (56%) experienced disease recurrence, whereas 6 of 19 patients without high NLR (32%) had recurrent disease. High NLR and CEA positivity were significant poor prognostic factors in patients with cT3-4 CLNSCLC, and only high NLR was an independent predictor. Our findings may be helpful in selecting optimal treatments for advanced CLNSCLC.

Dancing with the Surgeon: Neoadjuvant and Adjuvant Immunotherapies from the Medical Oncologist's Perspective.

Perioperative treatment with conventional cytotoxic chemotherapy for resectable non-small cell lung cancer (NSCLC) has proven clinical benefits in terms of achieving a higher overall survival (OS) rate. With its success in the palliative treatment of NSCLC, immune checkpoint blockade (ICB) has now become an essential component of treatment, even as neoadjuvant or adjuvant therapy in patients with operable NSCLC. Both pre- and post-surgery ICB applications have proven clinical efficacy in preventing disease recurrence. In addition, neoadjuvant ICB combined with cytotoxic chemotherapy has shown a significantly higher rate of pathologic regression of viable tumors compared with cytotoxic chemotherapy alone. To confirm this, an early signal of OS benefit has been shown in a selected population, with programmed death ligand 1 expression ≥50%. Furthermore, applying ICB both pre- and post-surgery enhances its clinical benefits, as is currently under evaluation in ongoing phase III trials. Simultaneously, as the number of available perioperative treatment options increases, the variables to be considered for making treatment decisions become more complex. Thus, the role of a multidisciplinary team-based treatment approach has not been fully emphasized. This review presents up-to-date pivotal data that lead to practical changes in managing resectable NSCLC. From the medical oncologist's perspective, it is time to dance with surgeons to decide on the sequence of systemic treatment, particularly the ICB-based approach, accompanying surgery for operable NSCLC.

Prognostic impact of lymph node spreading pattern in N2 NSCLC patients

ABSTRACT Background One-third of non-small cell lung cancer (NSCLC) patients are diagnosed with locally advanced disease. Long-term survival in stage IIIA/B-N2 remains poor; this may also be due to lymph node spreading pattern. Therefore, we compared the overall survival of stage IIIA/B-N2 patients with superior mediastinal lymph nodes (SML) with infracarinal- or inferior mediastinal lymph nodes (IML) and with multilevel disease (MLD). Research design and methods One-, three-and five-year survival rates were measured. Kaplan-Meier curves and Cox proportional hazards model assessed survival and were used to identify prognostic factors. Results We reviewed data of stage IIIA/B-N2 patients (n = 129) who underwent surgery for NSCLC between 2012 and 2020. Patients with SML (n = 62) were compared to ILM (n = 37) and MLD (n = 30). SML patients showed significantly better one- (SML: 95.2% vs. IML: 78.6% vs. MLD: 69.4%, p = 0.03), three- (78.8% vs. 27.7 vs. 13.3%; p = <0.001) and five-year (61.1% vs. 17.1 vs. 3%; p < 0.001) survival rates, than IML and MLD patients. Kaplan-Meier curves showed prolonged overall survival for SML patients (log-rank SML, ILM, MLD p < 0.0001). Conclusions This study showed significantly better long-term survival of SML patients than IML and MLD patients. The long-term survival of ILM and MLD patients was equally poor.

Precision Surgery in NSCLC

Non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. This is mostly because the majority of lung cancers are discovered in advanced stages. In the era of conventional chemotherapy, the prognosis of advanced NSCLC was grim. Important results have been reported in thoracic oncology since the discovery of new molecular alterations and of the role of the immune system. The advent of new therapies has radically changed the approach to lung cancer for a subset of patients with advanced NSCLC, and the concept of incurable disease is still changing. In this setting, surgery seems to have developed a role of rescue therapy for some patients. In precision surgery, the decision to perform surgical procedures is tailored to the individual patient; taking into consideration not only clinical stage, but also clinical and molecular features. Multimodality treatments incorporating surgery, immune checkpoint inhibitors, or targeted agents are feasible in high volume centers with good results in terms of pathologic response and patient morbidity. Thanks to a better understanding of tumor biology, precision thoracic surgery will facilitate optimal and individualized patient selection and treatment, with the goal of improving the outcomes of patients affected by NSCLC.

A comparative study of four thoracic mortality scores.

The percentage of patients in resectable stages at initial diagnosis of non-small cell lung cancer (NSCLC) raises due to better screening programs. Therefore, risk prediction models are becoming more critical. Here, we validated and compared four established scoring models, the Thoracoscore, Epithor, Eurloung 2, and the simplified Eurolung 2 (2b), in their ability to predict 30-day mortality. All consecutive patients undergoing anatomical pulmonary resection were included. The performance of the four scoring systems was assessed with Hosmer-Lemeshow goodness-of-fit test (calibration) and receiver operating characteristic (ROC) curves (discrimination). We compared the area under the curve (AUC) of the ROC curves by DeLong's method. A total of 624 patients underwent surgery for NSCLC at our institution between 2012 and 2018 30-day mortality was 2.2% (14 patients). The AUC for Eurolung 2 and the simplified Eurolung 2 (0.82) were greater than those of the other scoring systems, Epithor (0.71) and Thoracoscore (0.65). In addition, the DeLong analysis showed a significant superiority of Eurolung 2 and Eurolung 2b over the Thoracoscore (p = 0.04); there were no significant differences compared to Epithor. Eurolung 2 and the simplified Eurolung 2 were the favorable scoring systems for predicting 30-day mortality compared to Thoracoscore and Epithor. Therefore, we recommend using Eurolung 2 or the simplified Eurolung 2 for preoperative risk stratification.

Perioperative lidocaine and dexmedetomidine intravenous infusion reduce the serum levels of NETs and biomarkers of tumor metastasis in lung cancer patients: A prospective, single-center, double-blinded, randomized clinical trial.

Neutrophil extracellular traps (NETs) can enhance the metastasis of non-small cell lung cancer (NSCLC). As biomarkers of tumor metastasis, metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) together with NETs are essential to endothelial-to-mesenchymal transition (EMT). We hypothesized that intravenous infusion of lidocaine and dexmedetomidine could reduce the production of NETs and biomarkers of tumor metastasis after video-assisted thoracic surgery (VATS) in NSCLC patients. The trial included 132 NSCLC patients undergoing VATS. The patients were equally randomized to a placebo group (Group C), a lidocaine group (Group L, intravenous lidocaine 8 mg/kg/h for 15 minutes before anesthesia, 2 mg/kg/h during surgery, and 1 mg/kg/h until 24 hours after surgery), a dexmedetomidine group (Group D, intravenous dexmedetomidine 2 μg/kg/h for 15 minutes before anesthesia, 0.5 μg/kg/h during surgery, and 0.25 μg/kg/h until 24 hours after surgery), and a dexmedetomidine plus lidocaine group (Group LD, combination use of lidocaine and dexmedetomidine). The primary outcome was the production of myeloperoxidase (MPO) and citrullinated histone-3 (H3Cit), biomarkers of NETs, on postoperative day (POD) 1. MMP-3, MMP-9, and VEGF-α, as biomarkers of tumor metastasis, were also evaluated on POD 1. The baseline patient characteristics and perioperative data did not differ between the study groups. MPO was significantly decreased in Groups L, D, and LD (-197.08 ± 34.01, -137.37 ± 32.41, and -189.45 ± 33.73 U/ml, P<0.001, respectively) compared with Group C (-106.51 ± 25.44 U/ml). H3Cit was also lessened in Groups L, D, and LD (-49.51 ± 9.11, -34.80 ± 10.37, and -51.82 ± 8.98 ng/ml, P<0.001, respectively) compared with Group C (-24.73 ± 7.65 ng/ml). Lidocaine and dexmedetomidine also reduced MMP-3 (-69.08 ± 13.22, -52.84 ± 13.78, -85.34 ± 12.59 vs. -40.55 ± 10.71 ng/ml in Group L, D, LD vs. Group C, P<0.001, respectively), MMP-9 (-8.46 ± 1.68, -6.07 ± 1.82, -9.67 ± 1.43 vs. -4.28 ± 1.29 ng/ml in Group L, D, LD vs. Group C, P<0.001, respectively), and VEGF-α (-95.55 ± 22.53, -71.65 ± 18.77, -104.89 ± 15.49 vs. -51.73 ± 16.27 pg/ml in Group L, D, LD vs. Group C, P<0.001, respectively) on POD 1. In NSCLC patients, continuous perioperative intravenous infusion of lidocaine and dexmedetomidine significantly reduced the production of NETs and tumor metastasis biomarkers on POD 1. Meanwhile, it also decreased inflammation, protected cellular immune function, reduced pain and opioid consumption, and improved the quality of postoperative recovery. chictr.org.cn, identifier: 187049.

Plain language summary of the CheckMate 816 study results: nivolumab plus chemotherapy given before surgery for non-small-cell lung cancer.

In this article, we summarize results from the ongoing phase 3 CheckMate 816 clinical study that were published in The New England Journal of Medicine in 2022. The goal of CheckMate 816 was to find out if nivolumab, an immunotherapy that activates a person's immune system (the body's natural defense system) to fight cancer, plus chemotherapy works better than chemotherapy alone when given before surgery in people with non-small-cell lung cancer (NSCLC) that can be removed surgically (resectable NSCLC). Adults who had not previously taken medications to treat NSCLC and whose cancer could be removed with surgery were included in CheckMate 816. During this study, a computer randomly assigned the treatment each person would receive before surgery for NSCLC. In total, 179 people were randomly assigned to receive nivolumab plus chemotherapy, and 179 people were randomly assigned to receive chemotherapy alone. The researchers assessed whether people who received nivolumab plus chemotherapy lived longer without the cancer geting worse or coming back and whether there were any cancer cells left in the tumor and lymph nodes removed by surgery. The researchers also assessed how adding nivolumab to chemotherapy affected the timing and outcomes of surgery and whether the combination of these drugs was safe. Researchers found that people who took nivolumab plus chemotherapy lived longer without the cancer getting worse or coming back compared with those who took chemotherapy alone. More people in the nivolumab plus chemotherapy group had no cancer cells left in the tumor and lymph nodes removed by surgery. Most people went on to have surgery in both treatment groups; the people who took nivolumab plus chemotherapy instead of chemotherapy alone had less extensive surgeries and were more likely to have good outcomes after less extensive surgeries. Adding nivolumab to chemotherapy did not lead to an increase in the rate of side effects compared with chemotherapy alone, and side effects were generally mild and manageable. Results from CheckMate 816 support the benefit of using nivolumab plus chemotherapy before surgery for people with resectable NSCLC. Clinical Trial Registration: NCT02998528 (ClinicalTrials.gov).