Surgery For Non-small Cell Lung Cancer Research Articles

Correlation between pre-anesthesia anxiety and emergence agitation in non-small cell lung cancer surgery patients.

Preoperative anxiety is a common emotional problem during the perioperative period and may adversely affect postoperative recovery. Emergence agitation (EA) is a common complication of general anesthesia that may increase patient discomfort and hospital stay and may be associated with the development of postoperative complications. Pre-anesthetic anxiety may be associated with the development of EA, but studies in this area are lacking. To determine the relationship between pre-anesthetic anxiety and EA after radical surgery in patients with non-small cell lung cancer (NSCLC). Eighty patients with NSCLC undergoing surgical treatment between June 2020 and June 2023 were conveniently sampled. We used the Hospital Anxiety and Depression Scale's (HADS) anxiety subscale (HADS-A) to determine patients' anxiety at four time points (T1-T4): Patients' preoperative visit, waiting period in the surgical waiting room, after entering the operating room, and before anesthesia induction, respectively. The Riker Sedation-Agitation Scale (RSAS) examined EA after surgery. Scatter plots of HADS-A and RSAS scores assessed the correlation between patients' pre-anesthesia anxiety status and EA. We performed a partial correlation analysis of HADS-A scores with RSAS scores. NSCLC patients' HADS-A scores gradually increased at the four time points: 7.33 ± 2.03 at T1, 7.99 ± 2.22 at T2, 8.05 ± 2.81 at T3, and 8.36 ± 4.17 at T4. The patients' postoperative RSAS score was 4.49 ± 1.18, and 27 patients scored ≥ 5, indicating that 33.75% patients had EA. HADS-A scores at T3 and T4 were significantly higher in patients with EA (9.67 ± 3.02 vs 7.23 ± 2.31, 12.56 ± 4.10 vs 6.23 ± 2.05, P < 0.001). Scatter plots showed the highest correlation between HADS-A and RSAS scores at T3 and T4. Partial correlation analysis showed a strong positive correlation between HADS-A and RSAS scores at T3 and T4 (r = 0.296, 0.314, P < 0.01). Agitation during anesthesia recovery in patients undergoing radical resection for NSCLC correlated with anxiety at the time of entering the operating room and before anesthesia induction.

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

8078 Background: Translation of ctDNA MRD in NSCLC has been hampered by suboptimal sensitivity of 1st-generation assays. Here, we explore how improvements in analytical sensitivity can drive improved clinical sensitivity for MRD after surgery in NSCLC. Methods: To understand MRD kinetics, we analyzed longitudinal ctDNA in early stage NSCLC using data from the TRACERx study. Patient-specific mathematical models were generated to predict MRD levels at the postsurgical landmark and estimate the impact of an assay’s 95% limit of detection (LOD95) on clinical sensitivity. To test these predictions, tumor-informed ctDNA testing was performed using an SNV-based assay (CAPP-Seq) and a phased variant-based assay (PhasED-Seq, Foresight Diagnostics) on 269 samples from 46 patients. We also assessed MRD performance for predicting 1) patient outcomes at the landmark timepoint and 2) the effect of adjuvant treatment. Results: ctDNA MRD dynamics were assessed in 23 patients from TRACERx with ≥3 consecutive samples with detectable ctDNA without intervening therapy. MRD kinetics strongly correlated with exponential growth, with a median ctDNA doubling time of 51 days. Extrapolating MRD levels to the postsurgical landmark predicted that improving MRD assay LOD95 from 100 ppm (0.01%) to 1 ppm could increase clinical sensitivity by 2.1-fold. We then evaluated 46 NSCLC cases using two assays. The median LOD95 was 1 ppm for PhasED-Seq and 84 ppm for CAPP-Seq. Twelve cases were MRD+ by PhasED-Seq, all of whom recurred (100%), with MRD levels as low as 0.19 ppm. In contrast, 6 cases were MRD+ by the SNV-based approach, of whom 5 (83%) recurred. Accordingly, PhasED-Seq had a higher clinical sensitivity than the SNV-based method (12/18 [67%] vs. 5/18 [28%], P = 0.022). Kaplan Meier analysis for freedom from recurrence revealed significantly worse outcomes for patients with detectable MRD regardless of the method used; however, outcomes were better stratified using PhasED-Seq (HR 3.1 vs. 11.4). Patients who were MRD- after surgery by both assays had similar outcomes regardless of adjuvant therapy (chemotherapy and/or radiotherapy). However, MRD+ patients by PhasED-Seq receiving adjuvant therapy had significantly better outcomes than those who did not (HR 8.2, P = 0.00035). A similar benefit for adjuvant therapy was not observed with the SNV-based assay. Using PhasED-Seq, 80% (4/5) of MRD+ patients receiving adjuvant therapy cleared their MRD, compared to 0% (0/3) without adjuvant treatment. Conclusions: Ultrasensitive ctDNA detection improved the clinical sensitivity of MRD at key landmarks in early stage NSCLC. PhasED-Seq detected MRD at levels below 1 ppm and was associated with significantly better outcomes, revealing potential benefits of adjuvant therapy in MRD+ patients. This suggests that ultrasensitive MRD detection is promising for use in risk-adapted trials in early stage NSCLC.

Surgical outcomes for non-small cell lung carcinoma by race and surgical facility types in the United States.

11167 Background: Successful outcomes of surgical treatment of cancer requires expertise and high-quality supportive services for surgical care. Previous studies have shown that case volume and availability of other in-house supportive services affect surgical outcomes. Latest studies have shown that this gap has now significantly reduced. Issues related to access, availability of funding for latest technologies and continuous medical education still exist and likely still impact the surgical outcomes. The objective of the study is to understand the impact of surgical center related factors on survival outcomes for cancer patients based on race and other demographic features. Methods: We conducted a retrospective analysis of patients diagnosed with Stage I-III Non-small cell lung cancer (NSCLC) between 2004 to 2020 using the National Cancer Database (NCDB). Patients were divided into 4 cohorts of NCDB assigned facility type (Community Cancer Program, Comprehensive Community Cancer Program, Academic/Research Program, Integrated Network Cancer Program). Racial and other demographic data was analyzed for each of the facility types. Differences in categorical variables were evaluated using a Chi-square test. Results: 298,393 adenocarcinoma and 129,144 squamous cell carcinoma patients underwent surgery for NSCLC between 2004-2020. 326,798 patients with clinical stages I-III were selected for the analysis. Most surgeries were performed at the academic/research programs and comprehensive community programs. Utilization of each facility type was uniform across all races. The 30-day mortality rate was lowest for the academic/research programs (Community Cancer Program 3.1%, Comprehensive Community Cancer Program 2.6%, Academic/Research Program 1.8%, Integrated Network Cancer Program 2.3%; p=0.000). 30-day mortality rate was higher for American Indian, Aleutian, or Eskimo racial subgroups amongst all age-groups at all the surgical facility types especially for Stage IIIB NSCLC (White: 6%, Black: 3.4%, American Indian, Aleutian, or Eskimo: 14.3%, p=0.006). For each race, the 30-day mortality rate was better at the academic/research programs. Females had lower 30-day mortality for all racial subgroups. Having private insurance was associated with the lowest 30-day mortality rate. This was noted for all races across all the facility types. Lower income status was associated with higher mortality rates across all facility types. This difference was statistically significant for white patients. Majority of patients had less than 10 days of length of stay at all the surgical facility types. Conclusions: Outcomes of NSCLC surgery are significantly better at academic/research programs where a higher number of procedures are performed and access to latest surgical technologies is available. Short-term mortality rates are higher for American Indian, Aleutian, or Eskimo racial subgroup.

In-hospital thromboprophylaxis variation and the risk of venous thromboembolism after lung cancer surgery: a nationwide cohort study.

Venous thromboembolic event (VTE) is a severe complication in patients with lung cancer undergoing thoracic surgery. Nevertheless, because of insufficient evidence, there are no clear guidelines, and VTE prophylaxis practices vary widely. This nationwide cohort study was a comparative study investigating VTE risk in surgical departments that routinely administered in-hospital thromboprophylaxis with low-molecular-weight heparin compared to those that did not. We identified all patients with non-small-cell lung cancer (NSCLC) who underwent surgery in Denmark during 2010-2021. Thoracic surgery was exclusively performed in the 4 university hospitals. Three hospitals implemented in-hospital thromboprophylaxis as standard care since 2000, while the fourth adopted this practice in September 2016. VTE events were assessed at 6-month follow-up according to hospital and study period, using an inverse probability of treatment weighting approach. We identified 9615 patients. During 6-month follow-up, a total of 190 VTE events were observed, resulting in a weighted rate of 4.5 events per 100 person-years and an absolute risk of 2.2%. There was no clear trend according to hospital site or use of in-hospital thromboprophylaxis with a 2.2% risk in the hospital not using thromboprophylaxis compared to 1.7-3.1% in those that did. Use of in-hospital thromboprophylaxis did not affect the risk of VTE after surgery for NSCLC, suggesting that relying solely on in-hospital thromboprophylaxis may be insufficient to mitigate VTE risk in these patients. Further research is warranted to investigate the potential benefits of extended thromboprophylaxis in reducing VTE risk in selected NSCLC surgical patients.

A randomized phase III trial of postoperative surveillance for pathological stage II and IIIA non-small cell lung cancer (JCOG2012, PHOENIX).

The goal of postoperative surveillance following non-small cell lung cancer surgery is to detect recurrence and second primary malignancies while curative treatment is still possible. Although several guidelines recommend that patients have computed tomography (CT) scans every 6months for the first 2years after resection, then once a year, there is no evidence that it is effective for survival, especially in locally advanced non-small cell lung cancer. In October 2022, we launched a multi-institutional, randomized controlled phase III trial for pathological stage II and IIIA non-small cell lung cancer patients to confirm the non-inferiority of less intensive surveillance with less frequent CT scans versus standard surveillance in terms of overall survival. The primary endpoint is overall survival. We intend to enroll 1100 patients from 45 institutions over 4years. The trial has been registered in the Japan Registry of Clinical Trials under the code jRCT1030220361 (https://jrct.niph.go.jp/latest-detail/jRCT1030220361).

Pathological Pleural Invasion is a Risk Factor for Late Recurrence in Long-Term Survivors of Non-small Cell Lung Cancer after Complete Resection.

Information regarding late recurrence after pulmonary resection for non-small cell lung cancer (NSCLC) is limited. This study aimed to analyze the risk factors for late recurrence after surgery for NSCLC in the current era. We conducted a retrospective study of patients who underwent complete resection for pathological I-III NSCLC between 2006 and 2015. Late recurrence was defined as a recurrence that met the following conditions: (1) the patient underwent chest computed tomography (CT) at or after 54 months after surgery and recurrence was not detected at that time, and (2) recurrence that occurred more than 5 years after surgery. The factors influencing late recurrence, relapse-free survival (RFS), and overall survival (OS) after surgery were analyzed. A total of 1275 with 5-year relapse-free survival after surgery were enrolled in this study. The mean age of the patients was 66.4 years and 54% of the patients were men. The median interval between surgery and the latest follow-up examination was 98 months. In total, 35 patients (2.7%) experienced late recurrence and 138 patients have died thus far. The cumulative recurrence, RFS, and OS rates at 10 years were 3.9%, 84.9%, and 86.3%, respectively. A multivariate analysis revealed that pleural invasion was an independent risk factor for late recurrence. Pleural invasion was a poor prognostic factor for both RFS and OS. Pleural invasion was a predictor of late recurrence. Age>67 years, preoperative serum carcinoembryonic antigen (CEA)>5 ng/ml, non-adenocarcinoma, and pleural invasion were poor prognostic factors for RFS.

Impact of Modified Frailty Index on Readmissions Following Surgery for NSCLC.

Analyzing the risk factors that predict readmissions can potentially lead to more individualized patient care. The 11-factor modified frailty index is a valuable tool for predicting postoperative outcomes following surgery. The objective of this study is to determine whether the frailty index can effectively predict readmissions within 90 days after lung resection surgery in cancer patients within a single health care institution. Patients who underwent elective pulmonary resection for nonsmall cell lung cancer (NSCLC) between January 2012 and December 2020 were selected from the hospital's database. Patients who were readmitted after surgery were compared to those who were not, based on their data. Propensity score matching was employed to enhance sample homogeneity, and further analyses were conducted on this newly balanced sample. A total of 439 patients, with an age range of 68 to 77 and a mean age of 72, were identified. Among them, 55 patients (12.5%) experienced unplanned readmissions within 90 days, with an average hospital stay of 29.4 days. Respiratory failure, pneumonia, and cardiac issues accounted for approximately 67% of these readmissions. After propensity score matching, it was evident that frail patients had a significantly higher risk of readmission. Additionally, frail patients had a higher incidence of postoperative complications and exhibited poorer survival outcomes with statistical significance. The 11-item modified frailty index is a reliable predictor of readmissions following pulmonary resection in NSCLC patients. Furthermore, it is significantly associated with both survival and postoperative complications.

Time-resolved fluorescence and diffuse reflectance for lung squamous carcinoma margin detection.

A major challenge in non-small cell lung cancer surgery is the occurrence of positive tumor margins. This may lead to the need for additional surgeries and has been linked to poor patient prognosis. This study aims to develop an in vivo surgical tool that can differentiate cancerous from noncancerous lung tissue at the margin. A time-resolved fluorescence and diffuse reflectance bimodal device was used to measure the lifetime, spectra, and intensities of endogenous fluorophores as well as optical properties of lung tissue. The tumor and fibrotic tissue data, each containing 36 samples, was obtained from patients who underwent surgical removal of lung tissue after being diagnosed with squamous carcinoma but before any other treatment was administered. The normal lung tissue data were obtained from nine normal tissue samples. The results show a statistically significant difference between cancerous and noncancerous tissue. The results also show a difference in metabolic related optical properties between fibrotic and normal lung tissue samples. This work demonstrates the feasibility of a device that can differentiate cancerous and noncancerous lung tissue for patients diagnosed with squamous cell carcinoma.

Comparison of Treatment Outcomes Between Thoracoscopic Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

Objective: To compare the risk of death, tumor recurrence, metastasis, and disease progression in early-stage non-small cell lung cancer (NSCLC) patients treated with thoracoscopic surgery and stereotactic body radiotherapy (SBRT). Methods: Patients who underwent radical surgery and SBRT for NSCLC between April 2010 and November 2021 were retrospectively analyzed. Continuous and categorical variables were compared using the Mann-Whitney U and Chi-square test, respectively. Kaplan-Meier curves were used to evaluate the survival outcomes of each patient group. Cox proportional hazard regression analyses were performed to estimate the risk of death, tumor recurrence, metastasis, and disease progression. Results: A total of 167 patients were enrolled, of whom 75 and 92 underwent SBRT and surgery, respectively. The median follow-up was 45 months (range, 4-105 months). SBRT patients were observed to be significantly older (median, 76.0 vs 67.0 years; P < .001), and associated with significantly higher mortality rate (42.7% vs 26.1%, P = .024). However, no significant difference in overall survival duration was seen between the SBRT and surgery groups (45.0 vs 41.0 months; P = .199). SBRT patients demonstrated significantly lower rates of metastasis (12.0% vs 30.4%, P = .004), and significantly longer metastasis-free survival (39.0 months vs 35.5 months, P = .020). The remaining outcomes, including tumor recurrence and disease progression rates, were similar between the groups. Compared to surgery, SBRT did not significantly associate with death, recurrence, or disease progression. Kaplan-Meier curves showed significant differences in overall, tumor recurrence-free, and disease progression-free survival between the groups (log-rank P < .05). Conclusions: SBRT demonstrated similar overall survival compared to radical surgery, and associated with significantly reduced risk of tumor metastasis. Our study thereby suggests SBRT as the best treatment option for patients with inoperable NSCLC.

The effect of platelet-to-lymphocyte ratıo (PLR) and glasgow prognostıc score (GPS) on recurrence, and survıval ın patıents undergoıng lobectomy for early-stage non-small cell lung cancer (NSCLC).

Tumor markers are indicators that can be used not only for cancer diagnosis but also for determining prognosis. Unfortunately, there is currently no tumor marker that reliably predicts the prognosis of lung cancer. In this study, we investigated the prognostic impact of the platelet-to-lymphocyte ratio (PLR) and Glasgow Prognostic Score (GPS), known as inflammation markers in peripheral blood, in patients who underwent resection for early-stage non-small cell lung cancer (NSCLC). We retrospectively analyzed the medical records of a total of 3300 patients who underwent surgery for NSCLC between 2010 and 2020. Among these patients, 250 met the inclusion criteria of lobectomy, pT1-T2N0 stage, and histology of adenocarcinoma or squamous cell carcinoma. Preoperative albumin, C-reactive protein (CRP), preoperative PLR, and postoperative 5th-day PLR values were determined from patient's peripheral blood data. The impact of these values on postoperative recurrence and survival was investigated. GPS was calculated based on preoperative CRP and albumin values, and patients were divided into 3 groups: 0 (mild), 1 (moderate), and 2 (severe). The relationship between preoperative GPS and survival was analysed. Among the included patients, 155 (62%) had adenocarcinoma and 95 (38%) had squamous cell carcinoma. A total of 185 (74%) patients had pT1 tumors, while 65 (26%) had pT2 tumors. During the postoperative follow-up period, local recurrence was observed in 28 (11.2%) patients and distant metastasis in 51 (20.4%) patients. The overall mortality rate was 19.6%. The 5-year survival rates for pT1 and pT2 tumors were 80.4% and 72.5%, respectively. Significant associations were found between preoperative PLR, postoperative PLR, and recurrence (p = 0.005 and p = 0.011). The expected overall survival (OS) was 103.4months in the mild GPS group, 91.8months in the moderate GPS group, and 50months in the severe GPS group. The relationship between GPS groups and OS was statistically significant (p = 0.005). Preoperative analysis of PLR and GPS may provide prognostic value in NSCLC patients who undergo surgical resection. Our study provides a rationale for further investigation of peripheral blood immune markers for prognostic purposes.

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.