Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience.

BACKGROUND: In recent years, the anti-programmed cell death 1 (PD-1) drug pembrolizumab (Keytruda) was approved for treatment of unresectable advanced non-small cell lung cancer (NSCLC) as first- or second-line therapy depending on the clone 22C3-programmed death-ligand 1 (PD-L1) immunohistochemical expression score by the companion diagnostic assay. We herein evaluated 22C3-PD-L1 expression of NSCLC in a single institution experience and compared it with clinicopathologic features. MATERIALS AND METHODS: We assessed 22C3-PD-L1 expressions of 411 patients with NSCLC from our institution, including in past specimens. Programmed death-ligand 1 immunohistochemistry (IHC) testing was performed using the PD-L1 clone 22C3 pharmDx kit (Agilent Technologies/Dako, Carpinteria, CA, USA). Patients were separated into 3 groups with <1% (no expression), 1% to 49% (low expression), or ⩾50% (high expression) positive tumor cells. RESULTS: In all, 137 patients (33%) did not express PD-L1, 155 (38%) showed low expression, and 119 (29%) demonstrated high expression. Archival samples showed lower PD-L1 expression than that of recent samples, and the ratios of no expression case significantly increased by using paraffin blocks embedded particularly in more than 4 years ago. Programmed death-ligand 1 positivity was significantly associated with male sex, smoking, higher tumor grade, squamous cell carcinoma in histologic type, wild-type EGFR, and ALK rearrangement positive. CONCLUSIONS: The rate of 22C3-PD-L1 expression of NSCLC detected in this study was similar to the frequencies of the previous reports, although the ratio of expression case decreased when using old paraffin blocks.

A High PD-L1 Expression in Pulmonary Pleomorphic Carcinoma Correlates with Parietal-pleural Invasion and Might Predict a Poor Prognosis.

Objective Pleomorphic carcinoma (PC) is a rare pulmonary epithelial malignant tumor with a poor prognosis. The objective of the present study was to investigate the programmed death-ligand 1 (PD-L1) expression in PC and its correlation between the clinicopathological factors and prognosis. Methods Clinical and pathological data of 35 patients with surgically resected PC encountered from 2002 to 2016 at our institution were collected. The PD-L1 expression on tumor cells was evaluated via immunohistochemistry (clone 22C3). We examined the correlation between the PD-L1 expression and patients' clinicopathological factors and their prognosis. Results A high PD-L1 expression (≥50%) was seen in 21 (60%) patients, and parietal-pleural invasion was significantly correlated with a high PD-L1 expression (p=0.012). The 5-year overall survival and relapse-free survival were 68.2% and 43.2%, respectively. Tumor size ≥50 mm (p=0.021), lymph node metastasis (p=0.023), and a high PD-L1 expression (p=0.047) were correlated with a short relapse-free survival. Since lymph node metastasis was an independent risk factor of a poor overall survival (p=0.012), patients with a high PD-L1 expression also tended to have a worse overall survival than those with low levels (p=0.081). Conclusion A high PD-L1 expression is frequently seen in PC. The PD-L1 expression is associated with parietal-pleural invasion and might indicate a poor prognosis.

A phase I/II trial of pemetrexed plus radiotherapy in elderly patients with locally advanced non-small cell lung cancer.

Background Radiotherapy (RT) is an effective treatment for elderly patients with locally advanced non-small-cell lung cancer (NSCLC); however, no clinical trials have investigated combination RT with pemetrexed (PEM) in chemotherapy-naive patients ≥71 years old. We conducted a phase I/II study to evaluate the appropriate PEM dose, efficacy, and safety of PEM plus RT in elderly patients. Methods Patients ≥71 years with performance status (PS) scores of 0-2 who had pathologically confirmed stage IIIA/IIIB NSCLC received PEM (500 mg/m2 on day 1 of a 28-day cycle, 4 courses) and RT (a single 2 Gy daily fraction on 5 consecutive days weekly from day 1; 60 Gy total). The primary endpoint was the objective response rate (ORR); the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results Forty-one patients with a median age of 79 years were enrolled; 31 were men. Eighteen patients had squamous cell carcinoma, 27 had stage IIIA disease, and 38 had PS scores 0-1. The ORR was 80.5%, while the median OS and PFS rates were 24.9 and 6.9 months, respectively. Two treatment-related deaths occurred owing to RT-related pneumonitis and severe infection, respectively. Common hematological AEs were leucopenia and neutropenia; common non-hematological AEs were anorexia and constipation. Three patients developed PEM-induced interstitial lung disease; however, most AEs were RT-related. Conclusions Combination PEM and RT shows promising efficacy but relatively severe RT-related toxicities. Therefore, this treatment should be prescribed to elderly patients with caution. Trial registration UMIN 000005036 .

Association between family satisfaction and caregiver burden in cancer patients receiving outreach palliative care at home.

ABSTRACTObjective:Little is known about the associations between family satisfaction with end-of-life care and caregiver burden. We conducted a researcher-assisted questionnaire survey to clarify the impact of caregiver burden on family satisfaction and to determine the types of burden that decrease family satisfaction. METHOD: Bereaved family caregivers of patients with advanced cancer who received our outreach palliative care service were retrospectively identified. Family satisfaction with the end-of-life care provided by the palliative care service and caregiver burden were quantified using the Japanese versions of the FAMCARE Scale and the Zarit Burden Interview (ZBI), respectively. RESULTS: Our study subjects included 23 family caregivers. The mean scores on the FAMCARE Scale and the ZBI for the total population were 72.8 ± 11.2 and 22.8 ± 17.3, respectively, indicating moderate-to-high satisfaction and low-to-moderate burden. Caregiver burden had a strong negative correlation to family satisfaction with end-of-life care (Spearman's rho [ρ] = -0.560, p = 0.005), which remained after adjustment for potential confounders (standardized beta [ß] = -0.563, p = 0.01). Several burden items-including loss of control, personal time, social engagement with others, feeling angry with the patient, feeling that the patient wants more help than he/she needs, and a wish to leave the care to someone else-were associated with decreased satisfaction. The major cause of dissatisfaction for family members included the information provided regarding prognosis, family conferences with medical professionals, and the method of involvement of family members in care decisions. SIGNIFICANCE OF RESULTS: Caregiver burden can be a barrier to family satisfaction with end-of-life care at home. A home care model focused on caregiver burden could improve end-of-life experiences for patients and family caregivers.

Combination of virtual bronchoscopic navigation, endobronchial ultrasound, and rapid on-site evaluation for diagnosing small peripheral pulmonary lesions: a prospective phase II study.

BACKGROUND: The diagnostic yield of peripheral pulmonary lesions (PPLs) by flexible bronchoscopy (FB) is still insufficient. To improve the diagnostic yield of bronchoscopy, several techniques such as endobronchial ultrasound (EBUS), virtual bronchoscopic navigation (VBN), and rapid on-site evaluation (ROSE) have been examined. The primary purpose of the present study was to evaluate the usefulness of combining EBUS, VBN, and ROSE for diagnosing small PPLs. METHODS: Patients with PPLs 30 mm or less on chest computed tomography (CT) were prospectively enrolled. We determined the responsible bronchus for the target lesions using VBN before bronchoscopy was performed. EBUS and ROSE were performed during the examination to determine whether the bronchus and specimen were adequate. On the basis of previous studies, we assumed that the diagnostic yield of 85% among eligible patients would indicate potential usefulness, whereas, the diagnostic yield of 75% would indicate the lower limit of interest. The required number of patients was estimated as 45 for a one-sided α value of 0.2 and a ß value of 0.8. The primary study endpoint was the diagnostic yield. RESULTS: Between June 2014 and July 2015, we enrolled 50 patients in the present study, and we excluded 5 patients. The total diagnostic yield of 45 PPLs was 77.7%. In cases of lung cancer, the diagnostic yield was 84.2%. The sensitivity, specificity, positive predictive value, and negative predictive value of ROSE were 90.6%, 92.3%, 96.7%, and 80.0%, respectively. The diagnostic yield of PPLs from 20 to 30 mm was 87.5%, and the diagnostic yield of PPLs less than 20 mm was 66.7%. PPLs for which the probe was located within the lesion had the highest diagnostic yield. CONCLUSIONS: We could not demonstrate usefulness for diagnosing small PPLs by combining EBUS, VBN, and ROSE. However, combining these techniques may be useful for diagnosing lung cancer.

Impact of metastatic status on the prognosis of EGFR mutation-positive non-small cell lung cancer patients treated with first-generation EGFR-tyrosine kinase inhibitors.

The aim of the present study was to analyze the impact of metastatic status on the prognosis of epithelial growth factor receptor (EGFR) mutation-positive patients with non-small cell lung cancer (NSCLC) treated with first-generation EGFR-tyrosine kinase inhibitors (TKIs). A total of 178 EGFR mutation-positive patients with stage IIIB-IV and relapsed NSCLC who were treated with gefitinib or erlotinib as the first-line treatment were enrolled in the present study. Metastatic status, progression-free survival (PFS), overall survival (OS) and treatment-response rates were investigated. The association between the number of metastatic organ sites and patient prognosis was also investigated. The median age at the time of treatment was 72 (range, 39-91) years. A total of 168 patients had adenocarcinoma; 156 were treated with gefitinib. Patients with brain metastases, bone metastases, liver metastases and pleural effusion exhibited a significantly reduced PFS and OS time in the univariate analysis, compared with patients without each of these symptoms. In the multivariate analysis, bone metastasis was associated with a poorer PFS (hazard ratio, 2.11; 95% confidence interval, 1.44-3.09; P<0.001) and brain metastasis was associated with a poorer OS (hazard ratio, 2.41; 95% confidence interval, 1.46-3.95; P<0.001). No association was observed between metastatic status and treatment response rates. Higher numbers of different sites of organ metastases were associated with significantly poorer PFS and OS. Bone, brain metastasis and higher numbers of metastatic organ sites are negative prognostic factors for EGFR mutation-positive NSCLC patients treated with first-generation EGFR-TKIs.