[A Case of Multiple Brain Tumors Successfully Diagnosed with Liquid Biopsy and Treated with Osimertinib].

A seventy‒year‒old man complaining of left arm weakness and gait disturbance was diagnosed with multiple tumors and severe edema in the brain as well as right lung mass lesion, suggesting brain metastases. He started whole brain radiation therapy but had to discontinue it since his neurological symptoms were worsened including paralysis, aphasia, and coma. These symptoms made it difficult to perform tumor biopsy for cancer diagnosis as well as oncogene mutations. Liquid biopsy, which examines EGFR gene mutations in plasma sample, revealed EGFR L858R point mutation. Treatment with osimertinib improved his symptoms, resulting in discharge to home. Even a patient severely ill with metastatic brain tumors can benefit from the molecular‒targeted therapy using liquid biopsy to diagnose EGFR‒mutated lung cancer, suggesting an important differential diagnosis in such patients.

Feasibility Study of Adjuvant Chemotherapy with Carboplatin and Nab-Paclitaxel for Completely Resected NSCLC.

PURPOSE: Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors >4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC. PATIENTS AND METHODS: Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m2, on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit. RESULTS: Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4-83.7). Two-year RFS was 56.8% (95% CI, 29.7-76.9). CONCLUSION: The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.

Overexpression of CD 133 and BCL-2 in non-small cell lung cancer with neuroendocrine differentiation after transformation in ALK rearrangement-positive adenocarcinoma.

Transformation to small cell lung cancer is one phenomenon of acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in ALK rearrangement-positive non-small cell lung cancer (NSCLC). Few case reports have focused on other types of histological transformation. We report a case of transformation of ALK rearrangement-positive adenocarcinoma to NSCLC with neuroendocrine differentiation during alectinib therapy. A 36-year-old woman presented with a tumor in the left lower lobe and bone metastases. She was diagnosed with ALK rearrangement-positive adenocarcinoma by histopathology of the primary tumor. Alectinib had been effective for 8 months before new lesions appeared. Histopathological re-examination of a recurrent tumor revealed poorly differentiated carcinoma with insulinoma-associated protein 1 (INSM1) expression, which remained ALK-positive. Expression of CD133, BCL-2, and SOX2 was positive in comparison to the initial tumor. Expression of SOX2 became more strongly positive than it was before treatment. The immunohistochemical findings of these markers associated with cancer stem-like cells and/or neuroendocrine differentiation suggest that cancer stem cells play a role in the mechanisms of histological transformation and acquired resistance of ALK rearrangement-positive cancer. To our knowledge, this is the first report to suggest an association between cancer stem-like cells and histological transformation in ALK rearrangement-positive lung cancer.

Baseline Tumor Size as a Predictive and Prognostic Factor of Immune Checkpoint Inhibitor Therapy for Non-small Cell Lung Cancer.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICI) are a novel medication for non-small cell lung cancer (NSCLC). Recent reports indicated that baseline tumor size (BTS) relates to the efficacy of ICI therapy for melanoma, but no study exists for NSCLC. This study aimed to evaluate the utility of BTS for ICI therapy. PATIENTS AND METHODS: Data from 58 patients diagnosed with NSCLC who underwent ICI monotherapy, were retrospectively analyzed. Patients were divided into two groups according to BTS (below 101 mm, above 101 mm). The primary endpoint was progression-free survival (PFS) and the secondary endpoint was overall survival (OS). RESULTS: PFS of patients with a large BTS was significantly shorter than that of those with a small BTS (median; 2.07 [95% confidence interval [CI]=0.99-6.77] months versus 6.39 [95%CI=4.17-11.50] months) (p=0.044). OS of patients with large BTS was also significantly shorter (p<0.01). CONCLUSION: BTS is a predictive and prognostic negative factor of ICI therapy for NSCLC.

Successful Treatment of ROS1-rearranged Lung Cancer Complicated by Hypertrophic Pulmonary Osteoarthropathy with Crizotinib Therapy.

Hypertrophic pulmonary osteoarthropathy (HPO) is a paraneoplastic syndrome characterized by digital clubbing, arthritis, and periostitis. Tumor removal usually leads to the resolution of these symptoms. We herein report the efficacy of crizotinib treatment for treating the symptoms of HPO associated with c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer. A 71-year-old woman presented with a pulmonary tumor and arthritis. She was diagnosed with a ROS1-rearranged lung adenocarcinoma [stage IIIB (cT4N2M0) ] with HPO. Crizotinib dramatically reduced the tumor size and resolved the symptoms. After two months of crizotinib treatment, she underwent lobectomy, and a pathological evaluation revealed ypstage IIIA (ypT3a, ypN1). Crizotinib treatment was effective for reducing the tumor size and improving the symptoms of HPO.

Prognostic Value of Red Blood Cell Distribution Width in Non-small Cell Lung Cancer Treated With Anti-programmed Cell Death-1 Antibody.

BACKGROUND/AIM: Red cell distribution width (RDW) has been reported to reflect the inflammation and nutrition status and predict prognosis of non-small cell lung cancer (NSCLC) patients treated with anti-programmed cell death-1 (PD-1) antibody. The aim of this study was to analyze the correlation between RDW and prognosis of NSCLC patients. PATIENTS AND METHODS: We collected retrospective data on consecutive NSCLC patients treated with anti-PD-1 antibody from December 2015 to April 2018 at the Kobe University Hospital, Japan. RESULTS: Forty-seven patients were treated. Patients with RDW ≥16% had a significantly shorter OS (p=0.010) compared to those with RDW <16%. In multivariate analysis, RDW ≥16% was an independent factor predicting poor prognosis (p=0.019). CONCLUSION: Pre-treatment RDW ≥16% is an indicator of poor prognosis. RDW is an inexpensive, convenient, and routinely available marker of prognosis.