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Introduction: Data on the clinical outcomes of patients receiving adjuvant chemotherapy for surgically resected high-grade pulmonary neuroendocrine carcinoma (HGNEC) (large-cell neuroendocrine carcinoma and small-cell lung cancer) are limited. This study aimed to evaluate the prognostic significance of adjuvant chemotherapy in patients with HGNEC. Methods: We retrospectively analyzed patients with surgically resected HGNEC at five institutions in Japan between January 2006 and May 2016. Results: A total of 143 patients were enrolled. Among them, 65 received adjuvant chemotherapy. Four patients who participated in clinical trials were excluded; the remaining 61 patients were included in the study. Fifty-six patients received adjuvant small-cell lung cancer-based chemotherapy. Twenty-five of 29 patients who relapsed after postoperative adjuvant chemotherapy received chemotherapy. The most commonly administered chemotherapy agent was amrubicin. The 3-year relapse-free and overall survival rates were 55.2% and 66.8%, respectively. The median relapse-free and overall survival times for the 25 patients who received chemotherapy after relapse were 12.9 and 27.5 months, respectively. Among them, 22 relapsed within 2 years. Patients who received platinum-doublet chemotherapy after relapse tended to have better time to progression disease and overall survival than those who received single-agent chemotherapy. Conclusions: Most patients with HGNEC received small-cell lung cancer-based regimens as postoperative adjuvant chemotherapy. Those who relapsed after adjuvant chemotherapy were mainly treated with amrubicin. Our findings suggest that platinum-doublet chemotherapy tends to improve the time to progression disease and overall survival in patients who relapse after postoperative adjuvant chemotherapy.

Background Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy‐induced nausea and vomiting and is also superior to neurokinin‐1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)‐induced nausea and vomiting in patients with thoracic malignancies. Materials and Methods We conducted a prospective, open‐label, single‐arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0–120 hours). Results Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0–120 hours), acute (0–24 hours), and delayed phases (24–120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed. Conclusion Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three‐drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA‐based regimen. Clinical trial identification number: UMIN000031267. Implications for Practice The results of this phase II trial indicated that the prophylactic administration of low‐dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high‐dose carboplatin chemotherapy., This article reports the results of a study that investigated the efficacy and safety of a three‐drug combination of low dose olanzapine combined with granisetron and dexamethasone in the treatment of chemotherapy‐induced nausea and vomiting in Japanese patients with thoracic malignancies treated with carboplatin.

Background Lung cancer is the leading cause of cancer-related deaths. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective for advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations, some patients experience little or no response. The Glasgow prognostic score (GPS) is an inflammation-related score based on C-reactive protein (CRP) and albumin concentrations, and has prognostic value in various cancer settings. This study aimed to evaluate whether GPS could predict response of NSCLC to EGFR-TKIs. Methods This retrospective multicenter study evaluated patients with NSCLC harboring EGFR mutations who received EGFR-TKI monotherapy from October 2006 to December 2016. GPS values were determined using CRP and albumin concentrations from before initiation of EGFR-TKIs. The Kaplan-Meier method and Cox proportional hazard models were used to evaluate progression-free survival (PFS) and overall survival (OS). Results In 214 patients, 141, 43, and two patients had GPS values of 0, 1, and 2, respectively. The GPS independently predicted the efficacy of EGFR-TKIs; good GPS (0-1) conferred significantly better PFS (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.38-0.96, P = 0.03) and OS (HR: 0.56, 95% CI: 0.33-0.96, P = 0.03). Multivariate analysis confirmed that a good GPS (0-1) independently predicted good PFS and OS among patients who had PS of 0-1. Good GPS (0-1) independently predicted good OS among patients receiving treatment in first-line settings. Conclusions The GPS independently predicted the efficacy of EGFR-TKIs for EGFR-mutated NSCLC; however, further studies are needed to validate our findings. Key points SIGNIFICANT FINDINGS OF THE STUDY: Glasgow prognostic score (GPS) independently predicted the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutated NSCLC. What this study adds The findings presented in this paper will help to identify patients who will be expected to experience limited or no response to EGFR-TKI treatment by using GPS.

Immune checkpoint inhibitors (ICIs) are an effective subsequent-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether the efficacy and safety of subsequent-line ICI monotherapy in elderly patients (aged ≥ 75 years) are similar to that in non-elderly patients. Therefore, we aimed to investigate the efficacy and safety of ICI monotherapy in pretreated elderly patients with NSCLC. Between January 2016 and February 2018, 131 elderly patients with advanced NSCLC who received subsequent-line ICI monotherapy at 13 Japanese institutions were enrolled in this study. Baseline characteristics, the efficacy of ICI treatment, and adverse events were evaluated. Ninety-eight men and 33 women (median age 77 [range 75–87] years) were enrolled. Among those who received subsequent-line ICI monotherapy, the overall response, disease control rates, median progression-free survival (PFS), and overall survival (OS) were 27.4%, 61.8%, 4.5 months, and 16.0 months, respectively. Adverse events such as anorexia, fatigue, pneumonitis, and hypothyroidism were observed. There were two treatment-related deaths due to pneumonitis and thrombocytopenia. Subsequent-line ICI monotherapy in patients with good performance status (PS), receiving steroids for immune-related adverse events (irAEs), and exhibiting partial response (PR) was associated with improved PFS, as well as OS in patients with good PS and PR. Subsequent-line ICI monotherapy in elderly patients, with previously treated NSCLC, was effective, safe and showed outcomes equivalent to those in non-elderly patients. Immunotherapy provides a survival benefit for elderly patients, who exhibit its efficacy and a favorable general condition.

Pembrolizumab is an effective front-line treatment for advanced non-small cell lung cancer (NSCLC) in patients expressing high levels of programmed death-ligand 1 (PD-L1). However, it is unclear whether first-line pembrolizumab has similar efficacy among elderly (aged ≥ 75 years) and younger patients. This study aimed to investigate the safety and efficacy of front-line pembrolizumab monotherapy in older adults with NSCLC expressing high PD-L1. A total of 128 patients with advanced NSCLC expressing high PD-L1, including 47 older adults, received first-line pembrolizumab monotherapy at ten institutions in Japan, between February 2017 and February 2018. Data related to patient characteristics, efficacy of pembrolizumab therapy, and the type and severity of adverse events were recorded. Overall, 47 patients [40 men and 7 women; median age 79 (range 75–88) years] were included in our analysis. In patients who received first-line pembrolizumab monotherapy, overall response, disease control rates, median progression-free survival (PFS), and median overall survival (OS) were 53.1%, 74.4%, 7.0 months, and not reached, respectively. Common adverse events included anorexia, fatigue, skin rash, and hypothyroidism. Two treatment-related deaths were noted, due to pneumonitis and infection. First-line pembrolizumab monotherapy was associated with improved PFS in patients with non-progressive disease (PD). In patients with non-PD and good performance status (PS), pembrolizumab monotherapy improved OS. Elderly patients with NSCLC expressing high PD-L1 tolerated front-line pembrolizumab monotherapy well. Their survival outcomes were equivalent to those of younger patients. In patients with non-PD, first-line pembrolizumab monotherapy may improve PFS; in conjunction with good PS, it additionally improves OS.

Purpose Malignant pericarditis is observed in 5.1–7.0% of all cases of acute pericarditis, and malignant pericardial effusion (MPE) can lead to cardiac tamponade in the later stages of cancer. Breast cancer is the second most common primary cancer associated with MPE, but the efficacy and safety of intrapericardial carboplatin (CBDCA) have never been evaluated in breast cancer. In this study, we assessed the clinical significance of intrapericardial CBDCA following catheter drainage in patients with breast cancer-related MPE. Methods A catheter was inserted percutaneously into the pericardial space under echocardiographic guidance. After complete drainage, 150 mg of CBDCA was instilled into the pericardial space through the catheter. Results Eight patients with symptomatic breast cancer-related MPE were treated at the Gunma Prefectural Cancer Center, between July 2010 and March 2016. One month after treatment, 100% of MPE was controlled. The median survival time from the recurrence of breast cancer until death or study follow-up was 2336 days (range 293–3937 days), while that from intrapericardial CBDCA administration until death or study follow-up was 552 days (range 35–1673 days). Grade 1 fever, nausea, hypotension, fatigue, and chest discomfort were observed in one patient (12.5%) after intrapericardial CBDCA administration. Conclusions We found that intrapericardial administration of CBDCA after catheter drainage appears to be safe and effective in managing breast cancer-associated MPE. As the number of patients in this study was small, further studies are warranted to determine the safety and efficacy of intrapericardial CBDCA in the management of breast cancer-related MPE.

Background/aim It remains unclear which chemotherapeutic regimens are better for the addition of bevacizumab. We conducted an exploratory randomized phase II trial comparing first-line S-1 plus cisplatin with bevacizumab and pemetrexed plus cisplatin with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Patients and methods Chemotherapy-naive patients received S-1 (80 mg/m2) from day 1 to day 14 plus cisplatin (80 mg/m2) on day 1 with bevacizumab (15 mg/kg) on day 1, followed by maintenance with bevacizumab plus S-1 (SCB) on day 1 every 3 weeks and pemetrexed (500 mg/m2) on day 1 plus cisplatin (75 mg/m2) on day 1 with bevacizumab (15 mg/kg) on day 1 followed by maintenance bevacizumab plus pemetrexed (PCB) on day 1 every 3 weeks. The expression of thymidylate synthase (TS) was analyzed using immunohistochemistry. Results Forty-eight patients were enrolled in this study, and eligible patients were randomly assigned at 1:1 ratio to receive SCB (n=24) or PCB (n=24). The median number of chemotherapy and maintenance therapy for SCB and PCB was 4 (range, 1-6 cycles) and 4 (range, 2-6 cycles), and 5 (range, 0-39 cycles) and 5 (range, 0-28 cycles), respectively. The overall response rate (ORR) for PCB and SCB were 54.2% and 83.3%, respectively (p=0.06). The median progression-free survival (PFS) and overall survival (OS) for PCB and SCB were 406 and 351 days, (p=0.96), and 678 and 1190 days, respectively (p=0.23). The mild adverse events were observed in both regimens. TS expression was more predictive of the chemotherapeutic response in SCB compared to PCB, but not for PFS. Conclusion The combination regimen of SCB was identified as having a similar activity and tolerability to that of PCB in patients with advanced non-squamous NSCLC.

Background Topotecan is one of the most active chemotherapeutic drugs for small cell lung cancer (SCLC). However, its efficacy in elderly patients with SCLC has not been validated. This study evaluated the feasibility and efficacy of topotecan monotherapy in elderly patients with relapsed SCLC. Methods Between January 2000 and March 2017, 43 patients aged ≥ 70 years received topotecan monotherapy for relapsed SCLC at four institutions. The clinical outcomes and adverse events of treatment were retrospectively analyzed. Results Twenty-nine patients (median age 75 years; range: 70-83 years) had sensitive-type relapse, while 14 (median age 78 years; range: 71-82 years) had refractory relapse. The median number of treatment cycles was two (range: 1-6). The response rate was 7.0% (10.3% and 0% in sensitive and refractory patients, respectively), while the disease control rate was 23.2% (20.6% and 42.8% in sensitive and refractory patients, respectively). Median progression-free survival was 1.9 months in sensitive patients and 1.4 months in refractory patients (P = 0.87). The median survival time from the start of topotecan therapy was 5.5 months in sensitive patients and 4.0 months in refractory patients (P = 0.64). Grade ≥ 3 hematological toxicities were as follows: leukopenia, 37.2%; neutropenia, 51.1%; anemia, 0%; thrombocytopenia, 32.5%; and febrile neutropenia, 9.3%. No treatment-related deaths occurred. Conclusion Although hematological toxicities (particularly neutropenia) were severe, topotecan showed favorable disease control in both sensitive and refractory patients. Topotecan may thus be a preferred treatment for elderly patients with relapsed SCLC.

Background and Objectives: Naldemedine is a peripherally acting μ-opioid receptor antagonist that improves opioid-induced constipation. Although clinical trials have excluded patients with poor performance status (PS) and those started on naldemedine early after opioid initiation, clinical practice has used naldemedine for the same patients. Therefore, we investigated the treatment patterns of naldemedine in a real-world setting. Materials and Methods: This was a multicenter, retrospective chart review study of opioid-treated patients with cancer receiving naldemedine. Adverse events that occurred within 7 days of naldemedine initiation were evaluated in those who received one or more doses of the same. Effectiveness was assessed in patients who used naldemedine for more than 7 days. Results: A total of 296 patients satisfied the eligibility criteria, among whom 129 (43.6%) had a PS of ≥3 and 176 (59.5%) started naldemedine within 2 weeks of opioid initiation. Moreover, 203 (79.6%) patients had ≥3 bowel movements per week. Incidences of all grades of diarrhea and abdominal pain were 87 (29.4%) and 12 (4.1%), respectively. No patient had grade 4 or higher adverse events. Conclusions: Although nearly half of the patients receiving naldemedine in clinical practice belonged to populations that were not included in the clinical trials, our results suggested that naldemedine in clinical practice had the same efficacy and safety as that in clinical trials.

Background In patients with epidermal growth factor receptor (EGFR)‐mutated advanced non‐small‐cell lung cancer (NSCLC), epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) treatment has shown a good response. Subsequent treatments jeopardize the ability to determine the effect of first‐line chemotherapy on overall survival (OS). Therefore, using patient‐level data, we aimed to study the associations of progression‐free survival (PFS) and post‐progression survival (PPS) with OS after first‐line EGFR‐TKI treatment in patients with EGFR‐mutated NSCLC. Methods Between November 2006 and December 2016, we analyzed 92 patients with EGFR‐mutated NSCLC treated with first‐line EGFR‐TKI. The correlations of PFS and PPS with OS were analyzed for each patient. Results Spearman's rank correlation and linear regression analyzes showed that PPS correlated highly with OS (r = 0.85, P

Breast metastases of primary lung neuroendocrine tumors are rarely reported. The current report presents the case of a 41-year old female with no history of smoking who initially underwent surgery for a breast fibroadenoma, during which a neuroendocrine tumor of the right lung was detected via chest X-ray. The patient underwent surgery for the tumor and developed right breast nodules after adjuvant chemotherapy. Histological and immunohistochemical examinations of biopsies from these nodules indicated breast metastasis of the primary lung neuroendocrine tumor. The patient underwent mastectomy of the right breast but subsequently developed metastases in the left breast, for which local radiotherapy was administered. The observed metachronous bilateral breast metastases indicated that the contralateral breast should be considered during an investigation of metastasis.

// Nobuaki Mamesaya 1 , Kazushige Wakuda 1 , Katsuhiro Omae 2 , Eriko Miyawaki 1 , Mie Kotake 1 , Takumi Fujiwara 1 , Takahisa Kawamura 1 , Haruki Kobayashi 1 , Kazuhisa Nakashima 1 , Shota Omori 1 , Akira Ono 1 , Hirotsugu Kenmotsu 1 , Tateaki Naito 1 , Haruyasu Murakami 1 , Keita Mori 2 , Hideyuki Harada 3 , Masahiro Endo 4 , Takashi Nakajima 5 and Toshiaki Takahashi 1 1 Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan 2 Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan 3 Division of Radiation Therapy, Shizuoka Cancer Center, Shizuoka, Japan 4 Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan 5 Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan Correspondence to: Kazushige Wakuda, email: k.wakuda@scchr.jp Keywords: small-cell lung cancer; limited disease; prophylactic cranial irradiation; brain metastases Received: November 21, 2017 Accepted: March 02, 2018 Published: April 03, 2018 ABSTRACT 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.

This study was to determine the incidence and risk factors of febrile neutropenia in chemotherapy-naive Japanese patients treated systemically with etoposide plus platinum for lung cancer. The study was a retrospective analysis of 244 patients who were monitored for febrile neutropenia through multiple cycles of the combination of etoposide with platinum, and the associations between incidence of febrile neutropenia and patient characteristics were evaluated. Eighty-eight patients were treated with etoposide plus cisplatin and 156 were treated with etoposide plus carboplatin. Of the 244 patients treated, 198 (81.1%) completed 4 cycles for chemotherapy. Febrile neutropenia was observed in 48 of 244 patients (19.7%), including 18 of 88 (20.5%) patients who received etoposide plus cisplatin and 30 of 156 (19.2%) patients who received etoposide plus carboplatin. Grade 3 or 4 of neutropenia was experienced by a total of 208 patients (85.2%); 79 of 88 (89.8%) receiving etoposide plus cisplatin and 129 of 156 (82.7%) receiving etoposide plus carboplatin. Male gender and previous radiotherapy were identified by multivariate analysis as independent risk factors for febrile neutropenia. These results contrast with findings in Western patients and suggest that ethnic differences exist in the incidence of febrile neutropenia in patients receiving etoposide plus platinum chemotherapy. In addition, our results suggest that primary prophylaxis with granulocyte colony-stimulating factor should be considered for patients with these risk factors for febrile neutropenia prior to treatment with etoposide plus platinum.

Neuronal NO synthase (nNOS)-mediated cGMP accumulation has been shown to affect a variety of neuronal cell activities, regardless of whether they are detrimental or beneficial, depending on the amount of their levels, under the physiological and pathological situations. In the present study, we examined the role of proton-sensing G protein-coupled receptors (GPCRs), which have been identified as new pH sensors, in the acidic pH-induced nNOS/cGMP activity in N1E-115 neuronal cells. In this cell line, ovarian cancer G protein-coupled receptor 1 (OGR1) and G protein-coupled receptor 4 (GPR4) mRNAs are expressed. An extracellular acidic pH increased cGMP accumulation, which was inhibited by nNOS-specific inhibitors. Acidic pH also activated phospholipase C/Ca 2 + pathways and Akt-induced phosphorylation of nNOS at S1412, both of which have been shown to be critical regulatory mechanisms for nNOS activation. The acidic pH-induced activation of the phospholipase C/Ca 2 + pathway, but not Akt/nNOS phosphorylation, was inhibited by small interfering RNA specific to OGR1 and YM-254890, an inhibitor of G q/11 proteins, in association with the inhibition of cGMP accumulation. Moreover cGMP accumulation was inhibited by 2-aminoethoxydiphenyl borate, an inhibitor of inositol 1,4,5-trisphosphate channel; however, it was not by wortmannin, a phosphatidylinositol 3-kinase inhibitor, which inhibited Akt/nNOS phosphorylation. In conclusion, acidic pH stimulates cGMP accumulation preferentially through the OGR1/G q/11 proteins/phospholipase C/Ca 2 + /nNOS in N1E-115 neuronal cells. Akt-mediated phosphorylation of nNOS, however, does not appreciably contribute to the acidification-induced accumulation of cGMP.

Oxidatively damaged proteins and lipid peroxidation products have been shown to accumulate in the brain of neurodegenerative diseases, such as Alzheimer’s disease and multiple sclerosis, and oxidized lipoprotein is considered to be toxic and neurodegenerative. However, the role of lipoprotein and its oxidized form in neurite remodeling has not been well understood. In the present study, we have aimed to clarify whether and, if so, how high-density lipoprotein (HDL) and oxidized HDL (oxHDL) affect neuritogenesis. In the presence of nerve growth factor, exposure of PC12 cells to either HDL or oxHDL induces a rapid neurite retraction, which is followed by re-outgrowth of neurites in either case; however, oxHDL-treated cells exhibit much longer outgrowths than do basal and HDL-treated cells. Thus, processes in the morphological changes of neuronal cells after lipoprotein treatment are composed of two phases: the reversible retraction phase and the extension phase. Characterization of the active fractions of lipids and experiments with desensitization and knockdown of receptors have indicated that the reversible retraction phase involves mainly sphingosine 1-phosphate for HDL and lysophosphatidic acid for oxHDL. The change in the components responsible for the retraction response is comparable with the change in sphingosine 1-phosphate and lysophosphatidic acid contents by the oxidation of HDL. In the extension phase, lysophosphatidylcholine, which is increased by the oxidation of HDL, may play a stimulatory role in neurite outgrowth. We conclude that lipoprotein and its oxidized form differentially regulate neuritogenesis through lipoprotein-associated lysolipid molecules.

Background: In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. Methods: Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. Results: Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R2 = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R2 = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Conclusions: In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS.

The aim of our study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin in combination with thoracic radiotherapy for patients with locally advanced stage III non-small cell lung cancer (NSCLC). Weekly nab-paclitaxel plus carboplatin was administered intravenously for 6 weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 60/2; level 3, 80/2 (nab-paclitaxel [mg/m2]/carboplatin [area under the plasma concentration time curve mg/ml/min]). Concurrent thoracic radiotherapy was administered in 2-Gy fractions 5 times weekly, to a total dose of 60 Gy. Fourteen patients were enrolled in the present study. Eleven (78%) patients received full cycles (6 cycles) of chemotherapy, and 12 (86%) patients received 60 Gy of thoracic radiotherapy. At level 1, none of 3 patients experienced a dose-limiting toxicity (DLT). At level 2, 2 of 7 patients developed grade 3 diarrhea, grade 3 hyponatremia, grade 3 fatigue, and grade 3 esophagitis. Therefore, 4 patients were started at dose level 3 and none developed a DLT. No pulmonary toxicities, such as interstitial pneumonitis and treatment-related deaths, were observed at either level. Therefore, level 3 was considered the MTD and level 3 was defined as the RD. An objective response was observed in 71.4% of all patients. This regimen is feasible and well tolerated for the treatment of patients with unresectable locally advanced NSCLC.

Two cases of intravascular lymphoma (IVL) were diagnosed by endoscopic biopsy. Both patients were admitted to our hospital with a fever of an unknown origin. An elevated serum level of soluble interleukin-2 receptor antibody suggested IVL. An upper gastrointestinal endoscopy was performed. A biopsy of both the reddened and normal gastroduodenal mucosa (Case 1) and a biopsy of a gastric antral ulcer, multiple polyploid lesions resembling submucosal tumors in the duodenum, and the patient's normal mucosa (Case 2) revealed vascular infiltration by CD20-positive atypical lymphocytes, confirming the diagnosis of IVL. The performance of a gastrointestinal biopsy for suspected IVL is important, even if there are no visible endoscopic abnormalities.

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...

A 70-year-old woman suffered from hypoglycemic symptoms three or four hours after glucose intake for three months. At this time, the patient felt she had perspired more than in previous years. A diffuse elastic goiter without tenderness was palpable. Transient hyperthyroid state with little uptake by 123I-thyroid scintigram was shown and diagnosed as silent thyroiditis. Oral glucose ingestion test (OGTT) showed normal glucose response but high insulin response and hypoglycemia occurred at 240 minutes. We diagnosed reactive hypoglycemia for glucose intake. The frequency of hypoglycemia reduced after the glucose intake decrease. Hypoglycemia did not occur after glucose intake in the euthyroid state. Then OGTT showed a borderline pattern and delayed hyperinsulinemic response. Reactive hypoglycemia may have been the result of transient hyperthyroid state in the background of the pre-diabetic stage.

A 56-year-old woman was admitted due to fever, thirst, polydipsia, polyuria, posterior cervical pain and lumbago. Hyperglycemia and urine white blood cell elevation were detected. Computed tomography showed left perirenal abscess. Urine culture and blood culture revealed Escherichia coli. We diagnosed perirenal abscess followed by pyelonephritis due to untreated diabetes mellitus. We used 6g of ampicillin-sulbactum daily and from the 10th day 4g of sulfamethoxazole-trimethoprim for perirenal abscess, and 180mg of loxoprofen sodium daily for posterior cervical pain in addition to a diabetic diet and insulin therapy for diabetes mellitus. Although the patient's fever normalized and lumbago improved, posterior cervical pain level increased and bilateral 1, 2 and 3 finger-numbness occurred from the 18th day. Cervical magnetic resonance imaging showed cervical 4, 5 and 6 vertebra inflammation induced spine compression. Removal of the cervical abscess and fixation of the vertebra were performed at the 27th day. Treating diabetes mellitus is important for the prevention of severe infection.

A 72-year-old male diabetic patient was admitted due to autoimmune hemolytic anemia (AIHA).\nWe started 1mg/kg weight of prednisolone daily and multiple daily insulin infusion for hyperglycemia.\nGall bladder cancer and early stage gastric cancer were then diagnosed. We removed the gall bladder\nand the spleen for treatment of AIHA without prednisolone for better control of diabetes mellitus. Five\nweeks later, endoscopic gastromucosal resection (EMR) was performed for gastric cancer. The patient\nsuffered from fever and respiratory failure after 4 days. Chest computed tomography showed consolidation,\nbronchial wall thickening and a ground glass appearance in bilateral lungs. Although the sputum\nand blood culture were negative,β-D-glucan and mannan antigen increased. Neutrophilia (87％)was\nshown. The WBC count had not increased (7300/μl) compared with the CRP elevation (21.8mg/dl).\nTherefore, we diagnosed overwhelming postsplenectomy infection syndrome followed by atypical pathogen\ninfection. We used ciprofloxacin and fosfluconazol, respirator at low tidal volume ventilation,\nsivelestat sodium hydrate and methylprednisolone for respiratory failure and regular insulin aiming for\na blood glucose range of from 80 to 140mg/dl. The patient subsequently recovered

A 72-year-old male diabetic patient was admitted due to autoimmune hemolytic anemia (AIHA). We started 1mg/kg weight of prednisolone daily and multiple daily insulin infusion for hyperglycemia. Gall bladder cancer and early stage gastric cancer were then diagnosed. We removed the gall bladder and the spleen for treatment of AIHA without prednisolone for better control of diabetes mellitus. Five weeks later, endoscopic gastromucosal resection (EMR) was performed for gastric cancer. The patient suffered from fever and respiratory failure after 4 days. Chest computed tomography showed consolidation, bronchial wall thickening and a ground glass appearance in bilateral lungs. Although the sputum and blood culture were negative, β-D-glucan and mannan antigen increased. Neutrophilia (87%) was shown. The WBC count had not increased (7300/μl) compared with the CRP elevation (21.8mg/dl). Therefore, we diagnosed overwhelming postsplenectomy infection syndrome followed by atypical pathogen infection. We used ciprofloxacin and fosfluconazol, respirator at low tidal volume ventilation, sivelestat sodium hydrate and methylprednisolone for respiratory failure and regular insulin aiming for a blood glucose range of from 80 to 140mg/dl. The patient subsequently recovered.

e20010 Background: 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 standard component of initial staging or follow-up. The aim of this study was to evaluate the efficacy of PCI for LD-SCLC patients with brain MRI immediately before PCI administration. Methods: This single-center, retrospective study included patients with LD-SCLC who achieve a good response to initial therapy without BM confirmed by MRI between 09/2002 and 06/2015. Responses were classified as CR and PR, according to RECIST. We categorized these patients into three groups: C: patients who achieved CR and received PCI; P: patients who achieved PR and received PCI; N: patients who did not receive PCI, regardless of responses. We compared OS, progression free survival (PFS), and the cumulative incidence of BM at 3 years (3yBM) among these groups. Results: A total of 79 patients were included in this study. At baseline, age and PS differed significantly between C and N. In P, patients were also younger than N. Although there were no statistical significances in OS and PFS between C and N, differences in 3 years OS rate and median PFS were numerically large. The 3yBM in C revealed marginal significance compared with N. However, No differences were observed with OS, PFS, and 3yBM between P and N. Conclusions: PCI may not add clinical benefit to LD-SCLC patients who did not achieve CR after initial therapy if absence of BM could be confirmed by MRI immediately before PCI administration. [Table: see text]

A 60-year-old woman complained of chest and axillary pain, which had initially appeared three months previously and had recently become worse. A chest CT revealed hilus-mediastinal lymphadenopathy. Because an increased serum ACE level was observed, sarcoidosis was suspected and further investigations performed. The number of lymphocytes had also increased in the BALF (67%) and the CD4/CD8 ratio was significantly higher than normal (7.5). A histological examination of a specimen obtained by TBLB revealed epithelioid cell granuloma. FDG-PET CT showed an increased uptake in the hilus-mediastinal lymph node and thoracic spinal cord. An abnormal image suggesting extradural epithelioid cell granuloma was identified at the C7-Th8 levels of the thoracic spinal cord by MRI. The pain was thus suspected to have been caused by compression of the spinal cord due to the presence of the epithelioid cell granuloma. Oral administration of prednisolone (50mg/day) improved her symptoms as well as the findings on both FDG-PET CT and MRI.