Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC. MATERIALS AND METHODS: From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus. RESULTS: Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]). CONCLUSION: Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

Validity and Reliability of Korean Version of Simplified Nutritional Appetite Questionnaire in Patients with Advanced Cancer: A Multicenter, Longitudinal Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. Nutrition risk screening aims to increase awareness and allow early recognition and treatment of cancer cachexia. Therefore, screenings should be brief, inexpensive, highly sensitive, and have good specificity. Simplified Nutritional Appetite Questionnaire (SNAQ) is a simple screening tool including four questions, and validated to predict weight loss within 6 months in community-dwelling adults and nursing home residents. Our study aimed to translate the SNAQ into Korean, and to assess the validity and reliability of the translated screening tool in advanced cancer patients. MATERIALS AND METHODS: The SNAQ was translated into Korean according to linguistic validation. The internal consistency of the SNAQ was evaluated by Cronbach's alpha coefficient. Test-retest reliability was evaluated using the intraclass correlation coefficient. Concurrent validity was evaluated by measuring the Pearson's correlation coefficient between the SNAQ and Mini-Nutritional Assessment (MNA) and Patient-Generated Subjective Global Assessment (PG-SGA). RESULTS: In the 194 patients included in full analysis set, cancer stage was predominantly metastatic (98.5%), the mean age was 60 years (range, 23 to 81 years), and the mean body mass index was 24 kg/m² (range, 15.6 to 39.6 kg/m²). According to MNA score ≤ 11, 57 patients (29.4%) were malnourished. The mean score (±standard deviation) of the Korean version of the SNAQ was 13.8±2.5 with a range of 6-19. Cronbach's alpha coefficient was 0.737, and intraclass correlation coefficient was 0.869. The SNAQ was moderately correlated with MNA (r=0.404, p 5% of the original bodyweightwithin 6 months occurred in 46 of the 186 patients (24.7%). SNAQ score ≤ 14 predicted > 5% weight loss with a sensitivity of 56.5% and a specificity of 44.3%. CONCLUSION: The Korean version of the SNAQ had high validity and reliability. SNAQ is useful for the screening tool for advanced cancer patients. The SNAQ had a limitation to predict impending weight loss in advanced cancer patients.

Clinical Significance of Peroxisome Proliferator-Activated Receptor gamma and TRAP220 in Patients with Operable Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARgamma or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). MATERIALS AND METHODS: A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARgamma and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. RESULTS: Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARgamma and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARgamma positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARgamma and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). CONCLUSION: TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARgamma and TRAP220 represents a biomarker for good prognosis in CRC patients.

Clinical Features and Treatment of Collecting Duct Carcinoma of the Kidney from the Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Collecting duct carcinoma (CDC) of the kidney is an aggressive disease with a poor prognosis, accountings for less than 1% of all renal cancers. To date, no standard therapy for CDC has been established. The aim of this study is an investigation of clinicopathologic findings of CDC and correlation of the disease status with a prognosis. MATERIALS AND METHODS: From 1996 to 2009, 35 patients with CDC were treated at eight medical centers. The diagnosis of CDC was made based on nephrectomy in 27 cases and renal biopsy in eight cases. RESULTS: Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4 months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was 8.6 months (95% CI 0 to 23.3), which showed a statistically significant difference (p=0.01). In addition, among patients with Stage IV, the OS of patients who received a palliative treatment (immunotherapy, chemotherapy, or targeted therapy) was 18.4 months, which was higher than the OS of patients without treatment of 4.5 months. CONCLUSION: CDC is a highly aggressive form of renal cell carcinoma. Despite most of the treatments, PFS and OS were short, however, there were some long-term survivors, therefore, conduct of additional research on the predictive markers of the several clinical, pathological differences and their treatments will be necessary.

Phase II Study of Vinorelbine Plus Trastuzumab in HER2 Overexpressing Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes / 한국유방암학회지

PURPOSE: The role of first-line trastuzumab-based therapy has been firmly established in patients with human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer. In this trial, we evaluated the efficacy and safety of a vinorelbine and trastuzumab combination chemotherapy in patients who were pretreated with anthracyclines and taxanes. METHODS: Thirty-three patients with HER2 overexpressing metastatic breast cancer, all of whom had previously been treated with anthracyclines and taxanes, were included in this study. The patients were treated with 25 mg/m2 of vinorelbine (over a 15-minute infusion) on days 1 and 8 every 3 weeks. Additionally, trastuzumab was administered at an initial dose of 4 mg/kg over 90 minutes, and was subsequently administered at weekly doses of 2 mg/kg (over 30 minutes). RESULTS: The median age of the patients was 53 years (range, 39-72 years). The overall response rate was 30.3% (10 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 6.8 months (95% CI, 5.3-8.2 months). The median overall survival was 12.4 months (95% CI, 10.3-14.6 months). In the 194 cycles of treatment, the incidence rates of grade > or =3 neutropenia and anemia were 7.2% and 1.0%, respectively. Neutropenic fever was detected in three cycles (1.5%). The non-hematological toxicities were not severe: grade 1 or 2 nausea or vomiting was detected in 15.2%, and grade 2 neuropathy was noted in 6.1% of patients. None of the patients experienced any serious cardiac toxicity, and no treatment-related deaths occurred. CONCLUSION: These results show that a combination chemotherapy consisting of vinorelbine and trastuzumab is useful in patients with HER2-overexpressing metastatic breast cancer who were pretreated with anthracyclines and taxanes, with a favorable toxicity profile.

Predictive Value of In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay in Advanced Gastric Cancer Patients Who Received Oral 5-Fluorouracil after Curative Resection / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To assess the usefulness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results in advanced gastric cancer patients receiving adjuvant chemotherapy. MATERIALS AND METHODS: Sixty-two patients underwent curative surgical resection between January, 2006 and December, 2008. Their highly purified surgical specimens were evaluated by ATP-CRAs. Of the 62, 49 had successful assay results and they received either oral 5-fluorouracil or other chemotherapies. We retrospectively analyzed data for 24 patients who were treated with oral 5-fluorouracil and whose assays were successful. RESULTS: The median observation time was 24.6 months (range, 10.1 to 40.9 months). The median treatment time was 11.2 months (range, 1.2 to 17.7 months). The median age was 66 years (range, 30 to 81 years). Patients were grouped into sensitive- and resistant-groups according to adenosine triphosphate-based chemotherapy response results for fluorouracil. The sensitive-group showed a significantly longer time to relapse (not reached in the sensitive-group vs. 24.8 months in the resistant-group, p=0.043) and longer overall survival compared to the resistant-group (not reached in the sensitive-group vs. 35.7 months in the resistant-group, p=0.16, statistically insignificant). CONCLUSION: Patients who receive curative surgical resection significantly benefit from sensitive adjuvant chemotherapy according to ATP-CRA results for time to relapse.

A Case of 5-Fluorouracil Induced Encephalopathy / Journal of the Korean Cancer Association, 대한암학회지

Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at risk for experiencing serious adverse effects following 5-fluorouracil (5-FU) based chemotherapy. Neurotoxicity is considered an extremely rare side effect of 5-FU. We report here on an unusual case of 5-FU induced encephalopathy. A 38-year-old woman with advanced gastric carcinoma was treated with adjuvant chemotherapy that consisted of infused 5-FU (1,000 mg/m2) for 5 days and cisplatin (60 mg/m2) on day 1 following total gastrectomy. Nineteen days after starting chemotherapy, the patient displayed a sudden onset of slurred speech, confusion, cognitive disturbances and paranoia. A magnetic resonance image (MRI) of the brain showed no structural abnormalities, and the other laboratory tests provided no explanations for her symptoms, other than a slightly elevated ammonia level. The patient was treated with a lactulose retention enema and thiamine infusion, the 5-FU was halted and her symptoms then recovered after 7 days.

Clinical Outcomes in Patients with Triple-negative Breast Cancer and Brain Metastases / 한국유방암학회지

PURPOSE: Patients with triple-negative breast cancer (TNBC) are known to carry an increased risk of distant metastasis and poor survival. The principal objective of this study was to investigate survival after brain metastases in patients with TNBC. METHODS: The authors retrospectively evaluated clinical data obtained from 66 patients who had been diagnosed with breast cancer and brain metastasis from 2003 to 2009. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) statuses were determined via immunohistochemical staining. TNBCs were defined as those that were ER-negative, PR-negative, and HER2-negative. The time interval from initial diagnosis to brain metastasis and overall survival after brain metastasis was evaluated via the Kaplan-Meier method. RESULTS: Twenty four (40.0%) of 60 patients were diagnosed with TNBC. The clinicopathologic characteristics did not differ between the TNBC and non-TNBC patients. The disease-free survival durations of the TNBC and non-TNBC subjects were 17.9 and 25.6 months, respectively (p=0.135). The time intervals from initial diagnosis to brain metastasis were 25.5 and 43.7 months, respectively (p=0.027). The time intervals from distant metastasis to brain metastasis were 8.4 and 19.5 months, respectively (p=0.006). Overall survival durations from brain metastasis to death were 4.3 and 7.6 months, respectively (p=0.046). CONCLUSION: Patients with TNBC were more likely to develop brain metastasis earlier, and exhibit poor overall survival. Triple receptor status may be utilized as a prognostic marker for breast cancer patients with brain metastasis.

Incidence and clinical characteristics of clonal cytogenetic abnormalities of acquired aplastic anemia in adults

BACKGROUND: Cytogenetic abnormalities (CAs) have been reported frequently in patients with otherwise typical aplastic anemia (AA), but their implications in the prognosis and in the evolution to hematologic malignancies are controversial. METHODS: We retrospectively analyzed 127 adult AA patients who had successful cytogenetic analysis at initial diagnosis. RESULTS: The patients were classified into 3 groups according to the initial and follow-up results of cytogenetic profiles. Group 1 included patients who had persistent AA with normal cytogenetic profiles (N=117); Group 2, those who had a normal cytogenetic profile at initial diagnosis but later acquired CA (N=4, 3.1%); and Group 3, those who had CA at the initial diagnosis, regardless of follow-up cytogenetic status (N=6,4.7%). In Group 2, 2 patients later developed CA without progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS); the other 2 patients later progressed to AML. None of the patients in Group 3 progressed to AML or MDS. There was no significant difference in overall survival between Groups 1 and 3. CONCLUSION: AA patients with CA at initial diagnosis or follow-up may not be at greater risk for evolution to AML or MDS, or show shorter survival periods. Prospective studies and a larger patient samples are needed to establish the clinical relevance of CA.

A case of subdural hematoma in patient with chronic myeloid leukemia treated with high-dose imatinib mesylate

Imatinib mesylate (IM) is used to treat a wide range of diseases, including Philadelphia chromosome-positive chronic myeloid leukemia (CML), on account of its high tolerability and low incidence of minor adverse events. Hemorrhage is thought to be a rare complication of IM. Recently, IM has been associated with reduced alpha2-plasmin inhibitor and platelet dysfunction. We report here the case of a 33-year-old female patient with CML who experienced subdural hematoma after an incremental increase in IM dosage due to a loss of complete molecular response. This case indicates that physicians should be alert to this atypical cause of headache in patients taking high-dose IM.

Fludarabine-based myeloablative regimen as pretransplant conditioning therapy in adult acute leukemia/myelodysplastic syndrome: comparison with oral or intravenous busulfan with cyclophosphamide

BACKGROUND: A combination of busulfan (Bu) and cyclophosphamide (Cy) has been used as a standard myeloablative regimen for allogeneic hematopoietic stem cell transplantation (HSCT). Recent studies postulate that fludarabine (Flu) is a less toxic substitute for Cy. METHODS: Forty-two patients who were diagnosed with acute leukemia or myelodysplastic syndrome and received BuFlu (n=17) or BuCy (n=25) from August, 1999 to July, 2009 at Dong-A University Medical Center were retrospectively analyzed. RESULTS: The median follow-up duration was 39.75 months. The BuFlu group showed a lower incidence of mucositis (P=0.005), but there was no significant intergroup difference in the time of engraftment, nausea/vomiting, acute/chronic graft-versus-host disease, hepatic veno-occlusive disease, or hemorrhagic cystitis. Moreover, the 2 groups showed no significant difference in the cumulative risk of relapse, event-free survival, or overall survival. CONCLUSION: BuFlu administration can be employed as a preparative regimen for allogeneic HSCT and shows efficacy and transplant-adverse effects comparable to those of BuCy. However, randomized prospective studies in more patients are warranted.

Allopurinol hypersensitivity syndrome and pure red cell aplasia associated with allopurinol treatment / 대한내과학회지

Allopurinol is widely used to reduce serum uric acid levels and, generally, has mild side effects. Rarely, allopurinol hypersensitivity syndrome occurs and this consists of severe systemic skin lesions, fever, reduced kidney and liver function, and leukocytosis with eosinophilia. Extremely rarely, allopurinol-induced pure red cell aplasia is reported. We report a case of allopurinol hypersensitivity syndrome and pure red cell aplasia following allopurinol therapy for eight weeks and the disease response to steroid therapy in a patient with chronic renal insufficiency.

Phase II Study of Vinorelbine Plus Ifosfamide in Patients with Taxane-resistant Metastatic Breast Cancer / 한국유방암학회지

PURPOSE: The patients with metastatic breast cancer are routinely exposed to taxane and anthracycline as neoadjuvant, adjuvant, and palliative chemotherapeutic agents. This study was designed to evaluate the efficacy and safety of using a vinorelbine and ifosfamide (VI) combination treatment in patients with taxane-resistant metastatic breast cancer. METHODS: We evaluated the use of a VI regimen (25 mg/m2 vinorelbine administered on days 1 and 8 plus 2,000 mg/m2 ifosfamide administered on day 1-3 every 3 weeks) for breast cancer patients who evidenced tumor progression after palliative taxane treatment. RESULTS: Overall, 35 patients were enrolled in this study: Their median age was 50 years (range, 38-72 years). The overall response rate was 40.0% (14 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 4.5 months (95% CI, 3.5-5.4 months). The median overall survival was 18.3 months (95% CI, 12.9-23.6 months). In the 190 cycle of treatment, the incidence of grade > or =3 neutropenia, anemia, and thrombocytopenia was 29.3%, 4.2%, and 2.0%, respectively. Neutropenic fever was noted in 6 cycles (3.1%). The non-hematological toxicities were not severe: grade 1 or 2 vomiting was observed in 22.8% of the patients. CONCLUSION: Our results suggest that the use of vinorelbine and ifosfamide (VI) combination chemotherapy appears to be effective and it showed an acceptable toxicity profile in the patients with taxane-resistant metastatic breast cancer.

A Case of Acute Myeloid Leukemia with Mediastinal Sarcoma

Myeloid sarcoma (MS) is a solid extramedullary tumor that is composed of immature myeloid cells. The incidence of MS in patients with acute myeloid leukemia (AML) has been reported to be 3~8%. Lymph nodes are the most frequent site of presentation for MS, and other clinical presentations such as an abdominal mass with bowel involvement, a pancreatic mass, isolated central nervous system infiltration, a testicular mass and breast lumps have also been reported. AML with mediastinal MS is a relatively rare disease. The patients with AML with mediastinal MS has been reported to have complex cytogenetic abnormalities and a poor long-term prognosis. The optimal treatment of AML with MS remains to be determined. We report here on an unusual case of a 37-year-old man who presented multiple lymph node enlargements on the neck and a huge mediastinal mass that was considered to be lymphoma. He was finally diagnosed as AML with MS according to the surgical excisional biopsy of a left supraclavicular lymph node and bone marrow examination. He achieved complete remission and the multiple enlarged lymph nodes on the neck and the mediastinal mass disappeared after remission induction chemotherapy. Thereafter, he received HLA-matched unrelated allogenic hematopoietic stem cell transplantation.

Acute Renal Failure Due to Severe Stenosis of Fibromuscular Dysplasia in a Single Kidney / 대한신장학회지

Among complications of fibromuscular dysplasia are uncontrolled hypertension, aneurysm and, albeit very rare, renal failure, especially in a single kidney. We report a case of severe stenosis of fibromuscular dysplasia leading to renal failure, in need of temporary hemodialysis in 29-year-old hypertensive woman. When she was 13-year-old, she underwent a left nephrectomy because of the left renal cyst and she was treated with antihypertensive medication for several years. A few day before admission, she complained of oliguria, generalized edema and aggravated dyspnea. On the day of admission, she took emergency hemodialysis. A renal angiogram showed focal irregular stenosis in the right proximal renal artery, compatible with fibromuscular dysplasia; therefore, we performed percutaneous renal artery angioplasty. Following successful renal angioplasty, her urine output increased and creatinine level was normalized.

Effect of Preoperative Sonographic Venous Mapping on Formation of Vascular Access / 대한신장학회지

PURPOSE: Active venous mapping by ultrasonography much increased the rate of autologous graft operations while significantly decreasing the rate of maturation failures. Reports on this phenomenon, however, have been rare in Korea. We here the effect of venous mapping by ultrasonography. METHODS: From 2005.1 to 2006.6, we selected 73 patients with autologous or artificial vessel or tunneled catheter and put them into 2 groups: the group that had operation after venous mapping by ultrasonography (n=40) and the control group (n=33) and rate of autologous vessels and the frequency and cause of maturation failure were analysed retrospectively. RESULTS: Patient's age, patient ratio of age, DM ratio in the map group against the control group were respectively 58.95+/-19.93 (25-86) vs 60.76+/-11.93 (39-80), 20/40 vs 17/33, 14/40 vs 19/33 showing no signficant differences between them. Gender ratios (M/F) were 12/28 vs 21/12 showing more females in the mapping group. As for the rate of autologous vessel, 34 out of 40 in map group, and 31 out of 33 in the control group showed no significant difference. After the first operation, 36 out of 40 in map group and 16 out of 33 in the control group were using autologous vessel. The map group had tendency to use higher rate of autologous vessels than the control group (p=0.059). MF ratio was significantly low in the mapping group (p=0.000). CONCLUSION: Carrying out preoperative venous mapping would promote development of appropriate techniques, together with increased use of autologous vessels. It is also thought that MF reduced the chance of reoperation.

A Case of IgA Nephropathy Associated with Acute Myeloid Leukemia / 대한신장학회잡지

The incidence of glomerulonephritis associated with malignancy is not common. Membranous glomerulonephritis associated with carcinomas and minimal change nephrotic syndrome with Hodgkin's disease has been occasionally reported. The pathogenesis of glomerular injury associated with malignancy is not well known. The IgA nephropathy associated with malignancy, though rare, has been reported. IgA nephropathy associated with acute myeloid leukemia, however, is yet to be reported. We hereby report a case of IgA nephropathy associated with acute myeloid leukemia (AML M2).

A Case of IgA Nephropathy Associated with Acute Myeloid Leukemia / 대한신장학회잡지

The incidence of glomerulonephritis associated with malignancy is not common. Membranous glomerulonephritis associated with carcinomas and minimal change nephrotic syndrome with Hodgkin's disease has been occasionally reported. The pathogenesis of glomerular injury associated with malignancy is not well known. The IgA nephropathy associated with malignancy, though rare, has been reported. IgA nephropathy associated with acute myeloid leukemia, however, is yet to be reported. We hereby report a case of IgA nephropathy associated with acute myeloid leukemia (AML M2).