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Purpose To evaluate postoperative patient-reported quality of life (QOL) and pain with and without a metal rib spreader (MRS) in patients with stage I lung cancer who underwent lobectomy through axillary mini-thoracotomy (AMT). Methods This single-institution prospective observational study enrolled patients between January 2015 and April 2018. Their QOL and pain were evaluated using the EQ-5D and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30 items (QLQ-C30). The EQ-5D was completed preoperatively (Pre) and on days 1/3/5/7 (D1/3/5/7), at 1 month (M1), and at 1 year postoperatively (Y1). The EORTC QLQ-C30 was completed at Pre, M1, and Y1. Results The data of 140 patients were analyzed (video-assisted without MRS: VA/noMRS: 67, AMT with MRS: AMT/MRS: 73). Although the AMT/MRS group had more preoperative comorbidities, longer operative times, and more blood loss than the VA/noMRS group, the EQ-5D visual analog scale scores were not significantly different at any assessment point (Pre/D1/D3/D5/D7/M1/Y1) (VA/noMRS: 82/48/60/67/73/77/85, AMT/MRS: 80/46/60/66/73/76/85). Postoperative pain in the EQ-5D descriptive system and the EORTC QLQ-C30 was comparable between the groups. Conclusion VA/noMRS and AMT/MRS showed similar postoperative QOL and pain scores, indicating that MRS negligibly impacts the postoperative QOL and pain.

Background Early detection of lung cancer in asymptomatic patients remains challenging, especially for stage I. Considering the substantial interaction with tumor immunogenicity, we hypothesized that lung cancer-associated TCR (LC-aTCR) may serve as potential biomarker in early detection of stage I lung cancer. Methods Individuals who received low-dose computed tomography (LDCT) screening were enrolled in the study. Surgical tissues and peripheral blood specimens were collected and performed with DNA-based T cell repertoire (TCR) sequencing. The motif-based algorithm was used to deconstruct specific lung cancer-associated TCRs (LC-aTCRs). Results A total of 146 individuals participating in the real-world LDCT screening project were enrolled in this study, including 52 patients with pathologically-confirmed stage I lung cancer and 94 non-cancer controls. We developed a motif-based algorithm to define 80 LC-aTCRs in the training cohort. Moreover, in the validation cohort, high sensitivity and specificity was showed in stage I lung cancer with 72% and 91% respectively, and the AUC of the ROC curve was 0.91 (95% CI: 0.85 ∼ 0.96). Conclusion This work provides inspiration for stage I lung cancer detection by using blood TCR profiling data. The combination of TCR-based assay and routine screening deserves further testing in larger cohorts.

Objectives The prognostic role of interstitial pneumonia with emphysema in lung cancer is not fully understood. This study aimed to examine the prognostic role of the presence of emphysema in patients with clinical stage I lung cancer and interstitial pneumonia. Methods The presence of interstitial pneumonia and emphysema was evaluated on preoperative high-resolution computed tomography. In total, 836 consecutive patients with clinical stage I lung cancer who underwent complete resection between April 2007 and March 2016 were retrospectively analyzed using the log-rank test and Cox proportional hazard model to examine survival differences. Results There was a significant difference in 5-year overall survival between patients with interstitial pneumonia and emphysema (n = 65) and those without (n = 771) (62.6% vs. 86.5%; P Conclusions The presence of emphysema was not an independent prognostic factor for overall survival in patients with clinical stage I lung cancer with interstitial pneumonia. Poor survival of patients with IP and emphysema may be due to the presence of interstitial pneumonia.

Background Although sublobar resection has become widely used for lung cancer treatment, very limited data comparing outcomes following complex segmentectomy or wedge resection have been available. Questions remain regarding mortality, morbidity, surgical margin, lymph node dissection, and long-term survival outcomes. This study compares operative and postoperative outcomes of complex segmentectomy and wedge resection. Patients and Methods A total of 216 patients with clinical stage I lung cancer who underwent complex segmentectomy (n = 110) or wedge resection (n = 106) between April 2007 and March 2017 were retrospectively reviewed, and 61 propensity score–matched pairs were analyzed. Operative and postoperative results were compared. Factors affecting survival were assessed using the Kaplan-Meier method. Results Although the complex segmentectomy group tended to have higher overall complications (26.2% vs. 16.4%; P = .27) and prolonged air leakage (11.5% vs. 6.6%; P = .53) rates than the wedge resection group, major complications (≥grade IIIa) (0% vs. 3.3%; P = .50) and 30-day mortality (0% vs. 0%; P = 1.00) rates were comparable between both groups. Complex segmentectomy provided better median surgical margin distance (15.0 vs. 10.0 mm; P = .052) and number of dissected lymph nodes (6.0 vs. 0.0 nodes; P = .0002) than wedge resection. The complex segmentectomy group tended to have better prognosis than the wedge resection group (5-year overall survival rates, 94.7% vs. 79.4% and 5-year recurrence-free survival rates, 94.0% vs. 76.5%, respectively). Conclusions Complex segmentectomy could provide better oncological and survival outcomes with acceptable perioperative safety compared with wedge resection.

Background Complex segmentectomy creates several intricate intersegmental planes; however, it has not been fully established in lung cancer treatment. We compared the oncologic outcomes of complex segmentectomy and lobectomy through a large cohort, multicenter database using propensity score-matched analysis. Methods We retrospectively analyzed data from 1517 patients with clinical stage I lung cancer with a solid component size 2.0 cm or less, who underwent surgical resection at 3 institutions between 2010 and 2018. Complex segmentectomy (n = 240) and location-adjusted lobectomy (n = 851) as well as surgical results were analyzed for all patients and their propensity score-matched pairs. Results The prognosis of patients undergoing complex segmentectomy was not significantly different from that of patients undergoing lobectomy (5-year cancer-specific survival [CSS] rate, 96.4% versus 97.2%, P = .69; and 5-year recurrence-free interval [RFI] rate, 95.8% versus 93.4%, P = .19). This trend was also identified in subanalyses for pure solid tumors. However, there were major differences in clinicopathologic features between the 2 groups. After propensity score-matched analysis, proper matching of patients was ascertained. In 219 propensity score-matched pairs, long-term outcomes were similar between patients undergoing complex segmentectomy (5-year CSS, 96.0%; 5-year RFI, 95.5%) and lobectomy (5-year CSS, 97.8%; 5-year RFI, 95.9%). Propensity score-adjusted multivariable analysis for RFI revealed that prognosis associated with complex segmentectomy was comparable to the prognosis obtained with lobectomy (hazard ratio = 0.98; 95% confidence interval, 0.33-2.40; P = .98). Conclusions Complex segmentectomy provides acceptable oncologic outcomes in clinical stage I lung cancer treatment.

Circulating tumour cells (CTCs) were enriched in the peripheral blood of four patients with Stage I non-small cell lung cancer (NSCLC). Octamer-binding transcription factor-4 positive (OCT4+) and negative (OCT4−) CTCs were identified and captured by interphase fluorescence in situ hybridisation (iFISH). Single cell whole exome sequencing (WES) was performed and the corresponding bioinformatics data were analysed. OCT4+ cells were successfully detected in peripheral blood collected from all four Stage I lung cancer patients. Moreover, the tumour mutational burden (TMB) values observed for OCT4+ samples from the same patients were slightly smaller than those of the OCT4− samples; the difference was not statistically significant (P> 0.05). Thirteen and six characteristic mutations were found in negative samples and positive samples, respectively. The findings indicate that this methodology provides a potential diagnostic index for the early detection of NSCLC.

This study evaluated the correlation between radiation-induced lung injury (RILI) and dosimetric parameters on computed tomography (CT) images of stage I non-small cell lung cancer (NSCLC) patients undergoing intensity-modulated radiotherapy (IMRT). Sixty-three stage I NSLC patients who underwent IMRT were enrolled in the study. The patients underwent CT within 6 months (acute phase) and 1.5 years (late phase) after radiotherapy. These were fused with the planned irradiation CT. The range of RILI was measured from 10% to 100%, with an IC in 10% increments. The median interval from completion of radiotherapy to acute and late phase CT was 92 and 440 days, respectively. The median RILI ranges of the acute and late phases were in the 80% (20–100%) and 70% dose regions (20–100%), respectively. The significantly narrower range of RILI when lung V20 in the acute phase was less than 19.2% and that of V5 in the late phase was less than 27.6% at the time of treatment planning. This study showed that RILI occurred in a localized range in stage I NSCLC patients who underwent IMRT. The range of RILI was correlated with V20 in the acute phase and V5 in the late phase.KEY MESSAGESRILI correlated with V20 in acute and V5 in late phase.The shadow of RILI occurred in 80% dose region in acute and 70% in late phase.No relationship exists between radiographic changes in RILI and PTV volume. RILI correlated with V20 in acute and V5 in late phase. The shadow of RILI occurred in 80% dose region in acute and 70% in late phase. No relationship exists between radiographic changes in RILI and PTV volume.

Purpose The use of three-dimensional (3D) thoracoscope provides improved depth perception and accuracy in video-assisted thoracoscopic surgery (VATS). This study aimed to compare the surgical outcomes between two-dimensional (2D) and 3D VATS lobectomy for stage I lung cancer. Methods From January 2013 to May 2018, 354 patients underwent VATS lobectomy and mediastinal lymph node dissection for clinical stage I lung cancer. The 3D VATS system was introduced in July 2016 in our center. A total of 182 patients underwent 2D VATS lobectomy from January 2013 to June 2016, and 172 patients underwent 3D VATS lobectomy from July 2016 to May 2018. Results The thoracotomy conversion rate was lower (1.2% vs. 6.4%, P= 0.011) in the 3D VATS group than in the 2D VATS group. Operation time (mean: 119.0 minutes vs. 151.4 minutes, P< 0.001), operative blood loss (median: 100 mL vs. 150 mL, P< 0.001), and length of hospital stay after surgery (median: 5 days vs. 6 days, P< 0.001) were significantly lower in the 3D VATS group than in the 2D VATS group. A higher number of lymph nodes was resected in 3D VATS (mean: 15.9 vs. 13.8, P= 0.006). No significant difference was observed between 3D and 2D VATS in terms of operative complications (Clavien-Dindo classification grade ≥ 1; 14.7% vs. 14.6%, P= 0.322). None of the patients died postoperatively. Conclusion Our retrospective data showed that the 3D thoracoscope had better surgical outcomes than 2D thoracoscope for VATS lobectomy in patients with clinical stage I lung cancer.

Background: Comorbidity is an important prognostic marker and a treatment indicator for lung cancer patients. Register-based studies often describe the burden of comorbidity by the Charlson comorbidity index (CCI) based on hospital discharge data. We assessed the association between somatic and psychiatric comorbidity and death within one year in early lung cancer and, furthermore, the burden of comorbidity according to treatment type. Material and methods: We conducted a population-based matched case-control study of stage I lung cancer identifying all treated patients who died (all-cause) within one year after diagnosis (early death group, cases). On the basis of data from the Danish Lung Cancer Registry these patients were then matched with two controls who survived more than one year (survivors). Through a review of the medical records, we validated inclusion criteria and collected data on somatic and psychiatric comorbidity. We assessed the association between comorbidity and early death with multivariate conditional logistic regression. Results: We included 221 cases and 410 controls. The mean CCI score in the early death group was 2.3 vs. 1.3 in the survivor group (p

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: does percutaneous transthoracic needle biopsy (PTNB) increase the risk of pleural recurrence in patients with stage I lung cancer? Altogether, 298 papers were found using the reported search, of which 7 cohort studies and 1 meta-analysis represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Four cohort studies suggested an association between PTNB and pleural recurrence in patients with stage I lung cancer, while the other 3 cohort studies found that PTNB had no impact. One meta-analysis (the largest study) including 5 of the cohort studies above concluded that PTNB increased the risk of pleural recurrence among patients with stage I lung cancer with subpleural lesions. Based on the available evidence, it was suggested that there may be an association between PTNB and pleural recurrence in patients with stage I lung cancer, especially for patients with subpleural lesion.

Early detection of lung cancer has a higher likelihood of curative treatment and thus improves survival rate. Low-dose computed tomography (LDCT) screening has been shown to be effective for high-risk individuals in several clinical trials, but has high false positive rates. To evaluate the risk of stage I lung cancer in the general population not limited to smokers, a retrospective study of 133 subjects was conducted in a medical center in Taiwan. Regularized regression was used to build the risk prediction model by using LDCT and health examinations. The proposed model selected seven variables related to nodule morphology, counts and location, and ten variables related to blood tests and medical history, achieving an area under the curve (AUC) value of 0.93. The higher the age, white blood cell count (WBC), blood urea nitrogen (BUN), diabetes, gout, chronic obstructive pulmonary disease (COPD), other cancers, and the presence of spiculation, ground-glass opacity (GGO), and part solid nodules, the higher the risk of lung cancer. Subjects with calcification, solid nodules, nodules in the middle lobes, more nodules, and diseases related to thyroid, liver, and digestive systems were at a lower risk. The selected variables did not indicate causation.

Background For stage I non-small cell lung cancer (NSCLC), lobectomy and segmentectomy are still controversial operations. Extended segmentectomy was proposed to make larger safe margins than segmentectomy. Image-guided video-assisted thoracoscopic surgery (iVATS) is useful to accomplish extended segmentectomy. We aimed to compare the effects of iVATS extended segmentectomy to the effects of traditional segmentectomy for stage I NSCLC. Methods This study is a retrospective analysis in a single institute. Patients with stage I NSCLC who received segmentectomy between January 2017 and September 2020 were included. Patients were distributed to iVATS extended segmentectomy (group A), and traditional segmentectomy (group B). The impacts of the different surgical methods on resection margin were assessed. Results There were 116 patients enrolled in this study. Sixty-two patients distributed in group A, and the other 54 patients in group B. The resection margin to a staple line was 17.94 mm in group A versus 14.15 mm in group B, p = 0.037. The margin/tumor diameter ratio was 2.08 in group A versus 1.39 in group B, p = 0.003. The enough margin rate was 75.81% and 57.41%, respectively, for group A and group B. The subgroup analysis of iVATS extended segmentectomy showed that T1a lesions had larger margin distances than did T1b lesions (19.85 mm vs. 14.83 mm, p = 0.026). Conclusions The iVATS extended segmentectomy can provide more resection margin than traditional segmentectomy. Segmentectomy is more suitable to perform when the nodule’s diameter is less than 10 mm.

Introduction With advances in treatments among patients with lung cancer, it is increasingly important to understand patients’ values and preferences to facilitate shared decision making. Methods Prospective, multicenter study of patients with treated stage I lung cancer. At the time of study participation, participants were 4–6 months posttreatment. Value clarification and discrete choice methods were used to elicit participants’ values and treatment preferences regarding stereotactic body radiation therapy (SBRT) and surgical resection using only treatment attributes. Results Among 114 participants, mean age was 70 years (Standard Deviation = 7.9), 65% were male, 68 (60%) received SBRT and 46 (40%) received surgery. More participants valued independence and quality of life (QOL) as “most important” compared to survival or cancer recurrence. Most participants (83%) were willing to accept lung cancer treatment with a 2% chance of periprocedural death for only one additional year of life. Participants also valued independence more than additional years of life as most (86%) were unwilling to accept either permanent placement in a nursing home or being limited to a bed/chair for four additional years of life. Surprisingly, treatment discordance was common as 49% of participants preferred the alternative lung cancer treatment than what they received. Conclusions Among participants with early stage lung cancer, maintaining independence and QOL were more highly valued than survival or cancer recurrence. Participants were willing to accept high periprocedural mortality, but not severe deficits affecting QOL when considering treatment. Treatment discordance was common among participants who received SBRT or surgery. Understanding patients’ values and preferences regarding treatment decisions is essential to foster shared decision making and ensure treatment plans are consistent with patients’ goals. Clinicians need more resources to engage in high quality communication during lung cancer treatment discussions.

The role of anatomic segmentectomy as an acceptable, lung parenchymal sparing alternative to pulmonary lobectomy for the small peripheral stage I lung cancer is under great scrutiny today. This is not a new consideration, particularly for the patient with impaired cardiopulmonary reserve where preservation of lung function may be a critical issue in deciding on surgical resection for local/regional control of their cancer. In this review, we discuss the oncologic issues along with past and present evidence supporting “anatomic” lung preservational surgery in the management of lung cancer.

OBJECTIVES Rheumatic heart disease (RHD) affects >33 000 000 individuals, mostly from low- and middle-income countries. The Cape Town Declaration on Access to Cardiac Surgery in the Developing World was published in August 2018, signalling the commitment of the global cardiac surgery and cardiology communities to improving care for patients with RHD. METHODS As the Cape Town Declaration formed the basis for which the Cardiac Surgery Intersociety Alliance (CSIA) was formed, the purpose of this article is to describe the history of the CSIA, its formation, ongoing activities and future directions, including the announcement of selected pilot sites. RESULTS The CSIA is an international alliance consisting of representatives from major cardiothoracic surgical societies and the World Heart Federation. Activities have included meetings at annual conferences, exhibit hall participation for advertisement and recruitment and publication of selection criteria for cardiac surgery centres to apply for CSIA support. Criteria focused on local operating capacity, local championing, governmental and facility support, appropriate identification of a specific gap in care and desire to engage in future research. Eleven applications were received for which 3 finalist sites were selected and site visits conducted. The 2 selected sites were Hospital Central Maputo (Mozambique) and King Faisal Hospital Kigali (Rwanda). CONCLUSIONS Substantial progress has been made since the passing of the Cape Town Declaration and the formation of the CSIA, but ongoing efforts with collaboration of all committed parties—cardiac surgery, cardiology, industry and government—will be necessary to improve access to life-saving cardiac surgery for patients with RHD.

BACKGROUND: Video-assisted thoracic surgery (VATS) is increasingly used in the surgical treatment of early lung cancer, but the oncological benefits are still controversial. We aimed to compare video-assisted lobectomy and open thoracotomy lobectomy in terms of lymphadenectomy and long-term survival depending on the location of lobectomy. METHODS: A retrospective, multicenter study was based on the Polish Lung Cancer Study Group and included patients with stage I lung cancer who were surgically treated between 2007 and 2015. We included 1410 patients after video-assisted lobectomy and 4,855 after open thoracotomy. RESULTS: The average number of lymph nodes removed in video-assisted lobectomy was 10.9 and in open thoracotomy lobectomy was 12.9 (P

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been widely used in the lung resections. Reports regarding three-dimension (3D) single-port VATS are very limited. The purpose of this study is to evaluate the perioperative outcomes of 3D single-port VATS in a single medical center. METHODS: Totally 523 clinical stage I lung cancer patients underwent surgical resection through VATS operation between September 2016 and October 2017 in our single institution were retrospectively collected and 374 were enrolled. The comparison between 3D single-port VATS and conventional VATS (c-VATS), single-port VATS was conducted focusing on intraoperative and postoperative outcomes. Continuous and categorical variables were analyzed through SPSS software. RESULTS: The 3D singe-port VATS demonstrated no significant difference neither on the intraoperative outcomes including the operative time and the intraoperative blood loss nor the postoperative outcomes including the length of drainage duration and postoperative complications when against c-VATS and single-port VATS. Besides, 3D singe-port VATS elucidated comparable ability of lymph node dissection with c-VATS in subgroup analysis (P=0.192), both of which were better than single-port VATS group (P

We aimed to validate the clinicopathologic characteristics and prognostic value of the presence of solid components in the mediastinal window of computed tomography scan in clinical stage I pulmonary subsolid nodules (SSNs).We retrospectively evaluated patients with pulmonary SSNs resected between 2011 and 2016. We classified SSNs into heterogeneous ground-glass nodules (HGGNs) (solid component detected only in lung window) and part-solid nodules (PSNs) (solid component detected both in lung/mediastinal windows).A total of 487 patients (216 PSNs) were included. PSNs were associated with higher frequencies of micropapillary or solid pathologic patterns (18.1% vs. 3.3%; P.001), epidermal growth factor receptor gene mutation (39.4% vs. 32.8%), and other types of gene mutations (2.3% vs. 1.1%; P = .043). Logistic regression analysis revealed that male sex (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.20-5.57; P = .016) and higher consolidation tumor ratio (CTR) (OR, 110.04; 95% CI, 8.56-1414.39; P.001) remained independent for invasive adenocarcinomas with poor differentiation. Receiver operating characteristic analyses revealed that solid component size in the mediastinal window (area under the curve [AUC], 0.731; 95% CI, 0.653-0.808; P.0001) showed a better predictive ability to poor differentiation compared with solid component size in the lung window and CTR. The 5-year recurrence-free survival (RFS) rate of PSNs was worse than that of HGGNs (94.6% vs. 99.1%; P = .019). Multivariate Cox regression revealed that positive lymph node status (hazard ratio, 22.99; 95% CI, 4.52-116.86; P.001) indicated worse RFS for PSNs.SSNs with solid components in mediastinal window demonstrated clinicopathologic and prognostic features different from those without in clinical stage I lung cancer. Solid components in mediastinal window was a strong predictor of poor differentiation.

INTRODUCTION: A large proportion of stage I cancers are found incidentally, which appears to be a prognostic factor. We investigated stage I lung cancers according to whether, or not, there had been clinical suspicion of lung cancer prior to referral and to see, if we could detect any difference regarding patient characteristics, work-up and mortality for incidental vs non-incidental findings as well as for asymptomatic vs symptomatic patients.METHODS: Medical records and referral documents for 177 patients diagnosed with stage I lung cancer were reviewed and divided based on whether the initial CT scan leading to diagnosis had been made due to suspicion of lung cancer or not. Patient characteristics and mortality between groups were compared, as well as mortality between patients with and without symptoms at the time of diagnosis.RESULTS: One-hundred-and-eight patients were diagnosed incidentally, while 69 patients were non-incidental findings. Among the incidental findings, 55% had no symptoms, whereas none in the non-incidental group were asymptomatic. Personal characteristics were comparable between the groups. Significantly more patients in the incidental group had malignant comorbidity. Non-malignant chronic co-morbidity was more prevalent in the non-incidental group, in particular lung disease. There was no difference in tumour size, histology, or survival for incidental vs non-incidental or for asymptomatic vs symptomatic patients.CONCLUSION: A large proportion of stage I lung cancers are found incidentally, especially in patients with malignant co-morbidity. We found no difference in survival to indicate that we did or should handle these patient groups differently.

BACKGROUND: Considering the complexity of vascular or bronchial variations and the difficulty of nodule localization during segmental resection, the three-dimensional (3D) reconstruction and printing model can provide a guarantee for safe operation and, to some extent, can simplify the surgical procedure. We conducted this study to estimate the avail of 3D reconstruction and personalized model in anatomical partial-lobectomy (APL). METHODS: We prospectively collected and retrospectively reviewed the data of 298 cases who underwent APL in our institute from April 2017 to May 2019. The patients were divided into “3D-reconstruction” group (131 patients), “3D model” group (31 patients) and “non-3D” group (136 patients). We adopted the ANOVA analysis and Chi-square test to compare the perioperative data between the three groups. Subjective satisfaction questionnaires for surgeons were provided to evaluate the value of personalized 3D printed model. RESULTS: The proportion of complex segmentectomy in 3D model group (87.1%) was significantly higher than that in the 3D-reconstruction group (60.3%) and non-3D group (55.9%) (P=0.006), and the average operation time of complex segmentectomy in 3D model group (99.56 minutes) was significantly shorter than that of the other group (all P

Background Postoperative prognosis of stage I non-small cell lung cancer (NSCLC) undergoing lymph node dissection is heterogeneous. Therefore, we sought to construct a novel survival prediction model for stage I NSCLC undergoing lymph node dissection. Method: Based on the data from the Surveillance, Epidemiology, and End Results (SEER) program, we successfully determined and incorporated independent prognostic markers to construct the nomogram. The constructed nomogram was further subjected to external validation with an independent cohort of patients. The performance of the survival prediction model was assessed by concordance index, calibration plots, and risk subgroup classification. Results A total of 23394 patients from SEER registries (training cohort), as well as 7016 patients (verification cohort) was included. Age, gender, race, histology, differentiation grade, stage, and lymph node dissection mode were identified as significant prognostic parameters. A novel nomogram was developed and externally validated. The model displayed good discrimination with a C-index of 0.666 (95% CI, 0.652 to 0.681) and good calibration. Calibration plots demonstrated an optimal consistency between the nomogram predicted and actual observed probability of survival. Conclusion This novel nomogram incorporating the age, gender, race, histology, differentiation grade, stage, and lymph node dissection mode could be conveniently used to facilitate the individual prognosis prediction in stage I NSCLC patients.

Highlights • Early diagnosis could improve lung cancer survival rate. • The availability of blood-based screening could increase lung cancer patient uptake. • An interdisciplinary mechanism combines metabolomics and machine learning methods. • Metabolic biomarkers could be potential screening biomarkers for early detection of lung cancer. • Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction., Early diagnosis has been proved to improve survival rate of lung cancer patients. The availability of blood-based screening could increase early lung cancer patient uptake. Our present study attempted to discover Chinese patients’ plasma metabolites as diagnostic biomarkers for lung cancer. In this work, we use a pioneering interdisciplinary mechanism, which is firstly applied to lung cancer, to detect early lung cancer diagnostic biomarkers by combining metabolomics and machine learning methods. We collected total 110 lung cancer patients and 43 healthy individuals in our study. Levels of 61 plasma metabolites were from targeted metabolomic study using LC-MS/MS. A specific combination of six metabolic biomarkers note-worthily enabling the discrimination between stage I lung cancer patients and healthy individuals (AUC = 0.989, Sensitivity = 98.1%, Specificity = 100.0%). And the top 5 relative importance metabolic biomarkers developed by FCBF algorithm also could be potential screening biomarkers for early detection of lung cancer. Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction. This research will provide strong support for the feasibility of blood-based screening, and bring a more accurate, quick and integrated application tool for early lung cancer diagnostic. The proposed interdisciplinary method could be adapted to other cancer beyond lung cancer.

Background To systematically evaluate the correlation between percutaneous transthoracic needle biopsy (PTNB) and recurrence in stage I lung cancer. Methods The databases of PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and China Biology Medicine disc were retrieved to collect relevant literatures about the correlation between PTNB and recurrence in stage I lung cancer. The retrieval time was limited from the time of their database establishment to April 30/2020.Screened the literature, extracted the data and assessed the quality of studies included. Then the meta-analysis was performed by using Stata l6.0 software. Results A total of 8 cohort studies involving 2760 lung cancer patients were included. The results of meta-analysis showed that PTNB did not increase the risk of total recurrence and pleural recurrence in the patients with stage I lung cancer. The result of subgroup analysis is according to the tumor location. For stage I lung cancer, PTNB will increase the risk of pleural recurrence in patients with sub-pleural lesions but not in those without sub-pleural lesions. Conclusions To stage I lung cancer, PTNB is not associated with the total recurrence and pleural recurrence but PTNB will increase the risk of pleural recurrence in patients with sub-pleural lesions.

Objective To evaluate the performance of low-dose computed tomography (LDCT) on lung cancer screening in high-risk populations in Sichuan. Methods From April 2014 to July 2018, LDCT was performed annually on 3185 subjects aged 50–74 years who had smoked ≥ 20 pack-years (or subjects having quit smoking within 5 years). Information about all deaths and lung cancer diagnoses were obtained by active investigation, or passive matching to disease surveillance system. Results The screening population had a median age of 60 years. 62.4 % of which were current smokers and had smoked 30 pack-years. After participating in the baseline screening, the compliance rates of subjects consecutively completing one round, two rounds, three rounds, and four rounds of annual screening were 67.22 %, 52.84 %, 43.24 %, and 40.04 %, respectively. The positive rates in baseline and annual screening were 6.53 % and 5.79 %, respectively. During the 5 rounds, a total of 9522 person-times were screened by LDCT with a screening sensitivity of 89.13 % (95 % CI: 76.96−95.27), specificity of 94.36 % (95 % CI: 93.88−94.81), positive predictive value of 7.13 % (95 % CI: 5.30−9.53), and negative predictive value of 99.94 % (95 % CI: 99.87−99.98). There were no statistically significant performance differences between baseline and annual screening. The difference in the proportion of screen-detected stage I lung cancer between baseline screening and annual screening was not statistically significant, neither. Conclusion The application of LDCT on lung cancer screening in high-risk populations shows favorable compliance and a high screening performance in the project area of Sichuan,China.

Stereotactic body radiation therapy (SBRT) is increasingly being offered for early stage non-small cell lung cancer (NSCLC). We sought to evaluate long-term survival outcomes after lobectomy and SBRT in patients aged 80 years or more with stage I NSCLC.The National Cancer Database was queried for patients with clinical stage IA and IB (size 40 mm or smaller) NSCLC who underwent SBRT or lobectomy. Only patients with no comorbidities were selected. Number of lymph nodes (LN) examined was used to stratify lobectomy patients into 0 LN, 1 to 6 LN, and 7 or more LN. Propensity score analysis was used to adjust treatment groups. Kaplan-Meier and multivariate Cox regression analysis were used for survival analysis.A total of 8964 patients with stage I NSCLC treated with lobectomy were compared with 286 patients who received SBRT. Using propensity matched pairs, lobectomy (7 LN or more) had significantly improved survival as compared with SBRT (median 74 vs 53.2 months, P.05); however, no survival differences were observed when 0 LN were sampled (median 53.8 vs 52.3 months, P = .88). In multivariate analysis, lobectomy was associated with significantly improved survival (hazard ratio 0.726; 95% confidence interval; 0.580 to 0.910; P = .005). In addition, age, sex, high grade, and tumor size were independent predictors of survival.Among healthy octogenarians with clinical stage I NSCLC who are good surgical candidates, lobectomy offers better survival than SBRT. Adequate LN dissection allows true nodal staging and opportunity for adjuvant treatment when unsuspected nodal metastases are found.

BACKGROUND: Information on the effect of the recurrence pattern on survival for stage I lung cancer following stereotactic ablative radiotherapy (SABR) is limited. MATERIALS AND METHODS: The recurrence pattern was analyzed for 100 consecutive stage I non small-cell lung cancer patients treated with SABR using predominantly 12 Gy x 4. Recurrences were classified as local, regional lymph nodes and distant. Distant recurrences included recurrences in the lung and outside the chest. Single lung recurrences were named solitary, if no other location was involved. Kaplan-Meier survival estimates were calculated for different locations of recurrence. Clinical and dosimetrical factors affecting survival were also analyzed. RESULTS: Median follow-up was 32 months (3-123), median age 70 years (49-95). 31 patients had recurrences after a median 21 months (4-60): 5 local; 10 regional; 8 distant outside the chest; 25 non-local lung recurrences, of which 15 were single – 10 of which solitary - and 10 multiple lung nodules. Patients with a solitary lung recurrence had longer survival compared to local or distant recurrences (p=0.04 each), and compared to multiple lung nodules (p=0.09). 3-year local recurrence-free survival was 92%, disease-free survival 69% and overall survival 59%. On multivariate analysis, disease-free survival was associated with statin use (p=0.038) and tumor location (p=0.035). Smoking history predicted for overall survival (p

Lymphovascular invasion (LVI) and Visceral Pleural Invasion (VPI) have been reported to be risk factors for stage I Non-Small Cell Lung Cancer (NSCLC). However, only VPI was incorporated into the current 8th Tumor-Node-Metastasis (TNM) classification. This study aimed to explore the prognostic effect of LVI and VPI on TNM staging in pathological stage I NSCLC.We retrospectively reviewed 2633 consecutive p-stage I NSCLC patients in the Shanghai Chest Hospital (2008-2012). By using the Kaplan-Meier method and Cox proportional hazard regression model, we identified the correlations between LVI, VPI, and clinical outcomes in p-stage 1 NSCLC.Of all 2633 p-stage I NSCLC patients, 222 were pathologically diagnosed with LVI and 836 pathologically with VPI. The 5-year recurrence free survival (RFS) and overall survival (OS) rates of patients with LVI was significantly worse compared to those without LVI (61.2% vs 82.0%, p 0.001; 73.3% vs 88.1%, p 0.001). The same results emerged for patients with VPI (70.1% vs 85.9%, p 0.001; 82.3% vs 90.0%, p 0.001). Using the univariable and multivariable analysis, we found that when tumor diameter was 3 cm or smaller, LVI (RFS: hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.86-3.50; p .001; OS: HR, 2.53; 95% CI, 1.72-3.71; p .001) and VPI (RFS: HR, 2.14; 95% CI, 1.71-2.67; p .001; OS: HR, 1.56; 95% CI, 1.12-2.04; p = 0.01) were significant prognostic factors for RFS and OS. When tumor size was between 3-4 cm, LVI (HR, 1.84; 95% CI, 1.03-3.29; p = 0.039) and VPI (HR, 2.56; 95% CI, 1.61-4.07; p .001) were associated with inferior OS.The presence of LVI significantly affected OS and RFS in stage I NSCLC patients. Our results suggested that it might be better to incorporate LVI as a T descriptor as VPI in the further TNM classification.

Background: Treatment strategies for octogenarians with lung cancer remain controversial. The purpose of this study was to compare surgical outcomes and survival between octogenarians and younger patients with stage IA and IB lung cancer. Methods: We reviewed the medical records of 34 consecutive octogenarians and 457 younger patients (＜70 years) with stage I lung cancer who underwent surgical resection from January 2007 to December 2015. We analyzed the survival and surgical outcomes of the 2 groups according to the lung cancer stage (IA and IB). Results: The only significant differences in the clinicopathological features between the groups were the higher proportion of sublobar resection (56.3% vs. 18.9%) and the smaller number of dissected lymph nodes (LNs) in octogenarians. There was no significant difference in hospital stay (11 days vs. 9 days), pneumonia (5.8% vs 1.9%), or operative mortality (0% vs 0.6%) between the 2 groups. Among patients with stage IA lung cancer, 5-year recurrence-free survival was not significantly different between the octogenarians (n=16) and younger patients (n=318) (86.2% vs. 89.1%, p=0.548). However, 5-year overall survival was significantly lower in octogenarians than in younger patients (79.4% vs. 93.4%, p=0.009). Among patients with stage IB lung cancer, there was no significant difference in 5-year recurrence-free survival (62.1% vs. 73.5%, p=0.55) or overall survival (77.0% vs 85.0%, p=0.75) between octogenarians (n=18) and younger patients (n=139). In multivariable analysis, male sex, the number of dissected LNs, and tumor size were factors related to survival (hazard ratio [HR], 5.795; p=0.017; HR, 0.346, p=0.025; and HR, 1.699; p=0.035, respectively). Conclusion: Surgical outcomes and survival after pulmonary resection for stage I lung cancer were comparable in octogenarians and younger patients. Continued careful selection of octogenarians for pulmonary resection is important to achieve good results.

Background and purpose In an era where little is known about the “abscopal” (out-of-the-field) effects of lung SBRT, we investigated correlations between the radiation dose proximally outside the PTV and the risk of cancer recurrence after SBRT in patients with primary stage I non-small cell lung cancer (NSCLC). Materials and methods This study included 217 stage I NSCLC patients across 2 institutions who received SBRT. Correlations between clinical and dosimetric factors were investigated. The clinical factors considered were distant metastasis (DM), loco-regional control (LRC) and radiation pneumonitis (RP). The dose (converted to EQD2) delivered to regions of varying size directly outside of the PTV was computed. For each feature, area under the curve (AUC) and odds ratios with respect to the outcome parameters DM, LRC and RP were estimated; Kaplan–Meier (KM) analysis was also performed. Results Thirty-seven (17%) patients developed DM after a median follow-up of 24 months. It was found that the mean dose delivered to a shell-shaped region of thickness 30 mm outside the PTV had an AUC of 0.82. Two years after treatment completion, the rate of DM in patients where the mean dose delivered to this region was higher than 20.8 Gy2 was 5% compared to 60% in those who received a dose lower than 20.8 Gy2. KM analysis resulted in a hazard ratio of 24.2 (95% CI: 10.7, 54.4); p Conclusions The results of this study suggest that the dose received by the region close to the PTV has a significant impact on the risk of distant metastases in stage I NSCLC patients treated with SBRT. If these results are independently confirmed, caution should be taken, particularly when a treatment plan results in a steep dose gradient extending outwards from the PTV.

Up to 20% of clinical stage I lung cancer patients harbor lymph node metastases that go undetected (missed) during the clinical staging evaluation. We investigated to what degree the addition of invasive nodal staging procedures to imaging, as currently practiced, prevents radiographically occult nodal metastases from being missed during the clinical staging evaluation.Treatment-naive patients, imaged by positron emission tomography and computed tomography, who underwent lobectomy for clinical stage I lung cancer from 2012 to 2017 in The Society of Thoracic Surgeons General Thoracic Surgery Database were studied. Rates of missed nodal metastases (MNM) (ie, nodal metastases in lobectomy specimens undetected during clinical staging evaluation) were determined. Risk factors were assessed with multivariable modeling.Of the 30,685 clinical stage I patients identified, 3895 (12.7%) underwent preoperative endobronchial ultrasound and 3341 (10.9%) underwent mediastinoscopy. Invasive staging was more common with tumors2 cm (66.4% vs 50.2%, P.001) and squamous histology (26.9% vs 16.9%, P.001). MNM were discovered in 14.7% of patients, including 20.1% of patients (95% confidence interval, 18.8%-21.5%) who had undergone endobronchial ultrasound and 18.2% (95% confidence interval, 16.7%-19.6%) who had undergone mediastinoscopy. Hilar nodes were most often "missed" (9.5%). Using cut-points in tumor size, histology, laterality, and age, patients could be stratified into particularly high-risk (25% MNM) and low-risk (6% MNM) cohorts.Substantial risk of occult lymph node metastases persists in patients with clinical stage I lung cancer despite negative invasive nodal staging, positron emission tomography, and computed tomography. In the absence of a thorough surgical nodal evaluation, early-stage lung cancer patients are at risk of under-treatment.

Background Stereotactic irradiation (SBRT) is a standard of care for inoperable stage I lung cancer and brain oligometastases from lung cancer but is controversial for extracranial oligometastases. We assessed outcomes of lung cancer patients with extracranial metastases in oligometastatic, oligorecurrent, oligopersistent and oligoprogressive settings (“oligometastatic spectrum”) under strategies using SBRT +/− systemic treatments. Methods A retrospective multicentric study of consecutive lung cancer adult patients with 1–5 extracranial metastases treated with SBRT was conducted. Results Of 91 patients (99 metastases, median age 63, 64.8% adenocarcinomas, 19.8% molecular alterations), 11% had oligometastases, 49.5% oligorecurrence, 19.8% oligopersistence and 19.8% oligoprogression. Of 36% of patients under systemic treatments at initiation of SBRT, systemic treatment interruption was performed in 58% of them. With median follow up of 15.3 months, crude local control at irradiated metastases was 91%, while median distant progression-free survival (dPFS) and overall survival were 6.3 and 28.4 months (2-year survival 54%). Initial nodal stage and oligometastatic spectrum were prognostic factors for dPFS; age, initial primary stage and oligometastatic spectrum were prognostic factors for survival on multivariate analysis. Patients with oncogene-addicted tumors more frequently had oligoprogressive disease. Repeat ablative irradiations were preformed in 80% of patients who had oligorelapses. Worst acute toxicities consisted of 5.5% and one late toxic death occurred. Conclusion The oligometastatic spectrum is a strong prognosticator in patients undergoing SBRT for extracranial metastases. Median survival was over two years but dPFS was about 6 months. Continuation of systemic therapy in oligoprogressive patients should be investigated.

Background: CyberKnife ® stereotactic radiotherapy allows for minimally invasive treatment with satisfactory results in patients with inoperable primary or metastatic lung cancer. The objective of this study was to identify factors influencing the probability of local control. Methods: Ninety-five patients (100 lung tumors) treated between January and December 2013 at our department by SBRT (stereotactic body radiation therapy) using CyberKnife ® were included in the study. There were 71 stage T1 or T2 primary tumors and 29 secondary tumors. The tracking methods were as follow: fiducial markers with Synchrony ® in 50 cases (gold seeds in 35, coils in 15 cases), spine with 4D-CT and Xsight ® Spine in 43 cases, and direct viewing by Xsight ® Lung in 7 cases. The methods were allocated according to the characteristics of each target. Results: With a median follow-up of 24 months, the probability of local control at 24 months was 88%. The probability of local control differed according to the size of the target (92% for tumors ≤35 mm and 54% for tumors >35 mm: P=0.013) and according to the distance of the fiducial markers in relation to the target (95% when Conclusions: The best results were obtained with small lesions. With Synchrony ® , the distance of the target relative to the fiducial markers should be less than 50 mm. Gold seeds are recommended, although coils may be used instead of gold seeds. The number of fiducial markers did not have a significant impact on the probability of local control. With an appropriate tracking method, stereotactic radiotherapy is an efficient treatment for stage I lung cancer and lung oligometastases.

BACKGROUND: There is paucity of evidence regarding the optimal follow-up (FU) regimen for lung cancer. Consequently, FU is organized differently across countries. The Danish FU regimen has short FU intervals with a computed tomography (CT) scan of the chest and upper abdomen every three months in the early phase (first 2 years), then every six months in the late phase of FU (3rd, 5th year). Characterizing recurrences missed by the FU program in terms of site, tumor histology, department, and phase of FU, could improve the FU program.MATERIAL AND METHOD: A case-control study of curatively treated stage I lung cancer patients who attended the Danish FU-program and had recurrence identified through the follow-up program (controls, FU group) or outside FU program (cases, symptomatic group).RESULTS: Of 233 included patients with recurrence, the FU group constituted 85% (n = 197). Among the 15% (n = 36) in the symptomatic group, 53% had involvement of the central nervous system compared with 3% in the FU group. The unadjusted odds ratio (OR) for having an isolated brain recurrence (IBR) in the symptomatic group was 52.3 (95%CI: 15.1-181.4) as compared with the FU group. The OR for having a symptomatic recurrence in the early phase of FU was 2.5 (95%CI: 0.7-8.7) compared with the late phase.CONCLUSIONS: The FU program did not identify the majority of patients with IBR. Including cerebral imaging in the FU program may result in an earlier detection of brain metastases. These matters should be studied in a prospective setting.

This study aimed to examine late radiological changes after proton beam therapy (PBT) for early-stage non–small cell lung cancer (NSCLC) and to clarify correlations between mass-like radiological changes and patient characteristics. CT scans of patients who underwent passive scattering PBT for T1-2N0M0 NSCLC were analyzed retrospectively. Patients were considered eligible if follow-up CT was performed for at least 2 years, with no definite evidence of local recurrence. The following five periods were defined: (i) 6–12 months, (ii) 12–24 months, (iii) 24–36 months, (iv) 36–48 months and (v) 48–60 months after PBT. Late (≥6 months) radiological changes were scored by consensus of three radiation oncologists according to classifications set forth by Koenig (Radiation injury of the lung after three-dimensional conformal radiation therapy. AJR Am J Roentgenol 2002;178:1383–8.). CT scans of 113 patients (median follow-up, 36 months; range, 24–137 months) were evaluated. Late radiological changes during Periods (i), (ii), (iii), (iv) and (v) included modified conventional pattern (80%, 79%, 72%, 58% and 56%, respectively), mass-like changes (8%, 9%, 14%, 22% and 18%, respectively), scar-like changes (4%, 9%, 11%, 17% and 24%, respectively) and no increased density (8%, 3%, 3%, 2% and 2%, respectively). Mass-like changes were observed in 23 patients (20%). Among patients who developed mass-like changes, the median interval between the initiation of PBT and the onset of mass-like changes was 19 months (range, 6–62 months). In multivariate analysis, a peripheral location was found to be a significant factor (P = 0.035; odds ratio: 4.44; 95% confidence interval: 1.12–21.28). In conclusion, mass-like changes were observed in 20% of patients who underwent PBT. Patients with peripheral tumors showed a higher incidence of mass-like changes.