The Impact of EGFR Mutation Status and Brain Metastasis for Non-Small Cell Lung Cancer Treated with Ramucirumab plus Docetaxel.

OBJECTIVES: Currently, combination therapy of ramucirumab (RAM) + docetaxel (DOC) must play a more important role as a second-line treatment. Epithelial growth factor receptor (EGFR) mutation accounts for around 50% of oncogenic driver mutations in patients with advanced non-small cell lung cancer (NSCLC) in Asian subsets. The number of brain metastases (BM) is relatively higher in EGFR mutation-positive patients compared to EGFR wild-type patients. The objective of this study is to evaluate the efficacy of RAM + DOC focusing on EGFR mutation and BM. METHODS: We retrospectively reviewed consecutive advanced NSCLC patients who received combination therapy of RAM + DOC at three institutions. A total of 112 patients with NSCLC were enrolled for efficacy analyses. We evaluated the efficacy of RAM + DOC for EGFR-mutated NSCLC with endpoints including progression-free survival (PFS), time to treatment failure (TTF) and overall survival. RESULTS: Median PFS was 5.7 months for the EGFR mutant group compared with 3.6 months for the EGFR wild-type group (HR 0.53, 95% CI 0.32-0.87; p = 0.01). Median TTF was 5.1 months for the EGFR mutant group compared with 2.8 months for the EGFR wild-type group (HR 0.53, 95% CI 0.33-0.85; p = 0.007). Median PFS and TTF of the EGFR mutant group was significantly longer than median PFS and TTF of the EGFR wild-type group. The multivariate analysis identified EGFR mutation status as an independent favorable factor of PFS. In subset analyses of BM, median PFS of the EGFR mutant group (2.8 months) was significantly shorter than that of the EGFR wild-type group (5.1 months) (HR 7.27, 95% CI 1.78-29.68; p = 0.002). CONCLUSION: This study revealed that EGFR mutation status and BM might be predictive or prognostic factors for PFS.

A case of tracheal stenosis due to anaplastic thyroid carcinoma treated using the stent-in-stent method.

Tracheal AERO stent collapse is a rare complication compared to bronchial AERO stent collapse due to differences in the nitinol framework thickness. A 58-year-old man with a bulky anaplastic thyroid carcinoma was referred to our hospital due to exacerbation of tracheal stenosis despite the administration of lenvatinib. His tracheal stenosis exhibited a severe extrinsic compression pattern with a length of 8 cm. Because tracheotomy was inappropriate, we placed an 18 × 80 mm AERO stent. Five months later, he was readmitted with severe dyspnea due to collapse of the distal portion of the stent caused by tumor growth. Because stent removal was difficult, we placed an additional AERO stent (18 × 60 mm) to cover the collapsed portion. The additional stent successfully expanded the collapse and improved his dyspnea. To our knowledge, this is the first case where a tracheal AERO stent collapse due to a poor prognosis tumor was treated with the stent-in-stent method.

Physical Activity Using a Wearable Device as an Alternative to Performance Status in Patients With Advanced Lung Cancer.

Importance: The Eastern Cooperative Oncology Group Performance Status (ECOG PS) is extensively used to guide treatment decisions in patients with advanced lung cancer. However, its assessment is subjective, potentially leading to discordance among observers. Objective: To investigate the association between measured physical activity and ECOG PS, as well as the potential prognostic value of physical activity measurements in patients with advanced lung cancer. Design, Setting, and Participants: This single-institution, prospective observational study enrolled 119 patients with advanced lung cancer scheduled to receive systemic therapy as outpatients at Matsusaka Municipal Hospital in Mie, Japan. Participants wore the wearable device amuelink (Sony) for up to 14 days to measure physical activity, including metabolic equivalent tasks, distance walked, and number of steps taken. ECOG PS was assessed at enrollment, which took place from December 2021 to August 2022. Main Outcomes And Measures: The primary end point was estimating the area under the curve (AUC) for classification into ECOG PS of 2 or higher using physical activity measurements. An analysis of the association with survival was also conducted. Results: Among the 119 patients (median [range] age, 72 (32-88) years; 71 [59.7%] male), mean distance walked (MDW) had the highest diagnostic value for classifying an ECOG PS of 2 or greater, with an AUC of 0.818 (95% CI, 0.703-0.934). Moreover, MDW was also associated with 6-month survival, with an AUC of 0.806 (95% CI, 0.694-0.918). Survival curves significantly diverged based on the MDW threshold, indicating a potential association with survival outcome (hazard ratio, 0.17; 95% CI, 0.05-0.57). Conclusions and Relevance: The cohort study suggests that MDW, as measured by a wearable device, was associated with ECOG PS and may serve as a predictor of health status alongside ECOG PS categories. It demonstrates the potential of objectively measured physical activity in complementing subjective ECOG PS assessments in patients with advanced lung cancer. Further research is needed to confirm the prognostic value of physical activity measurements.

The Current Achievements of Multi-Gene Panel Tests in Clinical Settings for Patients with Non-Small-Cell Lung Cancer.

Some multi-gene panel tests have been implemented in clinical settings to guide targeted therapy in non-small-cell lung cancer (NSCLC) in Japan. The current performance of multi-gene panel tests under the condition that the Oncomine Dx Target Test (ODxTT) and Amoy Dx® Pan Lung Cancer PCR panel (AmoyDx-multi) are available remains relatively unknown. We retrospectively reviewed consecutive patients with NSCLC, whose FFPE samples were considered for genetic testing. We assessed the submission rates, the success rates, and the driver oncogene detection rates of multi-gene panel tests. A total of 225 patients were histologically newly diagnosed with NSCLC or diagnosed with a recurrence of NSCLC without a previous multi-gene panel test at our institution. Among the 225 patients, the FFPE samples of 212 patients (94.2%) were submitted for multi-gene panel testing, including 191 samples (84.9%) for the ODxTT and 21 samples (9.3%) for the AmoyDx-multi. Among the 212 samples submitted to multi-gene panel tests, the success rate was 99.5% (211/212). The detection rate of driver oncogene alterations for all histologies was 52.4% (111/212), and that for adenocarcinoma was 69.7% (106/152). A favorable submission rate and success rate of multi-gene panel tests were shown, along with a favorable detection rate in recent clinical settings.

Physical Activity Estimated by the Wearable Device in Lung Disease Patients: Exploratory Analyses of Prospective Observational Study.

Background. Physical activity is a potential parameter to assess the severity or prognosis of lung disease. However, the differences in physical activity between healthy individuals and patients with lung disease remain unclear. Methods. The analyses in this report are a combined analysis of four cohorts, including a healthy control cohort, in a prospective study designed to evaluate wearable device-estimated physical activity in three cohorts: the lung cancer cohort, the interstitial pneumonia cohort, and the COPD cohort (UMIN000047834). In this report, physical activity in the lung disease cohort was compared with that in the healthy cohort. Subgroup analyses were performed based on age, sex, duration of wearable device use, and lung disease subtype. Results. A total of 238 cases were analyzed, including 216 patients with lung disease and 22 healthy cases. Distance walked and number of steps were significantly lower in the patient group compared to the healthy control group. ROC analysis for the diagnostic value of lung disease by mean distance walked and mean number of steps showed AUC of 0.764 (95%CI, 0.673 to 0.856) and 0.822 (95%CI, 0.740 to 0.905), respectively. There was a significant difference in physical activity by age, but not by gender nor by duration based on the threshold of 7 days of wearing the device. Conclusions. Lung disease decreases physical activity compared to healthy subjects, and aging may bias the estimation of physical activity. The distance walked or number of steps is recommended as a measure of physical activity, with a period of approximately one week and adjusted for age for future investigation.

Clinical importance of the range of detectable variants between the Oncomine Dx target test and a conventional single-gene test for EGFR mutation.

Although we have experienced some cases with discordant results between the Oncomine Dx target test (ODxTT) and conventional single gene tests for detecting EGFR alterations, the clinical efficacy of EGFR-TKIs in these discordant cases remains little known. We retrospectively reviewed consecutive patients with non-small-cell lung cancer whose FFPE samples were simultaneously submitted for the ODxTT, and a PNA-LNA PCR clamp test. We evaluated the clinical efficacy of EGFR-TKIs in patients with discordant results between the two tests, focusing on the common EGFR mutations. Among 444 successful results, 10 patients had discordant results for common EGFR mutations (9 Ex 19 deletion and 1 Ex 21 L858R mutation), and all of these were detected only by the PNA-LNA PCR clamp test. Among six discordant cases treated with EGFR-TKI, the mutations detected in 3 patients were not included in the list of detectable variants that are reportable by the ODxTT, while the mutations detected in the other 3 patients were included in the list. For all three discordant cases harboring the mutations not reportable by the ODxTT, good clinical responses were demonstrated. However, among the other three discordant cases harboring the mutations reportable by the ODxTT, only one patient had a clinical response with short duration. Among the discordant cases for common EGFR mutations between the ODxTT and the conventional single gene test, there are a certain number of suitable patients responsive to EGFR-TKIs, especially when the cause of the discordant results comes from the difference in the range of detectable variants that are reportable between the tests.

Clinicopathological and Molecular Characteristics Promoting PD-L1 Expression in Early-stage Lung Adenocarcinoma and Squamous Cell Carcinoma.

BACKGROUND/AIM: Lung adenocarcinoma and lung squamous cell carcinoma represent the most prevalent subtypes of non-small cell lung cancer eligible for surgery in the early stages. The emergence of immune checkpoint inhibitors as adjuvant therapy has shown promising potential in improving the postoperative prognosis of patients with lung cancer. Hence, a comprehensive understanding of the clinicopathological and molecular features of programmed cell death ligand-1 (PD-L1) expression in lung adenocarcinoma and squamous cell carcinoma is crucial. PATIENTS AND METHODS: In this retrospective study, we conducted a comparative analysis of clinicopathological features associated with the expression of PD-L1, stratifying patients who underwent surgical resection into two distinct groups: 289 patients with lung adenocarcinoma and 66 with lung squamous cell carcinoma. Furthermore, we investigated the associations between the expression of PD-L1 and genetic alterations in well-established oncogenic driver mutations. RESULTS: Among the cases, 52.9% exhibited negative PD-L1 expression, 32.9% had low PD-L1 expression, and 12.3% had high PD-L1 expression in adenocarcinoma, while the PD-L1 expression in squamous cell carcinoma showed a near-even distribution. Notably, male sex, smoking history, the presence of invasive pathological factors, and disease progression significantly influenced PD-L1 expression in adenocarcinoma, whereas none of these factors were associated with PD-L1 expression in squamous cell carcinoma. Additionally, the distribution of PD-L1 expression varied based on the type of specific driver gene mutation in adenocarcinoma. CONCLUSION: The present study revealed clinicopathological and molecular differences between lung adenocarcinoma and squamous cell carcinoma patients promoting the expression of PD-L1.

Close-to-lesion transbronchial biopsy: a novel technique to improve suitability of specimens for genetic testing in patients with peripheral pulmonary lesions.

Bronchoscopy with radial-probe endobronchial ultrasound, a guide sheath, and electromagnetic navigation can improve the diagnostic yield of peripheral lung nodules. However, the suitability of specimens for genetic analysis remains unsatisfactory. We hypothesized that a transbronchial biopsy performed after closely approaching the bronchoscope tip to the lesion might provide more suitable specimens for genetic analysis. We enrolled 155 patients with peripheral pulmonary lesions who underwent bronchoscopy with a thin or ultrathin bronchoscope. Bronchoscopy was performed using virtual bronchoscopic navigation and radial-probe endobronchial ultrasound with a guide sheath. The bronchoscope tip was placed closer to the lesion during bronchoscopy to collect larger specimens with higher malignant cell content. The patients who underwent a close-to-lesion biopsy had higher rates of overall diagnostic yield, histopathological diagnostic yield, and specimen quality for genetic testing than those who did not. The significant determinants of the specimen's suitability were the close-to-lesion approach, within-the-lesion image, the use of standard 1.9-mm-forceps, and the number of cancer-cell-positive specimens. The significant predictors of the specimen's suitability for genetic analysis were close-to-lesion biopsy and the number of malignant cell-positive tissue samples. This study demonstrates that the close-to-lesion transbronchial biopsy significantly improves the suitability of bronchoscopic specimens for genetic analysis.

An oldest-old non-small cell lung cancer patient with abscopal effect in a single lesion.

The abscopal effect without concomitant immunotherapy is a rare event, including among cases of lung cancer. Furthermore, the occurrence of limited abscopal effect for only a single lesion in the metastatic organ consistent with the irradiated organ would be an even more rare event. A 94-year-old man was diagnosed with advanced lung cancer with osteolytic bone metastases in his right iliac bone, and the right side of his axial vertebrae. After palliative radiation therapy to the right iliac lesion for pain relief without other anticancer therapy, the axial vertebral osteolytic lesion disappeared despite no reduction in the other lesions. This case furthers our understanding of the pathogenesis of the abscopal effect.

Good Response of Advanced Thymic Carcinoma with Low PD-L1 Expression to Chemotherapy plus Pembrolizumab as First-Line Therapy and to Pembrolizumab as Maintenance Therapy: A Case Report.

Thymic carcinoma is a rare malignant tumor with a poor prognosis. No standard treatment is currently available. The present case was a 64-year-old male smoker with no symptoms referred to our hospital because of abnormal chest radiological findings. The CT study showed a tumor between the anterior mediastinum and the right lung upper lobe, multiple nodular shadows along the right pleura, and pleural effusion. A CT-guided needle biopsy revealed squamous cell carcinoma. However, the differential diagnosis between thymic carcinoma and primary lung cancer was difficult. Treatment with carboplatin, nanoparticle albumin-bound paclitaxel, and pembrolizumab was initiated. The CT scan showed tumor shrinkage and good clinical response after four treatment cycles. Therapy was switched to maintenance therapy with pembrolizumab alone. Imaging studies showed further tumor shrinkage after twelve cycles of maintenance therapy with pembrolizumab. Sixteen cycles of maintenance therapy were continued without performance status deterioration. An abnormal radiological finding was detected after a twelve-month exacerbation-free period. The diagnosis was thymic carcinoma. Treatment with lenvatinib was initiated, and tumor-size reduction was observed. This is the first report of a case showing a successful maintenance therapy with pembrolizumab after effective first-line therapy with a combination of carboplatin-based chemotherapy plus pembrolizumab in advanced thymic carcinoma.

Comparison of the analytical performance of the Oncomine dx target test focusing on bronchoscopic biopsy forceps size in non-small cell lung cancer.

BACKGROUND: Next-generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide targeted therapy. Although the pathological diagnosis and biomarker tests for patients with advanced lung cancer have mostly been obtained with small biopsy samples, especially with bronchoscopic approaches, the performance for NGS with respect to the different sizes of biopsy forceps remains little known. METHODS: We retrospectively reviewed consecutive patients with non-small cell lung cancer, whose FFPE samples were obtained by endobronchial biopsy/transbronchial biopsy and were submitted for the Oncomine Dx Target Test (ODxTT). We compared the analytical performance for ODxTT with respect to the size of biopsy forceps. RESULTS: A total of 103 samples were identified. The success rate of the ODxTT for the group with all samples obtained with small forceps biopsies (70%) was lower than that of the group with some or all samples obtained with standard forceps biopsies (83%), although without a statistically significant difference (p = 0.20). With regard to the reason for unsuccessful analysis, the proportion of the samples which did not pass the nucleic acid concentration threshold in the former group (15%) was higher compared with that of the latter group (4%) (p = 0.08). The proportion of tissue size 4 mm2 or larger in the former group (70%) was lower than that in the latter group (93%) (p = 0.01). CONCLUSION: The analysis of ODxTT for specimens biopsied using only small forceps is prone to be unsuccessful due to an insufficient amount of nucleic acid.

Comparison of the 22-gauge and 25-gauge needles for endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive hilar mediastinal node sampling technique used for lung cancer staging and diagnosis of lesions. Besides the conventional 22-gauge (G) and 21G needles, a 25G needle is now available for this procedure. The objective of this study was to evaluate the efficacy of the 25G EBUS-TBNA needle. METHODS: We retrospectively reviewed consecutive patients who underwent EBUS-TBNA using both 22G and 25G aspiration needles from January 2017 through December 2017 at St. Marianna University School of Medicine. We identified 10 patients and compared the diagnostic yield and the sample volume for each needle. RESULTS: Six patients were diagnosed with lung cancer and four with sarcoidosis. Total diagnostic yield was 80% (8/10) for the 22G and 60% (6/10) for the 25G (P = 0.31). In patients with lung cancer, the diagnostic yield was 67% (4/6) for the 22G and 83% (5/6) for the 25G (P = 0.50). In patients with sarcoidosis, the diagnostic yield was 100% (4/4) for the 22G and 25% (1/4) for the 25G (P = 0.07). In patients with lung cancer, the median tissue area was comparable for each needle; however, in patients with sarcoidosis, the sample area was smaller for the 25G than for the 22G. We did not encounter any major complications or bleeding during EBUS-TBNA procedures. CONCLUSIONS: Although histologic specimens obtained by the 25G needle are expected to be useful for the diagnosis of lung cancer, we found the 25G needle inadequate for diagnosing sarcoidosis due to insufficient sample size.

Drug-induced Hypersensitivity Syndrome by EGFR-TKI in a Patient with Lung Cancer.

An 83-years-old woman diagnosed with advanced Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma was administered afatinib as a first-line treatment. On Day 17, the patient presented with grade 3 diarrhea and a blood test analysis showed an increased inflammatory response. Afatinib treatment was discontinued on the same day. On Day 26, the patient displayed blepharedema and multiple irregular erythema covering her entire body. Drug-induced hypersensitivity syndrome (DIHS) was suspected, and the systemic administration of 30 mg/day prednisolone was administered. The symptoms subsided thereafter. A blood test analysis 3 weeks after onset revealed a reactivation of Human herpesvirus 6 (HHV-6) and a diagnosis of DIHS due to afatinib therapy was confirmed.

Comparison of the analytical performance between the Oncomine Dx Target Test and a conventional single gene test for epidermal growth factor receptor mutation in non-small cell lung cancer.

BACKGROUND: Next-generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide targeted therapy; however, little is known about the performance of the Oncomine Dx Target Test compared with conventional single gene tests for detecting EGFR mutations. The objective of this study was to evaluate the performance of the Oncomine Dx Target Test compared with a PNA-LNA PCR clamp test to detect EGFR mutations. METHODS: We retrospectively reviewed consecutive patients with non-small cell lung cancer (NSCLC) from whom FFPE samples were simultaneously submitted for the Oncomine Dx Target Test, and a PNA-LNA PCR clamp test using the same specimen. We subsequently compared the analysis success rates and detection rates between the two tests. RESULTS: A total of 116 samples were identified. The success rates and detection rates of EGFR mutations in the total number of samples were 90% and 28%, respectively for the Oncomine Dx Target Test, and 100% and 35% for the PNA-LNA PCR clamp test. The Oncomine Dx Target Test was unable to analyze three samples (2%) due to the samples not passing the nucleic acid concentration threshold, and nine (8%) samples had invalid results. The exon 19 deletion was not detected by the Oncomine Dx Target Test in four cases (4%). CONCLUSIONS: The analytical performance of the Oncomine Dx Target Test analysis for EGFR mutations may not be comparable with conventional single gene tests due to both invalid and false-negative results. KEY POINTS: Significant findings of the study The success rate of the Oncomine Dx Target Test was significantly lower than the PNA-LNA PCR clamp test. Among the samples successfully analyzed, four exon 19 deletions were not detected by the Oncomine Dx Target Test. What this study adds The analytical performance of the Oncomine Dx Target Test may not be comparable with conventional single gene tests. We should revise the sampling procedures, and review the sample quality assessment methods, to improve the analytical performance.

Assessment of chemotherapy regimens on radiation pneumonitis in patients with unresectable stage III non-small-cell lung cancer after definitive chemoradiotherapy.

BACKGROUND: Consolidation therapy with durvalumab after concurrent chemoradiotherapy has been reported to significantly prolong progression-free survival and overall survival in patients with stage III unresectable non-small cell lung cancer (NSCLC). However, which chemotherapy regimen should be selected for consolidation therapy with durvalumab is currently unknown. METHODS: We retrospectively reviewed consecutive patients with unresectable stage III NSCLC who received concurrent definitive chemoradiotherapy with platinum-based chemotherapy. We reviewed the timing and severity of radiation pneumonitis by assessing chemotherapy regimens and histology. RESULTS: A total of 103 patients were identified. Fourteen patients (13.6%) developed grade 2 or greater radiation pneumonitis within 42 days after chemoradiotherapy. No adenocarcinoma patients treated with a regimen of cisplatin plus pemetrexed developed grade 2 or greater radiation pneumonitis within 42 days; however, 20% of patients who were treated with carboplatin plus paclitaxel developed grade 2 or greater radiation pneumonitis. Furthermore, the objective response rates and disease control rates of cisplatin plus pemetrexed were equal to or greater than those of carboplatin plus paclitaxel in adenocarcinoma patients. CONCLUSION: Cisplatin plus pemetrexed regimen may be a preferable option to consider for subsequent consolidation therapy with durvalumab in patients with unresectable stage III adenocarcinoma.

The Potential of Digital Polymerase Chain Reaction for Improving Diagnostic Yield of Nontuberculous Mycobacteria Pulmonary Disease.

INTRODUCTION: Many patients with nontuberculous mycobacteria pulmonary disease are asymptomatic. The disease diagnosis is confirmed in only a small proportion of patients with radiological findings suspicious for nontuberculous mycobacteria pulmonary disease. Thus, many patients remained undiagnosed. Here, we evaluated the diagnostic value of digital polymerase chain reaction (PCR) in nontuberculous mycobacteria pulmonary disease. METHODS: We prospectively evaluated 123 patients with radiological findings suspicious for nontuberculous mycobacteria pulmonary disease. Digital PCR was performed using bronchial lavage fluid, sputum, saliva, blood, and urine. RESULTS: The culture of bronchial washing fluid was positive for nontuberculous mycobacteria in 53 patients and negative in 70. The positive detection rate of nontuberculous mycobacteria by digital PCR in patients with positive culture (n = 53) was as follows: bronchial lavage fluid 100%, sputum 62.9%, saliva 41.5%, blood 7.5%, and urine 3.8%. All patients with two or more positive partitions for nontuberculous mycobacteria in the digital PCR of bronchial lavage fluid showed nontuberculous mycobacteria growth in the bronchial lavage fluid culture. The digital PCR analysis of the bronchial lavage fluid showed a high sensitivity (100%), specificity (85.7%), positive predictive value (84.1%), negative predictive value (100%), and a high concordance rate (91.9%) with the bronchial lavage fluid culture results. In addition, the culture of bronchial lavage fluid was positive for nontuberculous mycobacteria in patients with two or more positive partitions in the digital PCR of sputum and saliva with a combined positive predictive value of 81.1%. CONCLUSION: Digital PCR analysis of nontuberculous mycobacteria in bronchial lavage fluid shows a high concordance rate with the bronchial lavage fluid culture results and a high positive predictive value using both sputum and saliva, suggesting the potential usefulness of dPCR for diagnosis of nontuberculous mycobacteria pulmonary disease in clinical practice.

The efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer.

BACKGROUND: Ramucirumab plus docetaxel (RAM+DOC) is expected to prolong survival in patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy and safety for older patients remains unknown. The objective of this study was to evaluate the efficacy and safety of RAM+DOC in patients 75 years and older. METHODS: We retrospectively reviewed consecutive patients with advanced NSCLC who had received RAM+DOC treatment at three institutions. We compared the efficacy and safety in patients 75 years and older to those under 75 years of age. RESULTS: A total of 114 patients were identified. The median progression-free survival, time to treatment failure and overall survival was 3.6 (95% CI: 0.4-6.7), 3.1 (95% CI: 2.4-3.9) and 11.2 months (95% CI: 5.6-16.8) in the older group (N = 23), and 4.2 (95% CI: 3.3-5.0), 3.4 (95% CI: 3.3-5.0) and 12.2 months (95% CI: 9.1-15.4) in the younger group (N = 91), respectively. Survival curves were similar for each group, while the objective response rate was 30.4% (95% CI: 13.2-52.9%) in older patients and 35.2% (95% CI, 25.4-45.9%) for the younger group. A total of 22 older patients (95.7%) and 73 (80.2%) younger patients received primary prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF). Four older patients (17.3%) and 14 younger patients (15.3%) discontinued RAM+DOC due to adverse events. CONCLUSIONS: RAM+DOC is expected to be efficacious and tolerable in older patients when supported with prophylactic PEG-G-CSF therapy. KEY POINTS: Significant findings of the study ・PFS, OS, and ORR in older patients were similar to those under 75 years of age. ・Safety of RAM+DOC was well tolerated in older patients with prophylactic PEG-G-CSF. ・Prophylactic PEG-G-CSF with RAM+DOC may contribute to better efficacy. What this study adds ・This study suggests that RAM+DOC with prophylactic PEG-G-CSF is expected to be a useful option in older patients with advanced NSCLC.

Use of Ultrathin Bronchoscope on a Need Basis Improves Diagnostic Yield of Difficult-to-Approach Pulmonary Lesions.

There are cases of peripheral lung nodules that are difficult to approach despite using ancillary diagnostic devices during multimodal bronchoscopy. The use of ultrathin bronchoscopes has shown superiority over standard thin bronchoscopes. We retrospectively evaluated whether substitution of the thin-bronchoscope by the ultrathin device during multimodal bronchoscopy improves lesion ultrasound visualization and diagnostic yield in patients with difficult-to-approach pulmonary lesions. The study comprised 44 out of 338 patients that underwent multimodal bronchoscopy at Matsusaka Municipal Hospital. The thin-bronchoscope with an external diameter of 4 mm was substituted by the ultrathin-bronchoscope with an external diameter of 3 mm when the radial endobronchial ultrasound showed that the probe position was not within the target lesion. The median diameter of the pulmonary tumors was 17.5 mm (range: 6.0-5.2.0 mm). The endobronchial ultrasound showed the probe's position adjacent to the lesion in 12 cases and no visible lesion in 32 cases using a thin-bronchoscope. However, the endobronchial ultrasound views changed from adjacent to the lesion to within the lesion in nine cases, from no visible lesion to within the lesion in 17 cases, and from no visible lesion to adjacent to the lesion in nine cases after bronchoscope substitution. After substitution, the diagnostic yield was 80.8% in cases with the radial probe within the target lesion, 72.7% in cases with the probe adjacent to the target lesion, and 0% in cases with no visible lesion. The overall diagnostic yield was 65.9% after bronchoscope substitution. The substitution of the thin bronchoscope by the ultrathin device on a need basis improves the position of the radial endobronchial ultrasound probe and diagnostic yield of pulmonary lesions during multimodal diagnostic bronchoscopy.