Haruki Kobayashi

Modified GAP index for prediction of acute exacerbation of idiopathic pulmonary fibrosis in non-small cell lung cancer

Predicting the incidence rate of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) and its prognosis in patients with non‐small cell lung cancer (NSCLC) and IPF is difficult. The aim was to study the incidence of IPF‐AE during the clinical course of the disease and its prognosis in patients with both NSCLC and IPF.

Response to the treatment immediately before nivolumab monotherapy may predict clinical response to nivolumab in patients with non-small cell lung cancer

BackgroundCurrently, no markers predictive of response to nivolumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) are currently recognized in Japan. The present study was undertaken to identify such markers.Materials and methodsMedical records of 50 patients with advanced NSCLC and treated with nivolumab monotherapy at Shizuoka Cancer Center between December 2015 and April 2016 were retrospectively reviewed. The parameters studied were age, sex, Eastern Cooperative Oncology Group performance status, smoking history, histological diagnosis, epidermal growth factor receptor or anaplastic lymphoma kinase status, therapeutic line of nivolumab, efficacy of treatment immediately before nivolumab monotherapy, and time since previous therapy.ResultsThe objective response rate to nivolumab monotherapy was 18% [95% confidence interval (CI) 10–31]. Multivariate logistic regression identified “squamous histology” [odds ratio (OR) 0.00054; 95% CI 0–0.27] and “response to the treatment immediately before nivolumab monotherapy” (OR 0.0011; 95% CI 0–0.092) as independently associated with response to nivolumab monotherapy.Conclusion“Response to the treatment immediately before nivolumab monotherapy” might be a predictive marker of response to nivolumab in patients with advanced NSCLC.

A favorable clinical effect of an expectorant in allergic bronchopulmonary mycosis caused by Schizophyllum commune

An 80-year-old Japanese woman with wet cough and dyspnea was diagnosed with pneumonia at a clinic. Antibiotics did not improve her symptoms; therefore, she was referred to our hospital one month after symptom onset. Chest radiograph findings revealed complete collapse of the left lung. Bronchoscopy showed white mucus plug in the left main bronchus, which could not be removed. She was initially treated with bromhexine. Subsequently, culture results of the mucus plug specimen obtained during bronchoscopy yielded Schizophyllum commune. After three weeks, improvement of the collapsed lung was observed on chest radiograph.

Efficacy of prophylactic cranial irradiation in patients with limited-disease small-cell lung cancer who were confirmed to have no brain metastasis via magnetic resonance imaging after initial chemoradiotherapy

Background Prophylactic cranial irradiation (PCI) is recommended for patients with limited-disease small-cell lung cancer (LD-SCLC) who achieved good response to definitive chemoradiotherapy. However, most clinical studies lacked brain imaging scans before PCI. Our study aimed to investigate whether PCI has a survival benefit in patients who have no brain metastases (BM) confirmed via magnetic resonance imaging (MRI) before PCI. Results Eighty patients were included in this study. Sixty patients received PCI (PCI group) and 20 patients did not (non-PCI group). OS was not significantly different between the two groups. The median OS time was 4.3 years (95% CI: 2.6 years–8.6 years) in the PCI group and was not reached (NR) (95% CI: 1.9 years–NR) in the non-PCI group (p = 0.542). Moreover, no differences were observed in the 3-year rates of PFS (46.2% and 44.4%, p = 0.720) and cumulative incidence of BM (24.0% vs. 27%, p = 0.404). Conclusions Our result suggests that PCI may not have a survival benefit in patients with LD-SCLC confirmed to have no BM after initial therapy, even if patients achieve a good response to definitive chemoradiotherapy. Patients and Methods We retrospectively evaluated patients with LD-SCLC who were confirmed to have no BM via MRI after initial chemoradiotherapy at the Shizuoka Cancer Center between September 2002 and August 2015. The overall survival (OS), progression-free survival (PFS), and cumulative incidence of BM were estimated using the Kaplan–Meier method between patients who received PCI and those who did not. Propensity score matching was used to balance baseline characteristics.

ILD-NSCLC-GAP index scoring and staging system for patients with non-small cell lung cancer and interstitial lung disease

BACKGROUND AND OBJECTIVE Patients with advanced non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) are commonly excluded from most clinical trials because of acute exacerbation (AE) of ILD triggered by chemotherapy. Data on the efficacy and feasibility of chemotherapy are limited in this patient population. Recently, the ILD-GAP index and staging system was reported as a clinical prognostic factor associated with mortality in patients with ILD. Therefore, we evaluated the incidence of ILD-AE during the surveillance term in this study and the prognosis in patients with NSCLC and ILD using a modified ILD-GAP (ILD-NSCLC-GAP) index scoring system. MATERIALS AND METHODS The medical records of patients with NSCLC and ILD who underwent a pulmonary function test before initiation of platinum-based chemotherapy as first-line treatment at the Shizuoka Cancer Center between September 2002 and December 2014 were reviewed retrospectively. Among these patients, we compared the incidence of ILD-AE, one-year survival rate, and overall survival (OS) between the ILD-NSCLC-GAP index scores and stages. RESULTS Of the 78 patients included, 21 (27%; 95% confidence interval [CI], 18%-38%) had ILD-AE during the surveillance term in this study. The one-year survival and median OS rates were 49% and 11.3 months, respectively. The incidence of ILD-AE increased gradually and the one-year survival and median OS rates decreased gradually with increasing ILD-NSCLC-GAP index scores and stages. CONCLUSION The ILD-NSCLC-GAP index scoring and staging system may be a useful tool to calculate a prediction of the incidence of ILD-AE and its prognosis for patients with NSCLC and ILD.

PD-L1 expression in patients with unresectable stage III non-small cell lung cancer receiving chemoradiotherapy.

e20530Background: Approximately 30% of patients with stage IV non-small cell lung cancer (NSCLC) are reported to have with high tumor PD-L1 expression (tumor proportion score: TPS ≥ 50%). PD-L1 sta...

Impact of Interstitial Lung Disease Classification on the Development of Acute Exacerbation of Interstitial Lung Disease and Prognosis in Patients with Stage III Non-Small-Cell Lung Cancer and Interstitial Lung Disease Treated With Chemoradiotherapy

Introduction: Data on the efficacy and risk of curative-intent chemoradiotherapy in patients with inoperable stage III non-small-cell lung cancer (NSCLC) and interstitial lung disease (ILD) are limited. The aim of this study was to explore the impact of ILD classification on acute exacerbation (AE) of ILD and prognosis in patients with stage III NSCLC and ILD treated with chemoradiotherapy. Materials and methods: We retrospectively reviewed the medical records of patients with stage III NSCLC and ILD treated with curative-intent chemoradiotherapy as the first-line treatment at the Shizuoka Cancer Center between June 2009 and May 2014. Results: Of 37 patients, 17 (46%) developed AE of ILD worse than grade 3 within 1 year after the last irradiation. In univariate analysis, the incidence rate of AE of ILD was lower in patients with a non-usual interstitial pneumonia (UIP) pattern than in those with a UIP pattern. Multivariate analysis showed that ILD classification was significantly associated with the incidence of AE of ILD. The median overall survival (OS) durations in patients with a non-UIP pattern and a UIP pattern were 16.5 and 9.3 months, respectively. In univariate analysis, patients with a non-UIP pattern showed better survival. Multivariate analysis showed that ILD classification was a significant independent prognostic factor. Conclusion: The incidence of AE of ILD was high in patients with stage III NSCLC and ILD treated with chemoradiotherapy as the first-line treatment. However, diagnosis of a non-UIP pattern could predict lower risk of AE of ILD and longer OS durations.

Efficacy of second-line chemotherapy in poor-risk patients with refractory-relapsed small-cell lung cancer

Background The treatment efficacy of second-line chemotherapy in poor-risk patients with refractory-relapsed small-cell lung cancer is unclear. Methods We defined refractory relapse as treatment-free interval <90 days and poor-risk as Eastern Cooperative Oncology Group Performance Status ≥2. We retrospectively examined the medical record data of patients who were treated at our hospital between September 2002 and December 2014. Results Twenty-three poor-risk patients with refractory-relapsed small-cell lung cancer were treated in our hospital. The characteristics of patients at the time of first-line treatment were as follows: median age (range) 71 (57-83) years; male 74%; extensive disease 96%; proportion of patients with PS 0 or 1 and those with 2-4 was 43 and 57%, respectively; median treatment-free interval 26 days. Amrubicin was the most commonly used drug and was administered in 15 patients (65%). The overall response rate of all patients was 22%. Median progression-free survival and overall survival was 2.2 and 3.7 months, respectively. Among patients treated with amrubicin, overall response rate was 13%, median progression-free survival was 2.2 months, and median overall survival was 3.9 months. The most common grade 3 or worse adverse events were hematologic toxicities, including leukopenia (66%), neutropenia (69%), thrombocytopenia (9%) and anemia (22%). Febrile neutropenia was observed in two patients (9%). Conclusions Second-line chemotherapy might have poor efficacy to poor-risk patients with refractory-relapsed small-cell lung cancer.

Changes in programmed death ligand 1 expression in non-small cell lung cancer patients who received anticancer treatments

BackgroundThe expression of programmed death ligand 1 (PD-L1) is considered a predictive biomarker of anti-programmed death 1 (PD-1)/PD-L1 cancer therapies. However, changes in PD-L1 expression of tumor cells during clinical courses have not been fully evaluated. We evaluated changes in PD-L1 expression for non-small cell lung cancer (NSCLC) patients who received anticancer treatments during clinical courses.MethodsIn 76 NSCLC patients, PD-L1 expression was evaluated before and after anticancer treatment by immunohistochemical (IHC) analysis using an anti-PD-L1 antibody. We defined two cut-off points of PD-L1 expression (1 and 50%) and three corresponding IHC groups (A: 0%, B: 1–49%, and C: ≥50%). IHC group B and C were considered to be positive expression, and we defined the difference of IHC group between pre- and post-treatment as ‘major change’ in PD-L1 expression.ResultsBefore anticancer treatment, PD-L1 expression was observed in 38/76 (50%) patients, and was significantly less common in patients harboring mutations in the epidermal growth factor receptor gene (EGFR) than in those without (P = 0.039). After anticancer treatment, PD-L1 expression was observed in 36/76 (47%) patients. Major increases in PD-L1 expression were seen in 11 (14%), and major decreases in 18 (24%) patients. Among 13 patients harboring EGFR mutations treated with EGFR tyrosine-kinase inhibitor (EGFR-TKI), five (38%) showed major increases.ConclusionMajor changes of PD-L1 expression in tumor cells were observed in 38% of NSCLC patients who received anticancer treatments. And, treatments with EGFR-TKI may increase PD-L1 expression in NSCLC patients harboring EGFR mutations.

Prophylactic cranial irradiation (PCI) in limited-disease small-cell lung cancer (LD-SCLC) patients with brain imaging.

e20010Background: PCI is recommended for patients with LD-SCLC who have a good response to initial therapy. But this recommendation has been made based on studies in which brain imaging was not a s...