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Abstract Introduction There have been few reports of spontaneous regression of malignant pleural mesothelioma, but the mechanism for this is unknown. We present a case report on a patient with malignant pleural mesothelioma showing apparent tumor disappearance in a local relapse after surgery. Case presentation A 73-year-old man presented with malignant pleural mesothelioma in the right thoracic cavity. A pleurectomy was performed, and as expected, the tumor locally relapsed with increasing chest pain. However, the symptoms suddenly improved while the tumor was apparently reduced, and spontaneous tumor regression was initially considered. The patient confessed that he had self-administered a mushroom extract with alternative parasympathetic nerve stimulation therapy thereafter. The complete disappearance of the tumor was clinically achieved during a 29-month follow-up with continuing self-treatment. Conclusion This is the first report describing a malignant pleural mesothelioma patient in Japan showing long-term complete disappearance of a local relapse after surgery. This event was a tumor regression possibly due to an immunological effect of combined complementary and alternative therapy.

Abstract: Introduction: To investigate the performance of combined 18F-FDG-PET/CT as a predictor of the WHO-classification based malignancy grade in thymic epithelial tumors. Methods: From 05/06 to 02/12, the data of 47 patients with thymic epithelial tumors assessed by 18F-FDG-PET/CT before being surgically treated were collected in 3 centers and retrospectively reviewed for the purposes of this study. The SUVmax and the SUVmax/T index (the ratio tumor-SUVmax to tumor-size) have been matched with specific subgroups of the WHO-classification: low-risk thymomas (types A–AB–B1), high-risk thymomas (types B2–B3) and thymic carcinomas (type C). Results: There were 22 men and 25 women (age range: 31–84 yrs). Mean tumor size was 44.7±19.0mm. The WHO-classification was: type-A #2, type-AB #11, type-B1 #9, type-B2 #9, type-B3 #9 and type-C #7. The SUVmax and the SUVmax/T were found to be predictive factors useful to distinguish thymomas from thymic carcinomas (SUVmax: area under ROC-curve: 0.955, p =0.0045; SUVmax/T-size: area under ROC-curve: 0.927, p =0.0022). Moreover, both parameters were found to be correlated with the WHO malignancy grade (low-risk thymomas; high-risk thymomas; thymic carcinoma), Spearman correlation coefficients being 0.56 (p <0.0001) and 0.76 (p <0.0001), respectively for the SUVmax and for the SUVmax/T index. In addition, the SUVmax is also significantly correlated with Masaoka stage (Spearman correlation coefficient: 0.30, p =0.0436) Conclusions: A significant relationship was observed between 18F-FDG-PET/CT findings and histologic WHO-classification for this cohort of thymic epithelial tumors. Thus, on the basis of these evidences, we infer that 18F-FDG-PET/CT may be useful to predict histology and the WHO classes of risk. [Copyright &y& Elsevier]

Background: Surgical resection followed by adjuvant chemotherapy is currently the first choice for the treatment of clinical N1 (cN1) non-small cell lung cancer (NSCLC). However, diagnosing cN1 correctly can be difficult, even with current imaging diagnostic technologies. We aimed to analyze the diagnostic accuracy of preoperative nodal status and the predictive factors for nodal upstaging of cN1-NSCLC., Methods: Patients receiving surgery for cN1-NSCLC in 2010 (n = 1040) were enrolled in the Japanese Joint Committee of Lung Cancer Registry Database. We investigated the diagnostic accuracy of cN1, predictive factors for nodal upstaging, and prognostic factors for overall survival (OS) and recurrence-free survival (RFS)., Results: The 5-year OS and RFS for all patients were 58.2% and 42.7%, respectively. The postoperative pathological nodal status included N0 (36.6%), N1 (39.7%), N2 (23.6%), and N3 (0.1%). In multivariate analysis, younger age (P = .005), no history of smoking (P = .006), and adenocarcinoma (P < .001) were significant predictive factors for nodal upstaging. Older age (P < .001) and higher clinical T (cT) factor (P < .001) were significant indicators for worse OS, while older age (P = .02), higher cT factor (P = .019), high carcinoembryonic antigen value (P = .002), and adenocarcinoma (P = .008) were significant indicators for worse RFS., Conclusions: The diagnostic accuracy of cN1 in this study was ~40%. No history of smoking and adenocarcinoma were significant predictors for nodal upstaging. Although younger age was a significant predictor for nodal upstaging, it was a significant factor for better prognosis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pulmonary nodules in patients with soft tissue sarcomas are likely pulmonary metastases, whereas synchronous primary pulmonary sarcomas are rare. Without surgery, determining whether a solitary pulmonary nodule is a primary or metastatic nodule is difficult. Herein, we report a rare case of a primary pulmonary sarcoma that presented synchronously with a primary dedifferentiated liposarcoma., Case Presentation: A 77-year-old man presented to another hospital with left inguinal swelling and a suspected recurrent inguinal hernia. Computed tomography revealed a left inguinal mass and pure-solid nodule in the left lung and the patient was referred to our hospital for detailed examination and treatment. The inguinal mass was pathologically diagnosed as a dedifferentiated liposarcoma using needle biopsy, whereas bronchoscopic biopsy revealed histological findings suggestive of a sarcoma; however, the primary site could not be determined. Positron emission tomography-computed tomography revealed no high-accumulation lesions except for the two sarcomas. We decided to perform surgery on both sarcomas for diagnostic and curative purposes. The surgical specimens showed that the two sarcomas were different. Based on the immunohistochemical staining findings of MDM2, a left inguinal dedifferentiated liposarcoma and primary pulmonary unclassified sarcoma were diagnosed. The patient displayed no evidence of recurrence 1 year after surgery., Conclusions: We encountered a rare case of synchronous multiple primary sarcomas, one presenting in the lung and the other in the soft tissue. Surgery was required to achieve a definitive diagnosis for the patient, who achieved disease-free survival at 1 year. This case suggests that proactive resection of pulmonary nodules in patients with soft tissue sarcomas may be feasible as a diagnostic treatment if complete resection is achieved., (© 2024. The Author(s).)

Purpose: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe., Methods: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis., Results: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38)., Conclusion: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe., (© 2024. The Author(s).)

Objective: Segmentectomy and mediastinal lymph node dissection (LND) may increasingly be used for non-small cell lung cancer (NSCLC). Lymph node metastasis (LNM) distribution varies by lower lobe segments; however, its segment-specific spread to the lower zone (#8, 9) (LZ) in lower lobe NSCLC is seldom reported., Methods: In total, 352 patients with clinical T1 lower lobe NSCLC who underwent lobectomy with systematic or lobe-specific LND were included for analysis between January 2006 and December 2018., Results: Fifty-eight (16.2%) patients had LNM (pN1: 24, pN2: 34), and nine (2.6%) had LZ metastasis. LZ metastasis was significantly more frequent in tumors with diameter > 2 cm, tumors without ground-glass opacity on radiological findings, left lung cancer, and basal segment lung cancer (respectively, p = 0.039, 0.006, 0.0177, 0.0024). None of the S6 NSCLC patients had LZ metastasis. Two patients with right basal segment NSCLC had LZ metastases (tumor on S10) as well as N1 lymph node and subcarinal zone metastasis. Seven (8.4%) patients with left basal segment NSCLC had LZ metastasis (tumor on S8: 3, tumor on S10: 4). Of them, three patients with left basal NSCLC had isolated LZ metastasis., Conclusions: The LND of the LZ can be omitted for clinical T1 patients with S6 NSCLC. In addition, the LND of the LZ may be omitted in right basal NSCLC if intraoperative confirmation of negative N1 and subcarinal zone lymph nodes is obtained; however, it is necessary for left basal segment NSCLC., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Objectives: The objective of this study was to clarify the clinicopathological features and prognostic factors of resected lung adenosquamous carcinoma (ASC) using a nationwide multi-institutional database., Methods: We retrospectively reviewed the records of 15,542 patients who underwent complete R0 resection for ASC (n = 326), adenocarcinoma (AC, n = 11,820), or squamous cell carcinoma (SC, n = 3396) from a Japanese lung cancer registry in 2010. To reduce the selection bias, an inverse probability of treatment weighting (IPTW) method using a propensity score was implemented., Results: The ASC group showed worse recurrence-free and overall survival (RFS and OS) than both the AC and SC groups (5-year OS: 57.5% in ASC, 83.9% in AC [< 0.001], and 62.3% in SC [P = .086]). In multivariate analyses, prognostic factors that affected OS for ASC included male, p-stage II-III, and postoperative complications within 30 days (grade ≥ 3 in the Clavien-Dindo classification). The sensitizing EGFR mutation was detected in 28 (21.5%) of 130 screened patients with ASC, but it did not affect either RFS, OS, or postrecurrence survival. Although more patients in the ASC group received adjuvant chemotherapy compared to the AC and SC groups, both multivariate and IPTW-adjusted analyses did not show positive impact of adjuvant chemotherapy on RFS and OS in ASC., Conclusions: In this nationwide registry study, lung ASC was more aggressive than both AC and SC. No apparent survival impact of conventional adjuvant chemotherapy prompted us to investigate novel adjuvant strategies to optimize survival outcomes., Competing Interests: Disclosure All of the authors declare that there are no conflicts of interest. We certify that this submission is our original work and is not under review by any other publication., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The optimal region of lymph node dissection (LND) during segmentectomy in patients with small peripheral non-small cell lung cancer requires clarification. Through a supplemental analysis of the Japan Clinical Oncology Group (JCOG) 0802/West Japan Oncology Group (WJOG) 4607L, we investigated the associated factors, distribution, and recurrence pattern of lymph node metastases (LNMs) and proposed the optimal LND region., Methods: Of the 1106 patients included in the JCOG0802/WJOG4607L, 1056 patients with LNDs were included in this supplemental analysis. We investigated the distribution and recurrence pattern of LNMs along with the radiologic findings (with ground-glass opacity, part-solid tumor; without ground-grass opacity component, pure-solid tumor)., Results: The radiologic findings were the only significant factor for LNMs. Of 533 patients with part-solid tumors, 8 (1.5%) had LNMs. Further, only 3 (0.5%) patients had pN2 disease, and no patients had interlobar LNMs from nonadjacent segments. Of the 523 patients with pure-solid tumors, 55 (10.5%) had LNMs, and 28 (5.4%) had pN2 disease. Five patients had metastases to nonadjacent interlobar lymph nodes (LNs). Two (2.0%) patients with S6 tumors had upper mediastinal LNMs. In addition, the incidence of mediastinal LN recurrence in patients with S6 lung cancer was greater in those who underwent selective LND than those who underwent systematic LND (P = .0455)., Conclusions: Nonadjacent interlobar and mediastinal LND have little impact on pathologic nodal staging in patients with part-solid tumors. In contrast, selective LND is recommended at least for patients with pure-solid tumors., Competing Interests: Conflict of Interest Statement H.Y. reported honoraria from Eli Lilly, Chugai, Boehringer Ingelheim, Nippon Kayaku, Astra Zeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Ono, Merck Biopharma, Taiho, Otsuka, Takeda, Novartis, Amgen, Nipro Pharma, Kyowa Kirin, and Pfizer (payments were made to the author) and consulting fees from Delta Fly Pharma (payments were made to the author). M.T. reported participation on a Data Safety Monitoring Board or Advisory Board, Chugai Pharmaceutical Co, Ltd. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: It has recently been suggested that the formation of pulmonary vein stump thrombus (PVST) after anatomical lung resection is an underlying cause of arterial thromboembolism including cerebrovascular infarction. This study aimed to investigate the incidence and risk factors of PVST and to evaluate the efficacy and safety of anticoagulant therapy for PVST., Methods: Patients who underwent anatomical lung resection for malignant lung tumors were eligible for inclusion in this study. Chest contrast-enhanced (CE) computed tomography (CT) was performed after surgery to detect PVST. If PVST was observed, patients received anticoagulant therapy. The size of the PVST was followed-up by repeated chest CE-CT., Results: In total, 176 patients were enrolled in this study. Chest CE-CT was performed on postoperative day 1-13 (median, postoperative day 6). PVST was detected in 22 (12.5%) patients. The median size of PVST was 9.5 (4.1-33.4) mm. Thrombus was most commonly observed in patients who underwent left upper lobectomy (9/36, 25.0%). Hypertension, dyslipidemia, arteriosclerosis, and arrhythmia were not associated with PVST formation. Anticoagulant therapy was administered to all 22 patients with PVST until the PVST disappeared. The median duration between the detection and disappearance of PVST was 77 days (range: 6-146 days). During the period between the detection and disappearance of PVST, cerebrovascular infarction or arterial thromboembolic events were not observed., Conclusions: Postoperative PVST is commonly observed, especially in patients who undergo left upper lobectomy. Anticoagulant therapy for PVST was safely introduced and was efficient to improve PVST without subsequent arterial thromboembolic events., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future., (© 2024. The Author(s).)

Background: Sarcomatoid carcinoma of the lung is a rare histological type of non-small cell lung cancer with a poor prognosis. We aimed to investigate the clinicopathological characteristics and prognostic factors of surgically resected sarcomatoid carcinoma of the lung., Methods: We retrospectively reviewed 14999 patients who underwent surgical resection for non-small cell lung cancer accumulated by the Japanese Joint Committee of Lung Cancer Registry in 2010. Clinicopathological characteristics and survival were compared between the sarcomatoid carcinoma and other non-small cell cancer groups. The prognostic factors in the sarcomatoid carcinoma group were identified using a multivariate Cox proportional hazard model., Results: Patients with sarcomatoid carcinoma comprised 1.4% of all patients. The sarcomatoid carcinoma group demonstrated a more aggressive pathology with presentation at more advanced stages, requiring more frequent extensive surgical resections. The sarcomatoid carcinoma group had remarkably poorer overall and recurrence-free survival than the other non-small cell lung cancer group. Adjuvant chemotherapy was associated with improved survival for pathological stage II-III sarcomatoid carcinoma cases rather than for pathological stage I disease. In the multivariate analysis, larger tumor size, lymphatic permeation, and no adjuvant chemotherapy were associated with the sarcomatoid carcinoma group's overall and recurrence-free survival., Conclusions: Surgically resected sarcomatoid carcinoma of the lung has a higher aggressive and metastatic potential and a worse prognosis than other non-small cell lung cancers. Adjuvant chemotherapy, which was associated with enhanced survival in patients with pathological stage II-III of the disease, could be considered for treating patients with pathological stage II-III sarcomatoid carcinoma of the lung., (© 2024. The Author(s).)

Background: Information regarding late recurrence after pulmonary resection for non-small cell lung cancer (NSCLC) is limited. This study aimed to analyze the risk factors for late recurrence after surgery for NSCLC in the current era., Patients and Methods: We conducted a retrospective study of patients who underwent complete resection for pathological I-III NSCLC between 2006 and 2015. Late recurrence was defined as a recurrence that met the following conditions: (1) the patient underwent chest computed tomography (CT) at or after 54 months after surgery and recurrence was not detected at that time, and (2) recurrence that occurred more than 5 years after surgery. The factors influencing late recurrence, relapse-free survival (RFS), and overall survival (OS) after surgery were analyzed., Results: A total of 1275 with 5-year relapse-free survival after surgery were enrolled in this study. The mean age of the patients was 66.4 years and 54% of the patients were men. The median interval between surgery and the latest follow-up examination was 98 months. In total, 35 patients (2.7%) experienced late recurrence and 138 patients have died thus far. The cumulative recurrence, RFS, and OS rates at 10 years were 3.9%, 84.9%, and 86.3%, respectively. A multivariate analysis revealed that pleural invasion was an independent risk factor for late recurrence. Pleural invasion was a poor prognostic factor for both RFS and OS., Conclusions: Pleural invasion was a predictor of late recurrence. Age > 67 years, preoperative serum carcinoembryonic antigen (CEA) > 5 ng/ml, non-adenocarcinoma, and pleural invasion were poor prognostic factors for RFS., (© 2024. Society of Surgical Oncology.)

Background: Adenocarcinomas show a stepwise progression from atypical adenomatous hyperplasia (AAH) through adenocarcinoma in situ (AIS) to invasive adenocarcinoma (IA). Immunoglobulin superfamily containing leucine-rich repeat (ISLR) is a marker of tumor-restraining cancer-associated fibroblasts (CAFs), which are distinct from conventional, strongly α-smooth muscle actin (αSMA)-positive CAFs. Fibroblast activation protein (FAP) has been focused on as a potential therapeutic and diagnostic target of CAFs., Methods: We investigated the changes in protein expression during adenocarcinoma progression in the pre-existing alveolar septa by assessing ISLR, αSMA, and FAP expression in normal lung, AAH, AIS, and IA. Fourteen AAH, seventeen AIS, and twenty IA lesions were identified and randomly sampled. Immunohistochemical analysis was performed to evaluate cancer-associated changes and FAP expression in the pre-existing alveolar structures., Results: Normal alveolar septa expressed ISLR. The ISLR level in the alveolar septa decreased in AAH and AIS tissues when compared with that in normal lung tissue. The αSMA-positive area gradually increased from the adjacent lung tissue (13.3% ± 15%) to AIS (87.7% ± 14%), through AAH (70.2% ± 21%). Moreover, the FAP-positive area gradually increased from AAH (1.69% ± 1.4%) to IA (11.8% ± 7.1%), through AIS (6.11% ± 5.3%). Protein expression changes are a feature of CAFs in the pre-existing alveolar septa that begin in AAH. These changes gradually progressed from AAH to IA through AIS., Conclusions: FAP-positive fibroblasts may contribute to tumor stroma formation in early-stage lung adenocarcinoma, and this could influence the development of therapeutic strategies targeting FAP-positive CAFs for disrupting extracellular matrix formation., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: Information on prognostic factors after repeat pulmonary metastasectomy (PM) is limited, and outcomes after a third PM are not well documented., Methods: A single-institute retrospective study was conducted. Between 2000 and 2020, 68 patients underwent repeat PM for pulmonary metastases from various cancers. Outcomes and prognostic factors for the second PM and outcomes after the third PM were analysed., Results: This study included 39 men and 29 women. The mean age at second PM was 53.2 years old. The primary tumours were soft tissue sarcoma in 24 patients, colorectal cancer in 19 and osteosarcoma in 10. The interval between the first PM procedure and detection of pulmonary metastasis after the first PM (months) was ≤12 in 37 patients and >12 in 31 patients. At the second PM, 20 patients underwent lobectomy or bilobectomy, and 48 underwent sublobar resection. Complete resection was achieved in 60 patients, and 52 patients experienced recurrence after the second PM. The 5-year relapse-free survival and overall survival rates after the second PM were 27% and 48%, respectively. Multivariable analysis revealed that the interval between the first PM and the subsequent detection of pulmonary metastasis (≤12 months) was a poor prognostic factor for both relapse-free survival and overall survival after the second PM. Seventeen patients underwent a third PM, 3 of whom achieved a 3-year disease-free survival., Conclusions: Patients with a period of >12 months between the first PM and the subsequent detection of pulmonary metastases showed favourable outcomes and are thus considered good candidates for second PM. A third PM may be beneficial for selected patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

In the open-label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event-free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non-small-cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB-IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment. The primary end-points (EFS and pCR) and safety were assessed in patients enrolled at 16 centers in Japan. Of the Japanese patients randomized, 93.9% (31/33) in the nivolumab plus chemotherapy arm and 82.9% (29/35) in the chemotherapy arm underwent surgery. At 21.5 months' minimum follow-up, median EFS was 30.6 months (95% confidence interval [CI], 16.8-not reached [NR]) with nivolumab plus chemotherapy versus 19.6 months (95% CI, 8.5-NR) with chemotherapy; hazard ratio, 0.60 (95% CI, 0.30-1.24). The pCR rate was 30.3% (95% CI, 15.6-48.7) versus 5.7% (95% CI, 0.7-19.2), respectively; odds ratio, 7.17 (95% CI, 1.44-35.85). Grade 3/4 treatment-related adverse events were reported in 59.4% versus 42.9% of patients, respectively, with no new safety signals identified. Neoadjuvant nivolumab plus chemotherapy resulted in longer EFS and a higher pCR rate versus chemotherapy alone in Japanese patients, consistent with findings in the global population. These data support nivolumab plus chemotherapy as a neoadjuvant treatment option in Japanese patients with resectable NSCLC., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease-free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction = 0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction = 0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Objectives: Prolonged air leak (PAL) is a common complication of lung resection. Research on predictors of PAL using a digital drainage system (DDS) remains insufficient. In this study, we investigated the predictive factors of PAL to establish a novel early postoperative prediction model for PAL., Methods: A retrospective cohort study and validation study were conducted. We examined patients who underwent lung resection with DDS at our institute. The relationship between the clinical factors and measurements of the DDS, including the difference between the set and measured intrapleural pressure (named: additional negative pressure [ANP]) at postoperative hour (POH) 3, with PAL was analyzed., Results: A total of 494 patients were enrolled, 29 of whom had PAL. Percent forced expiratory volume in 1 s <60%, ANP <1 cmH 2 O, air leak flow >20 mL/min and pleural adhesion findings at surgery were independent predictors of PAL according to a multivariable analysis. The PAL rate was clearly stratified according to our novel risk scoring system, which simply notes the presence of the above four factors, that is, the rate increases when the score increases. The area under the curve (AUC) of the receiver operating characteristic (ROC) analysis for this scoring system was 0.818. Analysis of the validation cohort (n = 133) revealed that this scoring system showed a sufficient ability to predict PAL., Conclusions: ANP at POH 3 is an independent predictor of PAL. Thus, the risk-scoring system proposed in this study is useful for predicting PAL in the early postoperative period., (© 2023 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: The efficacy of adjuvant chemotherapy (ACT) in elderly patients with completely resected p-stage II-IIIA non-small-cell lung cancer (NSCLC) remains unclear because all previous randomized controlled trials on ACT have been conducted among patients aged <75 years. Thus, this study aimed to evaluate the effectiveness of ACT in elderly patients with completely resected NSCLC., Patients: We extracted the nationwide data of 812 patients aged ≥75 years who underwent lobectomy with mediastinal nodal dissection in 2010 and were diagnosed with p-stage II-IIIA NSCLC, from nationwide registry data accumulated in 2016., Methods: We classified the 812 patients into 2 groups based on the ACT administration status and analyzed the differences in their postoperative overall survival (OS)., Results: Overall, 295 patients received ACT (36.3%; group A), whereas 517 patients did not (63.70%; group N). Group A showed significantly better OS as a whole (hazard ratio [HR]: 0.650 [95% confidence interval {CI}: 0.526-0.804]), in the p-stage II subset (HR: 0.688 [95% CI: 0.513-0.925]), and p-stage IIIA subset (HR: 0.547 [95% CI: 0.402-0.743]) than group N. Even after propensity score matching, group A showed significantly better OS as a whole (HR: 0.626 [95% CI: 0.495-0.792]), in the p-stage II subset (HR: 0.690 [95% CI: 0.493-0.964]), and p-stage IIIA subset (HR: 0.554 [95% CI: 0.398-0.772]) than group N., Conclusion: ACT is recommended even in elderly patients with completely resected p-stage II-IIIA NSCLC. Hence, physicians should not avoid ACT in patients with completely resected NSCLC based solely on age., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Segmentectomy and mediastinal lymph node dissection (MLND) are becoming standard procedures for small-sized (<2 cm) peripheral non-small cell lung cancer (NSCLC). Although the benefits of the less resected lung are proven, the extent of lymph node dissection remains unchanged., Methods: We studied 422 patients who underwent lobectomy with MLND (lobe specific or systemic) for small peripheral NSCLC with clinical N0 disease. Patients with middle lobectomy (n = 39) and a consolidation-to-tumor (C/T) ratio ≤0.50 (n = 33) were excluded. We investigated the clinical factors, lymph node metastasis distributions, and lymph node recurrence patterns of 350 patients., Results: Thirty-five (10.0%) patients had lymph node metastasis; none with C/T ratio <0.75 had lymph node metastasis and lymph node recurrence. None had solitary lymph node metastasis in the outside lobe-specific MLND. Six patients had mediastinal lymph node metastasis at the initial site of recurrence; none had mediastinal lymph node recurrence outside the lobe-specific MLND, except for two patients with S6 primary disease., Conclusion: NSCLC patients with small peripheral tumors and a C/T ratio <0.75 during segmentectomy may not require MLND. The optimal MLND for patients with a C/T ratio ≥0.75, except for those with S6 primary, may be lobe-specific MLND.

Objective: The efficacy of tegafur-uracil as adjuvant chemotherapy for patients with completely resected stage I non-small-cell lung cancer is proven; however, its efficacy for elderly patients remains unclear. Herein, we evaluated the effectiveness of adjuvant chemotherapy for elderly patients with completely resected stage I non-small-cell lung cancer based on real-world Japanese data using propensity score matching., Methods: This retrospective study extracted data from a nationwide registry study, performed in 2016, on patients ≥75 years who underwent lobectomy with mediastinal nodal dissection for non-small-cell lung cancer in 2010 and were diagnosed with p-stage IA (>2 cm) or stage IB non-small-cell lung cancer. We classified the 1294 patients into two groups-Group A, postoperative adjuvant chemotherapy (n = 295, 22.8%) and Group N, no adjuvant chemotherapy (n = 999, 77.2%)-and analyzed differences in postoperative overall survival between groups., Results: Group A showed no advantage in overall survival over Group N as a whole (hazard ratio: 0.824 [95% confidence interval: 0.631-1.076]), in p-stage IA (hazard ratio: 0.617 [95% confidence interval: 0.330-1.156]) and in p-stage IB (hazard ratio: 0.806 [95% confidence interval: 0.597-1.088]) subsets. Even after propensity score matching, Group A showed no significant advantage in overall survival over Group N as a whole (hazard ratio: 0.975 [95% confidence interval: 0.688-1.381]), in p-stage IA (hazard ratio: 1.390 [95% confidence interval: 0.539-3.586]) and in p-stage IB (hazard ratio: 0.922 [95% confidence interval: 0.633-1.343])., Conclusions: adjuvant chemotherapy for completely resected p-stage IA (>2 cm) and stage IB non-small-cell lung cancer showed no benefit for recommendation for elderly patients; considering the risk of adverse events, we do not recommend adjuvant chemotherapy for elderly patients., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: It is essential to collect a sufficient amount of tumor tissue for successful next-generation sequencing (NGS) analysis. In this study, we investigated the clinical risk factors for avoiding re-biopsy for NGS analysis (re-genome biopsy) in cases where a sufficient amount of tumor tissue could not be collected by bronchoscopy., Methods: We investigated the association between clinical factors and the risk of re-genome biopsy in patients who underwent transbronchial biopsy (TBB) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and required re-genome biopsy in cases enrolled in LC-SCRUM Asia, a prospective nationwide genome screening project in Japan. We also examined whether the frequency of re-genome biopsy decreased between the first and second halves of the enrolment period., Results: Of the 572 eligible patients, 236 underwent TBB, and 134 underwent EBUS-TBNA. Twenty-four TBBs required re-genome biopsy, and multivariate analysis showed that the risk of re-genome biopsy was significantly increased in lesions where the tumor lesion was centrally located. In these cases, EBUS-TBNA should be utilized even if the lesion is a pulmonary lesion. However, it should be noted that even with EBUS-TBNA, lung field lesions are at a higher risk of re-canalization than mediastinal lymph node lesions. It was also found that even when tumor cells were detected in rapid on-site evaluation, a sufficient amount of tumor tissue was not always collected., Conclusions: For centrally located pulmonary mass lesions, EBUS-TBNA, rather than TBB, can be used to obtain tumor tissues that can be analyzed by NGS., (© 2023. The Author(s).)