J-AVENUE: A retrospective, real-world study evaluating patient characteristics and outcomes in patients with advanced urothelial carcinoma treated with avelumab first-line maintenance therapy in Japan.

OBJECTIVES: The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. METHODS: Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. RESULTS: In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). CONCLUSIONS: Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.

A case of community-acquired Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (MRSA) necrotizing pneumonia successfully treated with two anti-MRSA drugs.

A 22-year-old Vietnamese man was referred to our hospital owing to cough, dyspnea, and difficulty moving. The patient was diagnosed with community-acquired Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and necrotizing pneumonia. Treatment involved vancomycin (VCM) and meropenem, and the MRSA bacteremia improved. However, lung tissue destruction progressed. Therefore, linezolid was added to the VCM regimen, and this intervention led to the patient's recovery, and he was discharged from the hospital. Here, we report a case in which the patient was treated with a combination of two anti-MRSA drugs and was cured.

The incidence and prognosis of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of the lung related to methotrexate: A retrospective study.

BACKGROUND AND OBJECTIVE: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung. METHODS: Patients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed. RESULTS: Among the 51 patients with OIIA-LPD, 16 (31.3%, 7 men, 9 women) had OIIA-LPD of the lung (median age, 69 [range, 63-82] years). Peripheral lesions were observed in 10 (62.5%), central lesions in two (12.5%), and both lesions in four (25.0%) patients. Nine of the 16 patients underwent bronchoscopic biopsy, seven were diagnosed (diagnostic yield, 77.8%) and, re-biopsy was performed in 2 patients. Eight (50.0%) patients had LPD and six (37.5%) had diffuse large B-cell lymphoma. In the 14 patients with confirmed treatment efficacy, the overall response rate to MTX withdrawal was 71.4%. However, chemotherapy was required in case of larger lesions (three patients). Death related to OIIA-LPD occurred in only one patient, and 11 of the 14 patients were alive during the study period (median follow-up time, 53.7 [range, 4.3-84.2] months). CONCLUSION: The incidence of OIIA-LPD of the lung is 31.3% and higher than that reported previously. The treatment effect of MTX withdrawal seems to be sufficient; however, in some cases, chemotherapy may be required from the beginning.

Talc slurry pleurodesis in patients with secondary intractable pneumothorax: A phase 2 study.

BACKGROUND: Secondary pneumothorax, which occurs most commonly in the elderly, is caused by underlying diseases. Cardiac dysfunction and other organ inefficiencies may render surgical repair impossible. Such non-operative and poor-risk cases are targets for pleurodesis, which involves the instillation of chemicals or irritants to the thoracic cavity through injection, bronchoscopic bronchial occlusion, or other procedures. Sterile graded talc has been used for pleurodesis mainly in Europe and the United States; however, only a few studies and case series investigating this topic have been published. This study evaluates the efficacy and safety of talc slurry pleurodesis. METHODS: Patients with inoperable secondary intractable pneumothorax, who were not candidates for surgical repair, were recruited. Four grams of sterilized talc was suspended in 50 mL of physiological saline and injected through a tube into the pleural cavity. Additional 50 mL of saline was subsequently injected through the same channel to clean the residual saline in the injection tube. Another additional talc instillation was allowed to control persistent air leakage. The primary endpoint was the proportion of drainage tube removal within 30 days after talc pleurodesis. RESULTS: Thirty-one patients were included in this study. In 23 out of 28 patients, the drainage tube could be removed within 30 days of talc instillation (82.1 %, 95 % CI = 63.1-93.9), exceeding the threshold of 36.0 % (p < 0.0001). The most common event was pain (11/28 patients, 39.3 %). CONCLUSIONS: Talc slurry pleurodesis is effective for intractable secondary pneumothorax, with minor side effects.

Immunotherapy for Unresectable Small Bowel Adenocarcinoma: A Case Series.

BACKGROUND/AIM: The efficacy of systemic therapy for unresectable small bowel adenocarcinoma that is refractory to fluoropyrimidines and oxaliplatin has not yet been established because of the rarity of this cancer. Although immunotherapy with anti-PD-1 antibodies has shown robust efficacy in the treatment of esophagogastric adenocarcinoma, its effectiveness in small bowel adenocarcinoma remains unclear. CASE REPORT: In the first case, a 75-year-old man was diagnosed with metastatic moderately differentiated adenocarcinoma of the jejunum with stable microsatellite instability. After receiving multiple lines of therapy, including fluoropyrimidines plus oxaliplatin, irinotecan, and paclitaxel, the patient was treated with nivolumab and achieved a partial response that lasted for 12 months. In the second case, a 65-year-old man was diagnosed with an unresectable locally advanced duodenal adenocarcinoma. High microsatellite instability was confirmed by polymerase chain reaction-based testing. After showing resistance to 5-fluorouracil and oxaliplatin, the patient received nivolumab and ipilimumab therapy. Although therapy was discontinued because of immune-related colitis and skin rash, a partial response was achieved. CONCLUSION: Treatment with immune checkpoint inhibitors is effective for refractory small bowel adenocarcinoma, irrespective of the microsatellite status.

Significance of micro-EGFR T790M mutations on EGFR-tyrosine kinase inhibitor efficacy in non-small cell lung cancer.

Small amounts of epidermal growth factor receptor (EGFR) T790M mutation (micro-T790M), which is detected using droplet digital PCR (ddPCR) but not conventional PCR, in formalin-fixed and paraffin-embedded (FFPE) samples have been investigated as a predictive factor for the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). However, the predictive value of micro-T790M remains controversial, possibly owing to the failure to examine artificial T790M in FFPE specimens. Therefore, we examined the predictive value of micro-T790M in first-generation (1G), second-generation (2G), and third-generation (3G) EGFR-TKI efficacy using a new method to exclude FFPE-derived artificial mutations in our retrospective cohort. The primary objective was time to treatment failure (TTF) of 1G, 2G, and 3G EGFR-TKIs according to micro-T790M status. In total, 315 patients with EGFR-positive non-small cell lung cancer treated with 1G, 2G, and 3G EGFR-TKIs were included in this study. The proportion of patients positive for micro-T790M in the 1G, 2G, and 3G EGFR-TKI groups was 48.2%, 47.1%, and 47.6%, respectively. In the micro-T790M-positive group, the TTF was significantly longer in the 2G and 3G EGFR-TKI groups than in the 1G TKI group. No differences in the micro-T790M-negative group were observed. Micro-T790M status detected using ddPCR, eliminating false positives, may be a valuable predictor of EGFR-TKI efficacy.

Augmenting Granzyme B-Expressing NK Cells by Invariant NKT Ligand-Loaded APCs in Patients with Postoperative Early Stage Non-Small Cell Lung Cancer: Results of a Randomized Phase II Study.

NK cells are major effector cells involved in the elimination of early tumors and prevent metastasis. They often have an impaired function in patients with cancer. Preclinical studies have demonstrated NK cell activation as the adjunctive effect of invariant NKT (iNKT) cells. Activation of iNKT cells after administration of the glycolipid ligand α-galactosylceramide, loaded with CD1d-expressing human PBMC-derived APCs (APC/Gal), is an attractive cancer therapy to optimize the use of NK cells. However, the subsets of NK cells that are activated following iNKT cell activation as well as the period of NK cell activation remain unclear. In this study, we report that the granzyme B-expressing NK cell response in postoperative lung cancer patients was enhanced 49 d after administration of APC/Gal in a phase II study. We found maximum IFN-γ production on day 49 in 13 out of 27 APC/Gal-treated patients. On day 49, 14 out of 27 patients (51.9%) had higher IFN-γ production by iNKT cells (>6-fold higher than the baseline level). This increment significantly correlated with granzyme B-expressing NK cells. Although IFN-γ production was lower in patients in the nontreated group, we detected maximum IFN-γ production 12 mo after the resection of lung cancer (9 out of 29 patients [31%]). These findings suggest that elimination of cancer cells leads to increased NK cell function, which can be further enhanced by APC/Gal therapy.

The Impact of Nutritional Support on Survival Outcomes in Patients with Advanced Gastric Adenocarcinoma Treated with Chemotherapy.

Malnutrition and cachexia occur commonly in patients with advanced gastric cancer (AGC). This study elucidated the effect of nutritional support (NS) on survival outcomes among patients with AGC undergoing chemotherapy. We retrospectively evaluated new AGC cases at our institute between January 2015 and January 2021. Inclusion criteria were unresectable or recurrent chemotherapy-treated gastric adenocarcinoma, ECOG performance status (PS) 0-2, and adequate organ function. Time to treatment failure (TTF) and overall survival (OS) were evaluated, and univariate and multivariate analyses identified prognostic factors. A total of 103 eligible patients were separated into groups: 69 patients (67%) into NS and 34 (33%) into routine care (RC). The median follow-up time was 11.0 mo, (0.5-92). NS was offered to patients with poorer PS (p = 0.03), Glasgow prognostic score (GPS) positivity (p = 0.001), and high neutrophil-to-lymphocyte ratios (cut-off ≤ 3, p = 0.02). Median OS and TTF in the RC and NS groups were 11.6 and 10.4 mo, (p = 0.99) and 4.2 and 5.5 mo, (p = 0.07), respectively. Multivariate analyses identified NS (hazard ratio [HR] = 0.53, p = 0.01) and GPS positivity for TTF, and low body mass index (HR = 2.03, p = 0.007) and GPS positivity (HR = 2.25, p = 0.001) for OS as significant prognostic factors. Thus, NS with chemotherapy is a potentially effective intervention for AGC.

Ultrathin bronchoscopic cryobiopsy of peripheral pulmonary lesions.

BACKGROUND AND OBJECTIVE: Ultrathin bronchoscopy aids in the diagnosis of peripheral pulmonary lesions. However, both the working channel and the specimens are small. A 1.1-mm ultrathin cryoprobe that can enter the working channel of the ultrathin bronchoscope is now available, which may overcome the limitations of small specimen size. The aim of this study was to evaluate the feasibility, efficacy and safety of ultrathin bronchoscopic cryobiopsy using an ultrathin cryoprobe for diagnosing peripheral pulmonary lesions. METHODS: Patients with peripheral pulmonary lesions ≤30 mm in diameter were prospectively enrolled in the study. All patients underwent forceps biopsy followed by cryobiopsy using a 3.0-mm ultrathin bronchoscope under radial probe endobronchial ultrasound guidance, virtual bronchoscopic navigation and fluoroscopic guidance. The primary endpoint was the feasibility of cryobiopsy. RESULTS: In total, 50 patients with peripheral pulmonary lesions were enrolled in the study; the median longest diameter on computed tomography was 17.9 mm. Cryobiopsy was performed successfully in 49 patients (98%). Forceps biopsy, cryobiopsy and the combination of these two methods provided a specific diagnosis in 54% (27/50), 62% (31/50) and 74% (37/50) of patients, respectively. The median size of specimens obtained via cryobiopsy was significantly larger than the median size obtained via forceps biopsy (7.0 vs. 1.3 mm2 , respectively, p < 0.001). Mild bleeding during cryobiopsy occurred in 47 patients (94%). No moderate/severe bleeding or pneumothorax occurred. CONCLUSION: Ultrathin bronchoscopic cryobiopsy is feasible, effective and sufficiently safe for the diagnosis of peripheral pulmonary lesions.

Differential properties of KRAS transversion and transition mutations in non-small cell lung cancer: associations with environmental factors and clinical outcomes.

BACKGROUND: KRAS-mutated non-small cell lung cancer (NSCLC) accounts for 23-35% and 13-20% of all NSCLCs in white patients and East Asians, respectively, and is therefore regarded as a major therapeutic target. However, its epidemiology and clinical characteristics have not been fully elucidated because of its wide variety of mutational subtypes. Here, we focused on two distinct base substitution types: transversion mutations and transition mutations, as well as their association with environmental factors and clinical outcome. METHODS: Dataset from the Japan Molecular Epidemiology Study, which is a prospective, multicenter, and molecular study epidemiology cohort study involving 957 NSCLC patients who underwent surgery, was used for this study. Questionnaire-based detailed information on clinical background and lifestyles was also used to assess their association with mutational subtypes. Somatic mutations in 72 cancer-related genes were analyzed by next-generation sequencing, and KRAS mutations were classified into three categories: transversions (G > C or G > T; G12A, G12C, G12R, G12V), transitions (G > A; G12D, G12S, G13D), and wild-type (WT). Clinical correlations between these subtypes have been investigated, and recurrence-free survival (RFS) and overall survival (OS) were evaluated. RESULTS: Of the 957 patients, KRAS mutations were detected in 80 (8.4%). Of these, 61 were transversions and 19 were transitions mutations. Both pack-years of smoking and smoking duration had significant positive correlation with the occurrence of transversion mutations (p = 0.03 and < 0.01, respectively). Notably, transitions showed an inverse correlation with vegetable intake (p = 0.01). Patients with KRAS transitions had the shortest RFS and OS compared to KRAS transversions and WT. Multivariate analysis revealed that KRAS transitions, along with age and stage, were significant predictors of shorter RFS and OS (HR 2.15, p = 0.01; and HR 2.84, p < 0.01, respectively). CONCLUSIONS: Smoking exposure positively correlated with transversions occurrence in a dose-dependent manner. However, vegetable intake negatively correlated with transitions. Overall, KRAS transition mutations are significantly poor prognostic factors among resected NSCLC patients.

EUS-B-FNA Enhances the Diagnostic Yield of EBUS Bronchoscope for Intrathoracic Lesions.

INTRODUCTION: Endobronchial ultrasound (EBUS) bronchoscopes have been used mainly through the airway for EBUS-guided transbronchial needle aspiration (EBUS-TBNA); however, they can also be used through the esophagus. The esophageal approach, endoscopic ultrasound with bronchoscope-guided fine needle aspiration (EUS-B-FNA), has gradually become popular, as it can evaluate lesions that cannot be accessed through the airway. PURPOSE: This study aimed to evaluate the value of adding EUS-B-FNA to EBUS-TBNA performed by pulmonologists for intrathoracic lesions in the clinical setting. METHODS: Between March 2009 and March 2020, all patients who underwent EUS-B-FNA and EBUS-TBNA for diagnostic purposes were included and retrospectively analyzed at a single institution. RESULTS: A total of 1794 procedures using an EBUS bronchoscope including, EBUS-TBNA, EUS-B-FNA, and the combination of EBUS-TBNA and EUS-B-FNA for evaluating intrathoracic lesions, were performed. We finally analyzed 276 patients who underwent EUS-B-FNA for diagnostic purposes. EUS-B-FNA provided diagnostic materials from only EBUS-TBNA-inaccessible lesions in 26 patients and in 18 patients whose conditions were inappropriate for bronchoscopy (e.g., respiratory failure, airway stenosis, etc.). EUS-B-FNA provided diagnostic results in four patients with non-diagnostic EBUS-TBNA results. EUS-B-FNA was preferable to EBUS-TBNA in 4.4% (48 of 1091) of patients; therefore, adding EUS-B-FNA to EBUS-TBNA increased the diagnostic yield from 72.6% (1043 of 1437) to 75.9% (1091 of 1437). CONCLUSION: Pulmonologists are able to enhance diagnostic yields by acquiring the EUS-B-FNA technique.

Thin bronchoscopic cryobiopsy using a nasobronchial tube.

BACKGROUND: Transbronchial lung cryobiopsy is useful when diagnosing lung lesions. However, prevention of associated bleeding complications is essential. This study aimed to evaluate the safety and efficacy of our novel bronchoscopic cryobiopsy technique, which uses a long nasobronchial tube to prevent blood flooding the central airway. METHODS: Patients with localized or diffuse lung lesions were prospectively enrolled and underwent cryobiopsy using a 1.9 mm diameter cryoprobe and a 4.0 mm diameter thin bronchoscope under conscious sedation. For cryobiopsy, a long silicone tube (inner diameter, 5.0 mm) was advanced through the nose to the target bronchus, then wedged to drain blood under thin-tube bronchoscopic control. The primary endpoint was the frequency of bleeding complications. RESULTS: Of the 80 patients initially enrolled, 73 that underwent at least one cryobiopsy were ultimately included. Mild bleeding during cryobiopsy occurred in 58 patients (79.5%), but there was no moderate or severe bleeding. Other complications occurred in four patients (two pneumothorax, one pneumomediastinum, and one pneumonia). Tube dislocation was noted in eight patients (11%). Cryobiopsy specimens were significantly larger than forceps biopsy specimens (9.0 mm2 vs. 2.7 mm2, P < .001) and allowed specific diagnoses in 50 patients (68.5%). CONCLUSIONS: Thin bronchoscopic cryobiopsy using a nasobronchial tube in consciously sedated patients is safe and effective. Trial registration Date of registration: 24/06/2019. UMIN-Clinical Trials Registry; Identifier: UMIN000037156 https://www.umin.ac.jp/ctr/index.htm.

Prognostic impact of pretreatment T790M mutation on outcomes for patients with resected, EGFR-mutated, non-small cell lung cancer.

BACKGROUND: Many previous studies have demonstrated that minor-frequency pretreatment T790M mutation (preT790M) could be detected by ultrasensitive methods in a considerable number of treatment-naïve, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) cases. However, the impact of preT790M in resected cases on prognosis remains unclear. METHODS: We previously reported that preT790M could be detected in 298 (79.9%) of 373 surgically resected, EGFR-mutated NSCLC patients. Therefore, we investigated the impact of preT790M on recurrence-free survival (RFS) and overall survival (OS) in this cohort by multivariate analysis. All patients were enrolled from July 2012 to December 2013, with follow-up until November 30, 2017. RESULTS: The median follow-up time was 48.6 months. Using a cutoff value of the median preT790M allele frequency, the high-preT790M group (n = 151) had significantly shorter RFS (hazard ratio [HR] = 1.51, 95% confidence interval [CI]: 1.01-2.25, P = 0.045) and a tendency for a shorter OS (HR = 1.87, 95% CI: 0.99-3.55, P = 0.055) than the low-preT790M group (n = 222). On multivariate analysis, higher preT790M was independently associated with shorter RFS (high vs low, HR = 1.56, 95% CI: 1.03-2.36, P = 0.035), irrespective of advanced stage, older age, and male sex, and was also associated with shorter OS (high vs low, HR = 2.16, 95% CI: 1.11-4.20, P = 0.024) irrespective of advanced stage, older age, EGFR mutation subtype, and history of adjuvant chemotherapy. CONCLUSIONS: Minor-frequency, especially high-abundance of, preT790M was an independent factor associated with a poor prognosis in patients with surgically resected, EGFR-mutated NSCLC.

TP53 Variant in the Blood of a Patient with Gastric Cancer Undergoing Tumor Profiling Tests Diagnosed as Clonal Hematopoiesis.

BACKGROUND Clonal hematopoiesis is the production of a specific single clonal type of cell in the blood and is often found in cancer genomic profiling tests. When the clone carries a pathogenic variant, it may be important to differentiate between somatic or germline origin. The variant in the blood that has a lower minor allele frequency could reflect heterozygous germline origin, somatic mosaicism, and clonal hematopoiesis. It is important to evaluate suspected variants to determine the course of treatment and follow-up of the patient, depending on the patient's medical condition and family situation. CASE REPORT We report a 53-year-old Japanese man with gastric cancer who underwent a cancer genomic profiling test searching for therapeutic agents. The profiling test detected a variant, TP53 c.559+2T>G minor allele frequencies of 9% (168/1865) in tumor tissue and 29.1% (58/199) in paired blood. Since the TP53 variant has the possibility of Li-Fraumeni syndrome, ancillary testing was performed using fingernails, buccal swab, and blood specimens. The genomic analysis revealed no TP53 variant in his fingernails. The patient had previously received platinum-based chemotherapies, suggesting that the variant reflected treatment-induced clonal hematopoiesis. CONCLUSIONS Identifying clonal hematopoiesis when performing genomic profiling tests for patients with cancer is important. Examining multiple tissues to determine whether a variant arises from clonal hematopoiesis or is of germline origin can provide more accurate genetic information and improve patient follow-up care.

Thoracic SMARCA2-deficient But SMARCA4-preserved Tumors With Undifferentiated Morphology Combined With Claudin-4 Negativity.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized tumor characterized by inactivation of SMARCA4, a SWItch/Sucrose NonFermentable chromatin remodeler, detectable by immunohistochemistry. SMARCA4-UT shows undifferentiated or rhabdoid morphology with claudin-4 negativity. However, thoracic undifferentiated tumors with the same histologic features as SMARCA4-UTs but a preserved SMARCA4 expression have so far been underrecognized. We herein report 3 cases of thoracic undifferentiated tumors with isolated loss of SMARCA2 but retained expression of SMARCA4 and SMARCB1. The present tumors were found in 2 men and 1 woman, 40 to 50 years old. All patients were heavy smokers (≥20 pack-years). The tumors were generally large masses located in the mediastinum, lung>chest wall, or lung and composed of relatively monotonous, round to epithelioid cells with variably rhabdoid cells. Immunohistochemically, the tumors showed claudin-4 negativity with variable expression of cytokeratin. All cases showed highly aggressive clinical behavior with overall survival of 2 to 10 months. These SMARCA2-deficient tumors with preserved SMARCA4 expression appeared to be clinicopathologically indistinguishable from SMARCA4-UTs, except for in their SMARCA4 status. This variant may expand the spectrum of SWItch/Sucrose NonFermentable-deficient undifferentiated tumors of the thoracic region beyond SMARCA4-UT.

The Role of Rigid Bronchoscopic Intervention for Bronchial Carcinoid.

Bronchial carcinoid is a rare malignant tumor that is categorized as a typical carcinoid or atypical carcinoid. Many institutions use flexible bronchoscopy for diagnosis. However, due to the hemorrhagic nature of the tumor, the amount of specimen obtained is often small, making it difficult to obtain an accurate diagnosis. The use of rigid bronchoscopy may not only contribute to obtaining a diagnosis but also be beneficial in the treatment plan. The aim of this study was to evaluate the efficacy of rigid bronchoscopic interventions for the diagnosis and treatment of bronchial carcinoids. All patients with bronchial carcinoids who underwent rigid bronchoscopic intervention under general anesthesia at our institution between June 2006 and August 2018 were analyzed retrospectively. Eight patients [3 men and 5 women; median age, 71 years (range 45-82 years)] were eligible for the analysis. None of the cases had accurate subtyping preoperatively before intervention. In contrast, all cases were diagnosed as carcinoid with subtypes (5 patients had typical carcinoid and 3 had atypical carcinoid) following rigid bronchoscopic intervention. All respiratory symptoms improved immediately after the procedure. One instance of bleeding occurred, and was easily controlled by argon plasma coagulation and intraluminal administration of epinephrine under flexible and rigid bronchoscopy. Four patients (3 with typical carcinoid and 1 with atypical carcinoid) underwent radical surgery sequentially, and no recurrences were observed. We conclude that rigid bronchoscopic intervention is safe and effective for accurate diagnosis and improvement of respiratory symptoms in patients with bronchial carcinoids.

Phase I Study of Carboplatin Plus Pemetrexed with Concurrent Radiotherapy for Locally Advanced Non-Squamous NSCLC (CJLSG0912).

Although concurrent chemoradiotherapy is the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC), no optimal concurrent chemoradiotherapy regimen has been identified in non-squamous NSCLC. We conducted an open-label, multicenter phase I trial to assess the safety of carboplatin (CBDCA) plus pemetrexed (PEM) with concurrent thoracic radiotherapy (TRT) of 60 Gy. The primary endpoint was determination of the maximum tolerated dose. In total, 6 patients were registered during the period from February 2012 through January 2014. Dose-limiting toxicities (DLTs) were observed in 2 patients (one case each of prolonged neutropenia and pneumonitis). The overall response rate was 83.3%, and median progression-free survival was 20.1 months. Since only two DLTs were observed in the phase I cohort, we concluded that CBDCA plus PEM with concurrent TRT was feasible in Japanese patients with unresectable stage III non-squamous NSCLCs. We will recommend the dose of CBDCA area under the curve 5 plus PEM 500 mg/m2 for the next phase II trial.

Successful Alectinib Treatment for Carcinoma of Unknown Primary with EML4-ALK Fusion Gene: A Case Report.

Gene alteration in anaplastic lymphoma kinase (ALK) is rare, and the efficacy of ALK inhibitors in the treatment of carcinoma of unknown primary (CUP) with ALK alteration remains unclear. The patient was a 56-year-old woman who presented with cervical lymph node swelling. Computed tomography revealed paraaortic, perigastric, and cervical lymph node swelling; ascites; a liver lesion; and a left adrenal mass. A cervical lymph node biopsy was performed, and pathological diagnosis of an undifferentiated malignant tumor was conducted. Finally, the patient was diagnosed with CUP and treated with chemotherapy. To evaluate actionable mutations, we performed a multigene analysis, using a next-generation sequencer (FoundationOne® CDx). It revealed that the tumor harbored an echinoderm microtubule-associated protein-like 4 (EML4) and ALK fusion gene. Additionally, immunohistochemistry confirmed ALK protein expression. Alectinib, a potent ALK inhibitor, was recommended for the patient at a molecular oncology conference at our institution. Accordingly, alectinib (600 mg/day) was administered, and the multiple lesions and symptoms rapidly diminished without apparent toxicity. The administration of alectinib continued for a period of 10 months without disease progression. Thus, ALK-tyrosine kinase inhibitors should be considered in patients with CUP harboring the EML4-ALK fusion gene.

Efficacy of trastuzumab deruxtecan in an advanced gastric cancer patient with brain metastasis.

BACKGROUND: There is no clinical evidence supporting the effectiveness of trastuzumab deruxtecan (T-DXd) for treating advanced gastric cancer (AGC) with brain metastasis. CASE REPORT: This is a case of a 65-year-old man with human epidermal growth factor-2 (HER2)-positive AGC. He was initially treated with capecitabine, cisplatin, and trastuzumab, followed by paclitaxel and ramucirumab, nivolumab, trifluridine and tipiracil, and irinotecan regimens in addition to radiation therapy for brain metastasis. The patient exhibited refractoriness to the standard regimen used for AGC and developed relapse of the brain metastasis after radiation accompanied by headache, nausea, and dizziness. In August 2020, following the approval of T-DXd for HER2-positive AGC, he received T-DXd therapy. After 5 cycles of T-DXd, contrast-enhanced computed tomography and magnetic resonance imaging demonstrated significant tumor shrinkage and improvement of symptoms. CONCLUSION: T-DXd demonstrated effectiveness for the treatment of brain metastasis arising from HER2-positive AGC.

Myoepithelial Carcinoma Occurring on the Ascending Aorta.

Myoepithelial carcinomas are rare malignant tumors that primarily develop in exocrine glands. We present a case of myoepithelial carcinoma located on the aorta of a 39-year-old Japanese woman. Complete resection of the tumor and aorta was performed using cardiopulmonary bypass. Histologic and immunohistochemical analyses confirmed the diagnosis. The patient was symptom-free after the operation, and no tumor recurrence was observed during 7 years of follow-up. We report a rare myoepithelial carcinoma occurring on the aorta.