Skin metastasis from small cell lung cancer.

Patients with skin metastasis always had disseminated metastases in many organs. We herein report an unusual case with skin metastasis from small cell lung cancer (SCLC). The patient was treated with platinum-containing chemotherapy, and the response to the therapy was evaluated as partial response. The patient had slowly progressive disease and died of SCLC 16 months after the diagnosis of the diseases. If skin lesions, whether it may be typical or not, are found in SCLC patients, biopsy from the lesion would be considered to perform. Although trunk may be the most common sites, it is important to suspect such metastasis occurs in patients with SCLC.

Real Clinical Practice of Combined Atezolizumab Plus Chemotherapy in Patients With Small Cell Lung Cancer.

BACKGROUND/AIM: Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival. PATIENTS AND METHODS: This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities. RESULTS: In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%). CONCLUSION: Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy.

Non-interventional management of small pneumothorax in the very elderly.

The non-interventional management (NIM) of elderly patients with small pneumothorax has rarely reported. We show herein three elderly cases of successful treated with NIM for small pneumothorax (< 20% on chest computerized tomography scan). With adequate evaluation of chest radiographs and careful cardiopulmonary monitoring, we evaluated that NIM for small pneumothorax can be a possible therapeutic choice even in the elderly.

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.

[Hemoptysis in a patient with old pulmonary tuberculosis showing atypical findings in chest computed tomography].

We report the case of an 85-year-old woman who had pulmonary tuberculosis when she was in her forties. She was referred to our hospital because of hemoptysis, which lasted for a few days. Her laboratory data was unremarkable. Chest computed tomography (CT) scan showed a thin-walled cavity with extensive calcification in the right S2. There was no infiltrative shadow or bronchiectatic changes observed around the cavity. Active bleeding was observed to be occurring from the right B2. After arterialization, embolization was performed in the right S2. On the basis of the findings from this case, we recommend that clinicians perform bronchoscopy in patients with hemoptysis even if imaging studies show no typical findings suggesting hemorrhage. Further, although rare, old tuberculosis lesions such as a thin-walled cavity with calcification can cause hemoptysis.

[A case of thymoma and Mycobacterium intracellulare infection].

A 69-year-old man, who underwent total thymectomy 5 years previously, was referred to our division because the chest radiograph revealed abnormal shadows in both the lungs. The chest radiograph and CT scan showed pleural thickening in both apexes and tree-in-bud signs in both the lower lobes, which suggested bronchiolitis. We had retrospectively confirmed similar centrilobular small nodules and tree-in-bud signs on the chest CT scan when the thymoma was diagnosed. Mycobacterium intracellulare was detected in the sputum by acid-fast staining and polymerase chain reaction. The coincidence of thymoma and Mycobacterium intracellulare infection appeared to be incidental. Thus, in patients with thymoma, clinicians should carefully evaluate the lung parenchyma as well as the mediastinum on the chest radiograph to identify occult diseases, including Mycobacterium intracellulare infections.

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.

Chronic eosinophilic pneumonia with subpleural curvilinear shadow.

We report a rare case of chronic eosinophilic pneumonia with subpleural curvilinear shadow. CT scan showed a patchy consolidation in the bilateral upper lungs. In addition, subpleural curvilinear shadow was found in the bilateral upper lungs. A bronchoalveolar lavage obtained from the right middle lobe showed 25 % eosinophils. Although very rare, we should therefore keep in mind that patients, who have patchy consolidation with areas of subpleural curvilinear shadow in the bilateral upper lungs, may have chronic eosinophilic pneumonia.

Lung adenocarcinoma with endobronchial growth.

We report a rare case of lung adenocarcinoma with endobronchial growth in a 65-year-old woman. Chest computed tomography revealed an ill-defined mass in the lower lobe of the left lung and multiple sized nodular shadows in the both lungs. An endobronchial polypoid tumor in the left B8 bronchus was found by bronchoscopic examination. A biopsy specimen obtained from the tumor diagnosed lung adenocarcinoma. Although very rare, we should therefore keep in mind that patients who have a pulmonary tumor adjacent to the bronchus with an endobronchial polypoid lesion may have lung adenocarcinoma.

Postoperative follow-up for patients with non-small cell lung cancer.

BACKGROUND: It is unclear whether postoperative follow-up by thoracic surgeons or chest physicians for non-small cell lung cancer (NSCLC) alters survival. PATIENTS AND METHODS: The charts of 1,398 NSCLC patients, diagnosed between 1980 and 2008, were reviewed. Prognostic factors contained therein were evaluated using univariate and multivariate analyses. Patients were divided into 2 groups according to the doctor in charge of their postoperative follow-up: the thoracic surgeon group and the chest physician group. The doctors in charge of following up the patients were also analyzed for prognostic significance. RESULTS: In the univariate and multivariate analyses, age 65 years or younger, female sex, early pathological stage, Charlson Index score of 0-1, absence of adjuvant therapy, and follow-up by a chest physician were significantly favorable prognostic factors. Examined overall, NSCLC patients in the chest physician group had longer survival than those in the thoracic surgeon group. The difference in survival of patients with advanced disease was also statistically significant between these 2 groups. CONCLUSIONS: Our results indicate that early detection of asymptomatic disease by regular follow-up including chest computed tomography scan may improve the chance of treatment with curative intent and thus may increase survival, irrespective of the doctor in charge of follow-up.

Serum KL-6 levels in lung cancer patients with or without interstitial lung disease.

BACKGROUND: It is not known whether lung cancer patients with interstitial lung disease (ILD) might have higher serum levels of KL-6, a high molecular weight glycoprotein classified as a polymorphic epithelial mucin. In addition, prognosis of these patients with elevated serum KL-6 levels might be poorer than that with normal KL-6 levels, but it has not been well clarified. METHODS: Serum KL-6 levels in 273 lung cancer patients with or without ILD, and prognostic significance of elevated serum KL-6 levels in these patients were studied using uni- and multivariate analyses. RESULTS: Serum KL-6 levels were elevated (>500 U/ml) in 73.5% of lung cancer patients with ILD and in 33.7% of those without ILD. Serum KL-6 levels in lung cancer patients with ILD were significantly higher than those without ILD. In lung cancer patients with ILD, elevated serum KL-6 has no prognostic significance, but in those without ILD, however, it was one of the unfavorable prognostic factors. CONCLUSIONS: Elevated serum KL-6 levels can be observed in lung cancer patients both with and without ILD. Having ILD has strong prognostic impact in patients with lung cancer. In those without ILD, however, elevated KL-6 levels may be related to poor prognosis.

Sarcoidosis and lung cancer.

BACKGROUND: Although sarcoidosis as well as lung cancer are frequently encountered common diseases, their metachronous or synchronous occurrence in the same patient is very rare. METHODS: The charts of lung cancer patients, diagnosed between 1980 and 2007 in our hospital, were reviewed. RESULTS: We found 3 cases with sarcoidosis and lung cancer. The first case had lung cancer 16 years after the diagnosis of sarcoidosis. The second case had two different metachronous lung cancers 18 and 10 years after the diagnosis of sarcoidosis. The third case detected these two diseases simultaneously. In simultaneously detected cases, it is difficult to determine whether noncaseating epithelioid cell granulomas coexisting with lung cancer represent sarcoid reaction or genuine systemic sarcoidosis. CONCLUSIONS: Either causality or coincidence, lung cancer, a condition that can be observed in patients with sarcoidosis, should be considered in the differential diagnosis when suspicious findings of it are discovered.

[Satisfactory outcome with erlotinib after failure with gefitinib in a patient with meningeal carcinomatosis secondary to non-small cell lung cancer].

A 60-year-old man was admitted to our hospital because of the radiologic findings of meningeal carcinomatosis after long-term disease control of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer, with cisplatin-based chemotherapy followed by gefitinib. Brain magnetic resonance imaging (MRI) revealed diffuse and linear enhancement on the surface of the midbrain and along the cerebellar folia. In addition, analysis of his cerebrospinal fluid (CSF) showed an increased WBC count and an elevated level of CEA. He presented no symptoms at the time of diagnosis of meningeal carcinomatosis; however, within 2 weeks, neurological symptoms such as disorientation, dysarthria, and ataxic gait became apparent. Since his symptoms seemed to worsen even under further treatment with different cisplatin-based chemotherapy or retreatment with gefitinib, we decided to initiate erlotinib treatment. His symptoms rapidly improved within a week of beginning treatment with erlotinib, and MRI and CSF examinations also showed remarkable improvement of the meningeal carcinomatosis. This case suggests that erlotinib may be effective in some patients with meningeal carcinomatosis previously treated with gefitinib. However, further studies are required to understand the differential efficacy of these drugs.

Clinicopathological Features in Elderly ALK-rearranged Non-small Cell Lung Cancer Patients.

AIM: To clarify the clinicopathological features in elderly anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A retrospective study was performed in 129 ALK rearranged NSCLC patients diagnosed between April 2008 and March 2019 in fifteen Institutions of the Ibaraki prefecture, Japan. RESULTS: Median age of patients was 63 years. In 59 patients aged 65 and older, the proportions of patients with advanced stage and those treated with ALK-tyrosine kinase inhibitor (TKI) were lower than those younger than 65 years. There was no difference in overall survival (OS) between the two age groups. Among the elderly patients, no difference was observed in OS between the patients aged 65-69 and those aged 70 and older. In 89 patients treated with TKI, no significant differences were observed in the progression-free survival of TKIs and OS between patients aged 65 and older and those younger than 65, respectively. CONCLUSION: Evaluation of ALK gene status and TKI treatment are desirable even for elderly patients.

Serum CEA and CYFRA Levels in ALK-rearranged NSCLC Patients: Correlation With Distant Metastasis.

AIM: To clarify the correlation between serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) and metastasis and survival in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: CEA and CYFRA levels in 131 ALK-rearranged NSCLC patients were determined using fluorescence in situ hybridization (FISH), real time-reverse transcription polymerase chain reaction, and immunohistochemistry, using biopsy specimens, cytology specimens, and plasma specimens. Cut-off value of each marker was determined as 10 ng/ml. RESULTS: In logistic regression analysis, higher levels of both markers had a positive relationship with bone metastases, and higher levels of CYFRA was relevant to liver metastases, and multiple-organ metastases. However, these markers were not proven to be poor prognostic factors in Cox's proportional model analysis. CONCLUSION: Elevated serum CEA and CYFRA levels seem to provide useful clinical information about presence of bone and liver metastasis and multiple-organ metastases, although they were not a powerful indicator of prognosis. These two markers may suggest the extension of metastasis and would be helpful in considering treatment options.

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.

Axillary lymph node metastasis in lung cancer.

STUDY OBJECTIVES: Axillary lymph node metastasis (ALNM) from lung cancer is rare. Its prognosis and effective treatments remain unknown. To evaluate clinicopatholgical characteristics of such lung cancer patients, we performed a retrospective study of them, who had ALNM at the time of initial presentation or developed ALNM in their clinical courses. METHODS: We reviewed the medical records and pathological reports of all patients at our division who had a diagnosis of primary lung cancer from January 1985 through August 2007. RESULTS: Ten (0.75%) of 1,340 patients had ALNM. In eight of them, ALNM was detected at the time of initial diagnosis, and two patients developed ALNM in their clinical courses. Lymphatic metastasis to mediastinum was evident in all patients. Supraclavicular and cervical lymph nodes were involved in five and three patients, respectively. One patient had direct chest wall invasion from the lung. Three patients had distant metastases other than axillary or cervical lymph nodes. Four patients received systemic chemotherapy, and another four patients received palliative chest irradiation or supportive care because of their poor performance status. Median survival time of 8 patients who were diagnosed as having ALNMs at initial presentation was 7 months. CONCLUSIONS: The most likely mechanism for axillary node involvement is intercostal lymphatics via spread from mediastinal lymph node metastasis. Routine palpation of the axillae is recommended if chest wall invasion, mediastinal and/or supraclavicular lymph nodes are found either at initial presentation or at follow-up of patients.

A population-based study of gefitinib in patients with non-small cell lung cancer.

Survival data for non-small cell lung cancer is typically reported from clinical trials that include patients fit enough to meet treatment criteria. The denominator of all patients from which the gefitinib-treated population is derived has rarely been reported and the impact of gefitinib on population-based outcomes is difficult to measure. We have retrospectively reviewed data of 626 patients who received gefitinib in Ibaraki Prefecture (with a population of 3 million) in Japan from July 2002 until September 2007. Overall response rate was found to 30.8%, and the median survival time was 8.0 months (95% confidence interval: 7.0-9.0 months). Female gender, good PS, and adenocarcinoma were significantly associated with prolonged survival. Adverse events were generally mild and were mostly skin reactions and diarrhea. Our population-based study has generated similar results to those previously reported in published clinical trials, which had restrictive criteria for eligible patients.