Junghoon Shin

The Effect of Induction Chemotherapy Using Docetaxel, Cisplatin, and Fluorouracil on Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Meta-Analysis

Purpose The purpose of this study was to compare the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (CRT) alone with that of patients undergoing induction chemotherapy (IC) using docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by CRT. Materials and Methods A search of the PubMed, EMBASE, and Cochrane Library databases was performed in April 2015 and abstracts from the American Society of Clinical Oncology meetings (2008-2014) were reviewed. Summaries of the results were pooled using a fixed-effect model, and the risk of bias was evaluated using the Cochrane tool. Results A total of six relevant trials comprising 1,280 patients were identified. There was no statistically significant overall survival (OS) advantage for TPF prior to CRT (TPF/CRT) over CRT alone (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.79 to 1.09; p=0.339). Progression-free survival (PFS) was significantly longer in the TPF/CRT arms (HR, 0.82; 95% CI, 0.70 to 0.95; p=0.009). Patients with non-oropharyngeal LA-HNSCC obtained the greatest OS and PFS benefits from TPF (HR, 0.68; 95% CI, 0.47 to 0.99; p=0.043 and HR, 0.67; 95% CI, 0.48 to 0.94; p=0.022, respectively). The complete response rate was significantly increased (risk ratio [RR], 1.34; 95% CI, 1.14 to 1.56; p < 0.001), and the distant metastasis rate tended to decrease (RR, 0.65; 95% CI, 0.40 to 1.04; p=0.071) in the TPF/CRT arms. Conclusion IC with TPF followed by CRT is not superior to CRT alone for OS. However, PFS and the complete response rate were significantly improved in the TPF/CRT arms. TPF/CRT for patients with nonoropharyngeal LA-HNSCC provided clear survival advantages.

Prognostic Impact of Newly Proposed M Descriptors in TNM Classification of Non–Small Cell Lung Cancer

Introduction: The International Association for the Study of Lung Cancer recently proposed new M descriptors for the next edition of the TNM classification for NSCLC, subdividing the current M1b category into two subcategories: M1b, which indicates a solitary extrathoracic metastasis in a single organ, and M1c, which indicates multiple extrathoracic metastasis. The purpose of this study was to validate the prognostic value of the newly proposed M descriptors in an independent cohort with multivariate and subgroup analysis. Methods: A total of 1024 patients in a consecutive lung cancer database who had stage IV NSCLC treated between 2011 and 2014 were analyzed. Newly proposed M staging was used for classification and comparison of survival. Adjustment for other clinical covariates and subgroup analysis was conducted. Results: According to the newly proposed M descriptors, 262 patients (25.6%), 152 patients (14.8%), and 610 patients (59.6%) were classified into the subgroups M1a, M1b, and M1c, respectively. The median overall survival times were 22.5, 17.8, and 13.6 months for the M1a, M1b, and M1c groups, respectively (p < 0.001). After adjustment for other covariates, Cox proportional hazards regression revealed statistically significantly shorter overall survival for the M1b group than for the M1a group (hazard ratio = 1.30; 95% confidence interval: 1.03–1.65, p = 0.03) and for the M1c than the M1b group (hazard ratio = 1.57; 95% confidence interval: 1.28–1.93, p < 0.001). These differences showed a consistent tendency regardless of pathologic and molecular subtypes. Conclusions: The newly proposed M descriptors have prognostic value in patients with stage IV NSCLC.

Human Herpesvirus 8–Unrelated Primary Effusion Lymphoma–Like Lymphoma in an Elderly Korean Patient with a Good Response to Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin’s lymphoma arising from a B-cell lineage characterized by the formation of malignant effusion in body cavities without evidence of a detectable tumor. The effusion contains tumor cells universally infected with human herpesvirus 8 (HHV8), which is the critical factor differentiating PEL from HHV8-unrelated PEL-like lymphoma (PEL-LL). This report describes a 77-year-old male patient with pleural effusion and ascites, containing lymphoma cells expressing a B-cell phenotype, but without markers of HHV8 in immunocytochemical analysis. The patient was diagnosed with PEL-LL and treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), which resulted in a complete remission. The patient is currently disease-free 15 months post-treatment. To the best of our knowledge, this is the first report on administration of R-CHOP in a PEL-LL patient in South Korea.

Oncogenic effects of germline mutations in lysosomal storage disease genes

Introduction Lysosomal storage diseases (LSDs) comprise inborn metabolic disorders caused by mutations in genes related to lysosomal function. As already observed in certain LSDs, the accumulation of macromolecules caused by lysosomal dysfunction may facilitate carcinogenesis. Methods Using whole genome sequencing data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network (Pan-Cancer cohort) and the 1000 Genomes project (1000 Genomes cohort), we analyzed the association between potentially pathogenic variants (PPVs) in 42 LSD genes and cancer. We evaluated age at diagnosis of cancer and patterns of somatic mutation and gene expression according to the PPV carrier status. Results PPV prevalence in the Pan-Cancer cohort was significantly higher than that of the 1000 Genomes cohort (20.7% versus 13.5%, P=8.7×10−12). Cancer risk was increased in individuals with a greater number of PPVs. Population structure-adjusted SKAT-O analysis revealed 37 significantly associated cancer type-LSD gene pairs. These results were validated using the ExAC cohort as an independent control. Cancer developed earlier in carriers of PPVs in pancreatic adenocarcinoma (MAN2B1, GALNS, and GUSB), skin cancer (NPC2), and chronic myeloid disorder (SGSH) as well as in the Pan-Cancer cohort. Analysis of RNA-Seq data from the pancreatic cancer cohort revealed 508 genes differentially expressed according to the PPV carrier status, which were highly enriched in the known core signaling pathways of pancreatic cancer. Conclusion Carriers of germline PPVs in LSD genes have an increased incidence of cancer. The available therapeutic options to restore lysosomal function suggest the potential of personalized cancer prevention for these patients.

A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea

Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML‐CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24‐month cumulative MR4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per‐patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR4, and MR4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML‐CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511.

Clinicopathological characteristics of extremely young Korean multiple myeloma patients: Therapeutic implications

Background/Aims Although multiple myeloma (MM) is typically a disease of the elderly, a certain subset of extremely young patients exists. It is necessary to establish clinicopathological characteristics for this population. Methods We reviewed the medical records of MM patients whose age was 40 years or younger at diagnosis. Results A total of 32 patients were analyzed (male to female ratio 19:13, median age 37 years). According to International Staging System, 29%, 48%, and 16% were in stage I, II, and III, respectively. Light chain myeloma accounted for 30%. Clinically significant anemia, hypercalcemia, azotemia, and hypoalbuminemia were present in 29%, 28%, 13%, and 28%, respectively. Three or more lytic bone lesions were detected in 45% of the patients, whereas 13% had no lytic bone lesions. Regarding treatment, 79% of patients received autologous hematopoietic stem cell transplantation. After a median follow-up duration of 64 months, the 1-, 3-, and 5-year overall survival (OS) rates were 84%, 62%, and 54%, respectively. The median OS was 61 months for the entire cohort. Conclusions In our study, MM patients aged 40 years or younger at diagnosis showed no superior survival compared to those of the moderately elderly patients based on historical data.

G.P.286

In silico prediction tools for genetic variation have now become the commodity in genetic analysis. Each tool utilizes their own algorithm to give us the results. Dysferlin (DYSF) is a transmembrane protein, crucial for sarcolemmal repair, and its recessive genetic defects bring about progressive muscular weakness either as Miyoshi distal myopathy or limb girdle muscular dystrophy 2B. The Leiden database lists one of the most corroborating data set on the pathogenicity of each genotype in the field of muscular dystrophy. In this study, we compared the in silico analysis results and the published pathogenicity of the dysferlin mutations listed on Leiden database. We suggest a new cut-off value that can be optimally used to test a new mutation with in silico tools. We used PROVEAN and SIFT online software to predict a possibly damaging mutation. This is a prediction tool used mainly to test the impact on the biological function of a protein by a missense mutation or amino acid substitution. We used the Leiden open variation database on dysferlin mutations and utilized the complete sequence variants data provided by the website. PROVEAN tool showed a remarkably better result to test dysferlin nonsense mutations than SIFT tool. On using PROVEAN tool for dysferlin missense mutation, we propose a new cut-off value of −5.365. Individualized cut-off values for other genes will expand the usefulness of in silico prediction tools.