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.

Intraoperative Frozen Cytology of Central Nervous System Neoplasms: An Ancillary Tool for Frozen Diagnosis

BACKGROUND: Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. METHODS: Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. RESULTS: Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. CONCLUSIONS: Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.

Epidermal growth factor receptor mutation and pattern of brain metastasis in patients with non-small cell lung cancer

BACKGROUND/AIMS@#We investigated the time taken for patients with metastatic non-small cell lung cancer (NSCLC) to develop brain metastases (BM), as well as their subsequent overall median survival following diagnosis, considering the epidermal growth factor receptor (EGFR) mutational status.@*METHODS@#We retrospectively investigated the medical records of 259 patients diagnosed with advanced NSCLC from January 2010 to August 2013, who were tested for EGFR mutations. The time from the diagnosis of advanced NSCLC to the development of BM and the overall median survival after BM development (BM-OS) were evaluated and compared by EGFR mutational status.@*RESULTS@#Sixty-seven patients (25.9%) developed BM. Synchronous BM occurred more often in patients with EGFR mutation type (MT) (n = 20, 27.4%) compared with EGFR wild type (WT) (n = 27, 14.5%, p < 0.009). The median BM-OS was significantly longer in patients with EGFR MT than in those with EGFR WT (25.7 months vs. 3.8 months, p < 0.001), and a similar trend was noticed for patients with synchronous BM (25.7 months for EGFR MT vs. 6.8 months for EGFR WT, p < 0.001). However, in patients with metachronous BM development, the difference in BM-OS between patients with EGFR MT (14.6 months) and EGFR WT (2.5 months) did not reach statistical significance (p = 0.230).@*CONCLUSIONS@#Synchronous BM was more common in NSCLC patients with EGFR MT than in those with EGFR WT. However, EGFR mutations were associated with significantly longer median BM-OS, especially when the brain was the first metastatic site.

Skull Metastasis of Gastric Gastrointestinal Stromal Tumor Successfully Managed by Surgery

Gastrointestinal stromal tumors (GISTs) are rare, but are the most common mesenchymal neoplasm of the gastrointestinal tract. The most common sites of metastasis are liver and peritoneum, while bone metastasis is rare. We report on a patient with skull metastasis after seven years of treatment with imatinib for metastatic GIST. She underwent metastasectomy consisting of craniectomy with excision of the mass, and cranioplasty and continued treatment with imatinib and sunitinib, without evidence of cranial recurrence. She died of pneumonia sepsis one year after metastasectomy. Skull metastasis of GIST is a very rare presentation, and an aggressive multidisciplinary approach should be considered whenever possible.

Baseline renal function as a prognostic indicator in patients with newly diagnosed diffuse large B-cell lymphoma

BACKGROUND: The association between baseline renal impairment (RI) and the prognosis of diffuse large B-cell lymphoma (DLBCL) was previously not defined. The aim of this study was to evaluate the prognostic value of RI in patients with DLBCL treated with three-weekly rituximab plus cyclophosphamide, Adriamycin, vincristine, and prednisolone immunochemotherapy (R-CHOP21). METHODS: Patients with newly diagnosed de novo DLBCLs treated with ≥1 cycle of R-CHOP21 were analyzed retrospectively. Pretreatment blood samples were collected and the glomerular filtration rate (GFR) was calculated. RI was defined by a GFR of <60 mL/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULTS: Of the 185 patients enrolled in the present study, 19 patients (10.3%) had RI. The reasons for baseline RI were pre-existing CKD (N=5), acute kidney injury due to either obstruction (N=2) or electrolyte imbalance (N=2) related to DLBCL, and undefined causes (N=10). Patients with baseline RI showed inferior overall survival (OS) compared to those without RI (P<0.001). In multivariate analysis, RI was identified as an International Prognostic Index (IPI)-independent prognostic indicator. A baseline hemoglobin level of <10 g/dL and the presence of RI effectively discriminated a portion of the patients with far inferior event-free survival and OS among the patients having high or high-intermediate risk cancers according to either the standard- or the National Comprehensive Cancer Network-IPI. CONCLUSION: Pretreatment RI was an independent prognostic marker for inferior OS in patients with DLBCL treated with R-CHOP21 immunochemotherapy.

Dexamethasone Inhibits TGF-β1-Induced Cell Migration by Regulating the ERK and AKT Pathways in Human Colon Cancer Cells Via CYR61 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: One of the features in cancer development is the migration of cancer cells to form metastatic lesions. CYR61 protein promotes migration and the epithelial-mesenchymal transition in several cancer cell types. Evidence suggests that CYR61 and dexamethasone are relevant to colorectal cancer. However, relationships between them and colorectal cancer are still unclear. Understanding the molecular mechanism of colorectal cancer progression related with CYR61 and dexamethasone, which is widely used for combination chemotherapy, is necessary for improved therapy. MATERIALS AND METHODS: We used colorectal cancer cells, HCT116, co-treated with transforming growth factor β1 (TGF-β1) and dexamethasone to examine the inhibitory migration effect of dexamethasone by migratory assay. Alternatively, both migratory pathways, expression of AKT and ERK, and the target factor CYR61 was also tested by co-treatment with TGF-β1 and dexamethasone. RESULTS: We report that dexamethasone significantly inhibited TGF-β1-induced cell migration, without affecting cell proliferation. Importantly, we observed that TGF-β1 promoted the epithelial-mesenchymal transition process and that dexamethasone co-treatment abolished this effect. ERK and AKT signaling pathways were found to mediate TGF-β1-induced migration, which was inhibited by dexamethasone. In addition, TGF-β1 treatment induced CYR61 expression whereas dexamethasone reduced it. These observations were compatible with the modulation of migration observed following treatment of HCT116 cells with human recombinant CYR61 and anti-CYR61 antibody. Our results also indicated that TGF-β1 enhanced collagen I and reduced matrix metalloproteinase 1 expression, which was reversed by dexamethasone treatment. CONCLUSION: These findings suggested that dexamethasone inhibits AKT and ERK phosphorylation, leading to decreased CYR61 expression, which in turn blocks TGF-β1-induced migration.

Metastasectomy for Recurrent or Metastatic Biliary Tract Cancers: A Single Center Experience

OBJECTIVE: Efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC) is not well established. We conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs. METHODS: The clinicopathological features and outcomes of consecutive patients with BTCs who underwent surgical resection for primary and metastatic disease at a tertiary referral hospital from 2003 to 2013 were reviewed retrospectively. RESULTS: We found 19 eligible patients. Median age of patients was 57 years old (range, 27 to 68 years old), and 11 patients (58%) were female. Primary sites were gallbladder cancer (seven patients, 37%), intrahepatic cholangiocarcinoma (five patients, 26%), distal common bile duct cancer (three patients, 16%), proximal common bile duct cancer (two patients, 11%), and ampulla of Vater cancer (two patients, 11%). Eight patients (42%) had synchronous metastasis, while 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, while four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval [CI], 13.6 to 22.9 months). Lower Eastern Cooperative Oncology Group performance status (P=0.023), metachronous metastasis (P=0.04), absence of lymph node metastasis (P=0.009), lower numbers of metastatic organs (P<0.001), normal postoperative carbohydrate antigen 19-9 level (P=0.034), and time from diagnosis to metastasectomy more than one year (P=0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSION: For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.

Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. MATERIALS AND METHODS: Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m(2) of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months. RESULTS: A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFR mutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. CONCLUSION: Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. MATERIALS AND METHODS: Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed. RESULTS: A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. CONCLUSION: Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials.

Oxaliplatin-Induced Immune-Mediated Thrombocytopenia: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

Oxaliplatin is a third-generation platinum derivative used for metastatic or advanced colorectal cancer treatment. Although myelosuppression is the most common cause of oxaliplatin-induced thrombocytopenia, rare cases of oxaliplatin-induced immune-mediated thrombocytopenia are reported. We report a case of a 57-year-old woman with colon cancer who developed gum bleeding and petechiae after oxaliplatin infusion. Laboratory tests revealed grade 4 thrombocytopenia and grade 4 neutropenia. She recovered from the thrombocytopenia and accompanying neutropenia within 4 days with no recurrence following discontinuation of oxaliplatin. Physicians need to be aware of the risk of severe acute thrombocytopenia following oxaliplatin administration.

Irinotecan and Cisplatin Combination Chemotherapy Plus Concurrent Thoracic Irradiation for Patients with Limited Disease Small Cell Lung Cancer

PURPOSE: To evaluate the antitumor activity and safety of irinotecan plus cisplatin combination chemotherapy with concurrent thoracic radiotherapy (TRT) in patients with limited disease (LD) small cell lung cancer (SCLC). MATERIALS AND METHODS: Patients with pathologically-confirmed LD SCLC with the following inclusion criteria were retrospectively analyzed: age > or =18 years; measurable lesion; Eastern Cooperative Oncology Group Performance Status 0~2; chemotherapy naive; and adequate bone marrow and organ function. Patients received an intravenous (IV) infusion of irinotecan (35 mg/m2 on days 1, 8, and 15) and cisplatin (60 mg/m2 on day 1), which was repeated every 4 weeks for up to 6 cycles. Concurrent TRT was administered with the beginning of chemotherapy. Irinotecan was increased to 60 mg/m2 after completion of TRT. Patients with a complete response (CR) subsequently received prophylactic cranial irradiation. RESULTS: Nineteen patients were analyzed. There were 8 patients (42.1%) with CR, 9 patients (47.4%) with partial response, and 1 patient each (5.3%) with stable disease and progressive disease (PD). The overall response rate was 89.5%. The median progression-free survival was 7.6 months (95% confidence interval [CI], 1.3~14.0 months) and the median overall survival was 12.4 months (95% CI, 0.5~24.2 months). The 2-year survival rate of the CR patients was 75.0%. No grade 4 hematologic toxicity was reported. Frequently reported toxicities were nausea (10 patients), radiation-induced pneumonitis (10 patients), and neutropenia (6 patients). Radiation-related severe toxicities were frequently reported. Three patients had treatment-related deaths. CONCLUSION: This study supports the activity and tolerability of irinotecan plus cisplatin with concurrent TRT in patients with LD SCLC.

Additional rituximab-CHOP (R-CHOP) versus involved-field radiotherapy after a brief course of R-CHOP in limited, non-bulky diffuse large B-cell lymphoma: a retrospective analysis / 대한혈액학회지

BACKGROUND: Standard treatment for stage I or non-bulky stage II diffuse large B-cell lymphoma (DLBCL) has been either a brief course of chemotherapy plus involved-field radiotherapy (IFRT) or prolonged cycles of chemotherapy. The introduction of rituximab has necessitated re-evaluation of the treatment for limited disease (LD) DLBCL. METHODS: Thirty-nine LD DLBCL patients (median age, 52 years; range, 24-85) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were retrospectively analyzed. Treatment outcomes were evaluated, and toxicity, event-free survival (EFS), and overall survival (OS) were compared according to the treatment and risk factors. RESULTS: The median follow-up duration was 34.6 months (range, 9.1-65.4). The 3-year EFS and OS were 76.0% and 86.0%, respectively. Among the 36 patients who underwent either 3-4 cycles of R-CHOP followed by IFRT (N=22) or 6-8 cycles of R-CHOP (N=14), there was no difference in the 3-year EFS (79.4% vs. 71.6%, P=0.638) and 3-year OS (85.7% vs. 92.9%, P=0.732). Severe neutropenia and neutropenic fever were more frequent in patients treated with R-CHOP alone, with 1 treatment-related mortality. Among the IFRT patients, 1 required hospital admission for IFRT-related complications. No events or deaths were reported among patients without adverse risk factors. CONCLUSION: The difference in outcomes between the 2 treatment options was not significant. Analysis of treatment outcomes suggested that baseline characteristics and expected toxicities should be considered in LD DLBCL treatment. Further studies are needed to define the optimal treatment in the rituximab era.

Recurrent and Metastatic Trichilemmal Carcinoma of the Skin Over the Thigh: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

Trichilemmal carcinoma (TC) is an uncommon cutaneous neoplasm that develops from the external root sheath of the hair follicle. It is considered to be a low-grade carcinoma with low metastatic potential. Local recurrence and metastasis are rare after surgical excision. We report here on a case of metastatic TC in the skin over the thigh, and this tumor was treated with cisplatin and cyclophosphamide combination chemotherapy.

A Case of Advanced Gastric Adenocarcinoma with Synchronous Gastric Diffuse Large B Cell Lymphoma / 대한소화기내시경학회지

Signet ring cell carcinoma is a subtype of adenocarcinoma that is characterized by abundant intracellular mucin accumulation. Diffuse large B-cell lymphoma is the most common histological subtyple of gastrointestinal lymphoma. The gastrointestinal tract is the most frequently involved extranodal site in non-Hodgkin's lymphoma. However, little is known about the coexistence of advanced gastric cancer and gastric diffuse large B cell lymphoma. We report a case of synchronous advanced gastric adenocarcinoma and gastric diffuse large B cell lymphoma in a 62-year-old woman.

Oxaliplatin, 5-fluorouracil and Leucovorin (FOLFOX-4) Combination Chemotherapy as a Salvage Treatment in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was designed to determine the efficacy and safety of FOLFOX-4 chemotherapy as a salvage treatment for patients with advanced gastric cancer (AGC). MATERIALS AND METHODS: The AGC patients with an ECOG performance status of 0~1 and progressive disease after prior treatments were registered onto this phase II trial. The patients received oxaliplatin (85 mg/m2 on day 1), leucovorin (200 mg/m2 on days 1 and 2) and 5-fluorouracil (400 mg/m2 as a bolus and 600 mg/m2 as a 22-hour infusion on days 1 and 2) every 2 weeks. RESULTS: For the 42 treated patients, a total of 228 chemotherapy cycles (median: 5, range: 1~12) were administered. Twenty-nine patients (69%) received FOLFOX-4 chemotherapy as a third-(50%) or fourth-line (19%) treatment. On the intent-to-treat analysis, 9 patients (21%) achieved a partial response, which was maintained for 4.6 months. The median progression-free survival and overall survival were 3.0 months and 6.2 months, respectively. The frequently encountered toxicities were neutropenia and gastrointestinal side effects, including anorexia. Although there was one possible treatment-related death, the toxicity profiles were generally predictable and manageable. CONCLUSION: Salvage chemotherapy with FOLFOX-4 is an effective and tolerable regimen for those heavily pretreated AGC patients who have a good performance status.

Clinical characteristics of lung cancer diagnosed from 2006 to 2008: Data from Gachon University Gil Hospital / 대한내과학회지

BACKGROUND/AIMS: This study examined the clinical characteristics of patients with lung cancer who were diagnosed at the Gachon University of Medicine and Science Gil Hospital from January 2006 to December 2008. METHODS: The lung cancer data were downloaded from the hospital medical information system using cancer registration information. The patient clinical characteristics were analyzed retrospectively. RESULTS: A total of 713 patients were diagnosed with lung cancer. Their median age was 69 years, 78.1% were over 60 years old, and 73.1% and 58.2% were men and smokers, respectively. Adenocarcinoma (32.7%) was the most common histologic type, followed by squamous carcinoma (25.9%), unclassifiable non-small-cell lung cancer (NSCLC) (17.3%), and small-cell carcinoma (SCLC) (15.0%). In the NSCLC group, the stage at diagnosis was IA (1.5%), IB (5.6%), IIA (1.3%), IIB (4.3%), IIIA (5.4%), IIIB (23.1%), IV (47.7%), and unknown (11.1%). In the SCLC group, 20.6% of the patients were in the limited stage, 76.6% were in the extensive stage, and 2.8% were unknown. The patients were treated by surgery (9.8%), concurrent chemoradiotherapy (6.7%), radiotherapy only (5.9%), chemotherapy (32.4%), or best supportive care only (29.7%). The median overall survival was 15.3 months (95% CI, 11.5~19.1). The median survival based on histology was adenocarcinoma (35.0 months), squamous (13.5 months), NSCLC (14.2 months), and SCLC (11.8 months) (p=0.0445). CONCLUSIONS: Adenocarcinoma was the most common histologic type at our institute. Most patients were over 60 years of age (78.1%) and had stage III/IV (76.3%) cancer. The survival of patients with adenocarcinoma was longer than that for the other histological types.

Analysis of Outcomes and Prognostic Factors Associated with Surgical Treatment Plus Postoperative Radiation Therapy for Stage II/III Pancreatic Cancer

PURPOSE: To evaluate treatment outcomes for patients with stage II/III pancreatic cancer who are treated with radiation therapy (RT) with or without chemotherapy (CTx) following surgery. METHODS: We retrospectively analyzed data from 17 patients who underwent surgery and post-operative RT with or without CTx between January 2000 and December 2008. Seven patients (41%) had stage II cancer and 10 (59%) had stage III cancer. Most were male (13 of 17; 76.5%). Age at diagnosis ranged from 42 to 82 (median 69) years. Whipple's operation was done in 9 patients (53%), distal pancreatectomy in 7 (41%), and subtotal pancreatectomy in 1 (6%). All patients received RT using a three-dimensional RT technique to spare critical normal structures. Median radiation dose was 54 Gy (range, 50.4~55.8 Gy). Variable CTx regimens were combined in 10 patients (58.8%); 5-FU in 4, UFTE-G in 4, gemcitabine in 1, and xeloda in 1. Acute toxicity was evaluated according to RTOG toxicity criteria. Survival analysis was done using the Kaplan-Meyer method. Univariate and multivariate prognostic factor analysis were done, respectively, using a log-rank test and Cox's proportional hazards model. RESULTS: The median follow-up period was 12.6 months. Locoregional and distant failures occurred in 8 (47.1%) and 8 patients (47.1%), respectively. Five patients (29.4%) developed both loco-regional recurrence and distant metastasis. The metastatic sites were liver in 4 patients, lung in 3, peritoneum in 1, and kidney in 1. Median overall survival (OS) was 12.6 months. The 1- and 2-year OS rates were, respectively, 58.8% and 24.5%. Median disease-free survival (DFS) was 8.3 months and the 1- and 2-year DFS rates were 46.3% and 30.9%, respectively. The 2-year OS was not different between RT and RT with CTx : survival rates were 28.6% and 17.5%, respectively (p=0.764). T stage and a postoperative CA 19-9 level of > or =180 U/ml were significant prognostic factors for OS in both univariate and multivariate analysis: the 2-year OS for T3 and T4 were 34.1% and 16.7%, respectively (p=0.0022), the 2-year OS for or =180 U/ml were 32.5% and 0%, respectively (p=0.0142) Acute toxicities were RTOG grade 1 (G1) nausea in 1 patient (5.9%), G1 vomiting in 2 (11.8%), and G1-2 enteritis in 5 (29.4%). The hematologic toxicities were G1 leukopenia in 5 patients (29.4%), G2 leukopenia 1 (5.9%), G1 thrombocytopenia in 1 (5.9%), and G1~2 anemia in 6 (35.3%). CONCLUSION: Survival results of the present study are comparable to those in other reports with acceptable toxicity. Significant prognostic factors for overall survival in pancreatic cancer are tumor stage and postoperative CA 19-9 level.

Pemetrexed versus Gefitinib versus Erlotinib in Previously Treated Patients with Non-Small Cell Lung Cancer

BACKGROUND/AIMS: The efficacy and safety of pemetrexed, gefitinib, and erlotinib administration in previously treated patients with non-small cell lung cancer (NSCLC) were compared. METHODS: The study patients met the following criteria: histologically confirmed, previously treated advanced (stage IIIB or IV) or recurrent NSCLC; a measurable lesion; > or = 18 years of age; Eastern Cooperative Oncology Group Performance status 0 to 2; and no prior exposure to the three study drugs. Patients received 500 mg/m2 of pemetrexed intravenously every 3 weeks with vitamin supplementation, gefitinib (250 mg/day per os), or erlotinib (150 mg/day per os). RESULTS: Of 57 patients (pemetrexed, 20; gefitinib, 20; and erlotinib, 17), 55 were evaluated for a response. The numbers of males, smokers, and squamous histology were increased in the pemetrexed group compared to the other groups. The objective response rates were 5.3%, 25.0%, and 12.5% (p = 0.22), and the disease control rates (DCR) were 5.3%, 40.0%, and 50.0%, respectively (p < 0.01). The median progression-free survival (PFS) was 1.7, 3.5, and 4.4 months (p < 0.01) and the median overall survival (OS) was 5.6, 21.8, and 21.5 months (p = 0.04), respectively. In subgroup analyses, patients with non-squamous histology, males, and a smoking history had a higher DCR and longer PFS with gefitinib and erlotinib than with pemetrexed. All three chemotherapeutic agents had manageable toxicities. CONCLUSIONS: Both oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) had comparable efficacy and safety. The superior PFS and OS of EGFR TKIs with more favorable baseline clinical characteristics than those of pemetrexed suggest the impact of baseline clinicopathological factors.

Prolonged Extreme Thrombocytosis in a Postsplenectomy Patient with Hereditary Spherocytosis / 대한혈액학회지

We report a case of prolonged extreme reactive thrombocytosis in a post-splenectomy patient with hereditary spherocytosis. A 29-year-old female patient presented with gall stones detected incidentally by abdominal ultrasonography. Her laboratory findings showed hemolytic anemia with spherocytosis on the peripheral blood smear and increased osmotic fragility. She was diagnosed with hereditary spherocytosis and underwent a laparoscopic cholecystectomy and splenectomy. After undergoing surgery, the hemolytic anemia was resolved but thrombocytosis was newly detected. Nineteen months after the splenectomy, the thrombocytosis was still persistent and extremely high. To our knowledge, this is the first report of a prolonged extreme reactive thrombocytosis after a splenectomy in Korea.

Epidermal Growth Factor Receptor Mutations and the Clinical Outcome in Male Smokers with Squamous Cell Carcinoma of Lung

Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) have been reported to be related to certain clinical characteristics (i.e., female, non-smokers with adenocarcinoma) and gefitinib responsiveness. This exploratory analysis was performed to determine the incidence of EGFR mutations in male smokers with squamous cell carcinoma, who were treated with EGFR tyrosine kinase inhibitor, gefitinib. Sixty-nine Korean NSCLC patients were treated with gefitinib in a prospective study. For a subset of 20 male patients with squamous cell carcinoma and a history of smoking, pretreatment tumor tissue samples were obtained and analyzed for EGFR mutations (exons 18 to 21). EGFR mutations were found in 3 (15%) patients, including in-frame deletions within exon 19 (n=2) and L858R missence mutation in exon 21 (n=1). These 3 patients with EGFR mutations responded to gefitinib, whereas only one of remaining 17 patients with wild-type EGFR achieved clinical response. Trend toward longer progression-free (5.8 vs. 2.4 months; P=0.07) was noted in patients with EGFR mutations compared to those with wild-type EGFR. Although male smokers with squamous cell carcinoma have not been considered ideal candidates for gefitinib treatment, significant incidence of EGFR mutations was observed. The molecular markers should be considered to predict clinical benefits from gefitinib.