Resection For Primary Lung Cancer Research Articles

Pre-Operative Measures of Systemic Inflammation Predict Survival After Surgery for Primary Lung Cancer

BackgroundMeasures of systemic inflammation (MSIs) have been developed and shown to help predict prognosis in patients with lung cancer. However, studies investigating the impact of MSIs on outcomes solely in cohorts of patients undergoing curative-intent resection of NSCLC are lacking. In the era of individualized therapies, targeting inflammatory pathways could represent a novel addition to the armamentarium of lung cancer treatment. MethodsA multicentre retrospective review of patients who underwent primary lung cancer resection between 2012 and 2018 was undertaken. MSIs assessed were neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune inflammation index (SII), advanced lung cancer inflammation index (ALI), prognostic nutritional index (PNI) and haemoglobin albumin lymphocyte platelet (HALP) score. Cox regression analysis was performed to assess the impact of MSIs on overall survival. ResultsA total of 5029 patients were included in the study. Overall 90-day mortality was 3.7% (n = 185). All MSIs were significantly associated with overall survival on univariable analysis. After multivariable Cox regression analyses, lower ALI (expressed as a continuous variable) (HR 1.000, 95% CI 1.000-1.000, P = .049) and ALI <366.43 (expressed as a dichotomous variable) (HR 1.362, 95% CI 1.137-1.631, P < .001) remained independently associated with reduced overall survival. ConclusionsMSIs have emerged in this study as potentially important factors associated with survival following lung resection for NSCLC with curative intent. In particular, ALI has emerged as independently associated with long-term outcomes. The role of MSIs in the clinical management of patients with primary lung cancer requires further investigation.

Abstract 3635: Insulin-like growth factor receptor predicts poor prognosis in early-stage non-small cell lung cancer

Abstract Introduction: Insulin like growth factor receptor (IGF1R) is involved in the proliferation and metastasis of various cancers. However, the clinical significance of IGF1R in non-small cell lung cancer (NSCLC) remains to be unclear. In this study, we retrospectively evaluated the correlation between IGF1R expression and clinicopathological features of NSCLC. Method: A total of 782 specimens of NSCLC patients who underwent surgical resection of primary lung cancer between 2010 and 2019 at Osaka Metropolitan University Hospital was enrolled in this study. Immunohistochemical staining of IGF1R were performed, and the correlation between IGF1R expression and clinicopathological features of NSCLC, especially in recurrence free survival (RFS) and overall survival (OS), was evaluated. We also evaluated an association between IGF1R and programmed death ligand 1 (PD-L1) expression. Results: IGF1R expression was positive in 279 (35.8%) patients. IGF1R-positive group had significantly longer smoking histories (median smoking index, 1,000 vs 600, p &amp;lt;0.01) and a higher proportion of squamous cell carcinomas (35.1% vs 14.1 %, p &amp;lt;0.01). IGF1R-positive group also significantly expressed PD-L1 (24.4% vs 6.4%, p&amp;lt;0.01). IGF1R-positive group had significantly worse RFS (10-year recurrence-free rate; 42.7% vs 53.7%, p &amp;lt;0.01) and OS (10-year survival rate; 54.4% vs 67.3%, p &amp;lt;0.01). RFS and OS were significantly worse in the IGF1R-positive NSCLC patients at stage 0 and stage I (10-year recurrence-free rate; 49.0% vs 62.9%, p &amp;lt;0.01, 10-year survival rate; 57.4% vs 74.2%, p&amp;lt;0.01), but not in stage II (10-year recurrence-free rate; 52.0% vs 43.8%, p=0.68, 10-year survival rate; 63.4% vs 47.5%, p=0.95) and III (10-year recurrence-free rate; 20.7% vs 20.8%, p=0.77, 10-year survival rate; 38.3% vs 54.6%, p=0.18). IGF1R expression was associated with poorer RFS and OS in early-stage NSCLC. Conclusion: IGF1R is a predictor of poor prognosis in resected early-stage NSCLC. Citation Format: Hiroaki nagamine, Masakazu Yashiro, Megumi Mizutani, Akira Sugimoto, Yoshiya Matsumoto, Yoko Tani, Kenji Sawa, Kazuhiro Yamada, Hiroyasu Kaneda, Tetsuya Watanabe, Kazuhisa Asai, Satoshi Suzuki, Tomoya Kawaguchi. Insulin-like growth factor receptor predicts poor prognosis in early-stage non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3635.

Enhanced Survival with Lymphadenectomy in Early-Stage Metachronous Second Primary Lung Cancer: A Retrospective Analysis

Introduction: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer (MSPLC) remains poorly understood. This retrospective study aimed to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. Methods: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score-matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score-matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% in the non-lymphadenectomy group (HR: 0.76; 95% confidence interval 0.64–0.90; p = 0.002). Conclusion: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggest the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.

Evaluation of the Factors Affecting Higher Hospitalization Cost of Lung Resection for Primary Lung Cancer: A Retrospective Cohort Study.

This study aims to evaluate the factors associated with the higher hospitalization cost of lung resection for primary lung cancer to contribute to the reduction of healthcare spending. A total of 435 consecutive primary lung cancer patients who underwent lung resection by a single surgeon at a single institution were enrolled. Baseline patient characteristics, operative procedures, postoperative complications, and postoperative courses were analyzed in relation to the hospitalization cost. Patients with higher costs (exceeding the third quartile [TQ]) were compared with patients with lower costs (less than TQ). Median and TQ medical costs for overall cases were 11177 US dollars (USD) and 12292 USD, respectively. Smoking history, history of coronary artery disease, previous thoracotomy, multiple sealant material use, transfusion, tumor factor T3 or higher, squamous cell carcinoma, postoperative complications, and longer postoperative hospital stay (>10 POD) were significant risk factors for increased hospitalization cost in multivariate analysis. The 5-year survival rate was significantly lower in the higher hospitalization cost group. In addition to postoperative complications and prolonged hospitalization, patient background, histological types, and intraoperative factors were also considered as the risk factors for higher medical costs.

ERASURE: early autologous blood pleurodesis for postoperative air leaks—a randomized, controlled trial comparing prophylactic autologous blood pleurodesis versus standard watch and wait treatment for postoperative air leaks following thoracoscopic anatomic lung resections

BackgroundThe prolonged air leak is probably the most common complication following lung resections. Around 10–20% of the patients who undergo a lung resection will eventually develop a prolonged air leak. The definition of a prolonged air leak varies between an air leak, which is evident after the fifth, seventh or even tenth postoperative day to every air leak that prolongs the hospital stay. However, the postoperative hospital stay following a thoracoscopic lobectomy can be as short as 2 days, making the above definitions sound outdated. The treatment of these air leaks is also very versatile. One of the broadly accepted treatment options is the autologous blood pleurodesis or “blood patch”. The purpose of this trial is to investigate the impact of a prophylactic autologous blood pleurodesis on reducing the duration of the postoperative air leak and therefore prevent the air leak from becoming prolonged.MethodsPatients undergoing an elective thoracoscopic anatomic lung resection for primary lung cancer or metastatic disease will be eligible for recruitment. Patients with an air leak of > 100 ml/min within 6 h prior to the morning round on the second postoperative day will be eligible for inclusion in the study and randomization. Patients will be randomized to either blood pleurodesis or watchful waiting. The primary endpoint is the time to drain removal measured in full days. The trial ends on the seventh postoperative day.DiscussionThe early autologous blood pleurodesis could lead to a faster cessation of the air leak and therefore to a faster removal of the drain. A faster removal of the drain would relieve the patient from all the well-known drain-associated complications (longer hospital stay, stronger postoperative pain, risk of drain-associated infection, etc.). From the economical point of view, faster drain removal would reduce the hospital costs as well as the costs associated with the care of a patient with a chest drain in an outpatient setting.Trial registrationGerman Clinical Trials Register (DRKS) DRKS00030810. 27 December 2022

Concomitant minimally invasive surgery for tricuspid valve papillary fibroelastoma and right lung cancer in an elderly patient: a case report and review of the literature

BackgroundIt is very common for patients with newly diagnosed lung masses to have heart disease. However, papillary fibroelastomas (PFEs) of the tricuspid valve (TV) combined with lung cancer are rarely reported. It is thus unclear whether a two-stage surgery or concomitant surgery is optimal.Case presentationWe report the case of a 73-year-old Chinese male who was diagnosed with PFEs on the TV by transthoracic echocardiography (TTE) examination while being evaluated to undergo video-assisted thoracic surgery (VATS) for a right lower lung nodule. We resected both the PFEs and the lung nodule via right minithoracotomy. The surgery was uneventful, and histopathology reports confirmed PFEs of the TV and moderately to poorly differentiated squamous cell carcinoma. The patient recovered uneventfully, and there was no sign of tumor recurrence during 15 months of follow-up.ConclusionsWe suggest that after careful evaluation, concomitant minimally invasive radical resection of primary lung cancer after cardiac PFE removal is an acceptable and safe treatment strategy and should be performed as soon as possible.

Routine perioperative blood tests predict survival of resectable lung cancer

There is growing evidence that inflammatory, immunologic, and metabolic status is associated with cancer patients survival. Here, we built a simple algorithm to predict lung cancer outcome. Perioperative routine blood tests (RBT) of a cohort of patients with resectable primary lung cancer (LC) were analysed. Inflammatory, immunologic, and metabolic profiles were used to create a single algorithm (RBT index) predicting LC survival. A concurrent cohort of patients with resectable lung metastases (LM) was used to validate the RBT index. Charts of 2088 consecutive LC and 1129 LM patients undergoing lung resection were evaluated. Among RBT parameters, C-reactive protein (CRP), lymphocytes, neutrophils, hemoglobin, albumin and glycemia independently correlated with survival, and were used to build the RBT index. Patients with a high RBT index had a higher 5-year mortality than low RBT patients (adjusted HR 1.93, 95% CI 1.62–2.31). High RBT patients also showed a fourfold higher risk of 30-day postoperative mortality (2.3% vs. 0.5%, p 0.0019). The LM analysis validated the results of the LC cohort. We developed a simple and easily available multifunctional tool predicting short-term and long-term survival of curatively resected LC and LM. Prospective external validation of RBT index is warranted.

Safety of curative-intent lung cancer surgery in older patients (octogenarians): A contemporary multicentre cohort study

IntroductionDespite octogenarians representing an ever-increasing proportion of patients with lung cancer, there is a paucity of evidence describing outcomes after lung resection for these patients. We aimed to evaluate short and mid-term outcomes for octogenarians after lung resection. Materials and MethodsA total of 5,470 consecutive patients undergoing lung resection for primary lung cancer from 2012-2019 in two UK centres were included. Primary outcomes were perioperative, 90-day, and one-year mortality in the octogenarian vs. non-octogenarian cohort. Appropriate statistical tests were used to compare outcomes between octogenarian and non-octogenarian patients. Secondary outcomes were post-operative complications and to validate the performance of the Thoracoscore model in the octogenarian cohort. ResultsOverall, 9.4% (n=513) of patients were aged ≥80. The rates of 90-day mortality, one-year mortality, and post-operative atrial fibrillation were significantly higher for octogenarians. The one-year mortality rate for octogenarians fell significantly over time (2012-2015: 16.5% vs 2016-2019: 10.2%, p=0.034). Subgroup analysis (2016-2019 only) demonstrated no significant difference in peri-operative, 90-day, or one-year mortality between octogenarian and non-octogenarian patients. Validation of the Thoracoscore model demonstrated modest discrimination and acceptable calibration. DiscussionMortality for octogenarians fell significantly over time in this study. Indeed, when confined to the most recent time period, comparable rates of both 90-day and one-year mortality for octogenarian and non-octogenarian patients were seen. Whilst preventative strategies to reduce the incidence of post-operative atrial fibrillation in octogenarians should be considered, these findings demonstrate that following appropriate patient selection, octogenarians can safely undergo lung resection for lung cancer.

Lobar or sublobar resection for early-stage second primary lung cancer ≤ 3 cm in size: a SEER population-based study

PurposeSurgical strategy for second primary lung cancer (SPLC) may be more conservative due to influence of first primary lung cancer (FPLC). The optimal surgical method for SPLC warrants discussion. We aimed to explore a more suitable surgical approach for early-stage (T1-T2N0, ≤ 3 cm) SPLC and provide insights for clinical practice.MethodsA retrospective study was conducted using data from the Surveillance, Epidemiology and End Results database between 2004 and 2018, and data of patients with early-stage SPLC who underwent secondary surgery were collected. Propensity score matching (PSM) reduced potential bias between lobar and sublobar resection groups. The effect of lobar and sublobar resection on overall survival (OS) was assessed in all patients and subgroups.ResultsA total of 714 patients who met the study entry criteria were enrolled, including 476 patients in the sublobar resection group (66.67%) and 238 patients in the lobar resection group (33.33%). There was no difference in OS between the lobar and sublobar resection groups before and after PSM (P = 0.289) and (P = 0.608), respectively. Subgroup analyses showed that lobar resection achieved a significantly better OS than sublobar resection only in patients with an SPLC tumor size of 2–3 cm (P < 0.05).ConclusionThe OS of sublobar resection was not significantly different from that of lobar resection for early-stage SPLC. For SPLC with a 2–3 cm tumor size, lobar resection is more advantageous than sublobar resection.

Impact of skip mediastinal lymph node metastasis on outcomes after resection for primary lung cancer

ObjectivesPatients with non-small cell lung cancer and nodal disease are a heterogeneous group with varied patterns of disease. The aim of this study was to assess long-term outcomes of patients with skip N2 disease in comparison to those with N1 or non-skip N2 disease. Materials and MethodsA retrospective review of 445 patients undergoing anatomical lung resection for primary lung cancer between 2012 and 2019 with post-operative histological confirmation of nodal disease was undertaken. Log rank analysis was used to assess differences in estimated median overall survival according to nodal status. Multivariable Cox regression analysis was performed to determine whether skip N2 disease was independently associated with overall survival. ResultsMean patient age was 67.0 years (standard deviation ± 9.2 years) and 48.1% (n = 214) were male. In total, 20.7% (n = 92) of patients had N1 disease, 32.1% (n = 143) had skip N2 disease and 47.2% (n = 210) had non-skip N2 disease. Post-operative upstaging took place in 33.0% (n = 147) of patients. Median follow-up time was 35 months (interquartile range 14–68 months). Skip N2 patients had significantly longer estimated median overall survival in comparison to their non-skip N2 counterparts (47 months vs 28 months, log rank analysis p = 0.029) and non-skip N2 disease remained independently associated with reduced overall survival after multivariable analysis (hazard ratio 1.421, 95% confidence interval 1.060–1.907, p = 0.019). ConclusionSkip N2 disease is a positive prognostic factor for patients with N2 lung cancer, suggesting that lung cancer staging guidelines should consider separating N2 disease into additional subgroups in order to improve prognostic accuracy.

Significance of programmed death-ligand 1 expression in resected lung cancer and its relationship with EGFR mutation.

Several studies have reported that the high expression of programmed death-ligand 1 (PD-L1) within tumor cells predicts a poor prognosis. However, the relationship between the PD-L1 expression and lymph node metastasis or driver mutations in lung cancer remains poorly understood. A total of 356 consecutive patients who underwent surgical resection for primary lung cancer were included in the study. There were 268 adenocarcinomas including 100 EGFR mutations, 67 squamous cell carcinomas (Sq), and 21 other histologies. The high expression of PD-L1 was defined as a tumor proportion score (TPS) of ≥50. The relationship between the PD-L1 expression and clinicopathological factors and recurrence-free survival (RFS) was analyzed. The PD-L1 expression was high in 75 patients. It was significantly related to smoking history, Sq histology, driver mutation negative, elevated serum carcinoembryonic antigen levels, and lymph node metastasis. Among patients with driver mutations, a high PD-L1 TPS was found in patients with EGFR G719X mutation. A significant difference in RFS was observed in adenocarcinoma patients. A multivariate analysis of adenocarcinoma cases revealed that tumor size and lymph node metastasis were independent prognostic factors for poor RFS, while the PD-L1 expression was not. A logistic regression analysis revealed that the absence of driver mutations, lymph node metastasis, and a history of smoking were significantly associated with the high expression of PD-L1. Lymph node metastasis was positively related with the high expression of PD-L1, resulting in poor RFS. A high PD-L1 TPS was observed in patients with the EGFR G719X mutation.

Segmentectomy versus lobectomy in the United States: Outcomes after resection for first primary lung cancer and treatment patterns for second primary lung cancers

ObjectiveThe study objective was to identify whether the results of JCOG0802 could be generalized to US clinical settings. MethodsPatients diagnosed with clinical stage IA (≤2 cm) non–small cell lung cancer who underwent segmentectomy versus lobectomy (2004-2017) in the National Cancer Database were identified. Overall survival of patients in the National Cancer Database was assessed using propensity score–matched analysis. A separate analysis of the Surveillance Epidemiology End Results database was conducted to evaluate treatment patterns of second primary lung cancers among patients who underwent segmentectomy versus lobectomy for a first primary lung cancer. ResultsOf the 23,286 patients in the National Cancer Database meeting inclusion criteria, 1397 (6.0%) underwent segmentectomy and 21,889 (94.0%) underwent lobectomy. In a propensity score–matched analysis of all patients in the study cohort, there were no significant differences in overall survival between patients undergoing segmentectomy versus lobectomy (5-year overall survival: 79.9% [95% CI, 76.7%-82.0%] vs 81.8% [95% CI, 78.7%-84.4%], log-rank: P = .72). In subgroup analyses by tumor grade and histologic subtype, segmentectomy was associated with similar overall survival compared with lobectomy in all subgroups evaluated. In a propensity score–matched analysis of patients in the Surveillance Epidemiology End Results database, there were no significant differences in treatment patterns of second primary lung cancers between patients who underwent segmentectomy and patients who underwent lobectomy for their first primary lung cancer. ConclusionsIn this national analysis of US patients diagnosed with stage IA (≤2 cm) non–small cell lung cancer, there were no significant differences in overall survival between segmentectomy and lobectomy in the overall cohort or in subgroup analyses by tumor grade or histologic subtype.

Diagnostic gastrointestinal markers in primary lung cancer and pulmonary metastases.

Histopathological diagnosis of pulmonary tumors is essential for treatment decisions. The distinction between primary lung adenocarcinoma and pulmonary metastasis from the gastrointestinal (GI) tract may be difficult. Therefore, we compared the diagnostic value of several immunohistochemical markers in pulmonary tumors. Tissue microarrays from 629 resected primary lung cancers and 422 resected pulmonary epithelial metastases from various sites (whereof 275 colorectal cancer) were investigated for the immunohistochemical expression of CDH17, GPA33, MUC2, MUC6, SATB2, and SMAD4, for comparison with CDX2, CK20, CK7, and TTF-1. The most sensitive markers for GI origin were GPA33 (positive in 98%, 60%, and 100% of pulmonary metastases from colorectal cancer, pancreatic cancer, and other GI adenocarcinomas, respectively), CDX2 (99/40/100%), and CDH17 (99/0/100%). In comparison, SATB2 and CK20 showed higher specificity, with expression in 5% and 10% of mucinous primary lung adenocarcinomas and both in 0% of TTF-1-negative non-mucinous primary lung adenocarcinomas (25-50% and 5-16%, respectively, for GPA33/CDX2/CDH17). MUC2 was negative in all primary lung cancers, but positive only in less than half of pulmonary metastases from mucinous adenocarcinomas from other organs. Combining six GI markers did not perfectly separate primary lung cancers from pulmonary metastases including subgroups such as mucinous adenocarcinomas or CK7-positive GI tract metastases. This comprehensive comparison suggests that CDH17, GPA33, and SATB2 may be used as equivalent alternatives to CDX2 and CK20. However, no single or combination of markers can categorically distinguish primary lung cancers from metastatic GI tract cancer.

Comparison of stereotactic body radiation therapy versus surgery for multiple primary lung cancers after prior radical resection: A multicenter retrospective study

BackgroundPatients who previously underwent surgical resection of initial primary lung cancer are at a high risk of developing multiple primary lung cancers (MPLCs). The purpose of this study was to compare the efficacy and safety between stereotactic body radiation therapy (SBRT) and surgery for MPLCs patients after prior radical resection for the first lung cancers. MethodsIn this multicenter retrospective study, eligible MPLC patients with tumor diameter of 5.0 cm or less at N0M0 who underwent SBRT or reoperation between January 2013 and August 2020 were enrolled. The primary endpoint was the 3-year locoregional recurrence and treatment-related toxicity. Kaplan-Meier method was used to calculate survival rates. The χ2 test was adapted to assess the difference of categorical variables between the two subgroup patients. ResultsA total of 203 (73 in the SBRT group and 130 in the surgery group) patients from three academic cancer centers were evaluated with a median follow-up of 38.3 months. The cumulative 1-, 2-, and 3-year incidences of locoregional recurrence were 5.6 %, 7.0 % and 13.1 % in the SBRT group versus 3.2 %, 4.8 % and 7.4 % in the surgery group, respectively [hazard ratio (HR), 1.97; 95 % confidence interval (CI), 0.74–5.24; P = 0.14]. The cancer-specific survival rates were 95.9 %, 94.5 % and 88.1 % versus 96.9 %, 94.6 % and 93.8 % in the SBRT and surgery groups respectively (HR, 1.72; 95 % CI, 0.67–4.44; P = 0.23). In the SBRT group, two patients (2.7 %) suffered from grade 3 radiation pneumonitis, while in the surgery group, grade 3 complications occurred in four (3.1 %) patients, and four cases were expired due to pneumonia or pulmonary heart disease within 90 days after surgery. ConclusionsSBRT is an effective therapeutic option with limited toxicity compared to surgery for patients with MPLCs after prior radical surgical resection, and it could be considered as an alternative treatment for those patients.

Restrictive Ventilatory Impairment as a Poor Prognostic Factor in Patients Who Undergo Surgical Resection for Metachronous Second Primary Lung Cancer.

To evaluate the prognostic impact of restrictive ventilatory impairment in patients who undergo pulmonary resection of metachronous second primary lung cancer. The clinical characteristics and surgical outcomes of 70 patients with metachronous second primary lung cancer were analyzed. The surgical procedures consisted of wedge resection in 40 patients, segmentectomy in 17, lobectomy in 12, and completion pneumonectomy in one. Patients who underwent ipsilateral pulmonary resection developed more perioperative complications (p = 0.0339). Three-year and 5-year overall survival rates were 78.2% and 69.2%, respectively. In univariate analysis, sex, restrictive ventilatory impairment, and histology of second primary lung cancer were significantly poor prognostic factors (all p <0.05). Multivariate analysis identified restrictive ventilatory impairment to be an independent predictor of a poor prognosis (p = 0.0193). In the 22 patients who died, the cause of death was lung cancer in 11 and other diseases, including pneumonia and respiratory failure, in 11. Death from another disease was significantly more common in patients with restrictive ventilatory impairment (p = 0.0216). Restrictive ventilatory impairment was an independent predictor of a poor prognosis in patients with a second primary lung cancer. Restrictive ventilatory impairment as a result of repeated thoracic surgery may increase the likelihood of death from another disease.

Theranostics application of tumor-initiating cell probe TiY in non-small cell lung cancer.

Background: Tumor-initiating cells (TIC) often elude conventional cancer treatment, which results in metastasis and cancer relapse. Recently, studies have begun to focus on the TIC population in tumors to provide better therapeutic options. Previously, we have reported the successful development of a TIC-specific probe TiY with the binding target as vimentin. While a low concentration of TiY showed a TIC visualization, at a high concentration, TiY induced selective toxicity onto TIC in vitro. In this study, we aim to assess TiY's applicability in theranostics purposes, from in vivo visualization to therapeutic effect toward TIC, in cancer mouse models. Methods: We performed cell experiments with the TIC line model derived from resected primary non-small cell lung cancer (NSCLC) patient tumor. The animal model studies were conducted in mice of NSCLC patient-derived xenograft (PDX). TiY was intravenously delivered into the mice models at different concentrations to assess its in vivo TIC-selective staining and therapeutic effect. Results: We demonstrated the TIC-selective identification and therapeutic effect of TiY in animal models. TiY treatment induced a significant ablation of the TIC population in the tumor, and further molecular study elucidated that the mechanism of TiY is through vimentin dynamics in TIC. Conclusion: The results underscore the applicability of TiY for cancer treatment by selectively targeting soluble vimentin in TIC.

Usefulness of serum S100A4 and positron-emission tomography on lung cancer accompanied by interstitial pneumonia.

The S100 calcium-binding protein A4 (S100A4) and the accumulation of [18F]-fluoro-2-deoxy-D-glucose (FDG) in noncancerous interstitial pneumonia (IP) area are predictors of postoperative acute exacerbation (AE) of IP after pulmonary resection for lung cancer with IP. However, the significance of combining these markers for predicting short-term outcome and long-term prognosis is not known. Patients diagnosed with IP on preoperative high-resolution computed tomography and who had undergone pulmonary resection for primary lung cancer between April 2010 and March 2019 at Hiroshima University were included in this study. Predictive factors for the cumulative incidence of death from other than lung cancer (CIDOL) were investigated using the Fine and Gray model. CIDOL, perioperative outcome, and cumulative incidence of all death (CIAD) were retrospectively compared based on serum S100A4 and FDG accumulation. A total of 121 patients were included in this study. High S100A4 (hazard ratio [HR], 2.541; p=0.006) and FDG accumulation (HR, 3.199; p=0.038) were significant predictors of CIDOL. AE of IP occurred only in patients with high S100A4/FDG (+). CIDOL of patients with high S100A4/FDG (+) was higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) (p < 0.001), and CIAD of patients with high S100A4/FDG (+) was also higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) patients (p=0.021). Serum S100A4 and FDG accumulation in the noncancerous IP area were significant predictors of CIDOL after lung resection for lung cancer with IP and may help decide the treatment strategy.

Long-term Surgical Outcomes in Oligometastatic Non-small Cell Lung Cancer: A Single-Center Study

We reviewed the clinical outcomes of patients with oligometastatic (OM) non-small cell lung cancer (NSCLC) who received multimodal therapy including lung surgery. We retrospectively analyzed 117 patients with OM NSCLC who underwent complete resection of the primary tumor from 2014 to 2017. The median follow-up duration was 2.91 years (95% confidence interval, 1.48-5.84 years). The patients included 73 men (62.4%), and 76 patients (64.9%) were under the age of 65 years. Based on histology, 97 adenocarcinomas and 14 squamous cell carcinomas were included. Biomarker analysis revealed that 53 patients tested positive for epidermal growth factor receptor, anaplastic lymphoma kinase, or ROS1 mutations, while 36 patients tested negative. Metastases were detected in the brain in 74 patients, the adrenal glands in 12 patients, bone in 5 patients, vertebrae in 4 patients, and other locations in 12 patients. Radiation therapy for organ metastasis was performed in 81 patients and surgical resection in 27 patients. The 1-year overall survival (OS) rate in these patients was 82.8%, and the 3- and 5-year OS rates were 52.6% and 37.2%, respectively. Patients with positive biomarker test results had 1-, 3-, and 5-year OS rates of 98%, 64%, and 42.7%, respectively. These patients had better OS than those with negative biomarker test results (p=0.031). Patients aged ≤65 years and those with pT1-2 cancers also showed better survival (both p=0.008). Surgical resection of primary lung cancer is a viable treatment option for selected patients with OM NSCLC in the context of multimodal therapy.

The majority of patients with resectable incidental lung cancers are ineligible for lung cancer screening

ObjectiveThe study objective was to determine what proportion of asymptomatic patients had resectable lung cancer detected through lung cancer screening versus incidentally. MethodsWe performed a retrospective study of patients who underwent resection for lung cancer between January 2015 and December 2020. We then assessed whether asymptomatic patients with incidentally found lung cancers were eligible for lung cancer screening using the National Comprehensive Cancer Network, United States Preventive Services Task Force, Centers for Medicare & Medicaid Services, American College of Chest Physicians, American Cancer Society, and American Society of Clinical Oncology guidelines. ResultsOf 539 patients who underwent resection for primary lung cancer, 437 (81%) were asymptomatic and 355 (66%) of these patients had lung cancer found discovered incidentally. Of the 355 patients with incidentally detected lung cancer, 10 were excluded for insufficient data. Of the remaining 345 patients, 110 (32%) would have been eligible for screening using National Comprehensive Cancer Network guidelines, 65 (19%) using 2021 United States Preventive Services Task Force guidelines, 53 (15%) using 2013 United States Preventive Services Task Force guidelines, 64 (19%) using 2022 Centers for Medicare & Medicaid Services guidelines, 52 (15%) using 2015 Centers for Medicare & Medicaid Services/American College of Chest Physicians guidelines, and 45 (13%) using American Cancer Society/American Society of Clinical Oncology guidelines. Of the 280 patients who were screen ineligible by 2021 United States Preventive Services Task Force criteria, 143 patients (51%) never smoked, 112 patients (40%) quit smoking more than 15 years ago, 89 patients (32%) did not smoke at least 20 pack-years, and 44 patients (16%) were ineligible due to age. ConclusionsThe majority of asymptomatic patients with resectable lung cancers had lung cancer identified incidentally and not through lung cancer screening. Most of these patients were not eligible for screening under current guidelines. This study suggests a need for improved lung cancer screening implementation and further investigation in the identification and assessment of risk factors for lung cancer.

Predicting pathological highly invasive lung cancer from preoperative [18F]FDG PET/CT with multiple machine learning models

PurposeThe efficacy of sublobar resection of primary lung cancer have been proven in recent years. However, sublobar resection for highly invasive lung cancer increases local recurrence. We developed and validated multiple machine learning models predicting pathological invasiveness of lung cancer based on preoperative [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) radiomic features.MethodsOverall, 873 patients who underwent lobectomy or segmentectomy for primary lung cancer were enrolled. Radiomics features were extracted from preoperative PET/CT images with the PyRadiomics package. Seven machine learning models and an ensemble of all models (ENS) were evaluated after 100 iterations. In addition, the probability of highly invasive lung cancer was calculated in a nested cross-validation to assess the calibration plot and clinical usefulness and to compare to consolidation tumour ratio (CTR) on CT images, one of the generally used diagnostic criteria.ResultsIn the training set, when PET and CT features were combined, all models achieved an area under the curve (AUC) of ≥ 0.880. In the test set, ENS showed the highest mean AUC of 0.880 and smallest standard deviation of 0.0165, and when the cutoff was 0.5, accuracy of 0.804, F1 of 0.851, precision of 0.821, and recall of 0.885. In the nested cross-validation, the AUC of 0.882 (95% CI: 0.860–0.905) showed a high discriminative ability, and the calibration plot indicated consistency with a Brier score of 0.131. A decision curve analysis showed that the ENS was valid with a threshold probability ranging from 3 to 98%. Accuracy showed an improvement of more than 8% over the CTR.ConclusionThe machine learning model based on preoperative [18F]FDG PET/CT images was able to predict pathological highly invasive lung cancer with high discriminative ability and stability. The calibration plot showed good consistency, suggesting its usefulness in quantitative risk assessment.