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.

Current Treatment Patterns and the Role of Upfront Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma: A Korean Nationwide, Multicenter Prospective Registry Study (CISL 1404) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. @*Materials and Methods@#Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. @*Results@#A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. @*Conclusion@#The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. @*Materials and Methods@#We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. @*Results@#Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). @*Conclusion@#In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

2020 Korean guidelines for the management of metastatic prostate cancer

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

2020 Korean guidelines for the management of metastatic prostate cancer

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

The impact of primary tumor location in patients with metastatic colorectal cancer: a Korean Cancer Study Group CO12-04 study

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.

Successful Treatment of Relapsed Acquired Amegakaryocytic Thrombocytopenia with Repeat Cyclosporine / 대한내과학회지

Acquired amegakaryocytic thrombocytopenia (AAMT) is an unusual disease characterized by severe thrombocytopenia resulting from a marked decrease in bone marrow megakaryocytes. Various pathogenic mechanisms have been suggested, and several treatments have been tried, with varying outcomes. In some case reports, cyclosporine and anti-thymocyte globulin have had good clinical results in the treat of AAMT. There are few reports on the treatment of relapsed AAMT with cyclosporine. We report a patient with relapsed AAMT who was treated successfully with an additional course of cyclosporine. The initial remission was achieved with cyclosporine 4 years earlier and a second remission was induced by cyclosporine. Cyclosporine may be effective for relapsed AAMT that previously responded to cyclosporine.

Progression of Extramedullary Plasmacytoma in a Multiple Myeloma Patient with No Increment in Serum M Protein Level / 대한내과학회지

A 76 year-old female who was diagnosed with multiple myeloma (IgG, lambda) had received bortezomib, melphalan and prednisolone as first-line treatment. After completing six cycles of chemotherapy, her serum monoclonal protein level decreased from 7.28 g/dL to 0.65 g/dL, indicating a partial response. However, at the next scheduled visit she complained of slowly progressing dyspnea. On chest X-ray, newly developed pleural effusion was found, and rapidly progressing extramedullary plasmacytoma was detected in the anterior mediastinum on chest computerized tomography. However, there was no change in her serum monoclonal protein level. In Korea, extramedullary involvement is encountered in 5% of patients with multiple myeloma. However, evaluation of treatment response using solely the serum monoclonal protein level may not accurately reflect disease status in these patients.

Two Cases of Treatment with Intrathecal Rituximab for Primary Central Nervous System Lymphoma / 대한내과학회지

Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin's lymphoma (NHL), usually composed of diffuse large B-cells. Although rituximab is known for its curative effect on B-cell NHL, data on the use of intrathecal rituximab for PCNSL are limited. In this report, we present two patients showing relapsed PCNSL with lymphomatous meningitis. Both patients were refractory to conventional methotrexate-based intrathecal chemotherapy. However, after intrathecal rituximab with or without conventional intrathecal chemotherapy, both patients showed stable disease on magnetic resonance brain imaging and cerebrospinal fluid analysis. There were no serious adverse events during each of 3 and 6 cycles with intrathecal rituximab immunotherapy.

ThinPrep Cytological Findings of Desmoplastic Small Round Cell Tumor with Extensive Glandular Differentiation: A Case Study

Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive neoplasm. The cytological diagnosis of this tumor has only been reported in a few cases. In most of these cases, the diagnosis was made using fine-needle aspiration cytology. Most DSRCTs resemble disseminated carcinomatoses in their clinical manifestation as well as cytomorphologically, even in young-adult patients. These authors report a case of using peritoneal-washing and pleural-effusion ThinPrep cytology to diagnose DSRCT, with extensive glandular differentiation and mucin vacuoles. We found that fibrillary stromal fragment, clinical setting, and adjunctive immunocytochemical staining were most helpful for avoiding misdiagnosis.

Angiosarcomas of the Bilateral Breast and Heart: Which One is the Primary Site?

A 29-year-old pregnant woman with recurrent pericardial effusion and a cardiac tumor, diagnosed as an angiosarcoma, was treated with surgical resection of the tumor followed by radiotherapy. Immediately after completion of radiotherapy, she developed bilateral breast masses, which were also confirmed as angiosarcomas. We thought this might be the first case of bilateral angiosarcoma of the breast metastasizing to heart mimicking a primary cardiac angiosarcoma, although we could not conclude with certainty that angiosarcoma of the heart was not the primary site.

A Case of Histiocytic Sarcoma Presenting with Primary Bone Marrow Involvement

Histiocytic sarcoma (HS) is a very rare neoplasm that often shows an aggressive clinical course and systemic symptoms, such as fever, weight loss, adenopathy, hepatosplenomegaly and pancytopenia. It may present as localized or disseminated disease. We describe here a 63-yr-old male who manifested systemic symptoms, including fever, weight loss and generalized weakness. Abdominal and chest computed tomography failed to show specific findings, but there was suspicion of multiple bony changes at the lumbar spine. Fusion whole body positron emission tomography, bone scan and lumbar spine magnetic resonance imaging showed multiple bone lesions, suggesting a malignancy involving the bone marrow (BM). Several BM and bone biopsies were inconclusive for diagnosis. Necropsy showed replacement of the BM by a diffuse proliferation of neoplastic cells with markedly increased cellularity (95%). The neoplastic cells were positive for lysozyme and CD68, but negative for T- and B-cell lineage markers, and megakaryocytic, epithelial, muscular and melanocytic markers. Morphologic findings also distinguished it from other dendritic cell neoplasms.

Modified Number of Extranodal Involved Sites as a Prognosticator in R-CHOP-Treated Patients with Disseminated Diffuse Large B-Cell Lymphoma

BACKGROUND/AIMS: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP) has improved survival in patients with diffuse large B-cell lymphoma (DLBCL) and weakened the prognostic power of the international prognostic index (IPI). We evaluated the efficacy of the IPI and revised IPI (R-IPI) in patients with DLBCL who were treated with R-CHOP, focusing on extranodal site number (ENS) because extranodal involvement occurs frequently in Koreans. METHODS: A total of 126 R-CHOP-treated patients with stage III/IV DLBCL were analyzed. We performed a retrospective analysis of the clinicopathologic factors and verified the predictive power of the standard IPI and R-IPI. Various numbers of extranodal sites were analyzed for further stratification, and we set the extranodal site-modified IPI (E-IPI) as the IPI when the number of extranodal sites was stratified as or = 3. RESULTS: A univariate analysis showed that ENS was associated with complete response (CR, p = 0.04), event-free survival (EFS, p = 0.01), and overall survival (OS, p or = 3. A multivariate analysis revealed that an ENS > or = 3 remained associated with EFS (p or = 3, rather than the original or = 2, was the most significant prognostic factor for EFS and OS. All three indices were predictive, but only the E-IPI identified the high-risk group of R-CHOP-treated Korean patients with disseminated DLBCL.

Three Cases of Paragonimiasis in a Family

Paragonimiasis typically results from the consumption of raw or improperly cooked crustacea, especially crabs and crayfish. Although previously endemic in Korea, the prevalence of this disease decreased in the early 1970s because of educational campaigns and fewer intermediate hosts as a result of ecological changes. Recently, we were presented with a family where all members were infected with Paragonimus after ingestion of Kejang (= drunken crab). The mother was hospitalized for general myalgia and weakness first, followed by the father, who was hospitalized for dyspnea 2 month later. After the parents were diagnosed with paragonimiasis, we recommended their daughter to visit our hospital for a checkup, because they all had eaten freshwater crabs soaked in soybean sauce. She complained of generalized myalgia, fever, and pleuritic pain, and was also diagnosed with paragonimiasis. Peripheral blood of the 3 patients revealed hypereosinophilia, and computed tomography (CT) scans of their chests showed pleural effusion. The results of antibody tests by ELISA were positive for paragonimiasis. We report here the case series of familial paragonimiasis in a modern urban city, rather than in a typical endemic area.

VPDL Chemotherapy for T-cell Lymphoblastic Lymphoma (T-LBL) in Adults: Comparison with Upfront Autologous Stem Cell Transplantation in a Single Center / 대한혈액학회지

BACKGROUND: Treatment of T-cell lymphoblastic lymphoma (T-LBL) with CHOP or CHOP-like chemotherapy has resulted in poor long-term outcomes. High-dose chemotherapy followed by ASCT has been applied for this dreaded disease. However, the efficacy is still controversial. T-LBL is considered the nodal/extranodal presentation of acute lymphoblastic leukemia. Favorable results with VPDL chemotherapy have been reported in the setting of adult lymphoblastic leukemia. We, therefore, treated T-LBL patients with modified VPDL chemotherapy and compared the outcomes with those achieved using upfront ASCT. METHODS: We retrospectively reviewed the outcomes of 24 T-LBL patients treated either with upfront ASCT (n=11) or VPDL chemotherapy without ASCT (n=13) between January 1996 and October 2005. RESULTS: The median follow-up duration for surviving patients was 17 months (range, 5~109 months). The two-year event-free survival (EFS) rates were 83.1% in the VPDL group and 27.3% in the upfront ASCT group (P=0.008). The two-year overall survival (OS) rates were 83.9% in the VPDL group and 27.3% in the upfront ASCT group (P=0.006). CONCLUSION: This study suggests that VPDL chemotherapy is very effective and may be superior to upfront ASCT in the treatment of T-LBL patients.

A Case of Cryptococcal Osteomyelitis with Paraspinal Abscess

Cryptococcosis is a disseminated infection caused by Cryptococcus neoformans. It usually causes pulmonary infection and meningitis in immunocompromised patients. However, osteomyelitis due to C. neoformans is extremely rare. It is generally known that cryptococcal osteomyelitis is a complication of disseminated cryptococcosis, appearing in 5-10%. We experienced a case of cryptococcal osteomyelitis with paraspinal abscess in a liver transplant patient.

A Case of Cryptococcal Osteomyelitis with Paraspinal Abscess

Cryptococcosis is a disseminated infection caused by Cryptococcus neoformans. It usually causes pulmonary infection and meningitis in immunocompromised patients. However, osteomyelitis due to C. neoformans is extremely rare. It is generally known that cryptococcal osteomyelitis is a complication of disseminated cryptococcosis, appearing in 5-10%. We experienced a case of cryptococcal osteomyelitis with paraspinal abscess in a liver transplant patient.

A case of pancreatic intraepithelial neoplasm (PanIN-III) manifesting as recurrent pancreatitis / 대한내과학회지

Acute recurrent pancreatitis has a variety of etiologies. We experienced a case of a tumor-forming pancreatitis in a 49 year old Korean woman who also had pancreatic intraepithelial neoplasm III (PanIN-III), and this manifested just like recurrent pancreatitis. She had a history of recurrent pancreatitis. She was found to have an early stage of pancreatic cancer via computed tomography and magnetic resonance cholangiopancreatography. EUS guided fine needle aspiration (FNA) showed only many acinar cells of the pancreas. But due to the possibility of her having pancreatic carcinoma, she underwent distal pancreatectomy and splenectomy with lymph node dissection. Pathologically, the tumor of the pancreatic body showed secondary changes with focal fibrosis from the localized chronic pancreatitis. PanIN-III was observed in the pancreatic duct within the tumor, and there were no cancerous findings in the 13 dissected lymph nodes.

A Case of Nephrotic Syndrome after Thymectomy due to Thymoma / 대한신장학회지

Thymoma is often accompanied by different paraneoplastic syndrome, such as myasthenia gravis, pure red-cell aplasia, systemic lupus erythematosus. Association of glomerulonephritis and thymic tumor is very rare, with only about 40 cases reported to date. The authors report here a case of nephrotic syndrome after thymectomy due to thymoma. A 68-year-old man presented with continuous coughing and mediastinal mass. The mass was found to be a thymoma of type AB and was resected completely. One month after removal of the thymoma, nephrotic syndrome appeared. Renal biopsy revealed diffuse foot process effacement, suggesting minimal change disease (MCD), with a focus of intraglomerular coagulation, suggesting thrombotic microangiopathy. There was no evidence of other autoimmune disease or causes of the nephropathy. Treatment with 500 mg methylprednisolone IV for three days followed by oral 60 mg prednisolone daily was started. After six weeks, his nephrotic syndrome was almost improved. To our knowledge, this is the second report of a patient with thymoma and MCD in Korea.

Plasma Exchange in a Patient with a High Serum Methotrexate Level after High Dose-MTX Chemotherapy / 대한수혈학회지

High-dose methotrexate (MTX) is frequently used for the treatment for various malignancies. The primary route of MTX excretion is through the kidneys, and so it may cause toxicities in patients with renal insufficiency. Prolonged high levels of serum MTX can result in renal dysfunction, pancytopenia and mucositis, but the strategies used for MTX removal have not been universally accepted. We report here on a case of a 55-year-old man with NK cell lymphoma and who was treated with high-dose MTX. He had been receiving hemodialysis due to acute renal failure that was induced by previous chemotherapy. After 24, 48, and 72 hours of MTX infusion, the serum MTX levels were markedly increased to 146.07micromol/L, 111.30micromol/L and 94.37micromol/L, respectively, and so leucovorin rescue was intensified. Therapeutic plasma exchange (TPE) was started on post-MTX day 4, which was after the day of the peak MTX concentration, and this was continued on days 5 and 7 to rapidly reduce the MTX level. The serum MTX level decreased to the normal range without any rebound phenomenon after 2 weeks. However, MTX-induced pancytopenia occurred and the patient then died of septic shock. It is suggested that if the MTX level is very high in spite of conventional treatments, then immediate TPE should be started to avoid MTX toxicities.