Atezolizumab for EGFR-mutated Non-small Cell Lung Cancer Patients: An Observation Study in Ibaraki Group (ATTENTION-IBARAKI).

BACKGROUND/AIM: Atezolizumab, an anti-programed death-ligand 1 monoclonal antibody, targets programed death-ligand 1 expressed on cancer cells and antigen-presenting cells and is now commonly used in combination with chemotherapy. We conducted a study to clarify the efficacy of atezolizumab in epidermal growth factor receptor (EGFR)-mutated patients who are considered less responsive to immune checkpoint inhibitors. PATIENTS AND METHODS: A retrospective review of patients with advanced non-small cell lung cancer (NSCLC) who received atezolizumab-containing therapy at 11 hospitals from April 2018 to March 2023 was performed. RESULTS: Median progression-free survival and overall survival in 33 EGFR-mutated patients treated with atezolizumab monotherapy were 2.0 and 9.0 months, respectively, and those in 19 patients who received combined atezolizumab plus chemotherapy were 12.0 and 17.0 months, respectively. When comparing EGFR-mutated and EGFR-negative patients after propensity score matching, there were no significant differences in progression-free survival and overall survival between the two groups, whether atezolizumab monotherapy or combined atezolizumab plus chemotherapy. Among EGFR-mutated patients, being male was a significant favorable factor in both atezolizumab treatment groups. None of the EGFR-mutated patients had grade 5 immune-related adverse events. CONCLUSION: Efficacy of atezolizumab in EGFR-mutated NSCLC patients could be comparable to that for EGFR-negative patients. To prolong the survival of EGFR-mutated NSCLC patients, appropriate selection and sequencing of EGFR for tyrosine kinase inhibitors, as well as immune checkpoint inhibitors, anti-tumor agents, and anti-angiogenic agents are important.

Atezolizumab Monotherapy for Non-small Cell Lung Cancer Patients: An Observational Study in Ibaraki Group (ATTENTION-IBARAKI).

BACKGROUND/AIM: Atezolizumab is a monoclonal antibody that targets programmed death-ligand 1 (PD-L1) expressed on cancer cells derived from various organs and antigen-presenting cells and is currently commonly used in combination with chemotherapy. We conducted a study to clarify the current status of response to atezolizumab monotherapy in clinical practice and clarify the factors that contribute to long-term response and survival. PATIENTS AND METHODS: We conducted a retrospective review of patients with advanced non-small cell lung cancer (NSCLC) treated with atezolizumab monotherapy from April 2018 to March 2023 at 11 Hospitals. RESULTS: The 147 patients evaluated had a progression-free survival (PFS) of 3.0 months and an overall survival of 7.0 months. Immune-related adverse events of any grade were observed in 13 patients (8.8%), grade 3 or higher in nine patients (6.1%), and grade 5 with pulmonary toxicity in one patient (0.7%). Favorable factors related to PFS were 'types of NSCLC other than adenocarcinoma'. Favorable factors for overall survival were 'performance status 0-1' and 'treatment lines up to 3'. There were 16 patients (10.9%) with PFS >1 year. No characteristic clinical findings were found in these 16 patients compared to the remaining 131 patients. CONCLUSION: Efficacy and immune-related adverse events of NSCLC patients associated with atezolizumab monotherapy were comparable to those of previous clinical trial results. Knowledge of characteristics of patients who are most likely to benefit from atezolizumab monotherapy is a crucial step towards implementing appropriate prescribing.

Identification of the Separation Range of an Incomplete Interlobar Fissure in Segmentectomy Using Near Infrared.

In segmentectomy for patients with incomplete interlobar fissures, insufficient dissection of the interlobar parenchyma may result in incomplete segmentectomy, while excessive dissection may lead to excessive bleeding and air leaks. Here, we report a case of left apicoposterior (S1+2) segmentectomy with incomplete interlobar fissure in which near-infrared thoracoscopy with indocyanine green was used to identify the separation range of interlobar fissure by dissecting the relevant vessels beforehand.

Prognostic Implication of PD-L1 Expression on Osimertinib Treatment for EGFR-mutated Non-small Cell Lung Cancer.

BACKGROUND/AIM: Real-world data on the clinical outcomes of first-line osimertinib treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations is lacking. This study aimed to reveal the treatment outcomes and prognostic factors of osimertinib as first-line therapy in clinical practice settings. PATIENTS AND METHODS: We retrospectively evaluated clinical outcomes of patients with EGFR-mutated NSCLC treated with osimertinib as first-line therapy across 12 institutions in Japan between August 2018 and March 2020. RESULTS: Among 158 enrolled patients, the objective response rate (ORR) was 68%, and the estimated median progression-free survival (PFS) was 17.1 months [95% confidence interval (CI)=14.5-19.7]. Subgroup analysis showed that PFS in the group with high programmed death-ligand 1 (PD-L1) expression was significantly shorter than that in groups with low or no PD-L1 expression (10.1 vs. 16.1 vs. 19.0 months; p=0.03). Univariate and multivariate analyses demonstrated that high PD-L1 expression was the only independent adverse prognostic factor of osimertinib outcome related to PFS (hazard ratio=2.71; 95%CI=1.26-5.84; p=0.01). In terms of anti-tumor response, there was no statistically significant correlation between PD-L1 expression and the ORR (67% vs. 76% vs. 65%; p=0.51). No significant correlation was also found between PD-L1 and the incidence of de novo resistance to osimertinib (p=0.39). CONCLUSION: Although PD-L1 expression was not associated with either the ORR or frequency of de novo resistance, high PD-L1 expression could be an independent adverse prognostic factor related to PFS in osimertinib treatment.

Guide sheath breakage during endobronchial ultrasonography.

This report describes a case of guide sheath breakage during endobronchial ultrasonography. While steering the guide sheath in the direction of a peripheral lung nodule using a guiding device/curette, the radiopaque band (RB) attached to the head of the guide sheath dislodged and remained in the peripheral bronchus near the tumour. The band could not be removed endoscopically. As the tumour was diagnosed as a colon cancer metastasis, we performed a partial lung resection to remove the RB and nodule together four months after bronchoscopy.

A population-based study of outcomes in patients with surgically resected non-small cell lung cancer with anaplastic lymphoma kinase-rearranged mutations: A matched-pair study.

The present study aimed to evaluate clinical outcomes in patients with surgically resected non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearranged mutations. A matched-pair analysis in completely resected ALK-rearranged NSLC patients and those with neither ALK nor epidermal growth factor receptor (EGFR) mutations diagnosed at 11 institutes was performed between April 2008 and March 2019. A total of 51 patients with surgically resected ALK-rearranged NSCLC were included. Women constituted 68.6%, and smokers 29.4%. The median age was 65 years. In matched-pair analysis, disease-free survival and overall survival did not differ between patients with ALK-rearranged mutations and those without mutations. Post-recurrence survival in patients with ALK mutations was longer than that of patients with neither ALK nor epidermal growth factor receptor mutations. ALK genetic testing should be performed, even in elderly patients with NSCLC. Favorable prognosis might be expected after appropriate treatment for patients with recurrent ALK-mutated disease.

Treatment of Patients With Non-small-cell Lung Cancer With Uncommon EGFR Mutations in Clinical Practice.

BACKGROUND/AIM: To describe real clinical outcomes in patients with non-small cell lung cancer who have uncommon epidermal growth factor receptor (EGFR) mutations. MATERIALS AND METHODS: We performed a retrospective chart review from 15 medical institutes that cover a population of three million people from April 2008 to March 2019. RESULTS: There were 102 patients with uncommon EGFR mutation. Progression-free survival (PFS) tended to be longer in patients receiving afatinib compared with first-generation EGFR tyrosine kinase inhibitors. PFS in patients treated with afatinib or osimertinib was significantly longer than in patients treated with gefitinib or erlotinib (p=0.030). Multivariate analysis also revealed the contribution of afatinib or osimertinib to increased survival. In patients with exon 20 insertions, chemotherapy was efficacious. CONCLUSION: In treating patients with uncommon EGFR mutations, our results indicate longer-term survival might be achieved with second-generation or later TKIs and cytotoxic chemotherapeutic drugs.

Real Clinical Practice in ALK-rearranged NSCLC Patients: A Retrospective Observational Study.

BACKGROUND/AIM: To describe real clinical outcomes when using systemic therapy to treat non-small cell lung cancer (NSCLC) patients who have anaplastic lymphoma kinase (ALK) fusion gene mutation. PATIENTS AND METHODS: We performed a retrospective chart review from April 2008 to March 2019 sourced from 16 medical institutes that cover a population of three million people. RESULTS: There were 129 ALK rearranged NSCLC patients. Among them, 103 patients including 40 recurrent disease cases received ALK-tyrosine kinase inhibitors (TKI) and chemotherapy. Our treatment results were comparable to previously reported clinical trials and clinical practice studies. First-line alectinib, treatment sequence of ALK-TKI followed by another ALK-TKI, and pemetrexed-containing chemotherapy contributed to the outcome of treatment. CONCLUSION: By arrangement of treatment such as treatment sequence of ALK-TKI and chemotherapy regimen, it might be possible to obtain a treatment outcome almost equivalent to those of clinical trials even in real clinical practice.

Chemotherapy alters subjective senses of taste and smell but not dietary patterns in Japanese lung cancer patients.

PURPOSE: To investigate how outpatient-based chemotherapy would alter the senses of taste and smell and affect daily dietary intake in patients with lung cancer. METHODS: The self-reported taste and smell alteration (TSA) in 35 Japanese patients with lung cancer as well as their patterns of dietary intake at home were tested using a questionnaire. RESULTS: The patients experienced considerable TSA, and smoking was shown to contribute to this alteration. Specifically, current or past smokers were more likely to experience subjective taste change during chemotherapy than never smokers were. Chemotherapy made steamed rice or sushi the most unfavorable food in the patients; on the other hand, Japanese-style noodles were the most preferred during chemotherapy. Nevertheless, the patients maintained their habit of consuming steamed rice at home at least once a day, suggesting the robustness of dietary habits despite the TSA caused by chemotherapy. CONCLUSIONS: Nutritional assessment as well as appropriate advice and intervention by dietitians is expected to improve the general conditions and quality of daily living in patients with cancer.

Neo-generation of neogenetic bullae after surgery for spontaneous pneumothorax in young adults: a prospective study.

BACKGROUND: To investigate the development of neogenetic bullae or blebs on 1-year postoperative chest computed tomography after video-assisted thoracic surgery (VATS) in young patients with primary spontaneous pneumothorax (PSP). METHODS: In this prospective study, 10- to 20-year-old patients with PSP were treated via VATS with additional procedures (bullectomy, cold coagulation, coverage, pleural abrasion, or chemical pleurodesis). All patients underwent the additional procedures and computed tomography of the chest 1 year postoperatively for the assessment of neogenetic bullae. Postoperative PSP recurrence was monitored, and recurrence-free survival was evaluated using Kaplan-Meier analysis. RESULTS: Fifty-seven patients (66 cases) aged 17 ± 2 years underwent VATS for PSP and were followed up for 938 ± 496 days. Of the 36 cases at 1-year follow-up, 23 (63.9%) showed neogenetic bullae, which were adjacent to the staple lines in 16 cases (69.6%). The 1- and 2-year recurrence-free survival rates were 88.9 and 85.1%, respectively. Nine of the 66 cases (13.6%) showed recurrence after 869 ± 542 days. A history of contralateral PSP was significantly associated with recurrence. CONCLUSIONS: VATS, combined with additional procedures, provides acceptable long-term results in young patients with PSP. Additional procedures reduce the recurrence rate of PSP but do not prevent the occurrence of neogenetic bullae. A history of contralateral PSP is a potential risk factor for post-VATS recurrence in young patients.

Thymectomy during Myasthenic Crisis under Artificial Respiration.

A 34-year-old man was diagnosed with thymoma, which was evaluated preoperatively as stage II or III, with myasthenia gravis (MG). The size of the tumor was 70 × 44 × 80 mm. No invasion to neighboring organs was observed. Prednisolone was prescribed for stabilization of MG. However, a myasthenic crisis (MC) occurred, and intensive care, including emergent endobronchial intubation followed by artificial ventilation, pulse steroid therapy, high-dose intravenous immunoglobulin, and tacrolimus hydrate, was initiated. A chest computed tomography on day 6 revealed tumor reduction to 50 × 30 × 60 mm. An extended total thymectomy by median sternotomy was performed, and artificial ventilation was continued after that. Scheduled artificial ventilation and steroid therapy together can, therefore, enable complete resection of thymoma in patients undergoing treatment for MC. While ventilation helps avert a respiratory failure, the steroid therapy temporarily reduces the tumor size, making resection easier.

Real Clinical Practice of Using Afatinib Therapy in NSCLC Patients with an Acquired EGFR T790M Mutation.

BACKGROUND/AIM: To describe real clinical outcomes when using afatinib therapy to treat non-small cell lung cancer patients who have an acquired EGFR T790M mutation. MATERIALS AND METHODS: A retrospective chart review was conducted from January 2013 to November 2017 sourced from 15 medical institutes that cover a population of three million people. RESULTS: There were 74 patients who met the above-mentioned criteria. Treatment outcomes with afatinib, in patients with or without tyrosine kinase inhibitor (TKI) therapy prior to afatinib, were similar to previously reported clinical trials. Stratification of patients by the presence or absence of TKI pretreatment before afatinib, and the presence or absence of an acquired T790M mutation found no statistical difference in overall survival. CONCLUSION: This population-based study found that the disadvantages of pretreatment before afatinib, and absence of an acquired T790M EGFR mutation, could be overcome by an appropriate treatment strategy in clinical practice.

Acquired EGFR T790M Mutation After Relapse Following EGFR-TKI Therapy: A Population-based Multi-institutional Study.

AIM: To describe the prevalence and determinants of acquired epidermal growth factor receptor (EGFR) T790M gene mutation in a clinical practice setting. MATERIALS AND METHODS: We performed a retrospective chart review study between January 2013 and November 2017 across multiple institutes, covering a population of 3 million people. RESULTS: We reviewed the charts of 233 patients non-small cell lung cancer with EGFR mutations. Of them, 99 (42.5%) patients had acquired T790M mutations in EGFR. Patients ≥75 years old and patients with an exon 19 deletion had higher rates of acquired T790M mutation than did younger patients and those with an exon 21 L858R mutation. In 75 patients treated with afatinib, 34 (45.3%) patients had acquired T790M mutation. The sensitivity of T790M mutation detection was lower in plasma specimens than in biopsy specimens. CONCLUSION: This population-based study confirms previous studies and highlights potential determinants of acquired T790M mutation to be considered in clinical practice.

[Surgical Treatment for Synchronous Double Cancer of the Thoracic Esophagus and Lung].

We herein report 2 cases of radical operation for synchronous double cancer of the thoracic esophagus and each side of the lung. Case 1:A 71-year-old woman with synchronous double cancer of the thoracic esophagus (Mt, T3N2M0, Stage III) and right lung (M, T2aN0M0, Stage I B) underwent esophagectomy concomitantly with right middle lobectomy through right thoracotomy (single-stage operation) after 2 courses of systemic chemotherapy with docetaxel, cisplatin and 5-fluorouracil( DCF regimen). Case 2:A 72-year-old man with synchronous double cancer of the thoracic esophagus( MtLt, T3N2M0, Stage III) and left lung( U, T1aN0M0, Stage I A) underwent 2-stage operation after 2 courses of the DCF therapy. Esophagectomy through right thoracotomy was performed followed by left upper lobectomy through left thoracotomy 3 months later. Treatment strategy for synchronous double cancer of the thoracic esophagus and lung is discussed based on our experiences and previous reports.

Primary and Secondary Spontaneous Pneumothorax: Prevalence, Clinical Features, and In-Hospital Mortality.

Background. Optimal treatment practices and factors associated with in-hospital mortality in spontaneous pneumothorax (SP) are not fully understood. We evaluated prevalence, clinical characteristics, and in-hospital mortality among Japanese patients with primary or secondary SP (PSP/SSP). Methods. We retrospectively reviewed and stratified 938 instances of pneumothorax in 751 consecutive patients diagnosed with SP into the PSP and SSP groups. Factors associated with in-hospital mortality in SSP were identified by multiple logistic regression analysis. Results. In the SSP group (n = 327; 34.9%), patient age, requirement for emergency transport, and length of stay were greater (all, p < 0.001), while the prevalence of smoking (p = 0.023) and number of surgical interventions (p < 0.001) were lower compared to those in the PSP group (n = 611; 65.1%). Among the 16 in-hospital deceased patients, 12 (75.0%) received emergency transportation and 10 (62.5%) exhibited performance status (PS) of 3-4. In the SSP group, emergency transportation was an independent factor for in-hospital mortality (odds ratio 16.37; 95% confidence interval, 4.85-55.20; p < 0.001). Conclusions. The prevalence and clinical characteristics of PSP and SSP differ considerably. Patients with SSP receiving emergency transportation should receive careful attention.

[Displaced B1+2 Found at Video Assisted Thoracic Surgery for Lung Cancer of Left Upper Lobe].

We report the case of an 83-year-old woman who presented with an abnormal pulmonary nodule suspected to be lung cancer in the left S3 segment. Bronchoscopy showed that the left main bronchus branched off into the B1+2, B3 plus lingular bronchus, and lower bronchus. Video-assisted thoracic surgery was performed, and the nodule was pathologically diagnosed as a primary lung cancer. Subsequently, left upper lobectomy was performed, and an abnormal bronchus was observed behind the main pulmonary artery. Intraoperative bronchoscopy indicated that the bronchus was the displaced B1+2. The B3 plus lingular bronchus existed at the common place of the upper bronchus. The displaced B1+2 and the other upper bronchus were transected separately. No other abnormalities were observed in the pulmonary arteries, veins, or bronchi. Preoperative examination is the best way to detect this bronchial abnormality;identification with intraoperative bronchoscopy can play a crucial role in determining the perioperative strategy.

S-1-containing chemotherapy for patients with non-small-cell lung cancer: A population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group.

To evaluate the efficacy and safety of S-1 monotherapy, S-1-containing combined chemotherapy and S-1 containing chemoradiotherapy for non-small cell lung cancer (NSCLC), a population-based observational study was performed. The efficacy and safety of the chemotherapies were evaluated at 13 institutes in a prefecture of Japan between April 2011 and March 2015. Datasets were obtained from 282 patients with NSCLC. For either wild-type or mutated epidermal growth factor receptor (EGFR), these three therapy groups generated almost identical response results and toxicity profiles as those in previously reported clinical trials, although the present study appeared to have slightly lower survival rates compared with those in the previous clinical trials. This may be due to the inclusion of patients in poor condition, and S-1 therapy being administered in the second, or later, line of therapy. In conclusion, the present study has confirmed that S-1-containing chemotherapy is effective against wild- and mutated-type EGFR NSCLC, and it is also tolerable in clinical practice.

Efficacy of first-line erlotinib in non-small cell lung cancer patients undergoing dose reduction and those with a low body surface area: A population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The aim of the present study was to evaluate the efficacy of erlotinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), in patients undergoing dose reduction and in those with a low body surface area (BSA). The association between dose reduction, low BSA and efficacy, including response rate, disease control rate, time to treatment failure and overall survival, were evaluated in patients prescribed first-line erlotinib for EGFR mutated non-small cell lung cancer patients between April 2012 and March 2015. A total of 22 patients received first-line erlotinib during the study period. A dose reduction of erlotinib for the reason of low BSA and poor performance status occurred in 14 (63.6%) of the patients: 6 (27.3%) had initial dose reduction, 6 (27.3%) had dose reduction in their clinical courses, and 2 (9.1%) had both. Dose reduction of erlotinib with the initial dose of erlotinib/BSA was >80 mg/m2, and longest-term prescribed dose of erlotinib/BSA was >50 mg/m2, which may have no association with a survival disadvantage. Dose-reduction estimation studies for TKIs may be crucial, particularly for patients with a low BSA. Future prospective studies and confirmation of these results in population-based retrospective ones investigating the incidence of dose reduction in patients with AEs and those with low BSA may be required for the efficient use of erlotinib in common clinical practice.

Invasive Thymoma with Pure Red Cell Aplasia and Amegakaryocytic Thrombocytopenia.

We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL), thrombocytopenia (platelet count, 0.6 × 104/µL), and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT). On Day 8 of admission, the patient received immunosuppressive therapy together with cyclosporine for the 2 severe hematologic diseases, which were stabilized within 2 months. Subsequently, total thymectomy was performed. The diagnosis of the tumor invading the left lung was invasive thymoma, Masaokakoga stage III. The histological diagnosis was World Health Organization type AB. Thymoma accompanied with PRCA and AAMT is very rare, and, based on our case, immunotherapeutic therapy for the hematologic disorders should precede surgical intervention.