Yuki Sasaki

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.

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI < 96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥ 96.8 (5-year OS, 61.2 vs. 84.4%, P < 0.001; 5-year PFS, 53.7 vs. 75.8%, P < 0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI < 96.8 than in those with a GNRI ≥ 96.8 (high-intermediate risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

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

A convenient prognostic score consisting of the Glasgow prognostic score and serum lactate dehydrogenase predicts clinical outcome in patients with diffuse large B-cell lymphoma

Yusuke Kanemasa, Tatsu Shimoyama, Yuki Sasaki, 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