Treatment pattern of chronic lymphocytic leukemia/small lymphocytic lymphoma in Korea: a multicenter retrospective study (KCSG LY20-06)

Background/Aims@#Little attention is paid to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Korea due to the rarity of the disease. With its rising incidence, we aimed to evaluate recent changes in treatment patterns and survival outcomes of patients with CLL/SLL. @*Methods@#A total of 141 patients diagnosed with CLL/SLL between January 2010 and March 2020 who received systemic therapy were analyzed in this multicenter retrospective study. @*Results@#The median patient age was 66 years at diagnosis, and 68.1% were male. The median interval from diagnosis to initial treatment was 0.9 months (range: 0–77.6 months), and the most common treatment indication was progressive marrow failure (50.4%). Regarding first-line therapy, 46.8% received fludarabine, cyclophosphamide, plus rituximab (FCR), followed by chlorambucil (19.9%), and obinutuzumab plus chlorambucil (GC) (12.1%). The median progression-free survival (PFS) was 49.3 months (95% confidence interval [CI], 32.7–61.4), and median overall survival was not reached (95% CI, 98.4 mo– not reached). Multivariable analysis revealed younger age (≤ 65 yr) (hazard ratio [HR], 0.46; p < 0.001) and first-line therapy with FCR (HR, 0.64; p = 0.019) were independently associated with improved PFS. TP53 aberrations were observed in 7.0% (4/57) of evaluable patients. Following reimbursement, GC became the most common therapy among patients over 65 years and second in the overall population after 2017. @*Conclusions@#Age and reimbursement mainly influenced treatment strategies. Greater effort to apply risk stratifications into practice and clinical trials for novel agents could help improve treatment outcomes in Korean patients.

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.

Comparison of three risk stratification models for non-clear cell renal cell carcinoma patients treated with temsirolimus as first-line therapy

Background/Aims@#For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. @*Methods@#This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. @*Results@#Twenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). @*Conclusions@#All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

Function of hepatocyte growth factor in gastric cancer proliferation and invasion / 영남의대학술지

Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N’-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.

Rapid progression from trochlear nerve palsy to orbital apex syndrome as an initial presentation of advanced gastric cancer / 영남의대학술지

The most cases with orbital metastases have been reported in patients with a prior established diagnosis of cancer and widespread systemic involvement. However, ocular symptoms can be developed as an initial presentation of cancer in patients without cancer history. We report a case of rapid progression from trochlear nerve palsy to orbital apex syndrome as an initial presentation of advanced gastric cancer.

Rapid progression from trochlear nerve palsy to orbital apex syndrome as an initial presentation of advanced gastric cancer / 영남의대학술지

The most cases with orbital metastases have been reported in patients with a prior established diagnosis of cancer and widespread systemic involvement. However, ocular symptoms can be developed as an initial presentation of cancer in patients without cancer history. We report a case of rapid progression from trochlear nerve palsy to orbital apex syndrome as an initial presentation of advanced gastric cancer.

Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data. MATERIALS AND METHODS: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016. RESULTS: A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patients was 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment. CONCLUSION: Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.

Rare Presentation of Richter's Transformation to Diffuse Large B Cell Lymphoma: a Case Report / 대한내과학회지

Richter's syndrome refers to the development of aggressive lymphoma in a patient with chronic lymphocytic leukemia (CLL). It occurs in about 2% to 10% of patients with CLL. The most frequent manifestation of Richter's syndrome is diffuse large B cell lymphoma (DLBCL). Extranodal involvement is rare but can occur. The prognosis of Richter's syndrome is very poor. We herein report a case of a rare presentation of Richter's syndrome. A 42-year-old man diagnosed with CLL 2 years previously developed nodules on the bilateral thighs and buttocks. A positron emission tomography (PET)-CT scan revealed high fluorodeoxyglucose uptake in multiple lymph nodes, skeletal muscles, and the myocardium. An ultrasonography-guided biopsy confirmed Richter's syndrome from CLL to DLBCL. The patient was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. After six cycles of chemotherapy, we performed a PET-CT scan that revealed a complete response. However, 3 months later, the syndrome recurred. The patient was undergoing salvage chemotherapy at the time of this writing.

Metastatic eyelid cancer from gastric adenocarcinoma / 영남의대학술지

Gastric cancer is the most common cancer in Korean males and can easily spread to distant organs such as the liver, lungs, brain, or bones. However, skin metastasis, particularly of the eye, is rare. Metastatic eyelid cancer is extremely rare; metastases from internal organs have not been reported so far. We recently experienced a patient with metastatic eyelid cancer from adenocarcinoma of the stomach. A 62-year-old female was admitted with a right upper eyelid mass and foreign body sensation. She had a history of stomach cancer of 3 years. She was treated by chemotherapy and radiotherapy for pathologic fracture. After receiving supportive care for 2 years, the mass appeared on her right pupil. Punch-biopsy of the mass was performed and histological examination revealed adenocarcinoma, the same as the initial histological result. We report this case with a review of related literature.

Immune thrombocytopenia associated with sarcoidosis / 영남의대학술지

Sarcoidosis is a systemic disease of unknown cause involving multiple organs and is characterized by noncaseating granuloma. Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased peripheral platelet destruction due to the presence of an antibody to the platelet and abnormal platelet production. There is no known pathogenesis that occurs concurrently with ITP and sarcoidosis. However, considering together of 2 known pathogenesis, abnormal immune response triggers either ITP or sarcoidosis. The disease that develops first stimulates secondary disease. After development of secondary disease, they stimulate each other. A few cases of ITP associated with sarcoidosis are well documented in English; however, the disease has rarely been reported in Korea. Here, we report on a case of ITP with sarcoidosis in a 29-year-old man. He suffered from easy bruising. The chest X-ray and the contrast-enhanced computed tomography scan showed bihilar lymphadenopathy and reticulonodular infiltrates. Bone marrow study and fluoroscopy-guided percutaneous needle biopsy were performed and the patient was diagnosed with sarcoidosis and ITP. He was put on 400 mg/kg of intravenous immunoglobulin for 5 days and administered oral steroids and further follow-up will be carried out. He has shown a good response without significant bleeding event. However, administration of more oral steroid and additional follow-up is required than for single disease, whether sarcoidosis or ITP.

Adenocarcinoma of Lung Cancer with Solitary Metastasis to the Stomach / 대한소화기학회지

Although hematogenous metastasis of cancer to the gastrointestinal track is rare, it sometime has been reported in patients with malignant melanoma and breast cancer. However, it is extremely rare for lung cancer to metastasize to the stomach, not to mention solitary gastric metastasis. Herein, the authors report a case of a 69-year-old man who was initially diagnosed with lung cancer with synchronous primary gastric cancer which proved to be lung cancer with solitary gastric metastasis after the operation.

Chronic myeloid leukemia as a secondary malignancy after diffuse large B-cell lymphoma

No abstract available.

A Case of Type 1 Neurofibromatosis Associated with Multiple Metastatic Gastrointestinal Stromal Tumors / 영남의대학술지

Type 1 neurofibromatosis (von Recklinghausen's disease, NF-1) is an autosomal-dominant neurocutaneous-disorder characterized by systemic cafe'-au-lait spots, multiple cutaneous neurofibromas, axillary or inguinal freckling, and Lisch nodules (pigmented iris hamartomas). Approximately 10-25% of NF1 patients have gastrointestinal neoplasms. Gastrointestinal stromal tumor (GIST) in patients with neurofibromatosis is most commonly found in the small bowel and the stomach, and approximately 60% of such patients have multiple tumors or multiple tumor sites. Although, the increased incidence of GIST in patients with neurofibromatosis is well documented in pathology literature in English, but has rarely been documented in Korea. Here, we report a case of multiple GISTs in a 48-year-old woman accompanied by NF1. She was admitted to Yeungnam University Hospital with complaints of melena and dyspnea. A contrast-enhanced computed tomography (CT) scan revealed that multiple soft tissue masses were occupying the entire peritoneal cavity. An ultrasonogram- guided biopsy was performed and the tumors were found to have been composed of tumor cells that were positive for c-kit protein. The patient was put on Imatinib mesylate treatment, and further follow-up will be carried out.

Effect of Dose Escalation with Single Opioid, Fentanyl Matrix in Patients Not Controlling Cancer Pain: A Multicenter, Prospective, Observational Study in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: End-of-dose failure (EOD) is a clinically common observation and many cancer patients increase the frequency of opioid administration. Fentanyl matrix use is known to be effective in patients with chronic cancer pain. To measure the effectiveness of increase in a single dose of fentanyl matrix in patients whose pain was not controlled sufficiently, we perform this study. MATERIALS AND METHODS: A multi-center, open-label, prospective, observational study was conducted in 30 hospitals in Korea, between August and December 2008. RESULTS: A total of 452 patients were enrolled; 404 patients completed the study. The mean pain intensity decreased from 5.27 at the first visit to 3.37 at the end of the trial. There was a significant difference in pain intensity (p < 0.001) between the first and last visits. The percentage of pain intensity difference was 30.1%. The prevalence of EOD at the first visit was 73% from the 452 enrolled patients. After the use of fentanyl patch, EOD decreased from 73% to 56%. Pain intensity of patients experiencing EOD was 5.64 at the baseline compared to 4.27 in patients without EOD. On final visit, pain intensity in patients with and without EOD was 4.02 and 2.54, respectively. The observed adverse events were mainly nausea, asthenia, constipation and diarrhea. CONCLUSION: This study demonstrated that increasing dose of fentanyl patch decreased pain intensity and decreased the rate of patients experiencing EOD. Thus, fentanyl patch may be an effective modality in cancer patients whose pain was previously not controlled sufficiently; the side effects were as could be expected with an opioid.

Down-regulation of survivin suppresses uro-plasminogen activator through transcription factor JunB

Survivin, a member of the inhibitors of apoptosis protein family, is expressed during development and in various human cancers. However, the clinical relevance of survivin in cancer is still a matter of debate. Genes induced by hepatocyte growth factor (HGF) were screened using cDNA microarray technology in the stomach cancer cell lines, NUGC3 and MKN28. The levels of JunB, survivin, and uro-plasminogen activator (uPA) were up-regulated in cells treated with HGF in a dose-dependent manner. HGF-induced up regulation of JunB, survivin, and uPA was inhibited by pre-treatment with a MEK inhibitor (PD 98059). HGF-induced up-regulation of uPA was repressed by survivin knockdown. HGF enhanced the binding activity of JunB to the survivin promoter in control cells, but not in the JunB-shRNA cells. Transfection with survivin-shRNA resulted in a decrement of cell proliferation, as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with survivin shRNA than control cells were able to invade across a Matrigel membrane barrier. In conclusion, survivin appeared to play an important role in the up-regulation of uPA induced by HGF via JunB and might contribute to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy.

Paratesticular Alveolar Rhabdomyosarcoma with Multiple Lymph Nodes Metastasis Successfully Treated with Chemotherapy / 영남의대학술지

Rhabdomyosarcomas are soft tissue sarcomas; while extremely rare in adults, they are one of the most common neoplasms in children and adolescents. Histologically, they can be classified into embryonal(ERMS), alveolar(ARMS), pleomorphic, and undifferentiated types. The ARMS type is very rare, and is associated with a poor prognosis. Common primary sites of ARMS are the trunk and extremities. We report on a case of paraaortic, supraclavicular, and axillary lymph node metastasis from paratesticular ARMS treated with VAC(vincristine, dactinomycin, cyclophosphamide)/ IE(ifosfamide, etoposide) chemotherapy in a young adult. Administration of six cycles of chemotherapy with VAC/ IE resulted in complete remission. The patient has maintained complete remission over the past 27 months.

Treatment of Hemangiopericytoma-Associated Hypoglycemia with Glucocorticoid Therapy / 영남의대학술지

Non-islet cell tumor-induced hypoglycemia (NICTH) is associated with mesenchymal tumor types, including hemangiopericytoma, fibrosarcoma, mesothelioma, and neurofibroma, as well as carcinoma of the liver, adrenal glands, and kidneys. Non-islet cell tumors induce hypoglycemia by overproducing an abnormal form of insulin-like growth factor II (IGF II). Complete removal of the tumor or reduction of the tumor mass is a successful therapeutic strategy in cases of NICTH. However, if the tumor re-grows, curative resection is nearly impossible, and hypoglycemia occurs repeatedly. Glucocorticoids are effective in terms of long-term relief from hypoglycemia through promotion of gluconeogenesis in the liver, tumor suppression, production of 'big'-IGF-II, and correction of the attendant biochemical abnormalities involving the growth hormone (GH)-IGF axis. We found that administration of corticosteroid therapy to a patient suffering from NICTH resulted in improvement of hypoglycemia associated symptoms.

Early or Late Gefitinib, Which is Better for Survival?: Retrospective Analysis of 228 Korean Patients with Advanced or Metastatic NSCLC / 영남의대학술지

BACKGROUND: The optimal timing of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI) in NSCLC patients has not yet been determined. METHODS: We separated 228 patients with advanced/metastatic NSCLC treated with gefitinib into an early gefitinib group (patients who received gefitinib as first- or second-line treatment) and a delayed gefitinib group (patients who received gefitinib as third or fourth-line treatment) and attempted to determine whether the timing of gefitinib treatment affected clinical outcomes. RESULTS: Median overall survival (OS), progression free survival (PFS), and median OS from first-line treatment of advanced/metastatic disease (OSt) for 111 patients in the early gefitinib group were 6.2 months, 3.3 months, and 11.6 months. However, median OS, PFS, and OSt for 84 patients in the delayed gefitinib group were 7.8 months, 2.3 months, and 22.7 months. No differences in OS and PFS were observed between the 2 groups. However, OSt was significantly longer in the delayed gefitnib group. Timing of gefitinib therapy was one of the independent predictors of OSt. Hb > or = 10 g/dl, and having never smoked, and ECOG performance status < or =1 were independent predictors of better PFS. CONCLUSION: Deferral of gefitinib therapy in patients with advanced or metastatic NSCLC may be preferable if they are able to tolerate chemotherapy.

Prognostic Factors in Patients with Localized Soft Tissue Sarcoma / 대한내과학회지

BACKGROUND/AIMS: We evaluated the independent prognostic factors for overall and disease-free survival in the treatment of soft tissue sarcoma. METHODS: Sixty-seven medical records were retrospectively reviewed. All the patients had presented with localized soft tissue sarcoma and had been treated with conservative surgery, followed by additional therapy or surgery. All were treated at the Yeungnam University Hospital between January 2000 and December 2006. Univariate and multivariate analyses were used to evaluate factors affecting overall and disease-free survival. RESULTS: The median age of the study sample was 50 (range, 15~70) years. Twenty patients (30%) had liposarcoma and nine (13%) had leiomyosarcoma. Seventeen patients (25%) had a tumor measuring greater than 10 cm. Nineteen patients (28%) had positive resection margins. The median overall survival was 62.7 months (95% CI: 25.7~99.4) and the median disease-free survival was 36.1 months (95% CI: 17.9~54.2). Factors that significantly affected the median overall survival were a tumor size greater than 10 cm and performance status. Positive resection margins and tumor site were independent prognostic factors associated with diseasefree survival. Other factors, such as histopathology, gender, age, and tumor grade, did not have prognostic value. Additionally, the chosen modality of treatment after surgery was not an independent predictor of the median overall or disease-free survival. CONCLUSIONS: Tumor size, positive resection margins, tumor site, and performance status were statistically significant independent predictors of poor prognosis.

A case of posttransplantation lymphoproliferative disorder in hematopoietic stem cell transplantation / 대한내과학회지

Posttransplantation lymphoproliferative disorder (PTLD) is a potentially fatal complication of hematopoietic stem cell transplantation (HPSCT) that occurs relatively early after the transplantation. The occurrence of PTLD is usually associated with Epstein-Barr virus (EBV) infection in patients who are treated by aggressive immunosuppressive therapy. PTLD presents as diverse manifestations, ranging from reactive lymphoid hyperplasia to high grade malignant lymphoma. In the present work, we describe a case of PTLD that was successfully treated with R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone) chemotherapy in a 21-year-old female who received HLA-matched sibling HPSCT for severe aplastic anemia. At 120 days after transplantation, she had symptoms of dysphagia and a foreign body sensation in the throat and was diagnosed as PTLD, diffuse large B cell lymphoma involving a tonsil, cervical lymph nodes, an adrenal gland, and the liver. Three courses of R-CHOP resulted in complete remission.