[Outcomes of Surgical Treatment for Chest Trauma].

BACKGROUND: Intra-thoracic organ bleeding and chest wall injury following chest trauma can easily lead to life-threatening emergencies and a delay in treatment may lead to fatal outcomes. Interestingly, the optimal timing, indications, and surgical techniques have not been standardized. METHOD: We retrospectively analyzed 35 patients who underwent surgical treatment for chest trauma. RESULTS: All patients with penetrating trauma (n=4) underwent emergency surgery for a hemothorax. There were no postoperative complications or hospital deaths. All patients with blunt trauma( n= 31) had multiple rib fractures;rib fixation was performed in 29 patients( 94%). Eight patients( 26%) had flail chest. The duration from injury to surgery averaged 7.5 days. The prognosis was generally favorable with no postoperative complications, but two patients died in the hospital due to multiple organ failure caused by high-energy trauma. Patients with flail chest or multiple organ injury had prolonged postoperative hospital stays. CONCLUSIONS: Patients who sustain chest trauma follow various clinical courses. Appropriate timing of surgical intervention at an early stage after injury can be life saving and hasten a functional recovery.

Impact of partial pressure of arterial oxygen and radiologic findings on postoperative acute exacerbation of idiopathic interstitial pneumonia in patients with lung cancer.

PURPOSE: To establish accurate diagnostic criteria and predictors of treatment response for postoperative acute exacerbation (AE) in patients with lung cancer and idiopathic interstitial pneumonia (IIP). METHODS: Among 93 patients with IIP who underwent surgery for lung cancer, suspected postoperative AE developed in 20 (21.5%). Patients were divided into a progressive AE group, comprising patients with bilateral alveolar opacities and decreasing PaO2 ≥ 10 mmHg (n = 5); an incipient AE group, comprising patients with unilateral alveolar opacities and decreasing PaO2 ≥ 10 mmHg (n = 10); and an indeterminate AE group, comprising patients with alveolar opacities but decreasing PaO2 < 10 mmHg (n = 5). RESULTS: The progressive AE group had significantly higher 90-day mortality (80%) than the incipient AE group (10%, P = 0.017) or the indeterminate AE group (0%, P = 0.048). Bilateral opacities may indicate advanced AE and poor prognosis, whereas unilateral opacities may indicate an early stage of AE and a good prognosis. PaO2 < 10 mmHg may indicate conditions other than AE. CONCLUSIONS: In patients with lung cancer and IIP, decreasing PaO2 and HRCT findings may allow for the initiation of rapid and accurate treatment strategies for postoperative AE.

[Validity of Video-assisted Thoracic Surgery for Thymoma].

OBJECTIVES: This study aimed to identify the validity of video-assisted thoracic surgery (VATS) for thymoma, including myasthenia gravis( MG). METHODS: A total of 20 patients who underwent VATS for thymoma at our institution between 2011 and 2019 were included in the study. Preoperative complications and prognosis were analyzed to detect the safety and efficiency of VATS thymectomy. MG improvement after VATS extended thymectomy was evaluated using a quantitative myasthenia gravis score( QMGS) and Myasthenia Gravis Foundation of America post-intervention status( MGFA-PIS). RESULTS: The median tumor size was 2.6 cm (range, 1.0-8.0 cm). All thymomas were classified as TNM stageⅠ. Two patients had type A thymoma, five had type AB, six had type B1, six had type B2, and one had type B3. Postoperative complications were only observed in one patient with pneumonia. The median follow-up period was 5.1 years;no recurrence and disease-related deaths were observed. However, three patients died of other diseases. In patients with MG, postoperative crisis was not observed, and the symptoms improved in all the patients as evaluated by QMGS and MGFA-PIS. CONCLUSIONS: VATS thymectomy and VATS extended thymectomy for patients with thymoma may be effective methods to improve not only prognosis but also MG, provided the range of resections are comparable to that of conventional open surgery.

[Surgical Technique and Prognosis of Limited Resection in High-risk Patients with Primary Lung Cancer].

OBJECTIVES: To identify adaptations of limited resection for poor-risk patients with primary lung cancer and the efficacy of ensuring an adequate surgical margin. METHODS: A total of 139 poor-risk patients who underwent limited resection for their primary lung cancer in our institution between 2005 and 2020 were included. The efficacy of ensuring a surgical margin was determined by analyzing the rate of recurrence, and the prognosis was analyzed via the Kaplan-Meier method. RESULTS: Wedge resection was performed for 105 patients, and segmentectomy was performed for 34 patients. Recurrence was observed in 29 (20.8%) patients, while stump recurrence was observed in only 4( 3.8%) patients with wedge resection. The median surgical margin was 15 mm, which was equal to the median tumor size, and all histopathological margins were negative. An analysis of the 68 patients excluding those with multiple lung cancer showed that the pathological stage was not related to the prognosis. Surgical death and severe complications were not observed, and only 3 patients died of lung cancer during the observational period of 3.4 years. CONCLUSIONS: Limited resection improves the patient's prognosis and ensures an adequate surgical margin to control recurrence.

Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine.

Rapid advances are being made in cancer drug therapy. Since molecularly targeted therapy has been introduced, personalized medicine is being practiced, pathological tissue from malignant tumors obtained during routine practice is frequently used for genomic testing. Whereas cytological specimens fixed mainly in alcohol are considered to be more advantageous in terms of preservation of the nucleic acid quality and quantity. This article is aimed to share the information for the proper handling of cytological specimens in practice for genomic medicine based on the findings established in "Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine (in Japanese)" published by the Japanese Society of Clinical Cytology in 2021. The three-part practical guidelines are based on empirical data analyses; Part 1 describes general remarks on the use of cytological specimens in cancer genomic medicine, then Part 2 describes proper handling of cytological specimens, and Part 3 describes the empirical data related to handling of cytological specimens. The guidelines indicated proper handling of specimens in each fixation, preparation, and evaluation.

Impact of accurate diagnosis of interstitial lung diseases on postoperative outcomes in lung cancer.

OBJECTIVE: The prognostic impact of interstitial lung disease (ILD) subclassification based on both high-resolution computed tomography (HRCT) scan findings and histopathological findings is unknown. METHODS: We retrospectively analyzed 104 patients who were diagnosed with clinical ILD according to HRCT scan findings and who underwent lung cancer surgery. Via an expert multidisciplinary discussion, we re-classified HRCT scan findings and validated the histopathological patterns of ILDs in lung specimens. RESULTS: There were several mismatches between HRCT scan findings and histological patterns. Moreover, 87 (83.7%) and 6 (5.8%) patients were diagnosed with definitive ILD and pathological non-ILD, respectively. Finally, 82 patients with idiopathic interstitial pneumonias (IIPs) were divided into the idiopathic pulmonary fibrosis (IPF) (n = 61) group and the other group (n = 21). The 5-year overall survival rate of the IPF group was significantly lower than that of the other group (22.8% vs 67.9%; p = 0.011). Sub-classification of IIPs was found to be an independent prognostic factor for overall survival in patients with lung cancer. CONCLUSION: An accurate diagnosis of IIPs/IPF according to both HRCT scan findings and histological patterns is important for providing an appropriate treatment among patients with lung cancer who presented with clinical ILD.

[Chest Wall Injury].

A traumatic chest wall injury is a condition that is often encountered in medical practice, but the underlying pathophysiology varies widely depending on the circumstances of the injury and the patient's background. The chest wall, which protects vital organs and provides respiratory movement, can be a life-threatening emergency when injured, thus it is important to respond promptly and appropriately. Because a penetrating chest wall trauma is often associated with intra-thoracic organ damage, it is important to consider an emergency thoracotomy in cases involving massive hemorrhage or air leakage. The ribs and sternum are primarily injured in patients with blunt wall trauma. Flail chest, which is defined as multiple bifocal fractures of the ribs or multiple rib fractures with a sternal fracture, causes respiratory failure secondary to paradoxical respiration. The main treatment for flail chest is ventilatory care and surgical treatment, although early rib fixation has been reported to improve prognosis in recent years. There are several types of devices to fix the ribs and sternum, but selection criteria have yet to be established.

Necessity of Multi-Step Surgical Treatment for Patients with Interstitial Lung Disease and a Pneumothorax.

PURPOSE: A pneumothorax occurs in 3%-8% of patients with idiopathic pulmonary fibrosis. A pneumothorax may predict a poor outcome in patients with interstitial lung disease (ILD), and it is difficult to treat patients with ILD and a pneumothorax. PATIENTS AND METHODS: We retrospectively studied data from all 12 patients with ILD and a pneumothorax who underwent surgical treatment at Toho University Omori Medical Center Hospital between 2009 and 2021. RESULTS: Of the 12 patients, 2 had home oxygen therapy preoperatively and were classified with grade IV interstitial pneumonia (IP). Six patients had preoperative pleurodesis and two had postoperative one using auto-blood. Three patients (25%) had multi-step surgery ≥2, and 5 patients had surgical resection of bullae. No patients had postoperative acute exacerbations and all were discharged from the hospital in a stable condition. The 5-year overall survival rate for all patients was 70.0%. The median survival time was not reached. One patient with unclassified IP was doing well 116 months after surgery. CONCLUSION: Patients with ILD and a pneumothorax were shown to require multi-step surgical treatment and can anticipate long-term survival.

Surgical lung biopsy for interstitial lung diseases-a single center study of 129 patients.

Background: According to guidelines for the diagnosis and treatment of interstitial lung diseases (ILDs), a diagnostic surgical lung biopsy should be used to obtain the differential diagnosis of an ILD in patients with ILDs, which are difficult to distinguish clinically. However, the risk of developing postoperative complications such as postoperative pulmonary fistula or acute exacerbation is a concern. The purpose of this study was to evaluate the safety of surgical lung biopsy for the differential diagnosis of ILDs. Methods: From October 2007 to July 2019, 129 patients thought to have ILD underwent a surgical lung biopsy at Toho University Omori Medical Center. We conducted a retrospective study on the diagnosis and safety of surgical lung biopsy for patients with ILD. Results: The 30- and 60-day mortality was 0%. Postoperative complications occurred in 13 of 129 (10.1%) patients. The complications included pneumothorax in 8 (6.2%) patients after removal of the chest tube, postoperative pneumonia in 2 (1.0%), and acute exacerbation in 1 (0.8%). Postoperative pneumothorax was observed in 4 of 13 patients (30.7%) who underwent a biopsy of the apex of the lung (right S1, left S1+2), which was a significantly higher rate of postoperative pneumothorax than seen for patients undergoing biopsy at other sites (P=0.0086). Conclusions: Surgical lung biopsy for the differential diagnosis of an ILD was performed safely. However, biopsy sites for ILDs need to be carefully selected to avoid postoperative complications.

Multifocal locules including the anterior mediastinum side as a surgical indicator in pleural infection.

Background: The indication for and the timing of surgery in patients with pleural infection remains unclear. Determining the need for surgery in patients with pleural infection may help in the early consultation of surgeons. Methods: Data of 167 consecutive patients with pleural infection were retrospectively reviewed. To detect a surgical indicator, the variables of patients who required surgery were compared with those of patients who were cured by non-surgical therapy (n=94) and patients resistant to the non-surgical therapy (n=73; 62 underwent surgery, and 11 showed recurrence or disease-related death after non-surgical treatment). Prognosis and timing of surgery were analyzed by comparing three groups: patients who underwent surgery within 7 days of admission (n=33), patients who underwent surgery after 7 days of admission (n=29), and patients who underwent non-surgical therapy (n=105). Results: The presence of multifocal locules, including a locule on the anterior mediastinum side (LAMS) was a significant indicator of resistance to initial non-surgical therapy, as compared to the absence of locules (P<0.0001), a single locule (P<0.0001), or multifocal locules without a LAMS (P=0.0041). Recurrence and mortality were not observed in the patients who underwent surgery within 7 days of admission, and the hospitalization period (P=0.0071) and duration of C-reactive protein (CRP) improvement (P<0.0001) were significantly shorter in these patients compared with those who that underwent surgery after 7 days. Conclusions: In patients with pleural infection, the presence of multifocal locules, including a LAMS, was associated with resistance to non-surgical therapy. Early surgery should be considered for these patients to shorten the hospitalization period and improve the prognosis.

Machine learning-based gene alteration prediction model for primary lung cancer using cytologic images.

BACKGROUND: Understanding the gene alteration status of primary lung cancers is important for determining treatment strategies, but gene testing is both time-consuming and costly, limiting its application in clinical practice. Here, potential therapeutic targets were selected by predicting gene alterations in cytologic specimens before conventional gene testing. METHODS: This was a retrospective study to develop a cytologic image-based gene alteration prediction model for primary lung cancer. Photomicroscopic images of cytology samples were collected and image patches were generated for analyses. Cancer-positive (n = 106) and cancer-negative (n = 32) samples were used to develop a neural network model for selecting cancer-positive images. Cancer-positive cases were randomly assigned to training (n = 77) and validation (n = 26) data sets. Another neural network model was developed to classify cancer images of the training data set into 4 groups: anaplastic lymphoma kinase (ALK)-fusion, epidermal growth factor receptor (EGFR), or Kirsten rat sarcoma viral oncogene homologue (KRAS) mutated groups, and other (None group), and images of the validation data set were classified. A decision algorithm to predict gene alteration for cases with 3 probability ranks was developed. RESULTS: The accuracy and precision for selecting cancer-positive patches were 0.945 and 0.991, respectively. Predictive accuracy for the EGFR and KRAS groups in the validation data set was ~0.95, whereas that for the ALK and None groups was ~0.75 and ~ 0.80, respectively. Gene status was correctly predicted in the probability rank A cases. The model extracted characteristic conventional cytologic findings in images and a novel specific feature was discovered for the EGFR group. CONCLUSIONS: A gene alteration prediction model for lung cancers by machine learning based on cytologic images was successfully developed.

Combination of mean CT value and maximum CT value as a novel predictor of lepidic predominant lesions in small lung adenocarcinoma presenting as solid nodules.

Lung adenocarcinomas presenting as solid nodules are occasionally diagnosed as lepidic predominant lesions. The aim of this study was to clarify the histological structure and to identify factors predictive of lepidic predominant lesions. We retrospectively reviewed 38 patients that underwent lobectomy for small (≤ 2 cm) adenocarcinoma presenting as solid nodules. Resected tumor slides were reviewed and histological components were evaluated. Clinical and radiological data were analyzed to identify factors predictive of lepidic predominant lesions. Of 38 solid nodules, 9 (23.7%) nodules were lepidic predominant lesions. Five-year disease-free survival (DFS) rates were 100% for lepidic predominant lesions (n = 9) and 74.6% for non-lepidic predominant lesions (n = 29). Mean CT values (p = 0.039) and maximum CT values (p = 0.015) were significantly lower in lepidic predominant lesions compared with non-lepidic predominant lesions. For the prediction of lepidic predominant lesions, the sensitivity and specificity of mean CT value (cutoff, - 150 HU) were 77.8% and 82.8%, respectively, and those of maximum CT value (cutoff, 320 HU) were 77.8% and 72.4%, respectively. A combination of mean and maximum CT values (cutoffs of - 150 HU and 380 HU for mean CT value and maximum CT value, respectively) more accurately predicted lepidic predominant lesions, with a sensitivity and specificity of 77.8% and 86.2%, respectively. The prognosis of lepidic predominant lesions was excellent, even for solid nodules. The combined use of mean and maximum CT values was useful for predicting lepidic predominant lesions, and may help predict prognosis.

Adenocarcinoma in situ detected on a thin-walled lung cavity: a case report.

BACKGROUND: Cavitary lesions pathologically diagnosed as adenocarcinoma in situ (AIS) have been rarely reported. The examination of these type of lesions is necessary for a better understanding of the mechanisms underlying their formation and development of more efficient diagnostic and treatment strategies. Here, we present the case of a patient with cavitary lung carcinoma, diagnosed as AIS, who underwent partial resection. CASE PRESENTATION: A 72-year-old man presented with an abnormal shadow on chest radiography. Computed tomography findings showed a nodule in the right upper lobe, which was later diagnosed as an adenocarcinoma via transbronchial biopsy. A thin-walled cavity with partial thickening in the right lower lobe was also noted. We suspected that the thin-walled cavitary lesion was malignant, and performed wedge resection during a right upper lobectomy. AIS was diagnosed based on the histopathological findings of the thickened part of the thin-walled cavity. CONCLUSIONS: This study highlights that, although rare, AIS may be observed in cavitary lung carcinoma cases, particularly in thin-walled lesions.

Perioperative Bypassing Agent Therapy for Pulmonary Pleomorphic Carcinoma with Acquired Hemophilia.

A 74-year-old man was admitted with lung cancer, and preoperative blood test showed abnormal activated partial thromboplastin time (APTT). Coagulation factor screening and APTT mixing test achieved a diagnosis of acquired hemophilia A (AHA). Bypassing agent therapy was indicated and lobectomy was successfully performed without bleeding complications. APTT returned to normal after the operation without any additional treatment for AHA. The pathogenesis of AHA is still unknown and there is no evidence for hemostatic strategy for AHA patients requiring surgery. This study supports the importance of hemostatic therapy and suggests that malignancy might cause AHA.

Surgical treatment for patients with idiopathic pulmonary fibrosis and lung cancer: postoperative acute exacerbation of idiopathic pulmonary fibrosis and outcomes.

Postoperative exacerbation of interstitial pneumonia in patients with interstitial lung disease and lung cancer has emerged as a serious problem. Therefore, we need to determine the risk factors for the development of postoperative exacerbation of interstitial pneumonia in this population. There are several subtypes of interstitial lung disease, which may lead to confusion about the treatment of patients with interstitial lung disease and lung cancer. Among the idiopathic forms of interstitial lung disease, we focused on idiopathic pulmonary fibrosis (IPF) and reviewed the surgical treatments used for patients with IPF and lung cancer.

Thoracoscopic resection of bilateral multiple superior mediastinal neurofibromas.

BACKGROUND: The indications for surgical resection concerning multiple bilateral neurofibromas in the superior mediastinum remain controversial, because vascular injury or development of postoperative Horne syndrome are concerned. CASE PRESENTATION: A 60-year-old woman presented with multiple nodules in her right neck and bilateral chest cavity tops which indicated neurofibromatosis. The thoracic masses grew slowly over 9 years, and she then underwent a 2-stage resection starting with the left to right side. Bilateral tumors were completely removed via video-assisted thoracic surgery. The patient's postoperative course was uneventful, without postoperative Horner syndrome. CONCLUSIONS: To the best of our knowledge, this is the first case of multiple bilateral superior mediastinal neurofibromas resected from the pulmonary apices via thoracoscopy. We selected a minimally invasive pure video-assisted thoracoscopic surgery approach and enucleated some tumors to avoid nerve injury. This approach may be safe and useful for multiple neurofibromas in patients with neurofibromatosis.

Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is often associated with asbestos exposure and carries an extremely poor prognosis. The present study assessed the effectiveness of argon plasma coagulation (APC) treatment in patients with MPM who underwent radical pleural decortication (PD). The clinical data from 11 patients who underwent radical PD treated with APC at Toho University Omori Medical Center from July 2015 to March 2020 were retrospectively analyzed. Clinical features, local recurrence, and clinical prognoses were evaluated. The median overall survival was 18.5 months, and the 1- and 2-year overall survival rates were 71.6 and 43.0%, respectively. One patient survived 5 years but had recurrent tumors. The median disease-free survival was 11.1 months. The 1- and 2-year disease-free survival rates were 49.9 and 12.5%, respectively. Three patients had no recurrences, two of whom were followed continuously (39.6 and 10.2 months). The present study revealed that APC treatment for MPM might be associated with good survival and prognosis. APC as an additional intraoperative treatment for patients with MPM may be further investigated with larger multi-center clinical trials to support its efficacy.

Necessity of Thin Section CT in the Detection of Pulmonary Metastases: Comparison between 5 mm and 1 mm Sections of CT.

BACKGROUND: The aim of this study was to evaluate the difference in the ability of 1-mm and 5-mm section Computed Tomography(CT) to detect pulmonary metastases in patients with pulmonary metastases. METHODS: We retrospectively analyzed the CT findings of 106 patients with pulmonary metastases due to malignancies treated at Toho University Omori Medical Center between 2013 and 2020. RESULTS: Cases with only one nodule evaluated by 5-mm section CT had significantly lower discordance with 1-mm section CT than cases with two or more nodules detected by a 5 mm section (p = 0.0161). After reference to a 1 mm section, cases with only one nodule reevaluated by 5-mm section CT had significantly lower discordance than cases with two or more nodules reevaluated using 5-mm section CT. In cases with only one nodule, reevaluation using a 5 mm section was consistent with evaluation using a 1 mm section. However, this was not observed in cases with two or more nodules, with a significant difference between one nodule and two or more nodules. CONCLUSIONS: If there are two or more nodules observed in 5-mm section CT it may be necessary to reevaluate using 1-mm section CT to determine the exact number of pulmonary metastases.

Prognostic and functional impact of perioperative LAMA/LABA inhaled therapy in patients with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting ß2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. METHODS: Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. RESULTS: Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). CONCLUSIONS: We believe this treatment combination is optimal for patients with lung cancer and COPD.

Quantification of BIM mRNA in circulating tumor cells of osimertinib-treated patients with EGFR mutation-positive lung cancer.

BACKGROUND: The response rate for osimertinib is high among patients with untreated epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). However, there exist no biomarkers to predict the efficacy of the same. This study investigated whether BIM-γ mRNA expression in circulating tumor cells (CTCs) predicts poor outcomes for osimertinib treatment in patients with EGFR mutation-positive NSCLC. METHODS: Patients with advanced EGFR-tyrosine kinase inhibitor-untreated NSCLC or post-operative recurrence with EGFR-sensitive mutations (exon 19 deletion or L858R mutation) were included. Informed consent was obtained from all participants. The candidate biomarker BIM-γ was measured in CTCs after blood collection (10 mL of whole blood) at baseline. CTCs were collected with the ClearCell FX system, and quantitative real-time PCR was performed. Relative expression of BIM-γ mRNA from CTCs, as normalized to the reference gene (GAPDH mRNA), was calculated using the KCL22 cell line for calibration. RESULTS: We enrolled 30 EGFR mutation-positive NSCLC patients treated with osimertinib during the period from April 2018 through December 2019. All the patients had an EGFR mutation at the primary site: exon 19 deletion in 15 cases and L858R in 15 cases. Median CTC count at baseline was 12 (range 3-127)/7.5 mL, and median BIM-γ mRNA expression was 0.073 (range 0-1.37). Furthermore, the response rate to osimertinib was worse in patients with high than in those with low BIM-γ mRNA expression (n = 15 each) (26.6% vs. 73.3%, respectively; p = 0.011). Progression-free survival did not significantly differ between groups (p = 0.13). CONCLUSIONS: BIM-γ mRNA overexpression in CTCs from EGFR mutation-positive NSCLC patients is a potential a biomarker for poor response to osimertinib. CLINICAL TRIAL REGISTRATION NUMBER: UMIN:00032055.