Genomic landscape of glioblastoma without IDH somatic mutation in 42 cases: a comprehensive analysis using RNA sequencing data.

PURPOSE: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing. PATIENTS AND METHODS: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes. RNA was extracted from frozen specimens and sequenced, and genetic analyses were performed using the CLC Genomics Workbench. RESULTS: The most common genetic alterations in the 42 glioblastoma specimens were TP53 mutation (28.6%), EGFR splicing variant (16.7%), EGFR mutation (9.5%), and FGFR3 fusion (9.5%). Novel genetic mutations were detected in 8 patients (19%). In 12 cases (28.6%), driver gene mutations were not detected, suggesting an association with PPP1R14A overexpression. Our findings suggest the transcription factors SOX10 and NKX6-2 are potential markers in glioblastoma. CONCLUSION: RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.

The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma.

Introduction: Immune checkpoint inhibitors have recently been approved for the treatment of early-stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. Methods: This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8+ tumor-infiltrating lymphocyte density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis. Results: A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo-not reached; n = 39) and 23.7 months (95% CI: 14.5-43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank p = 0.02, hazard ratio of 0.52 [95% CI: 0.29-0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions: PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.

Optimizing smartphone psychotherapy for depressive symptoms in patients with cancer: Multiphase optimization strategy using a decentralized multicenter randomized clinical trial (J-SUPPORT 2001 Study).

AIM: Patients with cancer experience various forms of psychological distress, including depressive symptoms, which can impact quality of life, elevate morbidity risk, and increase medical costs. Psychotherapy and pharmacotherapy are effective for reducing depressive symptoms among patients with cancer, but most patients prefer psychotherapy. This study aimed to develop an efficient and effective smartphone psychotherapy component to address depressive symptom. METHODS: This was a decentralized, parallel-group, multicenter, open, individually randomized, fully factorial trial. Patients aged ≥20 years with cancer were randomized by the presence/absence of three cognitive-behavioral therapy (CBT) skills (behavioral activation [BA], assertiveness training [AT], and problem-solving [PS]) on a smartphone app. All participants received psychoeducation (PE). The primary outcome was change in the patient health questionnaire-9 (PHQ-9) total score between baseline and week 8. Secondary outcomes included anxiety. RESULTS: In total, 359 participants were randomized. Primary outcome data at week 8 were obtained for 355 participants (99%). The week 8 PHQ-9 total score was significantly reduced from baseline for all participants by -1.41 points (95% confidence interval [CI] -1.89, -0.92), but between-group differences in change scores were not significant (BA: -0.04, 95% CI -0.75, 0.67; AT: -0.16, 95% CI -0.87, 0.55; PS: -0.19, 95% CI -0.90, 0.52). CONCLUSION: As the presence of any of the three intervention components did not contribute to a significant additive reduction of depressive symptoms, we cannot make evidence-based recommendations regarding the use of specific smartphone psychotherapy.

Impact of intrapulmonary tumour location of non-small-cell lung cancer on surgical outcomes for segmentectomy.

OBJECTIVES: While segmentectomy is considered a viable option for small peripheral non-small-cell lung cancer, its efficacy for central lesions remains uncertain. This study aimed to assess the oncological outcomes of segmentectomy for central lesions compared to peripheral ones. METHODS: We retrospectively examined 338 clinical stage IA non-small-cell lung cancer patients who underwent thoracoscopic anatomical segmentectomy at our institution from January 2013 to December 2021. Patients were divided into 2 groups based on intrapulmonary tumour location: inner two-thirds (central group, n = 82) and outer one-third (peripheral group, n = 256). RESULTS: The gender, body mass index, performance score, smoking, comorbidities and preoperative pulmonary function were similar in both groups. On computed tomography images, tumour diameter and consolidation-to-tumour ratio were comparable between the groups. The central group had significantly greater tumour-to-pleura distances [mm, 23 (18-27) vs 11 (8-14); P < 0.001], shorter margin distances [mm, 20 (15-20) vs 20 (20-20); P < 0.001] and larger resected lung volumes based on subsegment count [4 (3-6) vs 3 (3-5); P = 0.004] than the peripheral group. Surgery duration, bleeding, hospitalization or drainage period, mortality, readmission and pathological stage were equivalent between the groups. The central group showed significantly more postoperative pleural effusions (5% vs 1%; P = 0.03) than the peripheral group, with no adverse impact on postoperative pulmonary functions. During the follow-up period, local-only recurrence rates were 0% and 8% in the respective groups (Gray test P = 0.07), and total recurrence rates were 6% and 11% (Gray test P = 0.70), with no significant differences. Moreover, no significant inter-group difference in overall survival rates was observed (82% vs 93%; P = 0.15). CONCLUSIONS: Segmentectomy may be a promising therapeutic option for early-stage non-small-cell lung cancer located in the inner two-thirds of the parenchyma.

Current diagnosis and treatment of salivary gland-type tumors of the lung.

Salivary gland-type tumors of the lung are thought to originate from the submucosal exocrine glands of the large airways. Due to their rare occurrence, reports of their study are limited to small-scale or case reports. Therefore, daily clinical practices often require a search for previous reports. In the last 20 years, several genetic rearrangements have been identified, such as MYB::NF1B rearrangements in adenoid cystic carcinoma, CRTC1::MAML2 rearrangements in mucoepidermoid carcinoma, EWSR1::ATF1 rearrangements in hyalinizing clear cell carcinoma and rearrangements of the EWSR1 locus or FUS (TLS) locus in myoepithelioma and myoepithelial carcinoma. These molecular alterations have been useful in diagnosing these tumors, although they have not yet been linked to molecularly targeted therapies. The morphologic, immunophenotypic, and molecular characteristics of these tumors are similar to those of their counterparts of extrapulmonary origin, so clinical and radiologic differential diagnosis is required to distinguish between primary and metastatic disease of other primary sites. However, these molecular alterations can be useful in differentiating them from other primary lung cancer histologic types. The management of these tumors requires broad knowledge of the latest diagnostics, surgery, radiotherapy, bronchoscopic interventions, chemotherapy, immunotherapy as well as therapeutic agents in development, including molecularly targeted agents. This review provides a comprehensive overview of the current diagnosis and treatment of pulmonary salivary gland tumors, with a focus on adenoid cystic carcinoma and mucoepidermoid carcinoma, which are the two most common subtypes.

Development of predictive models for assessing the progression and invasiveness of satellite lesions in patients with multiple pulmonary ground glass nodules.

Background: Currently, the appropriate treatment of satellite lesions is still controversial. With this study, we aimed to construct a set of nomograms to determine the characteristics of satellite lesions in patients with multiple pulmonary ground glass nodules (MPGGNs) and propose a reference for the management of satellite lesions. Methods: We retrospectively analyzed patients with MPGGNs who had undergone multiple rounds of surgical resection of primary and satellite lesions, including pathologic examinations after surgical resection. Results: A total of 125 lesions from 105 patients were included in the analysis; 85 lesions were advanced and 40 lesions were not advanced. Among them, 55 invasive pulmonary adenocarcinomas (IPA) and 70 noninvasive pulmonary adenocarcinomas were identified. After the final regression analysis, the patients' age, satellite lesion location, consolidation tumor ratio (CTR), lesion border clarity, and lesion diameter were used to predict satellite lesion progression. Patients' gender, satellite lesion location, lesion diameter, and computed tomography (CT) attenuation values were used to predict the invasiveness of the satellite lesion. The constructed nomograms showed strong discrimination with concordance indices (C indices) of 0.816 and 0.823, respectively. Conclusions: We developed a set of nomograms that can predict the risk of advanced or invasive satellite lesions in patients with MPGGNs. The area under the receiver operating characteristic (ROC) curve (AUC), the C-index, and the calibration curve suggest that the nomogram may be useful in the clinical setting. This model has the potential to help clinicians make treatment recommendations for the remaining lesions while treating the primary lesion in patients with MPGGNs.

Lack of Association of Plasma Levels of Soluble Programmed Cell Death Protein 1, Programmed Death-Ligand 1, and CTLA-4 With Survival for Stage II to IIIA NSCLC After Complete Resection and Adjuvant Chemotherapy.

Introduction: Perioperative treatment in NSCLC has gained marked attention with the introduction of immune checkpoint inhibitors. Such a paradigm shift has given us additional opportunities to evaluate potential biomarkers in patients with these curable disease stages. Methods: This study (WJOG12319LTR) was designed as a biomarker study to evaluate whether soluble immune markers were prognostic or predictive on relapse-free survival in patients with stage II to IIIA NSCLC who underwent complete resection and adjuvant chemotherapy with cisplatin plus S-1, which is an oral fluoropyrimidine formulation that consists of tegafur, gimeracil, and oteracil, or S-1 alone in the previous WJOG4107 study. Archived plasma samples were assayed for soluble (s) forms of programmed cell death protein 1 (sPD-1), programmed death-ligand 1(sPD-L1), and CTLA-4 (sCTLA-4) with the highly sensitive HISCL system. Using time-dependent receiver operating characteristic curve analysis, the area under the curves were derived and optimal cutoff values were determined. Using the cutoff values, whether the marker was prognostic or predictive was assessed by survival analysis. Results: A total of 150 patients were included in the study. The time-dependent receiver operating characteristics analysis revealed that the area under the curves for sPD-1, sPD-L1, and sCTLA-4 were 0.54, 0.51, and 0.58, respectively. The survival analysis did not reject that hazard ratios were 1 in terms of the soluble immune marker and the treatment-marker interaction for all three markers. Conclusions: There was no proof that circulating concentrations of sPD-1, sPD-L1, and sCTLA-4 were prognostic or predictive factors of the outcome for adjuvant chemotherapy after complete resection in patients with NSCLC.

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.

BACKGROUND: Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes. METHODS: We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (≥1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally). RESULTS: A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P = 0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete response benefit were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the modified intention-to-treat population. CONCLUSIONS: In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. (Funded by AstraZeneca; AEGEAN ClinicalTrials.gov number, NCT03800134.).

Single-cell sequencing on CD8+ TILs revealed the nature of exhausted T cells recognizing neoantigen and cancer/testis antigen in non-small cell lung cancer.

BACKGROUND: CD8+tumor infiltrating lymphocytes (TILs) are often observed in non-small cell lung cancers (NSCLC). However, the characteristics of CD8+ TILs, especially T-cell populations specific for tumor antigens, remain poorly understood. METHODS: High throughput single-cell RNA sequencing and single-cell T-cell receptor (TCR) sequencing were performed on CD8+ TILs from three surgically-resected lung cancer specimens. Dimensional reduction for clustering was performed using Uniform Manifold Approximation and Projection. CD8+ TIL TCR specific for the cancer/testis antigen KK-LC-1 and for predicted neoantigens were investigated. Differentially-expressed gene analysis, Gene Set Enrichment Analysis (GSEA) and single sample GSEA was performed to characterize antigen-specific T cells. RESULTS: A total of 6998 CD8+ T cells was analyzed, divided into 10 clusters according to their gene expression profile. An exhausted T-cell (exhausted T (Tex)) cluster characterized by the expression of ENTPD1 (CD39), TOX, PDCD1 (PD1), HAVCR2 (TIM3) and other genes, and by T-cell oligoclonality, was identified. The Tex TCR repertoire (Tex-TCRs) contained nine different TCR clonotypes recognizing five tumor antigens including a KK-LC-1 antigen and four neoantigens. By re-clustering the tumor antigen-specific T cells (n=140), it could be seen that the individual T-cell clonotypes were present on cells at different stages of differentiation and functional states even within the same Tex cluster. Stimulating these T cells with predicted cognate peptide indicated that TCR signal strength and subsequent T-cell proliferation and cytokine production was variable but always higher for neoantigens than KK-LC-1. CONCLUSIONS: Our approach focusing on T cells with an exhausted phenotype among CD8+ TILs may facilitate the identification of tumor antigens and clarify the nature of the antigen-specific T cells to specify the promising immunotherapeutic targets in patients with NSCLC.

Divided method of intercostal nerve block reduces ropivacaine dose by half in thoracoscopic pulmonary resection while maintaining the postoperative pain score and 4-h mobilization: a retrospective study.

PURPOSE: This study investigated whether the divided method of multi-level intercostal nerve block (ML-ICB) could reduce the ropivacaine dose required during thoracoscopic pulmonary resection, while maintaining the resting postoperative pain scores. METHODS: This retrospective, single-cohort study enrolled 241 patients who underwent thoracoscopic pulmonary resection for malignant tumors between October 2020 and March 2022 at a cancer hospital in Japan. ML-ICB was performed by surgeons under direct vision. The differences in intraoperative anesthetic use and postoperative pain-related variables at the beginning and end of surgery between group A (single-shot ML-ICB; 0.75% ropivacaine, 20 mL at the end of the surgery) and group B (divided ML-ICB, performed at the beginning and end of surgery; 0.25% ropivacaine, 30 mL total) were assessed. The numerical rating scale (NRS) was used to evaluate pain 1 h and 24 h postoperatively. RESULTS: Intraoperative remifentanil use was significantly lower in group B (14.4 ± 6.4 µg/kg/h) than in group A (16.7 ± 8.4 µg/kg/h) (P = 0.02). The proportion of patients with NRS scores of 0 to 3 at 24 h was significantly higher in group B (85.4%, 106/124) than in group A (73.5%, 86/117) (P = 0.02). The proportion of patients not requiring postoperative intravenous rescue drugs was significantly higher in group B (78.2%, 97/124) than in group A (61.5%, 72/117) (P < 0.01). CONCLUSION: The divided method of ML-ICB could reduce the intraoperative remifentanil dose, decrease the postoperative pain score at 24 h, and curtail postoperative intravenous rescue drug use, despite using half the total ropivacaine dose intraoperatively.

Effects of a ground-glass opacity component on the recurrence and survival of pathological stage IA3 lung adenocarcinoma: a multi-institutional retrospective study.

Background: This study aimed to evaluate the effect of the presence of a radiographically manifested ground-glass opacity (GGO) component on the prognosis of patients with pathological stage IA3 lung adenocarcinoma. Methods: Patients diagnosed with pathological stage IA3 lung adenocarcinoma who underwent radical surgery at two medical institutions in China between July 2012 and July 2020 were enrolled. The cumulative incidence of recurrence (CIR) and cumulative incidence of death (CID) in patients with and without a GGO component were compared. Risk curves for the recurrence and tumor-related death overtime were analyzed between the two groups according to life table. In order to validate the prognostic value of GGO components, the recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated. Decision curve analysis (DCA) was performed to evaluate the clinical benefit rate of different models. Results: Among the 352 included patients, the presence of a GGO component was radiographically shown in 166 (47.2%) patients, while 186 (52.8%) displayed solid nodules. Patients exhibiting the absence of a GGO component had higher incidences of total recurrence (17.2% vs. 3.0%, P<0.001), local-regional recurrence (LRR) (5.4% vs. 0.6%, P=0.010), distant metastasis (DM) (8.1% vs. 1.8%, P=0.008), and multiple recurrences (4.3% vs. 0.6%, P=0.028) than the presence-GGO component group. The 5-year CIR and CID were 7.5% and 7.4% in the presence-GGO component group, and 24.5% and 17.0% in the absence-GGO component group, respectively, with statistically significant differences between the two groups (P<0.05). The risk of recurrence in patients with the presence of GGO components showed a single peak at 3 years postoperatively, while patients with the absence of GGO components showed a double peak at 1 and 5 years after surgery, respectively. However, the risk of tumor-related death peaked in both groups at 3 and 6 years postoperatively. Multivariate Cox analysis showed that the presence of a GGO component was a favorable independent risk factor for pathological stage IA3 lung adenocarcinoma patients (P<0.05). Conclusions: Pathological stage IA3 lung adenocarcinoma with or without GGO components are two types of tumors with different invasive abilities. In clinical practice, we should develop different treatment and follow-up strategies.

Thoracoscopic Anatomical Sublobar Resection Including Subsegmentectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Among anatomical sublobar resection techniques for non-small cell lung cancer (NSCLC), the clinical benefit of subsegmentectomy remains unclear. We investigated whether anatomical sublobar resection including subsegmentectomy-segmental resection with subsegmental additional resection or subsegmental resection alone-is an effective and feasible surgical procedure for NSCLC. METHODS: We retrospectively reviewed data of 285 patients with clinical stage I NSCLC who underwent anatomical sublobar resection at our institution from January 2013 to March 2021 and compared surgical outcomes between patients who underwent anatomical sublobar resection including (IS; n = 50) and excluding (ES; n = 235) subsegmentectomy. RESULTS: No significant intergroup differences were noted in terms of age, sex, smoking, comorbidities, tumor size or location, consolidation tumor ratio, and preoperative pulmonary function. The IS group had more preoperative computed tomography-guided markings (34 vs. 15%; p = .004) and smaller resected lung volumes converted to the total subsegment number [3 (2-4) vs. 3 (3-6); p = .02] than the ES group. No significant differences in margin distance [mm, 20 (15-20) vs. 20 (20-20); p = .93], readmission rate (2% vs. 3%; p > .99), and intraoperative (8% vs. 7%; p = .77) or postoperative (8% vs. 10%; p = .80) complication rates were observed, and the 5-year local recurrence-free survival (91% vs. 90%; p = .92) or postoperative pulmonary function change were comparable between both groups. CONCLUSIONS: Although further investigations are required, anatomical sublobar resection including subsegmentectomy for clinical stage I NSCLC could be an acceptable therapeutic option.

Risk-adjusted hazard analysis of survival after pulmonary metastasectomy for uterine malignancies in 319 cases.

Objective: There is little evidence of the outcome of pulmonary metastasectomy for uterine tumors when comparing different histologies. This study aimed to delineate the primary histology that leads to more favorable outcomes after pulmonary metastasectomy. Methods: The database of the Metastatic Lung Tumor Study Group of Japan for 1984 to 2016 was used to analyze the outcomes of patients with gynecologic malignancies who underwent pulmonary metastasectomy. Prognostic factors and long-term outcomes were compared according to the histology of the primary uterine tumors, specifically adenocarcinoma, squamous cell carcinoma, and sarcoma. The adjusted hazard risks according to disease-free intervals (DFIs) and the number and maximum size of resected tumors were also analyzed to delineate the pattern of risk trends. Results: A total of 319 patients were included in the analysis (122 with adenocarcinomas, 113 with squamous cell carcinomas, 46 with sarcomas, and 38 with other types). The 5-year survival rate was 66.5% for the entire cohort, 71.6% for the patients with adenocarcinoma, 61.3% for those with squamous cell carcinoma, and 55.4% for those with sarcoma. Multivariate analyses identified the positive prognostic factors as DFI ≥12 months in adenocarcinoma and sarcoma and the primary site (corpus) of uterine tumors in adenocarcinoma. The nonlinear adjusted hazard risks indicated that a shorter DFI was associated with an elevated risk of death in patients with adenocarcinoma and sarcoma. Conclusions: The survival outcome after pulmonary metastasectomy varies according to primary tumor histology, and the prognostic factors differ among histologic subtypes. Surgical indications should be determined based on the prognostic factors for each histology.

Mucous Gland Adenoma of the Lung: A Neoplastic Counterpart of Mucinous Bronchial Glands.

Mucous gland adenoma (MGA) is a rare benign tumor that usually arises in the proximal airway and consists of mucus-secreting cells resembling bronchial glands. Here, we report 2 cases of MGAs and describe their morphologic, immunohistochemical, and molecular profiles in comparison with 19 pulmonary tumors of 5 other histologic types with mucinous cells (invasive mucinous adenocarcinoma, mucoepidermoid carcinoma, mixed squamous cell and glandular papilloma, bronchiolar adenoma/ciliated muconodular papillary tumor, and sialadenoma papilliferum). Two MGAs were found in 1 male patient and 1 female patient, located in the bronchus and trachea, respectively. One MGA was examined by RNA sequencing, and no putative driver mutations (including BRAF, KRAS, and AKT1 mutations) or gene fusions were identified. In another case of MGA, V600E mutations of BRAF and E17K mutations of AKT1 were not detected by allele-specific real-time PCR or digital PCR, respectively. However, a gene expression analysis revealed that the MGA presented a specific RNA expression profile with multiple genes enriched in the salivary gland. The gene expression of NKX3.1 was significantly higher in the MGA case in comparison to normal control lungs (P < .001). We then examined NKX3.1 immunohistochemistry for 2 MGAs and 19 tumors of 5 other histologic types. NKX3.1 was positive in MGA (2/2, 100%), whereas all constituent cells, including mucinous cells, were negative for NKX3.1 in other histologic types (0%, 0/19). In normal lung tissue, NKX3.1 was positive for mucinous acinar cells of the bronchial glands. In conclusion, the gene expression profile, taken together with the histologic similarity between MGA and bronchial glands, and the preferred location of the tumors (proximal airways with submucosal glands) suggest that MGA is a neoplastic counterpart of mucinous bronchial glands. NKX3.1 immunohistochemistry can be a sensitive and specific ancillary marker that distinguishes MGA from other histologic mimics.

Segmentectomy for ground-glass-dominant lung cancer with a tumour diameter of 3 cm or less including ground-glass opacity (JCOG1211): a multicentre, single-arm, confirmatory, phase 3 trial.

BACKGROUND: Although segmentectomy is a widely used surgical procedure, lobectomy is the standard procedure for resectable non-small-cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of segmentectomy for NSCLC up to 3 cm in size, including ground-glass opacity (GGO) and predominant GGO. METHODS: A multicentre, single-arm, confirmatory phase 3 trial was conducted across 42 institutions (hospitals, university hospitals, and cancer centres) in Japan. Segmentectomy with hilar, interlobar, and intrapulmonary lymph node dissection was performed as protocol surgery for patients with a tumour diameter of up to 3 cm, including GGO and dominant GGO. Eligible patients were those aged 20-79 years with an Eastern Cooperative Oncology Group performance score of 0 or 1 and clinical stage IA tumour confirmed by thin-sliced CT. The primary endpoint was 5-year relapse-free survival (RFS). This study is registered with the University Hospital Medical Information Network Clinical Trials (UMIN000011819), and is ongoing. FINDINGS: A total of 396 patients were registered from Sept 20, 2013, to Nov 13, 2015, of whom 357 underwent segmentectomy. At a median follow-up of 5·4 years (IQR 5·0-6·0), the 5-year RFS was 98·0% (95% CI 95·9-99·1). This finding exceeded the 87% of the pre-set threshold 5-year RFS and the primary endpoint was met. Grade 3 or 4 early postoperative complications occurred in seven patients (2%), but no grade 5 treatment-related deaths occurred. INTERPRETATION: Segmentectomy should be considered as part of standard treatment for patients with predominantly GGO NSCLC with a tumour size of 3 cm or less in diameter, including GGO even if it exceeds 2 cm. FUNDING: National Cancer Centre Research and Development Fund and Japan Agency for Medical Research and Development.

The beginning of a new era in induction treatment for operable non-small cell lung cancer: a narrative review.

Background and Objective: The survival benefit of induction therapy for non-small cell lung cancer (NSCLC) remains controversial. Recently, the outcomes of systemic therapy for NSCLC have dramatically changed with the advent of molecular target drugs and immune checkpoint inhibitors (ICIs). The present review was conducted to investigate the outcomes of induction therapy with reference to randomized control trials (RCTs). Methods: We reviewed RCTs and ongoing clinical trials between 1990 and 2022 using relevant databases: PubMed, Web of Science, and EMBASE database. We investigated the outcomes of induction therapy. Key Content and Findings: Induction therapy was associated with longer overall survival in comparison to surgery alone in several RCTs for stage III disease. However, its benefit in early-stage (I-II) disease was unclear. Regarding induction chemotherapy and chemoradiotherapy, the safety and survival outcomes did not differ between the two arms. Epidermoid growth factor receptor (EGFR) tyrosine kinase inhibitors as induction therapy in patients with proven EGFR mutations may be a sufficient choice for the improvement of overall survival. In ongoing single arm clinical trials and a randomized control study, the administration of ICIs as induction therapy was associated with a good pathological response and satisfactory safety, which will lead to a better survival outcome. Long-term observation is needed to evaluate the toxicity and survival impact of induction therapy with ICIs. Conclusions: Induction chemotherapy and EGFR-TKIs for stage IIIA NSCLC may contribute to the improvement of survival outcomes although the effect of systemic therapy on stage I-II remains controversial. ICIs may be considered as a valuable treatment option because of their feasibility and safety for induction therapy.

Survival after Lung Metastasectomy from Esophageal Cancer: Results from a Multi-Institutional Database.

To clarify the clinical impact and to identify prognostic predictors of surgical intervention for pulmonary metastasis from esophageal cancer, a registry database analysis was performed. From January 2000 to March 2020, patients who underwent resection of pulmonary metastases from primary esophageal cancer at 18 institutions were registered in a database developed by the Metastatic Lung Tumor Study Group of Japan. An amount of 109 cases were reviewed and examined for the prognostic factors for pulmonary metastasectomy of metastases from esophageal cancer. As a result, five-year overall survival after pulmonary metastasectomy was 34.4% and five-year disease-free survival was 22.1%. The multivariate analysis for overall survival revealed that initial recurrence site, maximum tumor size, and duration from primary tumor treatment to lung surgery were selected as the significant prognostic factors (p = 0.043, p = 0.048, and p = 0.037, respectively). In addition, from the results of the multivariate analysis for disease free survival, number of lung metastases, initial recurrence site, duration from primary tumor treatment to lung surgery, and preoperative chemotherapy for lung metastasis were selected as the significant prognostic factors (p = 0.037, p = 0.008, p = 0.010, and p = 0.020, respectively). In conclusion, eligible patients with pulmonary metastasis from esophageal cancer selected based on the identified prognostic predictors would be good candidates for pulmonary metastasectomy.

Impact of a Ground-glass Opacity Component on c-Stage IA Lung Adenocarcinoma.

Studies have shown that tumors with ground-glass opacity (GGO) components are associated with favorable outcomes. However, this view should be confirmed in an international cohort. We aimed to verify the impact of a GGO component on clinical (c)-stage IA lung adenocarcinoma and to describe the biological discrepancies between the part-solid and pure-solid groups. We evaluated 1333 cases of surgically resected c-stage IA lung adenocarcinomas, including 484 part-solid and 849 pure-solid tumors. Furthermore, we matched the solid size between the 2 groups and examined 470 patients. We compared the prognoses between the 2 groups before and after matching. The prognostic and biological differences were described before and after matching. Compared with the pure-solid group, the part-solid group was associated with favorable outcomes [5-year overall survival (OS) 99.4% vs 87.6%, P < 0.001; 5-year recurrence-free survival (RFS) 96.9% vs 82.2%, P < 0.001]. Similar results were obtained after matching (5-year OS 98.9% vs 92.2%, P = 0.012; 5-year RFS 95.0% vs 88.5%, P = 0.007). Multivariable analyses revealed that GGO component appearance was a factor of better OS and RFS. The part-solid tumor, regardless of the size of the solid component, had a similar outcome to the pure-solid tumor of c-stage T1a classification. Also, more epidermal growth factor receptor, human epidermal growth factor receptor-2 mutations, and receptor tyrosine kinase ROS-1-positive were observed in the part-solid group. In comparison, more wild types and Kirsten-Ras were observed in the pure-solid group. Adenocarcinomas with a GGO component were associated with superior outcomes. The GGO component should be considereda new clinical T descriptor. Early-stage lung adenocarcinomas with and without a GGO component may be 2 distinct tumor types.