9562 Background: Neoadjuvant immune checkpoint inhibitors (ICIs) have demonstrated efficacy in resectable cutaneous melanoma and are recommended by current guidelines. Nevertheless, the clinical benefit of combining ICIs with chemotherapy as neoadjuvant setting in Chinese patients remains to be established. This study is being conducted to explore the efficacy and safety of neoadjuvant toripalimab combined with temozolomide in resectable stage III melanoma. Methods: This is a prospective, single-center, single-arm clinical trial (ClinicalTrials.gov identifier: NCT05827770). Patients with resectable stage IIIB-IIID acral or cutaneous melanoma and an ECOG performance status of 0-1 were enrolled and received two cycles of neoadjuvant temozolomide 200 mg/m² plus toripalimab 240 mg every 3 weeks, followed by radical surgery. The primary endpoint was the pathologic response rate (pRR). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), recurrence-free survival (RFS), overall survival (OS) and safety. Results: As of December 2025, 20 eligible patients with resectable stage IIIB-IIID melanoma were enrolled, with 14 (70%) acral, 5 (25%) cutaneous and 1 (5%) of unknown primary. Of 20 patients underwent surgery, nine achieved pRR (45%), including 3 with near pathologic complete response (near pCR) and 6 with partial pathologic response (pPR). Radiological assessment showed partial response in 5 patients, stable disease in 12 patients, and progressive disease in 3 patients, yielding an objective response rate of 25% (5/20) and a disease control rate of 85% (17/20) according to RECIST criteria. With a median follow-up of 12 months, 8 recurrence-free survival events had been observed; the median RFS and OS had not yet been reached. Notably, one patient who attained near pCR remained relapse free for 27 months. No new safety signals were observed with the combination therapy. We further performed single-cell-resolution spatial transcriptomics and single-cell RNA sequencing in the current cohort. Integrative multi-omics analyses identified a T cell-excluded tumor microenvironment preferentially associated with non-response. Leveraging these features, we robustly distinguished immunotherapy responders from non-responders. Conclusions: This study demonstrates the preliminary efficacy and tolerability of toripalimab combined with temozolomide in the neoadjuvant treatment of patients with resectable stage IIIB-IIID acral and cutaneous melanoma. Given the fact that ICIs alone has limited response rate in acral melanoma, further studies are warranted. Clinical trial information: NCT05827770 . Treatment outcomes. Pathologic Response Eligible patients (%)N=20 Radiological Response Eligible patients (%)N=20 Near pCR 3 (15) PR 5 (25) pPR 6 (30) SD 12 (60) pNR 11 (55) PD 3 (15) pRR (pCR+Near pCR+pPR) 9 (45) ORR (CR+PR) 5 (25) DCR (CR+PR+SD) 17 (85)

11561 Background: Neoadjuvant therapy may improve the R0 resection and limb salvage rates in locally advanced soft tissue sarcomas (STS). This phase II trial was designed to evaluate the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD) combined with anlotinib in the treatment of locally advanced STS. Methods: This single-center, single-arm phase II trial (NCT04765228) enrolled treatment-naïve patients with stage II/III. Patients received PLD (50 mg/m² intravenously on day 1) combined with anlotinib (12 mg orally daily on days 8-21) every 3 weeks for 2-4 cycles. Based on a one-proportion test, with α=0.05 (two-sided) and 80% power, to detect an increase in the objective response rate (ORR) from 10% to 26%, 45 patients were planned, accounting for a 20% dropout rate. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The exploratory endpoint was biomarker analyses. The corresponding two-sided 95% CIs were estimated using the Clopper-Pearson method. The PFS and OS were estimated using the Kaplan-Meier method. Results: A total of 40 eligible patients were treated between November 2020 and November 2022, of whom 34 (85.0%) underwent surgery. The median age was 46.5 years (range: 15-74 years), and 23 (57.5%) of the patients were male. Histologically, the 40 patients included 9 cases of liposarcoma (LPS), 6 cases of malignant peripheral nerve sheath tumor (MPNST), 6 cases of synovial sarcoma (SS), 3 cases of low-grade fibromyxoid sarcoma (LGFMS), 3 cases of myxofibrosarcoma (MFS), 3 cases of spindle cell sarcoma (SCS), 3 cases of undifferentiated pleomorphic sarcoma (UPS), 2 cases of leiomyosarcoma (LMS), and 5 cases of other STS. The most common sites of primary tumor were lower extremities (42.5%), waist/hip region (17.5%) and other regions. The ORR based on RECIST 1.1 was 15.0% (95% CI: 3.4%-26.6%), and the ORR of 36 patients based on Choi's criteria was 58.3%. The median PFS was 14 months (95% CI: 4.22 - 23.79 months), and the median OS was not reached. Pathological response was evaluable in 24 patients, with pathological complete response (pCR) and pathological partial response (pPR) observed in 4.2% (1/24) and 50.0% (12/24) of cases, respectively. Among 34 patients who underwent surgical resection, 30 (88.2%) achieved R0 resection, while 3 (8.8%) had R1 resection. Common treatment-related adverse events (TRAEs) of any grade included mucositis oral (52.5%), neutrophil count decreased (25.0%). Fifteen (37.5%) patients experienced at least one grade 3-4 AE. Conclusions: Neoadjuvant PLD combined with anlotinib exhibits promising efficacy and acceptable toxicity in patients with locally advanced STS. Results from multi-omics analyses will facilitate the screening of suitable patients in future clinical practice. Clinical trial information: NCT04765228 .

Purpose Squamous non-small cell lung cancer (sq-NSCLC) is a distinct subtype of NSCLC. This exploratory, phase II study investigated the feasibility and efficacy of a four-cycle perioperative regimen combining serplulimab with a taxane (paclitaxel or nab-paclitaxel) and carboplatin in patients with resectable stage II-IIIA sq-NSCLC. Methods This investigator-initiated, single-arm, phase II exploratory trial ( NCT05775796 ) enrolled patients with histologically confirmed, resectable clinical stage II-IIIA squamous NSCLC. Patients received two to three cycles of neoadjuvant serplulimab plus taxane-carboplatin, followed by curative-intent surgery and one to two cycles of adjuvant treatment. The primary endpoint was major pathological response (MPR). Secondary endpoints included pathological complete response (pCR), R0 resection rate, overall response rate (ORR), safety, event-free survival (EFS), and overall survival (OS). Results A total of 30 patients without actionable driver alterations were enrolled and 29 underwent surgery. The median age was 65 years, and most were male smokers (n=28, 93.33%). Surgery was performed in 29 patients, and R0 resection was achieved in 96.55% (28/29) of the surgically resected patients. Among all enrolled patients, MPR and pCR rates were 76.67% and 50.00%, respectively. Based on radiological assessments during the neoadjuvant phase, the ORR was 73.33% (95% CI 54.11% to 87.72%). Grade ≥3 treatment-related adverse events were predominantly hematologic and were generally manageable. Long-term EFS and OS data are not yet mature. Additionally, exploratory minimal residual disease analysis using circulating tumor DNA (ctDNA) in 27 patients showed a strong correlation between ctDNA clearance and pCR (p=0.004), suggesting ctDNA as a promising biomarker for immunochemotherapy response. Conclusions A four-cycle perioperative regimen of serplulimab combined with taxane-carboplatin demonstrated promising MPR and pCR rates with an acceptable safety profile in patients with resectable sq-NSCLC. Long-term follow-up and future phase III trials are warranted to confirm these exploratory findings. Trial registration number NCT05775796 .

Background:Preoperative detection of occult nodal metastasis (ONM) is essential for treatment planning and prognostic evaluation in lung adenocarcinoma (LUAD). This study aimed to develop and validate radiomics models capable of predicting ONM in patients with stage cT1a-bN0M0 LUAD. Methods:A total of 1,672 patients from six hospitals were enrolled and stratified into training (n=687), test (n=297) and external validation (n=688) sets. Predictive models including generalized linear model (GLM), support vector machine (SVM), random forest (RF), gradient boosting machine (GBM), and the combined clinical-radiomics (Clinic-Rad) model were constructed. Diagnostic performance was quantified via the area under receiver operating characteristic curve (AUC), with the De Long test used for comparisons. The Mantel test was employed to assess the correlations between radiomics features and pathological/genetic characteristics. Results:In external validation, the Clinic-Rad model integrating clinical predictors and radiomics score demonstrated superior diagnostic efficacy (AUC 0.813±0.019) compared to GLM (0.790±0.021), SVM (0.761±0.023), RF (0.708±0.026), GBM (0.769±0.022) (all P values <0.001). However, no significant intermodel differences were observed in test set, with the Clinic-Rad model achieving an AUC of 0.834±0.023, and GLM, SVM, RF, and GBM yielding AUCs of 0.827±0.024, 0.829±0.025, 0.838±0.023, and 0.826±0.024, respectively (all P values >0.05). The Clinic-Rad model exhibited a pooled sensitivity of 75.8-77.2%, a specificity of 72.0-72.7%, and an accuracy of 72.7-74.4%, with pooled AUC values of 0.802-0.820 and 0.797-0.917 for the solid and subsolid LUAD, respectively. Furthermore, radiomics models outperformed clinical predictors comprising solid-component diameter (AUC: 0.669-0.678), consolidation-to-tumor ratio (CTR) (0.542-0.600), carcinoembryonic antigen (CEA) level (0.571-0.613), and their combination (0.683-0.724) (all P values <0.001). The Mantel test indicated correlations between radiomics signatures and EGFR, ALK, ROS1, and RET expression, as well as histopathological markers of ONM. Conclusions:Radiomics-based models demonstrate clinical utility in predicting ONM in patients with stage cT1a-bN0M0 LUAD, with the integrated Clinic-Rad model providing superior diagnostic performance.

Background:Hypofractionated stereotactic radiotherapy (fSRT) is increasingly used for brain metastases (BMs) from non-small cell lung cancer (NSCLC). However, relevant data concerning treatment outcomes of fSRT and clinical utility of re-irradiation using fSRT (re-fSRT) remain scarce. Methods:Consecutive NSCLC patients with fSRT-treated BMs from May 2018 to May 2022 were included. The cumulative incidence of intracranial local recurrence (iLR), intracranial progressive disease (iPD) and symptomatic radiation necrosis (sRN) were calculated from the initiation of fSRT, choosing death as the competing event. Patients with limited iPD (number ≤5 and size ≤3 cm) and without iLR developed within 12 months, were classified as re-fSRT candidates. The clinical value of re-fSRT and dosimetric predictors of sRN were investigated. Results:With a median follow-up of 22.3 months, the 1-year, 2-year and 3-year cumulative incidence of iLR among the 218 identified patients were 8.1 %, 12.3 %, 17.8 %, respectively. Biological effective dose, total tumor volume and concurrent systemic therapy were associated with the risk of iLR. Notably, 45 (76.3 %) of the 59 patients with iPD were feasible for re-fSRT. Re-fSRT was performed in 19 (42.2 %) of the 45 candidates and associated with improved survival (p = 0.010). The 1-year, 2-year and 3-year cumulative incidence of sRN in the whole population were 4.5 %, 10.3 %, 17.7 %, respectively. Moreover, sRN occurred in 3 (15.8 %) patients receiving re-fSRT and Brain V20Gy was found to be associated with the risk of sRN. Conclusion:fSRT is a promising treatment for limited BMs from NSCLC and some patients may benefit from re-fSRT.

Accumulating evidence suggests local consolidative therapy may delay resistance and benefit metastatic NSCLC patients with oligo-residual disease (ORD) after effective systemic therapy. However, the incidence and clinical features of ORD in Alectinib-treated metastatic ALK-positive NSCLC remain unclear. We retrospectively reviewed serial scans of metastatic ALK-positive NSCLC patients treated with Alectinib. ORD was defined as the presence of five or fewer residual metastatic lesions (including the primary site) among those developed partial response as the best response after Alectinib treatment. Initial patterns of recurrence were classified as involving only residual-site recurrence (RR), only new-site recurrence (NR), or a combination of both (RNR). Among 128 patients, 62 patients had PR as the best response, among whom 18 (29.0%) had ORD. The median time to tumor volume nadir was 4.9 (range, 1.1-19.2) months and no independent predictor of ORD was found. To date, 50.0% (9/18) patients with ORD developed their initial progressive disease (PD), mostly (5, 55.6%) with only residual sites. Among the 9 PD patients, 6 patients (6/9, 66.7%) with brain lesions at baseline. Half (3/6, 50.0%) were involved in only brain residual sites. Our study found ORD is not rare in Alectinib treated ALK-positive NSCLC, with 55.6% having initial PD at originally involved sites. Similar recurrence pattern is also observed in PD patients with baseline BMs. These findings indicate that residual disease may enable the emergence of acquired resistance in both CNS and other organs, thus supporting potential clinical benefits for LCT in these ORD patients. Clinical trial number Not applicable.

INTRODUCTION:This study aimed to evaluate the safety of active surveillance and establish an individualized management approach for multifocal ground-glass opacities (GGOs). METHODS:This prospective multicenter trial (ECTOP1021, NCT06097910) enrolled patients with more than or equal to three GGOs (tumor diameter ≤ 2 cm, consolidation-to-tumor ratio ≤ 0.25). The primary end point was 5-year overall survival; secondary end points included lesion progression. The surgical curative time window was defined as tumor diameter less than or equal to 2.0 cm and consolidation-to-tumor ratio less than or equal to 0.25, a safe radiologic profile during which patients could achieve definite cure after resection. RESULTS:A total of 406 patients were recruited from five centers. The cohort consisted predominantly of females (75.6%) and never smokers (87.2%), with a median age of 53 years. In total, 1496 lesions were under surveillance, with a median of three GGOs per patient. The median diameter of the dominant lesion was 0.8 cm. At a median follow-up of 35.4 months, the 5-year overall survival was 100%. Progression occurred in 8.1% of patients, whereas 1.5% developed new lesions. The median increase in tumor diameter was 0.3 cm. Eight patients underwent surgery after enrollment, all pathologic stage IA1; four had invasive adenocarcinoma and four had minimally invasive adenocarcinoma. Patients were categorized into three groups based on estimated lung function loss if complete resection, with tailored strategies accordingly. CONCLUSIONS:Active surveillance within the surgical curative time window seems to be safe and feasible for patients with multifocal GGOs in the short term. It offers an alternative to immediate surgery and rationalized individualized, scenario-based management strategies.

PURPOSE:Systematic mediastinal lymph node dissection (LND) or sampling is currently recommended for patients with early-stage non-small cell lung cancer. We aimed to investigate whether no mediastinal LND was noninferior to systematic LND in patients with ground glass opacity (GGO)-dominant invasive lung adenocarcinoma. METHODS:We conducted a multicenter, open-label, phase III, noninferiority randomized controlled trial comparing systematic mediastinal LND versus no mediastinal LND in patients with GGO-dominant invasive lung adenocarcinoma, who were predicted to have no lymph node metastasis on the basis of criteria established in our previous trial. The primary end point was 3-year disease-free survival. An interim analysis was planned upon enrollment of 300 patients, with predefined termination criteria if no mediastinal lymph node metastasis is detected and life-threatening complications occur in the systematic LND arm. This trial is registered on ClinicalTrials.gov (ECTOP-1009, identifier: NCT04527419). RESULTS:Interim analysis of 302 patients revealed no lymph node metastasis in either study arm. The no LND arm had significantly reduced surgery duration (mean, 74 minutes v 109 minutes; P < .001), blood loss (mean, 44 mL v 82 mL; P = .033), and postoperative hospital stay (mean, 3.9 days v 4.5 days; P = .002). Complications observed in the systematic LND arm included chylothorax in one patient (0.7%) and intraoperative massive bleeding because of superior vena cava injury in one patient (0.7%). No lymphadenectomy-related complications occurred in the no LND arm. CONCLUSION:On the basis of interim findings and the principle of nonmaleficence, the trial should be terminated. Systematic mediastinal LND should no longer be recommended for patients with GGO-dominant lung adenocarcinoma.

Background: The radiologic and pathologic correlations of subsolid lung cancers are unclear. No study has used the whole-mount sections to analyze the correlations. This study aims to clarify the radiologic and pathologic correlations through the use of the whole-mount sections analysis. Methods: Patients with subsolid lung adenocarcinomas receiving segmentectomy or lobectomy were included. The whole-mount sections were made. The same radiologic and pathologic sections were identified. Radiologic and pathologic tumor and solid/invasive sizes were compared. Histologic features in the solid component and ground-glass opacity (GGO) regions were evaluated. Results: There were 102 patients with 20 pure GGO and 82 part-solid tumors analyzed. There was one adenocarcinoma in situ, 32 minimal invasive adenocarcinomas, and 69 invasive adenocarcinomas. For all patients or patients with the matched sections, radiologic tumor diameter was larger than pathologic one (P<0.001; P=0.009), while radiologic solid component diameter was smaller than that of pathologic invasive diameter (P=0.01; P<0.001). The clinical T stage was pathologically upstaged in nearly 50% of patients. For pure GGO tumors, prevalence of lepidic, acinar, and papillary subtypes was 100.0%, 84.2%, and 47.4%, with no micropapillary or solid subtype. For part-solid tumors, in the GGO region, prevalence of lepidic, acinar, papillary, and micropapillary subtypes was 100.0%, 83.3%, 57.1%, and 11.9%, no solid subtype existed. In the solid region, prevalence of lepidic, acinar, papillary, micropapillary, and solid subtypes was 19.0%, 95.2%, 59.5%, 26.2%, and 2.3%. Conclusions: For subsolid lung cancers, the pathologic invasive size was radiologically underestimated. There were acinar/papillary, but no micropapillary subtype in pure GGO tumors. In part-solid tumors, there were micropapillary subtypes in GGO region and micropapillary/solid subtypes in solid region.

Background: Ground glass opacity (GGO)-featured lung adenocarcinoma generally has excellent prognosis, and here is rarely the occurrence of lymph node metastasis. We conducted a retrospective cohort study to explore the prognostic impact of GGO component in node-positive lung adenocarcinomas. Methods: A total of 669 patients with pathologic N1/N2 lung adenocarcinoma receiving R0 resection and systemic lymph node dissection from 2008 to 2015 were reviewed, including 635 solid and 34 partsolid lesions. Propensity score matching (PSM) was performed to compare survival outcomes of solid and part-solid lesions, in order to determine the prognostic value of GGO component. Cox proportional hazard model was performed to identify significant prognostic factors for resected node positive lung adenocarcinoma. Results: About 5.1% (34 of 669) of resected node-positive lung adenocarcinoma presented as part-solid nodules on computed tomography (CT) images in this cohort. The median nodule size on CT of the 34 part-solid lesions was 31 mm (range, 15-68 mm), median solid component size on CT was 24 mm (range, 12-62 mm), and median consolidation/tumor ratio was 0.8 (range, 0.64-0.95). After 1:4 PSM, 136 patients and 34 patients were matched from the solid and part-solid groups. No significant difference in either recurrence-free survival (RFS) (P=0.71) or overall survival (OS) (P=0.82) was found between the solid and part-solid groups. Multivariable Cox regression showed that pN stage was the strongest prognostic factor for RFS and OS. GGO component was not an independent prognostic factor toward for RFS [P=0.75; hazard ratio (HR) =0.93; 95% confidence interval (CI): 0.59-1.46] or OS (P=0.53; HR =1.19; 95% CI: 0.69-2.05). Conclusions: A minority of resected node-positive lung adenocarcinoma presents as GGO component on CT. The presence of GGO component does not predict better prognosis in node-positive lung adenocarcinoma.

Purpose To construct radiomics models for predicting occult nodal metastasis (ONM) in cT1a-bN0M0-stage lung adenocarcinoma (LUAD) and evaluate the multi-center diagnostic performance of models. Methods 1672 patients from six hospitals were collected including training set (n = 687), test set (n = 297) and external validation set (n = 688). Generalized linear model (GLM), support vector machine (SVM), random forest (RF), gradient boosting machine (GBM) and the Clinical-Radiomics (Clinic-Rad) models were constructed and validated to predict ONM. Diagnostic performance was quantified by the area under receiver operative characteristic curve (AUC), and compared using De-Long test. Correlations of radiomics features with pathological characteristics were evaluated by Mantel-test. Results Compared to GLM-, SVM-, RF- and GBM-models, the Clinic-Rad model integrating clinical predictors and Radscore received superior diagnostic efficacy in validation set (0.813 ± 0.019 versus 0.790 ± 0.021, 0.761 ± 0.023, 0.708 ± 0.026, 0.769 ± 0.022; all P < 0.001), although no statistical differences in test set (0.834 ± 0.023 versus 0.827 ± 0.024, 0.829 ± 0.025, 0.838 ± 0.023, 0.826 ± 0.024; all P > 0.05). The pooled sensitivity, specificity, accuracy of the Clinic-Rad model was 77.2–75.8%, 72.0–72.7%, 72.7–74.4%. Besides, it was well predictive in solid- and subsolid-appearance LUAD respectively, with pooled AUC values of 0.802–0.820 and 0.797–0.917. Furthermore, radiomics models significantly outperformed clinical predictors including solid-component diameter, consolidation-to-tumor ratio, CEA level and the combined diagnosis (AUC values: versus 0.669–0.678, 0.542–0.600, 0.571–0.613 and 0.683–0.724; all P < 0.001). The Mantel-test demonstrated 88.9%(n = 16/18) of selected radiomics features, Radscore and predicted ONM possibilities were correlated with poorly-differentiated, lymph-vessel invasion, visceral pleura invasion. Conclusions Radiomics features are useful to predict ONM in cT1a-bN0M0-stage LUAD and the Clinic-Rad model shows the best diagnostic performance.

PurposeTo construct and validate a computed tomography (CT) radiomics model for differentiating lung neuroendocrine neoplasm (LNEN) from lung adenocarcinoma (LADC) manifesting as a peripheral solid nodule (PSN) to aid in early clinical decision-making.MethodsA total of 445 patients with pathologically confirmed LNEN and LADC from June 2016 to July 2023 were retrospectively included from five medical centers. Those patients were split into the training set (n = 316; 158 LNEN) and external test set (n = 129; 43 LNEN), the former including the cross-validation (CV) training set and CV test set using ten-fold CV. The support vector machine (SVM) classifier was used to develop the semantic, radiomics and merged models. The diagnostic performances were evaluated by the area under the receiver operating characteristic curve (AUC) and compared by Delong test. Preoperative neuron-specific enolase (NSE) levels were collected as a clinical predictor.ResultsIn the training set, the AUCs of the radiomics model (0.878 [95% CI: 0.836, 0.915]) and merged model (0.884 [95% CI: 0.844, 0.919]) significantly outperformed the semantic model (0.718 [95% CI: 0.663, 0.769], p both<.001). In the external test set, the AUCs of the radiomics model (0.787 [95% CI: 0.696, 0.871]), merged model (0.807 [95%CI: 0.720, 0.889]) and semantic model (0.729 [95% CI: 0.631, 0.811]) did not exhibit statistical differences. The radiomics model outperformed NSE in sensitivity in the training set (85.3% vs 20.0%; p <.001) and external test set (88.9% vs 40.7%; p = .002).ConclusionThe CT radiomics model could non-invasively, effectively and sensitively predict LNEN and LADC presenting as a PSN to assist in treatment strategy selection.

Background:The Japan Clinical Oncology Group (JCOG) 1211 suggested that segmentectomy should be considered as standard treatment for clinical T1N0 (cT1N0) ground glass opacity (GGO). However, over half of patients in JCOG1211 had pre-/minimal invasive adenocarcinoma. This study aims to retrospectively investigate the long-term survival of GGO featured cT1N0 invasive lung adenocarcinoma undergoing segmentectomy or lobectomy. Methods:This study screened patients with primary cT1N0 lung adenocarcinoma who received segmentectomy or lobectomy from 2010-2020. Prior computed tomography (CT) scans before surgery of all patients were reviewed and the inclusion was confirmed according to tumor diameter and consolidation tumor ratio (CTR). GGO nodules between 2-3 cm with CTR ≤0.5 or ≤2 cm with CTR between 0.25-0.5 were finally included. Patients with pathologically diagnosed pre-/minimally invasive lung adenocarcinoma were excluded. Long-term survivals between segmentectomy group and lobectomy group were compared after propensity score matching (PSM). Recurrence and postoperative complication events were also analyzed. Results:In total, 617 patients were enrolled, 159 received segmentectomy and 458 received lobectomy. Clinicopathological characteristics were well distributed between two groups. With a median follow-up time of 61.1 months (IQR: 42.3-71.7 months), after PSM, the 5-year overall survival rate was 98.8% (97.9-99.6%) for lobectomy and 99.3% (98.2-99.8%) for segmentectomy (P=0.42), the 5-year relapse-free survival rate was 95.3% (92.2-97.6%) for lobectomy and 95.2% for segmentectomy (92.3-98.7%) (P=0.81). The proportion of recurrence was 4.1% for lobectomy and 4.4% for segmentectomy (P=0.89). The proportion of grade 2 and above early postoperative complications was 9.6% for lobectomy and 8.8% for segmentectomy (P=0.86). Conclusions:For cT1N0 GGO featured invasive lung adenocarcinoma (2 cm < tumor diameter ≤3 cm, CTR ≤0.5 or tumor diameter ≤2 cm, 0.25< CTR ≤0.5), postoperative outcomes between segmentectomy group and lobectomy group were comparable. Concerning minimally invasive surgical strategy, segmentectomy should be confirmed as the standard surgical approach.

INTRODUCTION:We aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive NSCLC. METHODS:This is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio less than or equal to 0.5, segment location, lepidic-predominant adenocarcinoma (LPA), negative hilar nodes (stations 10-12), and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior, or inferior mediastinal zone. LPA, hilar node involvement, and VPI were diagnosed intraoperatively. All patients actually underwent systematic mediastinal LN dissection. The primary end point was the accuracy of the strategy in predicting LN involvement. If LN metastasis occurred in certain mediastinal zone that was predicted to be negative, it was considered as an "inaccurate" case. RESULTS:A total of 720 patients were enrolled. The median number of LN dissected was 15 (interquartile range: 11-20). All negative node status in certain mediastinal zone was correctly predicted by the strategy. Compared with final pathologic findings, the accuracy of frozen section to diagnose LPA, VPI, and hilar node metastasis was 94.0%, 98.9%, and 99.6%, respectively. Inaccurate intraoperative diagnosis of LPA, VPI, or hilar node metastasis did not lead to inaccurate prediction of node-negative status. CONCLUSIONS:This is the first prospective trial validating the specific mediastinal LN metastasis pattern in cT1N0 invasive NSCLC, which provides important evidence for clinical applications of selective LN dissection strategy.

Background: Patients harboring anaplastic lymphoma kinase (ALK) or rearranged during transfection (RET) rearrangements are usually diagnosed at a relatively late stage with nodal and distant metastasis, and rapid progression course of ALK/RET fusion-positive lung cancer were well-known. However, clinical characteristics and course of pre-/minimally invasive lung adenocarcinoma harboring ALK or RET fusions are poorly described. Identifying patients with gene fusions at early stage may offer surgical options that could cure those patients.Methods: We retrospectively included patients with surgically resected pre-/minimally invasive lung adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations or ALK/RET rearrangements, and further compared the patient clinical characteristics, nodule natural course, and survival outcomes. Radiological characteristics including ground-glass component, cystic airspace, pleural attachment, etc. were specially assessed for this study. EGFR (exons 18-22) was detected by Sanger sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the ALK/ RET rearrangements. Lung cancer-specific survival (LCSS), relapse-free survival (RFS), and overall survival (OS) were all evaluated.Results: Of 238 patients with pre-/minimally invasive lung adenocarcinomas, 226 patients had EGFR mutations, 7 patients had ALK fusions, and 5 patients had RET fusions. Average age at surgery was 45.3 years for ALK/RET-positive group and 52.6 years for EGFR-positive group (P=0.049). Radiologically, among the 12 patients with ALK/RET fusions, the majority of lesions (10/12) manifested as mixed ground-glass opacities (mGGOs), which was significantly more prevalent when compared with patients with EGFR mutations (83.4% vs. 24.3%, P<0.001). Moreover, a substantial proportion of cystic airspace was found in ALK/RET- positive group but not in EGFR-positive group (66.7% vs. 14.2%, P<0.001). Among four patients with ALK/ RET fusions undergoing surveillance over 1 year before surgery, two of them developed rapid radiologic progression. The 5-year LCSS and RFS were 100%, 100% for ALK/RET-positive group, and 100%, 100% for EGFR-positive group, respectively. Conclusions: ALK/RET-positive pre-/minimally invasive lung adenocarcinomas were mostly characterized as mGGOs with cystic airspace developing rapid nodule progression, and no recurrence occurred during long-term follow-up after resection. This provides insights into proper curative surgery timing in the management of patients with gene fusions. However, these findings must be treated with caution and validated in future multi-center studies with larger sample size.

Background Although subcentimeter nodules represent precursor or minimally invasive lung cancer in most cases, there are still a few that are subcentimeter invasive adenocarcinoma (IAC). The aim of this study was to investigate the prognostic effect of ground-glass opacity (GGO) and the optimal surgical procedure in this special group. Methods Patients with subcentimeter IAC were enrolled and were categorized into pure GGO, part-solid, and solid nodules based on the radiological appearance. Cox proportional hazards model and the Kaplan-Meier method were used for survival analyses. Results A total of 247 patients were enrolled. Among them, 66 (26.7%) were in the pure-GGO group, 107 (43.3%) were in the part-solid group, and 74 (30.0%) were in the solid group. Survival analysis demonstrated a significantly worse survival in the solid group. Cox multivariate analyses confirmed that the absence of GGO component was an independent risk factor for worse recurrence-free survival (RFS) and overall survival (OS). As for surgical procedures, lobectomy did not provide a significant better RFS or OS than sublobar resection in the whole cohort or in a subgroup of patients with solid nodules. Conclusions The radiological appearance stratified the prognosis of IAC with size of smaller than or equal to 1 cm. Sublobar resection may be feasible for subcentimeter IAC, even for those appearing as solid nodules; however, caution should be taken when applying wedge resection.

BACKGROUND:Previously, we have demonstrated that the 5-year recurrence-free survival after surgery of pure ground-glass opacity (GGO)-featured lung adenocarcinoma is 100%. This study aimed to reveal the long-term outcomes of these patients 10 years after surgery. METHODS:Lung adenocarcinoma patients who underwent surgery between December 2007 and December 2013 were reviewed. Patients with pure GGO-featured lung adenocarcinoma were enrolled. Postoperative survival and the risk of developing second primary lung cancer were analyzed. RESULTS:Overall, 308 cases of pure GGO-featured lung adenocarcinomas were included. Of these patients, 226 (73.4%) were female, 268 (87.0%) were nonsmokers, and 187 (60.7%) underwent sublobar resection. The median follow-up period after surgery was 112 months. The 10-year recurrence-free survival rate of these patients was 100%, and 10-year overall survival rate was 96.9%. Both 5-year and 10-year lung cancer-specific survival were 100%. There was no difference in 10-year recurrence-free survival rates between patients who underwent lobectomy or sublobar resection (P = .697). EGFR mutations were detected in 55.6% (84 of 151) of patients who underwent mutational analysis. The risk of developing secondary primary lung cancer for pure GGO-featured lung adenocarcinoma patients at 10 years after resection was 2.4%, and was not correlated with EGFR mutation status (P = .452). CONCLUSIONS:No recurrence was observed in patients with pure GGO-featured lung adenocarcinomas 10 years after surgery, even when pathologically evaluated as invasive adenocarcinoma. Pure GGO can be cured by surgery. Surgery is recommended for the appropriate time window with the view to cure. Our study emphasizes that radiologic pure GGO-featured lung adenocarcinomas should be distinguished from other lung adenocarcinomas.

Importance:It is currently unclear whether high-resolution computed tomography can preoperatively identify pathologic tumor invasion for ground-glass opacity lung adenocarcinoma. Objectives:To evaluate the diagnostic value of high-resolution computed tomography for identifying pathologic tumor invasion for ground-glass opacity featured lung tumors. Design, Setting, and Participants:This prospective, multicenter diagnostic study enrolled patients with suspicious malignant ground-glass opacity nodules less than or equal to 30 mm from November 2019 to July 2021. Thoracic high-resolution computed tomography was performed, and pathologic tumor invasion (invasive adenocarcinoma vs adenocarcinoma in situ or minimally invasive adenocarcinoma) was estimated before surgery. Pathologic nonadenocarcinoma, benign diseases, or those without surgery were excluded from analyses; 673 patients were recruited, and 620 patients were included in the analysis. Statistical analysis was performed from October 2021 to January 2022. Exposure:Patients were grouped according to pathologic tumor invasion. Main Outcomes and Measures:Primary end point was diagnostic yield for pathologic tumor invasion. Secondary end point was diagnostic value of radiologic parameters. Results:Among 620 patients (442 [71.3%] female; mean [SD] age, 53.5 [12.0] years) with 622 nodules, 287 (46.1%) pure ground-glass opacity nodules and 335 (53.9%) part-solid nodules were analyzed. The median (range) size of nodules was 12.1 (3.8-30.0) mm; 47 adenocarcinomas in situ, 342 minimally invasive adenocarcinomas, and 233 invasive adenocarcinomas were confirmed. Overall, diagnostic accuracy was 83.0% (516 of 622; 95% CI, 79.8%-85.8%), diagnostic sensitivity was 82.4% (192 of 233; 95% CI, 76.9%-87.1%), and diagnostic specificity was 83.3% (324 of 389; 95% CI, 79.2%-86.9%). For tumors less than or equal to 10 mm, 3.6% (8 of 224) were diagnosed as invasive adenocarcinomas. The diagnostic accuracy was 96.0% (215 of 224; 95% CI, 92.5%-98.1%), diagnostic specificity was 97.2% (210 of 216; 95% CI, 94.1%-99.0%); for tumors greater than 20 mm, 6.9% (6 of 87) were diagnosed as adenocarcinomas in situ or minimally invasive adenocarcinomas. The diagnostic accuracy was 93.1% (81 of 87; 95% CI, 85.6%-97.4%) and diagnostic sensitivity was 97.5% (79 of 81; 95% CI, 91.4%-99.7%). For tumors between 10 to 20 mm, the diagnostic accuracy was 70.7% (220 of 311; 95% CI, 65.3%-75.7%), diagnostic sensitivity was 75.0% (108 of 144; 95% CI, 67.1%-81.8%), and diagnostic specificity was 67.1% (112 of 167; 95% CI, 59.4%-74.1%). Tumor size (odds ratio, 1.28; 95% CI, 1.18-1.39) and solid component size (odds ratio, 1.31; 95% CI, 1.22-1.42) could each independently serve as identifiers of pathologic invasive adenocarcinoma. When the cutoff value of solid component size was 6 mm, the diagnostic sensitivity was 84.6% (95% CI, 78.8%-89.4%) and specificity was 82.9% (95% CI, 75.6%-88.7%). Conclusions and relevance:In this diagnostic study, radiologic analysis showed good performance in identifying pathologic tumor invasion for ground-glass opacity-featured lung adenocarcinoma, especially for tumors less than or equal to 10 mm and greater than 20 mm; these results suggest that a solid component size of 6 mm could be clinically applied to distinguish pathologic tumor invasion.

Background: The eighth T classification excluded lepidic and ground-glass opacity (GGO) components. Current studies demonstrated lepidic and GGO components showed independent prognostic significances. This study elucidated the correlations and prognostic impacts of pathological and radiological T descriptors in invasive lung adenocarcinoma. Methods: A total of 1,490 patients with invasive lung adenocarcinoma were retrospectively reviewed. Correlation between pathological invasive size (PIS) and radiological solid size (RSS), and lepidic ratio and GGO ratio were comprehensively evaluated. Impacts of these pathological and radiological T descriptors on recurrence-free survival (RFS) were comparatively analyzed. Results: Clinical (c)T-stage was more frequently downstaged than upstaged comparing with the pathological (p)T-stage (28.4% vs. 18.2%). The correlation between PIS and RSS in solid nodule was stronger than that in part-solid nodule (solid: R2=0.750 vs. part-solid: R2=0.355). Some pathological invasive components except solid component were featured as GGO. Among T1 patients, lepidic absent GGO showed better RFS than lepidic present solid nodule (pT1: P=0.001; cT1: P=0.021). Multivariable analysis revealed GGO ratio was an independent prognostic factor for RFS in T1 invasive lung adenocarcinoma, whereas lepidic ratio was not. Conclusions: Among T1 invasive lung adenocarcinoma, GGO ratio showed independent prognostic value for RFS, regardless of RSS. Meanwhile, lepidic ratio was not an independent RFS factor. GGO component rather than lepidic component should be considered as an additional T descriptor.

BACKGROUND: Traditional iliac screw, S2-alar iliac screw, and modified iliac screw are the 3 common techniques for lumbopelvic fixation. The application of the modified iliac technique in sacral spinal tumors has been rarely reported. OBJECTIVE: To report the feasibility and safety of modified iliac screws after sacral tumor resection and their preliminary clinical outcomes. METHODS: Twenty-seven patients who underwent sacral tumor resection with modified iliac screw fixation between August 2017 and August 2021 at our center were clinically and radiographically evaluated. RESULTS: A total of 59 iliac screws were inserted by freehand according to the anatomic landmarks. The mean operation time was 207 minutes (range, 140-435 minutes). The average estimated blood loss was 1396 mL (300-4200 mL). Computed tomography scans showed that 2 (3.4%) screws penetrated the iliac cortex, indicating a 96.6% implantation accuracy rate. There were no iatrogenic neurovascular or visceral structure complications observed. The mean minimal distances from the screw head to the skin were 24.9 and 25.8 mm on the left and right sides, respectively. The mean minimal distances from the screw head to the horizontal level of the posterior superior iliac spine were 7.9 and 8.3 mm on the left and right sides, respectively. Two patients (7.4%) underwent reoperation for wound infection. At the latest follow-up, no patient had complications of screw head prominence, pseudarthrosis, or instrument failure. CONCLUSION: The modified iliac screw is characterized by its minimal invasiveness and simplicity of placement. It is an ideal alternative for lumbopelvic fixation after sacral tumor resection.