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Introduction: This study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen. Methods: A subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs). Results: Overall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at cycle 1 increased. Conclusions: In real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated Cmax at cycle 1 may be associated with an increased frequency of AESIs.
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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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Pronóstico , Japón/epidemiología , Anciano de 80 o más Años , Adulto , Modelos de Riesgos Proporcionales , Carcinosarcoma/cirugía , Carcinosarcoma/patología , Carcinosarcoma/mortalidad , Quimioterapia Adyuvante , Neumonectomía/métodosRESUMEN
PURPOSE: We aimed to identify preoperative risk factors for secondary spontaneous pneumothorax surgery. METHODS: The National Clinical Database of Japan, with six annual datasets from 2014 to 2019, was used. All patients who underwent surgery for secondary spontaneous pneumothorax were included, excluding those < 15 years old and those with incomplete data. The effects of preoperative risk factors were analyzed for operative mortality (mortality during hospitalization or within 30 days, regardless of hospitalization status), 30-day mortality, and postoperative respiratory morbidities. RESULTS: Of the 18,309 patients enrolled in the study, operative mortality, 30-day mortality, and postoperative respiratory morbidities were observed in 654 (3.6%), 343 (1.9%), and 2258 (12.3%) patients, respectively. Increasing age, male sex, body mass index < 18.5 or > 30, performance status > 2, emergent surgery, interstitial pneumonia, and diabetes in preoperative co-morbidity, tumors, and other diseases in underlying lung disease were significant risk factors for operative mortality. Those for 30-day mortality included autoimmune disease instead of male sex and diabetes, while those for postoperative respiratory morbidities included lymphangiomyomatosis instead of a body mass index > 30. CONCLUSION: We identified many preoperative risk factors for operative mortality, 30-day mortality, and postoperative respiratory morbidities in secondary spontaneous pneumothorax surgery. These findings will assist in selecting appropriate surgical candidates.
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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.
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Carcinoma Adenoescamoso , Neoplasias Pulmonares , Sistema de Registros , Humanos , Masculino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Carcinoma Adenoescamoso/mortalidad , Carcinoma Adenoescamoso/patología , Carcinoma Adenoescamoso/cirugía , Femenino , Anciano , Japón/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Estadificación de Neoplasias , Neumonectomía/métodos , Neumonectomía/mortalidad , Receptores ErbB/genética , Mutación , Adulto , Anciano de 80 o más Años , Estudios de Seguimiento , Pueblos del Este de AsiaRESUMEN
OBJECTIVES: This study aimed to analyse the surgical outcomes for recurrent thymic epithelial tumours and identify the factors associated with post-recurrence survival, using an updated Japanese nationwide database. METHODS: The cohort that developed recurrence after the initial resection was extracted from an updated database of patients whose thymic epithelial tumours were treated surgically between 1991 and 2010. Furthermore, we reviewed clinicopathological and prognostic factors of re-resected cases. Post-recurrence survival outcomes and cause-specific deaths in non-re-resected cases were also reviewed. RESULTS: We enrolled 191 patients who underwent re-resection and 259 patients who did not. In the surgery group, more patients with early stage disease, less aggressive World Health Organization (WHO) histological classification, initial complete resection and shorter recurrence-free intervals were included. Non-thymic carcinoma, absence of preoperative treatment, longer recurrent-free interval, single-site recurrence and R0-1 re-resection were all significantly favourable prognostic factors for post-recurrence survival in the surgery group, according to univariable analyses. Non-thymic carcinoma histology, longer recurrence-free interval and R0-1 re-resection were identified as independent prognostic factors according to multivariable analysis. The post-recurrence survival of the entire cohort with R2 re-resection was significantly better than that of the non-surgery group, although it was not demonstrated that patients with thymoma who underwent R2 re-resection had significantly better post-recurrence and lower cause-specific death. CONCLUSIONS: R0-1 re-resection was newly identified as a prognostic factor after re-resection, in addition to non-thymic carcinoma histological classification and longer recurrence-free intervals, as documented in the initial report.
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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.
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BACKGROUND: Tracheobronchial injuries resulting from blunt trauma are relatively rare among chest injuries. However, if these injuries are not managed properly, they can be fatal. The prognosis is intricately linked to the precise diagnosis and treatment. We herein report three cases of tracheobronchial trauma that required surgical intervention. Case 1:A 17-year-old male sustained injuries when his torso became entangled in heavy machinery. The diagnosis revealed a tear in the right main bronchus, which required transportation with left single- lung ventilation. The patient was treated by tracheobronchial reconstruction. Case 2:A 71-year-old male experienced trauma when his car collided with a utility pole. He was transported to the hospital after tracheal intubation due to a laceration of the tracheal membranous area. The site of the injury was closed with sutures. Case 3:A 17-year-old female who had been struck by a train suffered acute respiratory failure and was transported to the hospital after intubation. Veno-venous extracorporeal membrane oxgenation (VV-ECMO) was initiated in response to poor oxygenation. Complete rupture of the right middle bronchial trunk and laceration of the right main bronchial membrane were observed, and bronchoplasty was performed. CONCLUSION: A swift and accurate diagnosis, coupled with timely and judicious therapeutic interventions, play a pivotal role in managing tracheal and bronchial injuries.
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Bronquios , Tráquea , Humanos , Masculino , Adolescente , Tráquea/lesiones , Tráquea/cirugía , Bronquios/lesiones , Bronquios/cirugía , Femenino , Anciano , Heridas no Penetrantes/cirugía , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/terapia , Traumatismos Torácicos/cirugía , Traumatismos Torácicos/complicacionesRESUMEN
The treatment of traumatic rib fractures and sternal fractures have focused on pain and respiratory management, and conservative treatment has been recommended. Recently, however, a number of case series from abroad have been reported and demonstrated the usefulness of surgical stabilization of rib fractures (SSRF) and sternal fractures (SSSF). We have experienced seven cases of SSRF and two cases of SSSF at International University Health and Welfare Narita Hospital and Atami Hospital. Based on our experienced cases, we have outlined the preoperative evaluation, indication for surgery, timing of surgery, surgical techniques, and postoperative course. Of these nine cases, the clinical course of two cases of SSRF and one case of SSSF were detailly presented. The surgical indications and techniques for traumatic rib fractures and sternal fractures vary from institution to institution, and there is no single optimal treatment. We hope that the accumulation of cases, and discussions will help to build a higher quality evidence for surgical treatment of thoracic trauma in Japan.
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Fracturas de las Costillas , Esternón , Humanos , Fracturas Óseas/cirugía , Fracturas de las Costillas/cirugía , Esternón/cirugía , Esternón/lesionesRESUMEN
The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006-2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments.
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Background: Home oxygen therapy (HOT) is used to treat chronic respiratory diseases and is sometimes required in patients with lung cancer after radical surgery. We aimed to identify the risk factors for postoperative home-based oxygen therapy in patients with lung cancer. Methods: Patients who underwent surgery for primary lung cancer at Chiba University Hospital between January 2019 and March 2021 were included. Patients who did not undergo complete resection, died in hospital after surgery, or used oxygen therapy preoperatively were excluded. Eligible patients were divided into HOT and non-HOT groups. They were retrospectively analyzed for risk factors for postoperative HOT using medical records in a multivariate analysis. Results: A total of 410 patients were included in this study, 24 (5.9%) of whom required HOT after surgery. The HOT group comprised significantly more men, heavy smokers, and patients with pulmonary comorbidities, low percent forced expiratory volume, percent forced vital capacity, predicted postoperative forced expiratory volume in 1 s, and postoperative pulmonary complications on univariate analysis. In a multivariate analysis, independent risk factors for postoperative HOT were pulmonary comorbidities [odds ratio (OR): 5.94; 95% confidence interval (CI): 1.64-21.5; P=0.002) and postoperative pulmonary complications (OR: 5.39; 95% CI: 2.14-13.5; P<0.001). The postoperative HOT application rate was calculated according to a formula developed for this purpose. Conclusions: Comorbid pulmonary diseases and postoperative pulmonary complications were significantly associated with postoperative HOT in patients with lung cancer.
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Background: Despite the low number of lung transplantations (LTs) in Japan, 10 LT facilities are accredited and good outcomes have been reported. A database review was conducted to clarify the impact of case volume at LT facilities in Japan on short- and long-term outcomes. Methods: All cadaveric LT cases treated between 2000 and 2021 in Japan were analyzed using the database of the Japanese Society of Lung and Heart-Lung Transplantation (JSLHT). The nine institutions represented were categorized into the low-volume (LV; <80 cumulative LT cases, <8 LTs/year, n=5) and high-volume (HV; ≥80 cumulative LT cases, ≥8 LTs/year, n=4) centers. Ninety-day and 1-year mortality, as well as 5- and 10-year survival data were evaluated. Results: A total of 658 cadaveric LTs were performed at the nine institutions. The 90-day rates of mortality at the HV and LV centers were 3.5% and 3.9%, respectively (P=0.801), while the 1-year mortality rates were 9.2% and 11.5%, respectively (P=0.199). Additionally, log-rank analysis of Kaplan-Meier curves showing case volume did not reveal a significant difference in long-term survival between the HV and LV centers (P=0.272), though the LV centers had wide differences for long-term outcomes (P=0.030). Conclusions: Case volume did not have effects on short- or long-term outcomes following LT in Japan, while there were large variations in long-term outcomes among the LV centers compared to those of the HV centers.
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Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines." Because new evidence had accumulated, we formulated the "Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition)." While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.
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Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Humanos , Japón/epidemiología , Fibrosis Pulmonar Idiopática/terapia , PronósticoRESUMEN
BACKGROUND: In advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations, those with impaired performance status (PS) treated with EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated comparable activities to good-PS patients. Due to the limited sample size and inclusion of older adult patients with good PS, these findings may not accurately depict the efficacy of EGFR-TKI in poor-PS patients. We investigated the benefit of EGFR-TKIs in this population and identified relevant prognostic factors. PATIENTS AND METHODS: This nationwide prospective registry study included 9872 patients with local or advanced NSCLC. Outcomes were compared between poor- and good-PS patients treated with EGFR-mutated lung cancer therapies. RESULTS: Of 9872 NSCLC patients, 1965 (19.9%) had EGFR mutations, with 1846 (93.9%) presenting common EGFR mutations. Poor PS (PS score ≥ 3) was noted in 171 patients (8.7%) and identified as an independent prognostic factor; those with poor PS had a significantly lower 1-year survival rate. The median overall survival (OS) for EGFR-TKI-treated good-PS patients was 31.5 (95% confidence interval, 29.6-33.4) months. Among poor-PS patients with EGFR mutations, 135 (78.9%) of whom were treated with EGFR-TKI had an OS of 15.5 (12.7-18.3) months, while those receiving only supportive care had an OS of 2.5 (1.4-3.6) months (P < .001). Hypoalbuminemia (< 3.5 g/dL), liver metastasis, and uncommon EGFR mutations were associated with poor prognosis. CONCLUSION: Poor PS at diagnosis was rare and associated with limited EGFR-TKI efficacy and a dismal prognosis. Liver metastasis and hypoalbuminemia may reduce EGFR-TKI efficacy in these patients.
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Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Inhibidores de Proteínas Quinasas , Sistema de Registros , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Femenino , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Persona de Mediana Edad , Japón , Pronóstico , Estudios Prospectivos , Anciano de 80 o más Años , Adulto , Tasa de Supervivencia , Metástasis de la Neoplasia , Pueblos del Este de AsiaRESUMEN
Patients with lung cancer complicated by interstitial pneumonia (IP) often lose treatment options early owing to acute exacerbation of IP concerns. Carbon-ion radiotherapy (CIRT) can provide superior tumor control and low toxicity at high dose concentrations. We conducted a retrospective analysis of the efficacy and tolerability of a single-fraction CIRT using 50 Gy for IP-complicated lung cancer. The study included 50 consecutive patients treated between April 2013 and September 2022, whose clinical stage of lung cancer (UICC 7th edition) was 1A:1B:2A:2B = 32:13:4:1. Of these, 32 (64%) showed usual interstitial pneumonia patterns. With a median follow-up of 23.5 months, the 3-year overall survival (OS), cause-specific survival, and local control rates were 45.0, 75.4, and 77.8%, respectively. The median lung V5 and V20 were 10.0 and 5.2%, respectively (mean lung dose, 2.6 Gy). The lung dose, especially lung V20, showed a strong association with OS (p = 0.0012). Grade ≥ 2 pneumonia was present in six patients (13%), including two (4%) with suspected grade 5. CIRT can provide a relatively safe and curative treatment for patients with IP-complicated lung cancer. However, IP increases the risk of severe radiation pneumonitis, and further studies are required to assess the appropriate indications.
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PURPOSE: The impact of the modified frailty index (mFI) on postoperative complications after lung cancer surgery was investigated. METHODS: Patients who underwent lung cancer surgery in 2017 were included. 30-day postoperative mortality and morbidity were evaluated according to their Clavien-Dindo classification. mFI values are presented as the sum of values of 11 included items. Logistic regression was used to assess the effect of mFI on postoperative severe complication incidence. RESULTS: Among 190 patients considered, severe postoperative complications (Grade 3 or more) were observed in 30 (16%). No patients died within 30 days of surgery. The incidence of severe complications was 3.6% in patients with mFI of 0, 16.2% in patients with mFI of 1, 23.4% in patients with mFI of 2, and 31.6% in patients with mFI of 3 or more, and was correlated with the grade of mFI. Univariate and multivariate analyses showed that the high mFI was significantly predictive of postoperative complications. Frail patients of mFI ≥ 2 were at 3.0-fold greater risk of severe complications than non-frail patients of mFI 0 or 1. CONCLUSION: mFI was associated with morbidity after lung cancer surgery. Preoperative frailty assessment and appropriate intervention to frail patients would be required to improve postoperative outcomes.
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Fragilidad , Neoplasias Pulmonares , Humanos , Fragilidad/complicaciones , Fragilidad/diagnóstico , Fragilidad/epidemiología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/complicaciones , Complicaciones Posoperatorias/etiología , Morbilidad , Incidencia , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Japón , Quimioterapia Adyuvante , Estadificación de NeoplasiasRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Gefitinib , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Investigación Biomédica Traslacional , Receptores ErbB/genética , Cisplatino , Vinorelbina/uso terapéutico , Mutación/genética , Inhibidores de Proteínas Quinasas/efectos adversos , Receptor Notch1/genética , Proteína de Unión a CREB/genéticaRESUMEN
Due to the scarcity of large-sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44-88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non-surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non-surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma.