A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. @*Materials and Methods@#Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. @*Results@#After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. @*Conclusion@#Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

Clinical Characteristics of Clear Cell Ovarian Cancer: A Retrospective Multicenter Experience of 308 Patients in South Korea / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in earlystage. @*Materials and Methods@#Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected. @*Results@#Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence. @*Conclusion@#Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in management of peritoneal carcinomatosis: Single center experience in Korea

PURPOSE: Peritoneal carcinomatosis (PC) has been considered a terminal condition and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIEPC) is regarded as an alternative therapeutic option. This study aimed to evaluate the 30-day clinical outcomes of CRS/HIPEC and the feasibility of the surgery by investigating the morbidity and mortality in Inje University Hospital.METHODS: Data were retrospectively collected from 19 patients with PC who underwent CRS/HIPEC at Inje University Hospital in 2018. We evaluated pre-, intra-operative parameters and postoperative clinical outcomes and early complications.RESULTS: The mean operating time was 506.95 minutes and the mean blood loss was 837.11 mL. Six cases (31.58%) had morbidity of grade III or above. A longer operating time (≥560 minutes, P=0.038) and large blood loss (≥700 mL, P=0.060) were positively correlated with grade III or worse postoperative complications.CONCLUSION: Our early experience with CRS/HIPEC resulted in a 31.58% morbidity rate of grade III and above, with risk factors being longer operating time and greater intraoperative blood loss. As the surgical team's skills improve, a shorter operating time with less intraoperative blood loss could result in better short-term outcomes of CRS/HIPEC.

S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Thapsigargin Increases IL-2 Production in T Cells at Nanomolar Concentrations

Thapsigargin (TGN) is a potent and selective inhibitor of sarco-endoplasmic Ca²⁺-ATPase, leading to rapid elevation of cytoplasmic Ca2+ concentration. Previous reports have shown that TGN increases the production of various cytokines from macrophages and dendritic cells. Here, we examine the effects of TGN on murine T cells. Nanomolar concentrations of TGN are a significant inducer of IL-2 production with full activity at 50 nM. Micromolar concentrations of TGN, however, are inhibitory to IL-2 production and T cell proliferation. The IL-2 production-inducing activity of TGN is much more prominent when T cells are primed with concanavalin A or anti-CD3 mAb, and is due to the increase of cytoplasmic Ca²⁺ concentration. TGN at 50 nM does not affect interferon-gamma or IL-4 production from T cells. Thus, the present study shows that low nanomolar concentrations of TGN could be useful in potentiating IL-2 production from antigen-primed T cells.

Retrospective analysis of palliative chemotherapy for the patients with bladder adenocarcinoma: Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee

BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. RESULTS: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.

A case of synchronous multiple myeloma and chronic myeloid leukemia

No abstract available.

Treatment outcomes of IMEP as a front-line chemotherapy for patients with peripheral T-cell lymphomas

BACKGROUND: This study aimed to assess the treatment outcomes of ifosphamide, mesna, etoposide, and prednisolone (IMEP) combination regimen as a front-line chemotherapy in patients with peripheral T-cell lymphomas (PTCLs). METHODS: Clinical data of 38 newly diagnosed PTCLs patients who underwent IMEP at Busan Paik Hospital from January 2002 to December 2013 were retrospectively analyzed. RESULTS: The overall response rate was 68.5%, with 21 (55.3%) complete response/complete response unconfirmed and 6 (15.8%) partial response (PR). The median follow-up duration was 25.5 months (range, 0.2-87.3). The median overall survival was not reached and 2-year survival rate was 67%. The median progression free survival was 23 months. The most frequently reported adverse effects higher than grade 3 were hematologic toxicities including neutropenia (68.4%), thrombocytopenia (42.1%). There was no treatment-related mortality. CONCLUSION: IMEP regimen is effective and safe as a front-line chemotherapy in patients with PTCLs.

Mixed-phenotype acute leukemia treated with decitabine

No abstract available.

Efficacy and Toxicity of Mammalian Target Rapamycin Inhibitors in Patients with Metastatic Renal Cell Carcinoma with Renal Insufficiency: The Korean Cancer Study Group GU 14-08 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the efficacy and toxicity of mammalian target rapamycin inhibitors in Korean patients with metastatic renal cell carcinoma (mRCC) with chronic renal insufficiency not requiring dialysis. MATERIALS AND METHODS: Korean patients with mRCC and chronic renal insufficiency not requiring dialysis treated with everolimus or temsirolimus between January 2008 and December 2014 were included. Patient characteristics, clinical outcomes, and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) durations were evaluated according to the degree of renal impairment. RESULTS: Eighteen patients were considered eligible for the study (median age, 59 years). The median glomerular filtration rate was 51.5 mL/min/1.73 m². The best response was partial response in six patients and stable disease in 11 patients. The median PFS and OS durations were 8 months (95% confidence interval [CI], 0 to 20.4) and 32 months (95% CI, 27.5 to 36.5), respectively. The most common non-hematologic and grade 3/4 adverse events included stomatitis, fatigue, flu-like symptoms, and anorexia as well as elevated creatinine level. CONCLUSION: Mammalian target rapamycin inhibitors were efficacious and did not increase toxicity in Korean patients with mRCC and chronic renal insufficiency not requiring dialysis.

Induction of Potent Antigen-specific Cytotoxic T Cell Response by PLGA-nanoparticles Containing Antigen and TLR Agonist

Previously we showed that biodegradable nanoparticles containing poly-IC or CpG oligodeoxynucleotide (ODN) together with ovalbumin (OVA) were efficient at inducing MHC-restricted presentation of OVA peptides in dendritic cells. The CTL-inducing activities of the nanoparticles were examined in the present study. Nanoparticles containing poly-IC or CpG ODN together with OVA were prepared using biodegradable polymer poly(D,L-lactic acid-co-glycolic acid), and then were opsonized with mouse IgG. The nanoparticles were injected into the tail vein of mice, and 7 days later the OVA-specific CTL activities were measured using an in vivo CTL assay. Immunization of mice with the nanoparticles containing poly-IC or CpG ODN together with OVA elicited potent OVA-specific CTL activity compared to those containing OVA only. In accordance with these results, nanoparticles containing poly-IC or CpG ODN together with OVA exerted potent antitumor activity in mice that were subcutaneously implanted with EG7.OVA tumor cells. These results show that encapsulation of poly-IC or CpG ODN together with antigen in biodegradable nanoparticles is an effective approach for the induction of potent antigen-specific CTL responses in vivo.

Nanoliposomes of L-lysine-conjugated poly(aspartic acid) Increase the Generation and Function of Bone Marrow-derived Dendritic Cells

BACKGROUND: Biodegradable polymers have increasingly been recognized for various biological applications in recent years. Here we examined the immunostimulatory activities of the novel poly(aspartic acid) conjugated with L-lysine (PLA). METHODS: PLA was synthesized by conjugating L-lysine to aspartic acid polymer. PLA-nanoliposomes (PLA-NLs) were prepared from PLA using a microfluidizer. The immunostimulatory activities of PLA-NLs were examined in mouse bone marrow-derived dendritic cells (BM-DCs). RESULTS: PLA-NLs increased the number of BM-DCs when added to cultures of GM-CSF-induced DC generation on day 4 after the initiation of cultures. Examination of the phenotypic properties showed that BM-DCs generated in the presence of PLA-NLs are more mature in terms of the expression of MHC class II molecules and major co-stimulatory molecules than BM-DCs generated in the absence of PLA-NLs. In addition, the BM-DCs exhibited enhanced capability to produce cytokines, such as IL-6, IL-12, TNF-alpha and IL-1beta. Allogeneic mixed lymphocyte reactions also confirmed that the BMDCs were more stimulatory on allogeneic T cells. PLA- NL also induced further growth of immature BM-DCs that were harvested on day 8. CONCLUSION: These results show that PLA-NLs induce the generation and functional activities of BM-DCs, and suggest that PLA-NLs could be immunostimulating agents that target DCs.

Nanoliposomes of L-lysine-conjugated poly(aspartic acid) Increase the Generation and Function of Bone Marrow-derived Dendritic Cells

BACKGROUND: Biodegradable polymers have increasingly been recognized for various biological applications in recent years. Here we examined the immunostimulatory activities of the novel poly(aspartic acid) conjugated with L-lysine (PLA). METHODS: PLA was synthesized by conjugating L-lysine to aspartic acid polymer. PLA-nanoliposomes (PLA-NLs) were prepared from PLA using a microfluidizer. The immunostimulatory activities of PLA-NLs were examined in mouse bone marrow-derived dendritic cells (BM-DCs). RESULTS: PLA-NLs increased the number of BM-DCs when added to cultures of GM-CSF-induced DC generation on day 4 after the initiation of cultures. Examination of the phenotypic properties showed that BM-DCs generated in the presence of PLA-NLs are more mature in terms of the expression of MHC class II molecules and major co-stimulatory molecules than BM-DCs generated in the absence of PLA-NLs. In addition, the BM-DCs exhibited enhanced capability to produce cytokines, such as IL-6, IL-12, TNF-alpha and IL-1beta. Allogeneic mixed lymphocyte reactions also confirmed that the BMDCs were more stimulatory on allogeneic T cells. PLA- NL also induced further growth of immature BM-DCs that were harvested on day 8. CONCLUSION: These results show that PLA-NLs induce the generation and functional activities of BM-DCs, and suggest that PLA-NLs could be immunostimulating agents that target DCs.

Immunomodulatory Effects of Hypocrellin A on MHC-restricted Antigen Processing

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the H-2K(b)-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.

Novel Sunitinib Strategy in Metastatic Renal Cell Carcinoma on Hemodialysis: Intermittent Dose of Sunitinib after Hemodialysis / Journal of the Korean Cancer Association, 대한암학회지

The proper dose and schedule of sunitinib have yet to be established for patients with metastatic renal cell carcinoma (RCC) on hemodialysis. We reviewed two patients with metastatic RCC on hemodialysis who had been treated with sunitinib in Yonsei Cancer Center, Yonsei University College of Medicine. Fifty milligrams of sunitinib was administered intermittently after each hemodialysis session (3 or 4 times a week). Overall responses were partial response in both cases. Progression-free survivals were 16 and 6 months, respectively, at the time of reporting (April 2010). Both subjects tolerated the treatment.

Clinicopathologic Features of Metachronous or Synchronous Gastric Cancer Patients with Three or More Primary Sites / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated the clinicopathologic information of patients with gastric cancer with multiple primary cancers (GC-MPC) of three or more sites. MATERIALS AND METHODS: Between 1995 and 2009, 105,908 patients were diagnosed with malignancy at Severance Hospital, Yonsei University Health System. Of these, 113 (0.1%) patients with MPC of three or more sites were registered, and 41 (36.3%) of these were GC-MPC. We retrospectively reviewed the clinical data and overall survival using the medical records of these 41 GC-MPC patients. We defined synchronous cancers as those occurring within 6 months of the first primary cancer, while metachronous cancers were defined as those occurring more than 6 months later. RESULTS: Patients with metachronous GC-MPC were more likely to be female (p=0.003) and young than patients with synchronous GC-MPC (p=0.013). The most common cancer sites for metachronous GC-MPC patients were the colorectum, thyroid, lung, kidney and breast, while those for synchronous GC-MPC were the head and neck, esophagus, lung, and kidney. Metachronous GC-MPC demonstrated significantly better overall survival than synchronous GC-MPC, with median overall survival durations of 4.7 and 14.8 years, respectively, and 10-year overall survival rates of 48.2% and 80.7%, respectively (p<0.001). CONCLUSION: Multiplicity of primary malignancies itself does not seem to indicate a poor prognosis. The early detection of additional primary malignancies will enable proper management with curative intent.

Hodgkin's Lymphoma-like Posttransplantation Lymphoproliferative Disorder after Allogeneic Hematopoietic Stem Cell Transplantation / 대한혈액학회지

Hematopoietic stem cell transplantation (HSCT) recipients have a risk of post-transplant lymphoproliferative disorder (PTLD), which normally develops in Epstein-Barr virus (EBV) transformed donor B lymphocytes. The incidence of Hodgkin's lymphoma (HL) ranges from 1.8% to 3.4% of PTLD after HSCT. There are no case reports of early onset HL-like PTLD that developed less than one year after HSCT. We encountered a case of early onset PTLD after an unrelated HSCT following reduced-intensity conditioning with cyclophosphamide/fludarabine/thymoglobulin. A 24 year old patient with severe aplastic anemia developed multiple lymphadenopathies at day 95 after HSCT. The excisional biopsy revealed HL-like PTLD, which tested positive to immunohistochemical staining for the EBV. The Ann Arbor stage was IIA. Immunosuppressive agents were discontinued for 2 weeks in order to induce a graft-versus-lymphoma effect without a response. A total 4 cycles of chemotherapy with doxorubicin (adriamycin)/bleomycin/ vinblastine/dacarbazine (ABVD) and radiotherapy (total dosage 3,400 cGy) were then carried out. The response to salvage treatment was complete remission. The patient showed no evidence of the disease at the follow-up performed 32 months after HSCT.

Gemcitabine, Etoposide, Cisplatin, and Dexamethasone in Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma

BACKGROUND/AIMS: To date, an effective salvage chemotherapy regimen for the treatment of refractory or relapsing non-Hodgkin's lymphoma (NHL) has not been discovered. This study was conducted to evaluate the efficacy and safety of gemcitabine, etoposide, cisplatin, and dexamethasone in relapsed or refractory NHL patients. METHODS: All patients had histologically proven relapsed or refractory NHL. Treatments consisted of gemcitabine 700 mg/m2 by continuous i.v. on days 1 and 8; etoposide 40 mg/m2 by i.v. on days 1-4; cisplatin 60 mg/m2 by i.v. on day 1; or dexamethasone 40 mg by i.v. on days 1-4 (GEPD) every 21 days. The primary end point was the patient response rate following two cycles of treatment. After two cycles, stem cells were harvested using mobilizing regimens (ESHAP or GEPD plus filgrastim), and this was followed by autologous stem cell transplantation or four additional cycles of GEPD. RESULTS: Between January 2005 and January 2006, 20 patients (13 males and 7 females) were enrolled in the study. The median age was 53 (range 16-75) years. The most common histology was diffuse large B-cell lymphoma (n=10). The median follow-up duration was 5.2 (range 1.0-16.0) months. After two cycles, the overall response rate was 50.0% (10/20), including two complete responses and eight partial responses. The doselimiting toxicity was myelosuppression. Grade IV neutropenia and thrombocytopenia occurred in 13 (65.0%) and 6 patients (30.0%), respectively. The median number of CD34-positive cells collected was 6.0 (range, 2.8-11.6)x10(6)/kg. Of the 17 patients < 66 years of age, 4 (23.5%) proceeded to autologous stem cell transplantation. CONCLUSIONS: GEPD chemotherapy in patients with refractory or relapsed NHL was effective as a salvage therapy and helpful for stem cell harvest followed by autologous transplantation.

Primary Isolated Bone Marrow Diffuse Large B-cell Lymphoma with Hemolytic Anemia as the First Manifestation / 대한혈액학회지

Primary isolated bone marrow disease as a presenting feature of diffuse large B-cell lymphoma is very rare. We describe the first Korean case of isolated bone marrow diffuse large B-cell lymphoma with hemolytic anemia as the first manifestation. A32-year-old man was admitted to our hospital presenting with fever and hematuria. He had severe anemia and high lactate dehydrogenase activity. His peripheral blood smear and laboratory findings were suggestive of intravascular hemolytic anemia. The bone marrow biopsy revealed involvement with diffuse large B-cell lymphoma. A computed tomographic scan showed splenomegaly, but no lymphadenopathy. Our case shared some clinical features with the Asian variant of intravascular B-cell lymphoma, but there was infrequent involvement of the sinusoids of lymphoma cells and no hemophagocytosis. Our patient was treated with R-CHOP regimen for six cycles and he is in remission after autologous peripheral blood stem cell transplantation.

A Case of Multiple Metastatic Renal Cell Carcinoma in an Adult Patient Presenting with Ventricular Tachycardia

Cardiac metastases of renal cell carcinomas are rare, and usually clinically silent. A case of a 53-year-old man without a significant medical history, who presented with ventricular tachycardia, which resulted in a cardiac mass of the right ventricle is reported. On chest X-ray, echocardiography, CT scanning, esophagogastroduode-noscopy and MRI, multiple metastatic masses were observed in both lungs, and the kidneys, adrenal, stomach and right ventricle. The kidney mass and the gastric polyp were revealed on biopsy to be a renal cell carcinoma mixed with sarcomatoid and conventional types.