Miho Tamura

The impacts of initial and relative dose intensity of R-CHOP on outcomes of elderly patients with diffuse large B-cell lymphoma

Yusuke Kanemasa, Tatsu Shimoyama, Yuki Sasaki, Miho Tamura, Takeshi Sawada, Yasushi Omuro, Tsunekazu Hishima and Yoshiharu Maeda Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; Department of Clinical Research Support, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan

Beta-2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B-cell lymphoma

Previous reports have evaluated the prognostic value of serum beta‐2 microglobulin (B2MG) level in patients with non‐Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B‐cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression‐free survival than those with a B2MG level <3.2 mg/L (3‐year OS, 50.9% vs. 89.4%, p < 0.001; 3‐year progression‐free survival, 45.3% vs. 79.7%, p < 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four‐risk groups: low (L, 0 factor), low‐intermediate (LI, 1–2 factors), high‐intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network‐International Prognostic Index (5‐year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B‐cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B‐cell lymphoma patients treated with R‐CHOP or R‐CHOP–like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m2), 58 (14.3%); normal weight (≥18.5 to <25 kg/m2), 262 (64.5%); overweight (≥25 to <30 kg/m2), 75 (18.5%); and obese (≥30.0 kg/m2), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5‐y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m2) had significantly inferior OS than those with a high BMI (≥25 kg/m2) (5‐y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5‐y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age.

Significant response to ramucirumab monotherapy in chemotherapy‑resistant recurrent alpha‑fetoprotein‑producing gastric cancer: A case report

Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is a relatively rare type of gastric cancer characterized by a high incidence of liver and lymph node metastases, and a poor prognosis. Few advanced AFPGC cases treated successfully with conventional chemotherapy have been reported thus far. Although the development of molecular-targeted therapy has improved the prognosis of various types of cancer, there are currently no tailored therapies for AFPGC. In the present report, the case of a chemotherapy-resistant recurrent AFPGC patient who exhibited a significant response to ramucirumab monotherapy is presented. Following six doses of ramucirumab, a metastatic lymph node displayed central necrosis, and the patients serum AFP levels decreased from 12,800 to 225 ng/ml. AFPGC is known to have increased vascular endothelial growth factor (VEGF) expression and rich neovascularization. Furthermore, in the present case, tumor cells were positive for VEGF. Ramucirumab is a monoclonal antibody for VEGF receptor-2 and the first anti-angiogenic drug approved for the treatment of advanced gastric cancer. However, the clinical efficacy of ramucirumab in patients with AFPGC has not been reported previously. The present report suggests that AFP production in gastric cancer can be a predictor for the response to anti-angiogenic drugs such as ramucirumab.

Early measurement of urinary N-acetyl-β-glucosaminidase helps predict severe hyponatremia associated with cisplatin-containing chemotherapy

BACKGROUND Although cisplatin is a widely used anticancer drug for treating various types of cancer, its clinical application is limited by severe systemic toxicities, such as nephropathy, hematologic toxicity, and gastrointestinal toxicity. There are no reliable and validated biomarkers to predict adverse events caused by cisplatin. METHODS Sixty-six patients who underwent cisplatin-containing first-line chemotherapy between June 2010 and November 2013 were retrospectively analyzed. Data on urinary N-acetyl-β-glucosaminidase activities measured 24-48 h after cisplatin infusion were retrieved, and adverse events during the first course of chemotherapy were recorded according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS Patient characteristics were: male/female 60/6, median age 65 (range 36-78) years, esophageal/gastric/other cancer 60/4/2, chemotherapy regimen docetaxel-cisplatin-fluorouracil/fluorouracil-cisplatin/S-1-cisplatin 54/8/4, cisplatin dose (mg/sm) 60/70/80 16/43/7. Grade 3/4 adverse events were leukopenia (40.9%), neutropenia (54.4%), febrile neutropenia (37.9%), hyponatremia (28.8%), and acute kidney injury (37.9%). Patients with 20 units/gram creatinine or higher urinary N-acetyl-β-glucosaminidase developed statistically lower minimum serum sodium concentration (median 126 vs. 134 mEq/L, p = 0.0053). There were no significant correlations between urinary N-acetyl-β-glucosaminidase and the development of other severe adverse events. CONCLUSION Early significant increase in urinary N-acetyl-β-glucosaminidase predicts subsequent development of severe hyponatremia after cisplatin-containing chemotherapy.

Chemotherapy for alpha-fetoprotein producing gastric cancers expressing human epidermal growth factor receptor 2

Although, gastric cancer is one of the most common cancers worldwide, alpha-fetoprotein (AFP) producing human epidermal growth factor receptor 2 (HER2) positive gastric cancers are rare. AFP producing gastric cancer has a poor prognosis and an appropriate treatment option has not been established to date. A 75-year-old woman with AFP- producing gastric cancer was treated with S-1, an oral fluoropyrimidine derivative, chemotherapy after distal gastrectomy. Recurrence of gastric cancer was observed after 18 months and immunohistochemistry analysis showed AFP and HER2 positive gastric cancer. The patient received combination therapy containing capecitabine, cisplatin, and trastuzumab. Computed tomography scans showed regression of the lymph node metastasis. The patients quality of life substantially improved after the treatment. Thus, the present case suggests that AFP and HER2 positive gastric cancer can be effectively treated with, capecitabine, cisplatin, and trastuzumab combination therapy.

O1-16-3Prognostic significance of CD30 expression in patients with diffuse large B-cell lymphoma

The comprehensive genomic analysis by Next generation sequencing can make us find many oncodriver gene mutations. And at the same time, we can find many gene structural mutations outside of oncodriver gene mutations. Most of such gene mutations are not identified about the pathologic significance, so that they are called variants of uncertain significant (VUS) gene mutations. And evaluations of their function are important for patient treatment. Recently, we had experienced an adult pancreatoblastoma case. Using commercially available the cancer panel, OncoDeep, we found a missense mutation in APC gene, which has not been reported in the UMD-APC mutations database. Immunohistochemically analysis revealed nuclear accumulation of the b-catenin protein. Because CTNNB1 was not mutated in this case, these results indicated that the missense mutation of APC lost its function and caused Wnt signal activation. To identify the structure mutation of APC gene in germ line, we have done target sequence of DNA extracted from oral mucosa. We found heterozygous of APC gene. It was assumed that loss of heterozygosis of APC gene causes Wnt signal activation in pancreatoblastoma cells in this case. The patient harboring pathological APC gene mutations in germ line generally develop colon polyposis, but this patient did not have the past history of colon polyposis. To make clear the APC mutation we found in this case causes functional loss, we have done functional assay with cell line model. The results indicated the APC gene mutation in this case causes partial loss of suppression of Wnt signal activation. This is a very important case report in NGS era in which we found many VUS gene mutations. We will present detail analyzed data together with clinical course.

O1-13-1Retrospective analysis of peripheral T cell lymphomas

Satoshi Kaito, Yusuke Kanemasa, Yuki Sasaki, Toshihiro Okuya, Tsukasa Yamaguchi, Miho Tamura, Tatsu Shimoyama, Yashshi Omuro, Tunekazu Hishima, Yoshiharu Maeda Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan, Department of Clinical Research Support, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan, Department of pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan