Peripheral Lung Adenocarcinoma Research Articles

European multicentre study evaluating the prognosis of peripheral early-stage lung adenocarcinoma patients operated on by segmentectomy or lobectomy.

To analyse impact of segmentectomy on oncological outcomes of different peripheral early-stage lung adenocarcinoma patterns. Retrospective multicentre study including patients who underwent either lobectomy or segmentectomy in 6 European centres from 2015 to 2021, for ≤2 cm pathological peripheral lung adenocarcinoma. Overall and disease-free survivals were assessed by cox-regression and lung cancer-specific survival by competing regression analyses to adjust for patient- and tumour-related factors both in the entire dataset and the in aggressive adenocarcinoma patterns dataset. Lobectomy and segmentectomy were performed in 481 (71%) and 193 (29%) patients, respectively. Propensity score matching was performed (n = 191). One hundred and 8 patients had a least an aggressive pattern. Five-year disease-free, overall and lung cancer-specific survivals were similar between patients who underwent lobectomy or segmentectomy in both entire and aggressive pattern datasets. In patients with aggressive pattern, 5-year disease-free (lobectomy 87.3%; segmentectomy 86.6%, P = 0.62), overall (lobectomy 86.4%; segmentectomy 95.6%, P = 0.61) and lung cancer-specific (lobectomy 100%; segmentectomy 95.6%, P = 0.13) survivals did not differ. Segmentectomy was not an independent risk factor for disease-free survival, neither for overall survival nor for lung cancer-specific survival in any of the 2 datasets. In patients with aggressive pattern, loco-regional recurrence (linearized risks: lobectomy 8.21; segmentectomy 11.3) was higher in patients who underwent segmentectomy. Resection should not be extended (to lobectomy) on patients who underwent segmentectomy for pathologically proven early-stage adenocarcinoma with aggressive patterns.

The insufficiency of CT examination in early detection of central lung squamous cell carcinoma and squamous epithelial precancerous lesions

BackgroundCT examination for lung cancer has been carried out for more than 20 years and great achievements have been made in the early detection of lung cancer. However, in the clinical work, a large number of advanced central lung squamous cell carcinoma are still detected through bronchoscopy. Meanwhile, a part of CT-occult central lung squamous cell carcinoma and squamous epithelial precancerous lesions are also accidentally detected through bronchoscopy.MethodsThis study retrospectively collects the medical records of patients in the bronchoscopy room of the Endoscopy Department of Zhejiang Cancer Hospital from January 2014 to December 2018. The inclusion criteria for patients includes: 1.Patient medical records completed, 2.Without history of lung cancer before the diagnosis and first pathological diagnosis of primary lung cancer, 3.Have the lung CT data of the same period, 4.Have the bronchoscopy records and related pathological diagnosis, 5.The patients undergoing radical surgical treatment must have a complete postoperative pathological diagnosis. Finally, a total of 10,851 patients with primary lung cancer are included in the study, including 7175 males and 3676 females, aged 22–98 years. Firstly, 130 patients with CT-occult lesions are extracted and their clinical features are analyzed. Then, 604 cases of single central squamous cell carcinoma and 3569 cases of peripheral adenocarcinoma are extracted and compares in postoperative tumor diameter and lymph node metastasis.Results115 cases of CT-occult central lung squamous cell carcinoma and 15 cases of squamous epithelial precancerous lesions are found. In the total lung cancer, the proportion of CT-occult lesions is 130/10,851 (1.20%). Meanwhile, all these patients are middle-aged and elderly men with a history of heavy smoking. There are statistically significant differences in postoperative median tumor diameter (3.65 cm vs.1.70 cm, P < 0.0001) and lymph node metastasis rate (50.99% vs.13.06%, P < 0.0001) between 604 patients with operable single central lung squamous cell carcinoma and 3569 patients with operable peripheral lung adenocarcinoma. Of the 604 patients with squamous cell carcinoma, 96.52% (583/604) are male with a history of heavy smoking and aged 40–82 years with a median age of 64 years.ConclusionsThis study indicates that the current lung CT examination of lung cancer is indeed insufficiency for the early diagnosis of central squamous cell carcinoma and squamous epithelial precancerous lesions. Further bronchoscopy in middle-aged and elderly men with a history of heavy smoking can make up for the lack of routine lung CT examination.

Effect of Preserving the Pulmonary Branch of Vagus Nerve on Postoperative Cough in Patients with Stage I Peripheral Lung Adenocarcinoma

Cough is one of the main complications after pulmonary surgery, which seriously affects the postoperative quality of life. Preserving the pulmonary branch of vagus nerve may reduce the incidence of postoperative cough. Therefore, the aim of this study was to investigate whether preserving the pulmonary branch of the vagus nerve could reduce the incidence of postoperative chronic cough in patients with stage I peripheral lung adenocarcinoma. A total of 125 patients who underwent single-port thoracoscopic radical resection for lung cancer in the Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China from June 2022 to June 2023 were retrospectively selected, and divided into two groups according to whether the vagopulmonary branch was preserved during the operation, namely, the vagopulmonary branch group (n=61) and the traditional group (n=64). The general clinical data, perioperative conditions, lymph node dissection, Mandarin Chinese version of The Leicester Cough Questionnaire (LCQ-MC) scores before and 8 weeks after operation were recorded in the two groups. Both the two groups were divided into tamponade group and non-tamponade group according to whether autologous fat or gelatin sponge was tamponade after lymph node dissection. LCQ-MC scores and postoperative chronic cough of both groups were calculated. The LCQ-MC score of the traditional group was significantly lower than that of the vagopulmonary branch group in physiological, psychological, social and total scores at 8 weeks after surgery, and the difference was statistically significant (P<0.05). There were more cough patients in the traditional group than the vagopulmonary branch group at 8 weeks after surgery, with significant difference (P=0.006). Subgroup analysis was conducted separately for the vagopulmonary branch group and the traditional group. Among the patients in the vagopulmonary branch group and the traditional group, the LCQ-MC scores of the non-tamponade group 8 weeks after surgery were lower than those of the tamponade group (P<0.05). There were more patients with cough in the group 8 weeks after surgery than in the tamponade group (P=0.001, P=0.024). For patients with stage I peripheral lung adenocarcinoma, the preservation of the pulmonary branch of vagus nerve is safe and effective, which can reduce the incidence of postoperative chronic cough and improve the postoperative quality of life of the patients.

The correlation between tumor radiological features and spread through air spaces in peripheral stage IA lung adenocarcinoma: a propensity score-matched analysis

BackgroundThe consolidation tumor ratio (CTR) is a predictor of invasiveness in peripheral T1N0M0 lung adenocarcinoma. However, its association with spread through air spaces (STAS) remains largely unexplored. We aimed to explore the correlation between the CTR of primary tumors and STAS in peripheral T1N0M0 lung adenocarcinoma.MethodsWe collected data from patients who underwent surgery for malignant lung neoplasms between January and November 2022. Univariate and multivariate analyses following propensity-score matching with sex, age, BMI, were performed to identify the independent risk factors for STAS. The incidence of STAS was compared based on pulmonary nodule type. A smooth fitting curve between CTR and STAS was produced by the generalized additive model (GAM) and a multiple regression model was established using CTR and STAS to determine the dose-response relationship and calculate the odds ratio (OR) and 95% confidence interval (CI).Results17 (14.5%) were diagnosed with STAS. The univariate analysis demonstrated that the history of the diabetes, size of solid components, spiculation, pleural indentation, pulmonary nodule type, consolidation/tumor ratio of the primary tumor were statistically significant between the STAS-positive and STAS-negative groups following propensity-score matching(p = 0.047, 0.049, 0.030, 0.006, 0.026, and < 0.001, respectively), and multivariate analysis showed that the pleural indentation was independent risk factors for STAS (with p-value and 95% CI of 0.043, (8.543–68.222)). Moreover, the incidence of STAS in the partially solid nodule was significantly different from that in the solid nodule and ground-glass nodule (Pearson Chi-Square = 7.49, p = 0.024). Finally, the smooth fitting curve showed that CTR tended to be linearly associated with STAS by GAM, and the multivariate regression model based on CTR showed an OR value of 1.24 and a p-value of 0.015.ConclusionsIn peripheral stage IA lung adenocarcinoma, the risk of STAS was increased with the solid component of the primary tumor. The pleural indentation of the primary tumor could be used as a predictor in evaluating the risk of the STAS.

Clinicopathological and computed tomography features associated with recurrence-free survival of patients with small-sized peripheral invasive lung adenocarcinoma after sublobectomy.

Sublobar resection is gradually becoming a standard treatment for small-sized (≤2 cm) peripheral non-small cell lung cancer (NSCLC), with lung adenocarcinoma (LADC) being the most frequent histologic subtype. However, the prognostic predictors for preoperatively determining whether sublobectomy is feasible for patients with early LADC have not yet been well identified. Therefore, this study aimed to investigate the clinicopathological and computed tomography (CT) features associated with the recurrence-free survival (RFS) of patients with small-sized invasive LADC (SILADC) after sublobar resection. This retrospective cohort study analyzed 107 patients with SILADC who underwent preoperative chest CT scan and sublobar resection from December 2012 to March 2019. The Kaplan-Meier survival was used to analyze the relationship between clinicopathological characteristics, preoperative chest CT findings, and RFS. The Cox proportional hazards regression was used to identify independent prognostic factors of poor RFS. For clinicopathological characteristics, RFS was shorter in patients aged ≥70 years, smokers, and those with micropapillary/solid-predominant adenocarcinomas (all P values <0.05). For preoperative CT features, RFS was shorter in patients with tumor size ≥1.4 cm, solid component size ≥1.1 cm, proportion of solid component ≥72%, solid density, spiculation, vascular convergence sign, peripheral fibrosis, and type II pleural tag (all P values <0.05). Multivariate analysis showed proportion of solid component ≥72% [hazard ratio (HR): 5.920; P=0.006; 95% confidence interval (CI): 1.686-20.794], spiculation (HR: 5.026; P=0.001; 95% CI: 2.008-12.581), and type II pleural tag (HR: 4.638; P=0.002; 95% CI: 1.773-12.136) were independent risk factors for poor prognosis in patients with SILADC after sub-lobectomy. Clinicopathological and CT characteristics are helpful for predicting the RFS of patients with SILADC after sublobar resection and can be used as an auxiliary tool for thoracic surgeons to choose the best surgical mode.

Prognostic impact of deep learning-based quantification in clinical stage 0-I lung adenocarcinoma.

To evaluate the performance of automatic deep learning (DL) algorithm for size, mass, and volume measurements in predicting prognosis of lung adenocarcinoma (LUAD) and compared with manual measurements. A total of 542 patients with clinical stage 0-I peripheral LUAD and with preoperative CT data of 1-mm slice thickness were included. Maximal solid size on axial image (MSSA) was evaluated by two chest radiologists. MSSA, volume of solid component (SV), and mass of solid component (SM) were evaluated by DL. Consolidation-to-tumor ratios (CTRs) were calculated. For ground glass nodules (GGNs), solid parts were extracted with different density level thresholds. The prognosis prediction efficacy of DL was compared with that of manual measurements. Multivariate Cox proportional hazards model was used to find independent risk factors. The prognosis prediction efficacy of T-staging (TS) measured by radiologists was inferior to that of DL. For GGNs, MSSA-based CTR measured by radiologists (RMSSA%) could not stratify RFS and OS risk, whereas measured by DL using 0HU (2D-AIMSSA0HU%) could by using different cutoffs. SM and SV measured by DL using 0 HU (AISM0HU% and AISV0HU%) could effectively stratify the survival risk regardless of different cutoffs and were superior to 2D-AIMSSA0HU%. AISM0HU% and AISV0HU% were independent risk factors. DL algorithm can replace human for more accurate T-staging of LUAD. For GGNs, 2D-AIMSSA0HU% could predict prognosis rather than RMSSA%. The prediction efficacy of AISM0HU% and AISV0HU% was more accurate than of 2D-AIMSSA0HU% and both were independent risk factors. Deep learning algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma. • Deep learning (DL) algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma (LUAD). • For GGNs, maximal solid size on axial image (MSSA)-based consolidation-to-tumor ratio (CTR) measured by DL using 0 HU could stratify survival risk than that measured by radiologists. • The prediction efficacy of mass- and volume-based CTRs measured by DL using 0 HU was more accurate than of MSSA-based CTR and both were independent risk factors.

Extent of surgical resection for radiologically subsolid T1N0 invasive lung adenocarcinoma: When is a wedge resection acceptable?

ObjectiveTo evaluate whether wedge resection (WR) was appropriate for the patients with peripheral T1 N0 solitary subsolid invasive lung adenocarcinoma. MethodsPatients with peripheral T1N0 solitary subsolid invasive lung adenocarcinoma who received sublobar resection were retrospectively reviewed. Clinicopathologic characteristics, 5-year recurrence-free survival, and 5-year lung cancer-specific overall survival were analyzed. Cox regression model was used to elucidate risk factors for recurrence. ResultsTwo hundred fifty-eight patients receiving WR and 1245 patients receiving segmentectomy were included. The mean follow-up time was 36.87 ± 16.21 months. Five-year recurrence-free survival following WR was 96.89% for patients with ground-glass nodule (GGN) ≤2 cm and 0.25< consolidation-to-tumor ratio (CTR) ≤0.5, not statistically different from 100% for those with GGN≤2 cm and CTR ≤0.25 (P = .231). The 5-year recurrence-free survival was 90.12% for patients with GGN between 2 and 3 cm and CTR ≤0.5, significantly lower than that of patients with GGN ≤2 cm and CTR ≤0.25 (P = .046). For patients with GGN≤2 cm and 0.25<CTR≤0.5, 5-year recurrence-free survival and lung cancer-specific overall survival were 97.87% and 100% following WR versus 97.73% and 92.86% following segmentectomy (recurrence-free survival: P = .987; lung cancer-specific overall survival: P = .199), respectively. For patients with GGN between 2 and 3 cm and CTR ≤0.5, 5-year recurrence-free survival following WR was significantly lower than that following SEG (90.61% vs 100%; P = .043). Multi-variable Cox regression analysis showed that spread through airspace, visceral pleural invasion, and nerve invasion remained independent risk factors for recurrence of patients with GGN between 2 and 3 cm and CTR ≤0.5 following WR. ConclusionsWR might be appropriate for patients with invasive lung adenocarcinoma appearing as peripheral GGN ≤2 cm and CTR ≤0.5, but inappropriate for those with invasive lung adenocarcinoma appearing as peripheral GGN between 2 and 3 cm and CTR ≤0.5.

CT radiomics model combined with clinical and radiographic features for discriminating peripheral small cell lung cancer from peripheral lung adenocarcinoma.

Exploring a non-invasive method to accurately differentiate peripheral small cell lung cancer (PSCLC) and peripheral lung adenocarcinoma (PADC) could improve clinical decision-making and prognosis. This retrospective study reviewed the clinicopathological and imaging data of lung cancer patients between October 2017 and March 2022. A total of 240 patients were enrolled in this study, including 80 cases diagnosed with PSCLC and 160 with PADC. All patients were randomized in a seven-to-three ratio into the training and validation datasets (170 vs. 70, respectively). The least absolute shrinkage and selection operator regression was employed to generate radiomics features and univariate analysis, followed by multivariate logistic regression to select significant clinical and radiographic factors to generate four models: clinical, radiomics, clinical-radiographic, and clinical-radiographic-radiomics (comprehensive). The Delong test was to compare areas under the receiver operating characteristic curves (AUCs) in the models. Five clinical-radiographic features and twenty-three selected radiomics features differed significantly in the identification of PSCLC and PADC. The clinical, radiomics, clinical-radiographic and comprehensive models demonstrated AUCs of 0.8960, 0.8356, 0.9396, and 0.9671 in the validation set, with the comprehensive model having better discernment than the clinical model (P=0.036), the radiomics model (P=0.006) and the clinical-radiographic model (P=0.049). The proposed model combining clinical data, radiographic characteristics and radiomics features could accurately distinguish PSCLC from PADC, thus providing a potential non-invasive method to help clinicians improve treatment decisions.

Multivariate analysis based on the maximum standard unit value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and computed tomography features for preoperative predicting of visceral pleural invasion in patients with subpleural clinical stage IA peripheral lung adenocarcinoma

Preoperative prediction of visceral pleural invasion (VPI) is important because it enables thoracic surgeons to choose appropriate surgical plans. This study aimed to develop and validate a multivariate logistic regression model incorporating the maximum standardized uptake value (SUVmax) and valuable computed tomography (CT) signs for the non-invasive prediction of VPI status in subpleural clinical stage IA lung adenocarcinoma patients before surgery. A total of 140 patients with subpleural clinical stage IA peripheral lung adenocarcinoma were recruited and divided into a training set (n = 98) and a validation set (n = 42), according to the positron emission tomography/CT examination temporal sequence, with a 7:3 ratio. Next, VPI-positive and VPI-negative groups were formed based on the pathological results. In the training set, the clinical information, the SUVmax, the relationship between the tumor and the pleura, and the CT features were analyzed using univariate analysis. The variables with significant differences were included in the multivariate analysis to construct a prediction model. A nomogram based on multivariate analysis was developed, and its predictive performance was verified in the validation set. The size of the solid component, the consolidation-to-tumor ratio, the solid component pleural contact length, the SUVmax, the density type, the pleural indentation, the spiculation, and the vascular convergence sign demonstrated significant differences between VPI-positive (n = 40) and VPI-negative (n = 58) cases on univariate analysis in the training set. A multivariate logistic regression model incorporated the SUVmax [odds ratio (OR): 1.753, P = 0.002], the solid component pleural contact length (OR: 1.101, P = 0.034), the pleural indentation (OR: 5.075, P = 0.041), and the vascular convergence sign (OR: 13.324, P = 0.025) as the best combination of predictors, which were all independent risk factors for VPI in the training group. The nomogram indicated promising discrimination, with an area under the curve value of 0.892 [95% confidence interval (CI), 0.813-0.946] in the training set and 0.885 (95% CI, 0.748-0.962) in the validation set. The calibration curve demonstrated that its predicted probabilities were in acceptable agreement with the actual probability. The decision curve analysis illustrated that the current nomogram would add more net benefit. The nomogram integrating the SUVmax and the CT features could non-invasively predict VPI status before surgery in subpleural clinical stage IA lung adenocarcinoma patients.

Ground glass nodules with scattered or eccentric island-shaped consolidations may have poor outcomes.

To explore the effect of scattered or eccentric shaped types of ground glass opacity (GGO) on outcomes of patients with solid-dominant peripheral lung adenocarcinoma. We evaluated patients with solid-dominant peripheral lung adenocarcinoma, who underwent radical surgery at Zhongshan Hospital, Fudan University, between January 2013 and December 2015. Morphologically heterogeneous solid-dominant lung adenocarcinoma in imaging findings was based on the last preoperative computed tomography(CT) scans. Endpoints were recurrence-free survival (RFS) and overall survival (OS). Kaplan-Meier analysis and the log-rank test were used to estimate survival differences. Impact factors were assessed by univariable logistic regression analysis. We retrospectively collected data from 200 patients, including 170 patients with central island-shaped CT imaging, 18 patients with scattered shaped CT imaging, and 12 patients with eccentric shaped CT imaging. Eleven patients experienced recurrence or metastases. Kaplan-Meier survival curves showed significant survival differences between the central island-shaped type and scattered shaped or eccentric shaped type for OS (c-stage IA: 5-year OS: 100% vs. 92.1%; HR = 0.019, p = 0.0025; p-stage IA: 100% vs. 95.2%; HR = 0.146, p = 0.1139) and RFS (c-stage IA: 5-year RFS: 100% vs. 59.7%; HR = 0.001, p < 0.0001; p-stage IA: 100% vs. 64.5%; HR < 0.001, p < 0.0001). Univariable logistic regression analysis showed that scattered and eccentric shaped types were related to poor outcomes (p < 0.012, odds ratio = 18.8). Relative spatial position of GGO and solid components may affect patient outcomes. Patients with scattered or eccentric shaped GGO may have a poor prognosis.

The efficacy and safety of wedge resection for peripheral stage IA lung adenocarcinoma: a real-world study based on a single center.

The effectiveness of segmentectomy for stage IA lung adenocarcinoma (IA-LUAD) has been well-documented. However, the efficacy and safety of wedge resection for peripheral IA-LUAD remains controversial. This study evaluated the feasibility of wedge resection in patients with peripheral IA-LUAD. Patients with peripheral IA-LUAD who underwent wedge resection by video-assisted thoracoscopic surgery (VATS) at Shanghai Pulmonary Hospital were reviewed. Cox proportional hazards modeling was performed to identify predictors of recurrence. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cutoffs of identified predictors. A total of 186 patients (female/male, 115/71; mean age, 59.9 years) were included. Mean maximum dimension of consolidation component (MCD) was 5.6 mm, consolidation-to-tumor ratio (CTR) was 37%, and mean computed tomography value of tumor (CTVt) was -285.4 HU. With a median follow-up of 67 months (interquartile range, 52-72 months), the 5-year recurrence rate was 4.84%. Ten patients occurred recurrence postoperatively. No recurrence was observed adjacent to the surgical margin. Increasing MCD, CTR, and CTVt were associated with a higher risk of recurrence, with corresponding hazard ratios (HRs) of 1.212 [95% confidence interval (CI): 1.120-1.311], 1.054 (95% CI: 1.018-1.092), and 1.012 (95% CI: 1.004-1.019) with optimal cutoffs for predicting recurrence of 10 mm, 60%, and -220 HU, respectively. When a tumor had characteristics under these respective cutoffs, no recurrence was observed. Wedge resection can be considered to be a safe and efficacious management strategy for patients with peripheral IA-LUAD, especially for MCD less than 10 mm, CTR less than 60% and CTVt less than -220 HU.

Computed tomography versus frozen sections for distinguishing lung adenocarcinoma: A cohort study of concordance rate

BackgroundComputed tomography (CT) imaging can help to predict the pathological invasiveness of early-stage lung adenocarcinoma and guide surgical resection. This retrospective study investigated whether CT imaging could distinguish pre-invasive lung adenocarcinoma from IAC. It also compared final pathology prediction accuracy between CT imaging and intraoperative frozen section analysis. MethodsThis study included 2093 patients with early-stage peripheral lung adenocarcinoma who underwent CT imaging and intraoperative frozen section analysis between March 2013 and November 2014. Nodules were classified as ground-glass (GGNs), part-solid (PSNs), and solid nodules according to CT findings; they were classified as pre-IAC and IAC according to final pathology. Univariate, multivariate, and receiver operating characteristic (ROC) curve analyses were performed to evaluate whether CT imaging could distinguish pre-IAC from IAC. The concordance rates of CT imaging and intraoperative frozen section analyses with final pathology were also compared to determine their accuracies. ResultsMultivariate analysis identified tumor size as an independent distinguishing factor. ROC curve analyses showed that the optimal cut-off sizes for distinguishing pre-IAC from IAC for GGNs, PSNs, and solid nodules were 10.79, 11.48, and 11.45 mm, respectively. The concordance rate of CT imaging with final pathology was significantly greater than the concordance rate of intraoperative frozen section analysis with final pathology (P = 0.041). ConclusionCT imaging could distinguish pre-IAC from IAC in patients with early-stage lung adenocarcinoma. Because of its accuracy in predicting final pathology, CT imaging could contribute to decisions associated with surgical extent. Multicenter standardized trials are needed to confirm the findings in this study.

Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK\xa0double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively

IntroductionAnaplastic lymphoma kinase (ALK) gene rearrangements, have been identified in approximately 2-7% of patients with lung adenocarcinoma (LUAD). However, co-occurrence of double ALK fusions in one patient was rare. Herein, we reported two Chinese female LUAD patients with confirmed double ALK fusion variants by next generation sequencing.Case presentationCase 1, a 38-year-old female was diagnosed as peripheral LUAD in left upper lobe with synchronous multiple intrapulmonary metastases (pT2N0M1b, stage IVa). And case 2, a 58-year-old female had left lower lobe primary LUAD and synchronous multiple lung metastases (pT4N2M1b, stage IVa). In both patients, tumor cells displayed strong expression of ALK protein. Genetic profiling by next generation sequencing showed both patients concurrently harbored two types of ALK rearrangements. Case 1 had an unreported ALK-SSH2/EML4-ALK double fusions, and case 2 had an another novel ARID2-ALK/EML4‐ALK double fusions. Both of these patients responded to ALK inhibitor crizotinib.ConclusionsOur study reported two novel ALK fusion partners never reported, which expands the knowledge of ALK fusion spectrum and provides insight into therapeutic options for patients with double ALK fusions.

Impact of Postoperative Radiotherapy on Overall Survival in Patients with pN1 Non-Small Cell Lung Cancer

Objective: to comparatively analyze overall survival (OS) in patients with non-small cell lung cancer (NSCLC) with affected lymph nodes (pN1) of the lung root after surgical and combination treatment with postoperative radiotherapy (PORT). Subjects and methods. OS was studied in 310 patients with grade 2-3 NSCLC. (pT1a-4N1M0): in 101 patients after lobectomy/bilobectomy, pulmonectomy with ipsilateral mediastinal lymphadenectomy and in 209 patients after combination treatment with the similar surgical volume and hypofractionated PORT (a single focal dose (SFD) of 3 Gy; 5 fractions per week, a cumulative focal dose (CFD) of 36-39 Gy (43.2-46.8 Gy-eq)) or classical fractionation (SFD2 Gy, 5 fractions per week, CFD44 Gy). An analysis was carried out in the groups of patients younger and older than 60 years with central or peripheral cancer, squamous cell carcinoma or adenocarcinoma, with different tumor grading according to the T criterion (T1-4). Results. PORT in radically operated patients with NSCLC increased 5- and 10-year OS rates only in central squamous cell lung cancer (56.1% and 39.5% vs.25.4% and 4.3%, p = 0.002). This group receiving combination therapy showed a statistically significant increasing trend in 5-year OS rates for both pT1-2 tumors (57.5% vs. 21.3%, respectively, p = 0.013) and pT3-4 tumors (53.9% versus 26.0%; p = 0.044), so did patients younger than 61 years (65.5% vs.29.4%, p = 0.008) and those over 60 years old (47.5% vs.21.3%, p = 0.047). Patients with peripheral squamous cell carcinoma or lung adenocarcinoma at any site exhibited no statistically significant increase in OS after PORT. In general, the 5- and 10-year OS rates in the compared groups were statistically significantly higher in the PORT group (47.9% and 28.9% vs. 27.1% and 11.4, p = 0.006). None of the analyzed subgroups showed a decrease in OS after PORT. Conclusion. In patients with pN1 NSCLC who had radical surgery via lobectomy/bilobectomy or pulmonectomy with ipsilateral mediastinal lymphadenectomy, PORT can be recommended only for those with central squamous cell carcinoma, regardless of tumor size and age group. In other subgroups of patients with pN1 NSCLC, PORT can only be performed within the scientific protocols. The expediency of PORT after bilateral mediastinal lymph node dissection needs to be investigated.

Development and validation of a CT-based nomogram to predict spread through air space (STAS) in peripheral stage IA lung adenocarcinoma.

To develop and validate a simple-to-use nomogram based on preoperative CT to predict spread through air space (STAS) status of stage IA lung adenocarcinoma (ADC). In this retrospective study, 434 patients with pathological proven periphery stage IA lung adenocarcinoma were included, which consisted of 349 patients from center I for training group and 85 patients from Center II for test group. STAS was identified in 53 patients (40 patient in the training group and 13 patients in the test group). On the basis of preoperative CT images, 19 morphological characteristics were analyzed. Univariable analysis was used to explore the association between clinical and CT characteristics and STAS status in the training group (P < 0.002). Independent risk factors for STAS were identified using multivariable logistic regression analysis and then used to build a nomogram for preoperative predicting STAS status. Type of nodules, diameter of solid component, lobulation and percentage of the solid component (PSC) were associated with STAS status of peripheral stage IA lung ADCs statistical significantly. Multivariate logistics regression analysis revealed that PSC and lobulation were independent risk factors for STAS. The nomogram based on these factors achieved good predictive performance for STAS with a C-index of 0.803 in the training group and a well-fitted calibration curve. Using a cut-off value which was obtained from Youden index of the receiver operating characteristic (ROC) curve, a diagnosis accuracy of 70.6% was obtained in the test group with sensitivity, specificity, positive prediction value (PPV) and negative prediction value (NPV) of 92.3%, 66.7%, 33.3% and 98.0%, respectively. The nomogram based on preoperative CT images could achieve good predictive performance for STAS status of lung adenocarcinomas. This simple-to-used model can facilitate surgeons for a rational operation pattern choice at bedside.

Should resection extent be decided by total lesion size or solid component size in ground glass opacity-containing lung adenocarcinomas?

BackgroundIndication for sublobar resections in early-stage lung adenocarcinomas has been controversial. The purpose of this study was to find appropriate selection criteria for sublobar resections in ground glass opacity (GGO)-containing early-stage lung adenocarcinomas.MethodsWe retrospectively studied 985 consecutive patients with clinical stage IA, peripheral GGO-containing lung adenocarcinomas ≤3 cm in size. According to their radiological appearance, they were divided into a pure GGO group and a part-solid nodule (PSN) group. The PSN group was further divided into a GGO-predominant subgroup and a solid-predominant subgroup. Propensity-score matching (PSM) was conducted first in PSNs with similar total lesion size and then in those with similar solid component size to eliminate potential confounders. Histological characteristics and prognosis were compared between matched patients to investigate the prognostic value of total lesion size and solid component size. Then solid component size was chosen as the selection criterion to compare the prognosis of patients receiving lobectomy or sublobar resections.ResultsComparing to PSNs, pure GGO lesions had significantly more favorable histological characteristics and prognosis, with 100% 5-year overall survival (OS), even though 33.3% of patients with pure GGO lesions >20 mm in total lesion size received sublobar resections. For 157 pairs of PSNs with similar total lesion size but different solid component size after the first PSM, the solid-predominant subgroup had significantly worse histological characteristics and prognosis than the GGO-predominant subgroup. After the second PSM, histological characteristics and prognosis were comparable between 73 pairs of PSNs with similar solid component size but different total lesion size. Multivariable analysis showed that solid component size, rather than total lesion size or consolidation-to-tumor ratio (CTR), was an independent prognostic factor. For PSNs containing solid component size ≤2 cm, relapse-free survival (RFS) was similar after sublobar resections or lobectomy (95.0% vs. 93.6%, P=0.592). The results remained similar for PSNs of total lesion size >2 cm but solid component size ≤2 cm (88.9% vs. 90.0%, P=0.893).ConclusionsSolid component size better predicts histological characteristics and prognosis than total lesion size in early-stage GGO-containing lung adenocarcinomas. Instead of total lesion size, solid component size ≤2 cm may be a more appropriate selection criterion for sublobar resections in such patients.

Development and Validation of a Combined Model for Preoperative Prediction of Lymph Node Metastasis in Peripheral Lung Adenocarcinoma.

BackgroundBased on the “seed and soil” theory proposed by previous studies, we aimed to develop and validate a combined model of machine learning for predicting lymph node metastasis (LNM) in patients with peripheral lung adenocarcinoma (PLADC).MethodsRadiomics models were developed in a primary cohort of 390 patients (training cohort) with pathologically confirmed PLADC from January 2016 to August 2018. The patients were divided into the LNM (−) and LNM (+) groups. Thereafter, the patients were subdivided according to TNM stages N0, N1, N2, and N3. Radiomic features from unenhanced computed tomography (CT) were extracted. Radiomic signatures of the primary tumor (R1) and adjacent pleura (R2) were built as predictors of LNM. CT morphological features and clinical characteristics were compared between both groups. A combined model incorporating R1, R2, and CT morphological features, and clinical risk factors was developed by multivariate analysis. The combined model’s performance was assessed by receiver operating characteristic (ROC) curve. An internal validation cohort containing 166 consecutive patients from September 2018 to November 2019 was also assessed.ResultsThirty-one radiomic features of R1 and R2 were significant predictors of LNM (all P < 0.05). Sex, smoking history, tumor size, density, air bronchogram, spiculation, lobulation, necrosis, pleural effusion, and pleural involvement also differed significantly between the groups (all P < 0.05). R1, R2, tumor size, and spiculation in the combined model were independent risk factors for predicting LNM in patients with PLADC, with area under the ROC curves (AUCs) of 0.897 and 0.883 in the training and validation cohorts, respectively. The combined model identified N0, N1, N2, and N3, with AUCs ranging from 0.691–0.927 in the training cohort and 0.700–0.951 in the validation cohort, respectively, thereby indicating good performance.ConclusionCT phenotypes of the primary tumor and adjacent pleura were significantly associated with LNM. A combined model incorporating radiomic signatures, CT morphological features, and clinical risk factors can assess LNM of patients with PLADC accurately and non-invasively.

Optimal margins for early stage peripheral lung adenocarcinoma resection

BackgroundA pathologically confirmed negative margin is required when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma. However, the optimal margin distance to ensure complete tumor resection while preserving healthy lung tissue remains unknown. We aimed to establish a reliable distance range for negative margins.MethodsA total of 52 intraoperative para-cancer tissue specimens from patients with peripheral lung adenocarcinoma with pathological tumors ≤2 cm in size were examined. Depending on the distance from the tumor edge (D), the para-cancer tissues were divided into the following five groups: D < 0.5 cm (group I); 0.5 cm ≤ D < 1.0 cm (group II); 1.0 cm ≤ D < 1.5 cm (group III); 1.5 cm ≤ D < 2.0 cm (group IV); and D ≥ 2.0 cm (group V). During pathological examination of the specimens under a microscope, the presence of atypical adenomatous hyperplasia or more severe lesions was considered unsafe, whereas the presence of normal lung tissue or benign hyperplasia was considered safe.ResultsGroup V, in which the margin was the farthest from the tumor edge, was the safest. There were significant safety differences in between groups I and V (χ2 = 26.217, P < 0.001). Significant safety differences also existed between groups II and V (χ2 = 9.420, P < 0.005). There were no significant safety differences between group III or IV and group V (P = 0.207; P = 0.610).ConclusionsWe suggest that when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma with pathological tumor sizes ≤2 cm, the resection margin distance should be ≥1 cm to ensure a negative margin.

Transition of Treatment for Ground Glass Opacity-Dominant Non-Small Cell Lung Cancer.

Lobectomy has been the standard surgical treatment for non-small cell lung cancer (NSCLC). Over the decades, with the dramatic development of radiographic tools, such as high-resolution computed tomography (HRCT), and the widespread practice of low-dose helical CT for screening, the number of cases diagnosed with small-cell lung cancers with ground glass opacity (GGO) at early stages has been increasing. Accordingly, mainly after 2000, many retrospective studies and prospective trials have shown that patients with lung adenocarcinoma with GGO have a good prognosis and may be candidates for sublobar resection. Previous studies indicated that HRCT findings including the maximum diameter of the tumor, GGO ratio, and a consolidation/tumor ratio (CTR) are simple and useful tools to predict tumor invasiveness and prognosis in patients with NSCLC with GGO. Thus, sublobar resection may be considered a “standard therapy” for peripheral GGO-dominant small-cell lung adenocarcinomas. Ultimately, some of such tumors might not require surgical resection. A multicenter, prospective study has just begun in Japan to evaluate the validity of follow-up for small-sized GGO-dominant small-cell lung cancer. Lung cancers that do not require surgery should be identified. This study reviewed retrospective and prospective studies on GGO tumors and discussed the treatment strategies for such tumors.

Predicting pathological lymph node status in clinical stage IA peripheral lung adenocarcinoma.

Even with current diagnostic technology, it is difficult to accurately predict pathological lymph node status (PLNS). This study aimed to develop a prediction model of PLNS in peripheral adenocarcinoma with a dominant solid component, based on clinical and radiological factors on thin-section computed tomography, to identify patients to whom wedge resection or other local therapies could be applied. Of 811 patients enrolled in a prospective multi-institutional study (JCOG0201), 420 patients with clinical stage IA peripheral lung adenocarcinoma having a dominant solid component were included. Multivariable logistic regression was performed to develop a model based on clinical and centrally reviewed radiological factors. Leave-one-out cross-validation and external validation analyses were performed, using independent data from 221 patients. Sensitivity, specificity and concordance statistics were calculated to evaluate diagnostic performance. The formula for calculating the probability of pathological lymph node metastasis included the following variables: tumour diameter (including ground-glass opacity), consolidation-to-tumour ratio and density of solid component. The concordance statistic was 0.8041. When the cut-off value associated with the risk of incorrectly predicting negative pathological lymph node metastasis (pN-) was 4.9%, diagnostic sensitivity and specificity in predicting PLNS were 95.7% and 46.0%, respectively. The concordance statistic for the external validation set was 0.7972, and diagnostic sensitivity and specificity in predicting PLNS were 95.4% and 40.5%, respectively. The proposed model is clinically useful and successfully predicts pN- in patients with clinical stage IA peripheral lung adenocarcinoma with a dominant solid component.