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Background JAK2 mutation status is a well-known risk factor for thrombosis in patients with myeloproliferative neoplasms. However, the clinical usefulness of JAK2 allele burden is under investigation. Methods We retrospectively evaluated the impact of the JAK2 V617F allele burden on clinical characteristics and outcomes of JAK2 V617F-positive polycythemia vera (PV) and essential thrombocythemia (ET). The JAK2 V617F allele burden was measured using sequencing. Results Altogether, 127 patients with JAK2 V617F mutation (PV, N=61; ET, N=66) were included in this study. JAK2 V617F allele burdens were positively correlated with white blood cell counts, hemoglobin values, lactate dehydrogenase levels, and platelet counts. The median values of JAK2 V617F allele burden in patients with PV and ET were 58% and 30%, respectively. A JAK2 V617F allele burden of ≥30%, older age, and a higher hemoglobin level were risk factors for thrombotic events in ET. In patients with PV, older age was the only thrombotic risk factor. The 8-year probabilities of overall survival (OS) were 82.9% in all patients. A high JAK2 V617F allele burden (≥58%) was associated with poor OS in patients with PV. For the patients with ET, the difference in 8- year OS based on the JAK2 V617F allele burden was not significant. Conclusion The JAK2 V617F allele burden was correlated with hematologic parameters and clinical outcomes. Assessing the JAK2 V617F allele burden can be helpful in predicting the thrombotic risk and disease course in patients with JAK2 V617F-positive PV and ET.

Background/Aims: For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of non-clear 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.

Purpose The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy. Materials and methods Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC). Results The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006). Conclusion KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

Purpose We compared two induction regimens, idarubicin (12 mg/m2/d for 3 days) versus high-dose daunorubicin (90 mg/m2/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m2/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.

Purpose Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). Materials and Methods Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). Results The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m2 (95.0%), and that of Genexol was 168.3±10.6 mg/m2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (pnon-inferiority=0.021, psuperiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. Conclusion Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

To investigate the association between quality of life (QOL) and breakthrough cancer pain (BTCP) intensity in patients who met the commonly accepted definition of BTCP. This study was a subset analysis of a South Korean multicenter, non-interventional, cross-sectional, nationwide survey. Participants were recruited from March 2016 to December 2017. BTCP was defined as a controlled background pain of less than a numeric rating scale (NRS) of 3 and any flare-up pain intensity. Pain intensity data were collected using the Brief Pain Inventory (BPI), which includes an interference assessment of the affective and physical domains. Patients were categorized by BTCP intensity into mild (NRS 1–3), moderate (4–6), and severe (7–10) groups. Of the 969 screened patients with cancer, 679 had ≤ NRS 3 background pain, of whom 438 completed the BPI. Of these 438 patients, 40, 204, and 194 were in the mild, moderate, and severe BTCP groups, respectively. The median NRS of BTCP was 6.0 (interquartile range = 5.0–8.0). Patients with moderate-severe BTCP had significantly higher interference with daily functioning (IDF) scores than did mild BTCP patients (3.3 vs. 5.7; p

BACKGROUND: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug–drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes. SUBJECTS, MATERIALS, AND METHODS: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first‐line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first‐line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi‐comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment‐related toxicity, and hospitalization using logistic regression and Cox regression analyses. RESULTS: In total, 301 patients (median age 75 years; range, 70–93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0–14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18–2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment‐related toxicity. CONCLUSION: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period. IMPLICATIONS FOR PRACTICE: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug–drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer.

Aim We performed a phase II study to evaluate the efficacy of combination chemotherapy consisting of gemcitabine, dexamethasone and oxaliplatin (GemDOx) as a biweekly regimen and salvage therapy in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Methods Gemcitabine (1000 mg/m2) and oxaliplatin (85 mg/m2) were administered intravenously on days 1 and 15, and dexamethasone (40 mg) was administered orally on days 1–4. Results Twenty-nine patients were enrolled, and most patients had diffuse large B-cell lymphoma (n = 18). The median age of the patients and median prior number of chemotherapy cycles were 53 (range, 26–74) years and 1 (range, 1–4) cycle, respectively. Only 17 (58.6%) and 9 (31.0%) patients completed two or more and four or more cycles, respectively, and the median number of received cycles was two (range, 1–8). Overall response rates were 27.6% (complete response in 13.8%) among intent-to-treat patients and 47.1% (complete response in 23.5%) among patients who had received at least two GemDOx cycles. Median progression-free survival and median overall survival were 3.9 and 20.5 months, respectively. The most-frequent grade 3 or 4 toxicity was neutropenia (22.9%), and no grade 3 or 4 peripheral neurotoxicity was noted. Conclusion GemDOx chemotherapy, therefore, showed modest activity against relapsed or refractory aggressive NHL, although toxicities were acceptable.

We performed a study on allogeneic hematopoietic cell transplantation (alloHCT) from an HLA-haplo-identical familial donor (haploFD) using a busulfan-fludarabine-antithymocyte globulin conditioning regimen for severe aplastic anemia (sAA) and hypoplastic myelodysplastic syndrome. For the comparison between a haploFD and an alternative donor (AD; matched unrelated or partially matched donor) for sAA in adults, we collected haploFD data retrospectively and prospectively. Forty-eight AD cases were selected for the comparison with 16 haploFD cases. All transplantation outcomes except for extensive chronic graft versus host disease (GvHD) were similar. The frequencies of hepatic sinusoidal obstruction syndrome (p = 1.000), acute GvHD (p = 0.769), grade 3/4 acute GvHD (p = 0.258), chronic GvHD (p = 0.173), extensive chronic GvHD (p = 0.099), primary neutrophil engraftment failure (p = 1.000), secondary graft failure (p = 1.000) and platelet engraftment failure (p = 0.505) were similar. Time to neutrophil engraftment was faster in haploFD (p = 0.003), while the cumulative incidence of platelet engraftment was similar (p = 0.505). Overall survival was also similar between AD and haploFD (p = 0.730). In conclusion, alloHCT from haploFD in sAA was comparable with alloHCT from AD, but extensive chronic GvHD seemed frequent in haploFD. Therefore alloHCT from haploFD could be an alternative approach for alloHCT from AD in adult sAA.

⋅Received:14 December 2015 ⋅Revised:23 December 2015 ⋅Accepted:29 December 2015 ⋅Correspondence to:Dae-Jun Kim Department of Internal Medicine, Oriental Medical Hospital, Daegu Haany University, Daegu, Korea. Tel:+82-53-770-2103, E-mail:emdkdj@naver.com ⋅This study was supported by a grant from the Ministry of Health & Welfare, Republic of Korea, 2011. Objectives: We carried out an observational study of the effects of Nei Guan (P6) and Gong Sun (SP4) acupuncture for the treatment of CINV, preparing for further randomized controlled trial study. This is a case series to explore the changes in the incidence of CINV by acupuncture. Methods: Patients reported a Rhodex index indicating the severity of nausea and vomiting and loss of appetite, before acupuncture, after acupuncture and 1-week follow-up examination. Twelve patients with CINV participated in this study. We included patients receiving chemotherapeutic agents that might induce moderate or severe nausea and vomiting. We conducted 5 treatment sessions with P6 and SP4 acupuncture over the course of 5 days. Results: The median Rhodex score were decreased in 5 patients over time, while we observed loss of appetite of 6 patients were improved over time. During the study, the mean of Rhodex of total patients revealed a decrease of Day 1, Day 7, Day 14; 0.74, 0.68, 0.38, respectively, while the mean of loss of appetite showed a decrease of Day 1, Day 7, Day 14; 5.25, 4.08, 4.00, respectively. Conclusions: The study gives a preliminary data that manual acupuncture of P6 and SP4 may reduce the severity of CINV and loss of appetite, and justifies further study.

Overall, more than 50% of marginal zone lymphoma (MZL) patients experience a relapse within 10 years. This phase II trial was conducted to assess the efficacy and safety of oxaliplatin-prednisone (Ox-P) chemotherapy for patients with relapsed or refractory MZL. Patients received oxaliplatin 130 mg/m(2) on day 1 and prednisone 100 mg/day on days 1-5 of each cycle. A total of 38 patients were enrolled. The median age of the 34 (16 males, 18 females) evaluated patients was 53 (range = 27-74) years. There were seven complete responses (20.6%) and 15 partial responses (44.1%) (Overall response rate = 64.7%). No treatment-related deaths occurred. The median progression-free survival was 14.2 months (95% CI = 2.1-26.3 months); 3-year overall survival rate was 77.7%. Thus, salvage Ox-P chemotherapy for patients with relapsed or refractory MZL at the stated dosage and schedule showed moderate clinical activity and was considerable in very few selected patients (NCT01068392).

581 Copyrightc 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 2014. 11. 28 Revised: 2015. 3. 4 Accepted: 2015. 4. 29

The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty-two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5-year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5-year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P

Relapsed or refractory acute myeloid leukemia (R/R AML) in elderly (≥60 yr old) patients were eligible. Induction chemotherapy consisted fludarabine and cytarabine (ARAC) as a 24-hr CI without idarubicin (C-FLAG), which was compared with the results of C-FLAG with idarubicin (CI-FLAG2) in younger patients' trial. A total of 33 and 68 patients were enrolled in C-FLAG and CI-FLAG2, respectively. CR, CRp, and CRi were achieved in 10 (30.3%), 3 (9.1%), and 2 (6.1%), respectively. When comparing outcomes between C-FLAG and CI-FLAG2, there were no difference in terms of CR rate (P = 0.572) and objective response rate (ORR; P = 0.899). Favorable predictors on ORR in C-FLAG were PB WBC ≤ 20K/uL at salvage (P = 0.024) and early evaluation peripheral BLAST = 0% (P = 0.013) on multivariate analysis. The overall survival of patients who achieve CR/CRp/CRi showed significantly prolonged survival compared with patients who did not in C-FLAG (P

Background: The rationale for developing an alternative paclitaxel formulation concerns Cremophor EL-related side effects, and a novel paclitaxel delivery system might augment its therapeutic efficacy. Genexol-PM is a novel polymeric micelle formulated paclitaxel free of Cremophor. The polymeric micelle formulation is composed of hundreds of low molecular weight, non-toxic, and biodegradable amphiphilic diblock copolymers which include monomethoxy poly (ethylene glycol)-block-poly (D,L-lactide). This multicenter phase III study was designed to evaluate the non-inferiority of efficacy of Genexol-PM compared to conventional CrEL-based paclitaxel. Methods: In this phase III study, 213 patients were enrolled onto the study and randomly assigned (1:1) to treatment group according to prior recurrent or metastatic breast cancer chemotherapy. The study evaluated the objective response rate for the primary objective, and others including overall survival (OS), progression free survival (PFS), time to tumor progression (TTP), duration of overall response and adverse events. Eligible patients were randomly assigned to receive either Genexol-PM or standard paclitaxel. Genexol-PM or standard paclitaxel was administered on the first day of every 3 weeks. Measurable disease was assessed by imaging using the RECIST 1.0 criteria. Results: The objective response rate (ORR) was higher by the administration of the study drug (39.05% v 24.30% in ITT, 56.92% v 39.29% in PP). One-sided 95% upper confidence limit was -4.36%, which is lower than the non-inferiority threshold (7%), indicating that the study group is not inferior to the control group. OS, PFS, TTP and duration of overall response were analyzed in the ITT population. The analysis of OS showed no significant difference (p=0.5878) (859 days, 95% CI : 732.00∼1,025.00 v 726 days, 95% CI : 553.00∼ -). Median PFS periods were 232 days (95% CI: 164.00∼274.00) vs. 191 days (95% CI: 159.00∼237.00). Median TTPs were 233 days (95% CI: 165.00∼286.00) vs. 191 days (95% CI: 159.00∼241.00) between the groups. Difference in PFSs and TTPs between the groups were not statistically significant. (p=0.2407, 0.2076, respectively) Genexol-PM was not significantly different from the comparator in terms of safety. Conclusion: Genexol-PM demonstrated non-inferior efficacy and comparable safety profile compared with standard paclitaxel in this patient population. Of note, Genexol-PM permits the delivery of a higher paclitaxel dose without additional toxicity achieved with CrEL-based formulation. In the absence of CrEL, no filter or special tubing is required that conventional PVC infusion sets can be used. Citation Format: Jung Sil Ro, Joo Hyuk Sohn, Sung Bae Kim, Keun Seok Lee, Joo Seop Chung, Jae Hoo Park, Soo Hyeon Lee, Tae You Kim, Kyung Hae Jung, Eun Kyung Cho, Yang Soo Kim, Hong Suk Song, Jae Hong Seo, Hun Mo Ryoo, Sun Ah Lee, So Young Yoon, Chul Soo Kim, Yong Tai Kim, Hwa Jung Sung, Si Young Kim, Yong Jin Lee. A open-label, randomized, parallel, phase III trial to evaluate the efficacy and safety of Genexol®-PM compared to Genexol®(conventional paclitaxel with cremorphor EL) in recurrent or metastatic breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-10-04.

BACKGROUND Patients receiving red blood cell (RBC) transfusions are at risk of iron overload, which can cause significant organ damage and is an important cause of morbidity and mortality. STUDY DESIGN AND METHODS This study was an open-label, single-arm, prospective clinical study to evaluate the efficacy and safety of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML). Patients with serum ferritin levels of at least 1000 ng/mL and ongoing transfusion requirements were enrolled. DFX was administered for up to 1 year. A total of 100 patients were enrolled. RESULTS Serum ferritin levels decreased significantly following treatment (from 2000 to 1650 ng/mL, p = 0.004). The median absolute reduction in serum ferritin levels was −65 ng/mL in AA (p = 0.037), −647 ng/mL in lower-risk MDS (MDS-LR; p = 0.007), and −552 ng/mL in higher-risk MDS (MDS-HR)/AML (p = 0.482). Mean labile plasma iron (LPI) levels decreased from 0.24 μmol/L at baseline to 0.03 μmol/L at 1 year in all patients (p = 0.036). The mean LPI reduction in each group was −0.17 μmol/L in AA, −0.21 μmol/L in MDS-LR, and −0.30 μmol/L in MDS-HR/AML. Gastrointestinal disorders were commonly observed among groups (16.0%). DFX was temporarily skipped for adverse events in seven patients (7.0%) and was permanently discontinued in 11 patients (11.0%). CONCLUSION DFX reduced serum ferritin and LPI levels in patients with transfusional iron overload. Despite the relatively high percentage of gastrointestinal side effects, DFX was tolerable in all subgroups.

Pain is one of the most common and distressing symptoms in patients with cancer, with a high prevalence of 90%. Appropriate pain assessment is very important in managing cancer pain.The aims of this study were to (1) evaluate patient satisfaction with pain control therapy using a self-reporting pain assessment tool, (2) explore the usefulness of a self-reporting assessment tool for patients and physicians, and (3) evaluate patient perception of pain management and opioid analgesics.We enrolled a total of 587 South Korean adult cancer patients hospitalized for five days or more. Pain assessment using a self-reporting pain assessment tool was performed by patients themselves from Day 1 to Day 5. The average pain intensity on a numeric rating scale (NRS) and the frequency of breakthrough pain between Day 1 and Day 5 were recorded with a self-reporting pain assessment tool. We evaluated patient satisfaction with pain control and the usefulness of a self-reporting pain assessment tool for patients and physicians on Day 5.Among the 587 enrolled patients, 551, excluding 36 patients who violated inclusion criteria, were analyzed. The pain satisfaction rate was 79.5%, and only 6.2% of assessed patients had a negative pain management index (PMI). However, symmetry analysis for pain intensity between patient and physician showed low agreement (kappa=0.21). The patients with dissatisfaction for cancer pain control expressed negative attitudes toward using opioid analgesics and misconceptions regarding pain management. The satisfaction for using a self-reporting pain assessment tool was 79.2% in patients and 86.4% in physicians, respectively.The use of a self-reporting pain assessment tool as a communication instrument provides an effective foundation for evaluating pain intensity in cancer pain management. A more individualized approach to patient education about pain management may improve patient outcome.

Purpose This study was conducted to evaluate outcomes in adult patients with Burkitt lymphoma (BL) or Burkitt-like lymphoma treated with an rituximab plus hyper-CVAD (R-hyper-CVAD) regimen by focusing on tolerability and actual delivered relative dose intensity (RDI). Materials and methods Patients ≥ 20 years of age and pathologically diagnosed with BL or Burkitt-like lymphoma were treated with at least one cycle of R-hyper-CVAD as the first-line treatment in this study. Eligible patients' case report forms were requested from their physicians to obtain clinical and laboratory data for this retrospective study. Results Forty-three patients (median age, 51 years) from 14 medical centers in Korea were analyzed, none of which were infected with human immunodeficiency virus. The majority of patients had advanced diseases, and 24 patients achieved a complete response (75.0%). After a median follow-up period of 20.0 months, 2-year event-free and overall survival rates were 70.9% and 81.4%, respectively. Eleven patients (25.6%) were unable to complete the R-hyper-CVAD regimen, including six patients due to early death. The RDIs of adriamycin, vincristine, methotrexate, and cytarabine were between 60% and 65%, which means less than 25% of patients received greater than 80% of the planned dose of each drug. Poor performance status was related to the lower RDIs of doxorubicin and methotrexate. Conclusion R-hyper-CVAD showed excellent treatment outcomes in patients who were suitable for dose-intense chemotherapy. However, management of patients who are intolerant to a dose-intense regimen remains problematic due to the frequent occurrence of treatmentrelated complications.

We previously assessed continuous infusion (CI) of fludarabine and cytarabine plus idarubicin (CI-FLAG1) for patients under 65 years of age with resistant acute myeloid leukemia. Induction chemotherapy consisted of idarubicin (IDA) plus fludarabine and cytarabine (ARAC) as a 24-hour CI. In response to induction, 31.6% of patients achieved complete remission (CR) and in 68.4% the treatment failed. We concluded that CI-FLAG1 carried a high risk of toxicity and reduced CI-FLAG doses were recommended. Therefore, we revised the protocol (CI-FLAG2) by reducing the dose of IDA and ARAC. In total, 38 and 68 patients were enrolled into CI-FLAG1 and CI-FLAG2, respectively. When comparing outcomes between CI-FLAG1 and CI-FLAG2, there were no differences in terms of the CR rate (p = 0.306) and the overall response rate (ORR; p = 0.206). The treatment failure patterns were different between CI-FLAG1 and CI-FLAG2. The median overall survival showed only a trend towards longer survival in CI-FLAG2 (p = 0.074). Among intermediate-risk patients, there were high response rates favoring CI-FLAG2 in terms of the CR rate (p = 0.108), the ORR (p = 0.031), and overall survival (p = 0.033). This represented a relatively improved response rate compared to our previous study. There was decreased aplasia with dose reductions at the expense of increased resistance. A reduced dose of CI-FLAG might be most beneficial for intermediate-risk groups.

This multicenter phase II clinical trial was designed to evaluate the efficacy and safety of weekly Genexol-PM® and gemcitabine combination chemotherapy in patients with unresectable or metastatic biliary tract cancer. Patients and methods Patients received 100 mg/m2 Genexol-PM® and 1,000 mg/m2 gemcitabine intravenously on days 1 and 8 every 21 days. Results Out of 39 patients, there were 10 partial responses (25.6%) and 18 with stable diseases (46.2%) were confirmed with median response duration 4.1 months. The median progression-free survival was 5.9±1.6 months and overall survival 11.9±1.4 months. The median number of cycles administered was 4.0 (range=1-10). Grade 3 or more neutropenia occurred in 12 patients (26.7%). The most common grade 3/4 non-hematological toxicities were febrile neutropenia (13.4%) and elevation of liver enzymes (6.7%). Conclusion Weekly Genexol-PM® combined with gemcitabine demonstrated sufficient antitumor activity to warrant further development when used as first-line chemotherapy for advanced biliary tract cancer.

We conducted a retrospective analysis of lenalidomide with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM) who were treated within the Korean patient access program. Lenalidomide has been approved for RRMM for several years in Europe and North America, but has not been accessible to Asian patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good partial response (VGPR) or better. The median time to progression (TTP) in this heavily pretreated patient population was 8.0 months, and median overall survival (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation were the most common adverse events. The number of previous treatment lines, previous exposure to thalidomide, refractoriness to thalidomide and bortezomib, pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p deletion were significant prognostic factors for TTP, and creatinine clearance, refractoriness to thalidomide and bortezomib, performance status, platelet count, and 17p deletion were significant for OS in univariate analysis. In multivariate analysis, WBC and platelet count were significant prognostic factors for TTP and performance status for OS. For Korean myeloma patients, lenalidomide showed considerable efficacy, and toxicities were comparable to the data published in Europe and North America.

Purpose We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. Materials and Methods A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively. Results The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p

To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5-7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.

The dose intensity of daunorubicin (DNR) delivered during the induction period represented the major prognostic factor for the outcome of adult acute lymphoblastic leukemia (ALL). The aim of this study was to determine the survival or toxicity of escalated doses of DNR in induction treatment of adult patients with acute lymphoblastic leukemia who are at least 15 years of age. For induction chemotherapy, all patients were given 90 mg/m(2)/day of DNR by continuous intravenous (IV) infusion over 24 h daily on days 1-3, 2 mg of vincristine IV push on days 1 and 8, and 60 mg/m(2)/day of prednisolone per oral (PO) on days 1-14 in conjunction with 4,000 units/m(2)/day of L-asparaginase intramuscular or subcutaneous on days 17-28. The median patient age was 32 years (range, 15-69). Complete remission (CR) was achieved in 169 (88.5 %) patients, while 4 died before CR was reached. Additionally, 11 patients died from leukemia progression, 4 had refractory disease, and 3 had follow-up loss. The median follow-up time was 697 days (range, 12-2,270). The 3-year cumulative incidence of relapse was 49.3 %. The probabilities of disease-free survival and overall survival at 3 years were 46.1 and 43.1 %, respectively. The dose of DNR was 100 % of the target dose, and there were no additional specific toxicities. The results show that escalated doses of DNR in induction chemotherapy are similar with the standard dose in response and toxicities. Our study indicates that a more effective regimen or better chemotherapy agents are needed to improve the CR rate and prolong survival in Philadelphia-negative adult ALL.

Aim The vascular endothelial growth factor (VEGF) or its family might play role in tumor-related angiogenesis in gastrointestinal stromal tumors (GIST), thereby affecting the prognosis. Accordingly, the present study analyzed the impact of VEGF and VEGF receptor-2 (VEGFR-2) gene polymorphisms on the prognosis for GIST patients. Methods In all, 213 consecutive patients with GIST from five medical centers were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tumor tissue, and four VEGF (−2578C/A, −1498C/T, −634G/C, and +936C/T) and one VEGFR-2 (+1416A/T) gene polymorphisms were determined using a Sequenom MassARRAY system. Results With a median follow up of 18.4 months, the estimated 5-year relapse-free survival and overall survival rates were 70 and 87%, respectively. In a multivariate analysis including age, sex, primary site of disease, pathology and risk stratification, no significant association was observed between the polymorphism of the VEGF and VEGFR-2 genes and survival. Conclusion None of the five VEGF and VEGFR-2 gene polymorphisms investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected GIST. However, further studies on a larger scale are warranted to clarify the role of VEGF and VEGFR gene polymorphisms as a prognostic biomarker for GIST patients.

The clinical outcomes of acute promyelocytic leukemia (APL) have improved greatly, but treatment failure still occurs. Identification of patients with poor prognosis is fundamental, and we propose a new clinical prognostic system (CBC-score) consisting of WBC, platelet count, and hemoglobin level. Between 1995 and 2009, 156 patients with APL from seven institutes in Korea were retrospectively reviewed. In the new CBC-score system, each of the following (WBC ≥10 × 109/L, platelet

The use of systemic chemotherapy after resection remains controversial in patients with resectable metachronous pulmonary metastases from colorectal cancer (CRC). This retrospective study compared systemic chemotherapy with observation alone after resection of pulmonary metastases from CRC.Between 2001 and 2015, 91 patients with metachronous pulmonary metastases underwent curative surgical resection at five centers. Patients with stage IV at diagnosis were excluded. Overall survival (OS) was defined as the time from pulmonary resection until death. The disease-free interval (DFI) was defined as the time from pulmonary resection until recurrence or death.Among the 91 patients, 63 were in the chemotherapy group, while 28 were in the observation alone group. The characteristics were similar between the two groups, except for the carcinoembryonic antigen level after pulmonary metastases and the use of adjuvant treatment after resection of the primary tumor. With a median follow-up duration of 46 months (11-126), the estimated 5-year DFI and OS rates were 32.8 and 61.4%, respectively. The chemotherapy following pulmonary resection was not significantly associated with the DFI (p = 0.416) and OS (p = 0.119).Systemic chemotherapy after pulmonary resection was not found to have a significant effect on survival.

Docetaxel/cisplatin (DP) and gemcitabine/cisplatin (GP) are standard treatment regimens for advanced non-small cell lung cancer (NSCLC). In spite of potent efficacy, the conventional 1-day DP is regarded as having more toxicity as compared with GP. There is increasing interest in a biweekly split administration of DP to reduce its toxicity. Hypothesis was that first-line biweekly DP is as safe as GP in the elderly or poor performance status (PS) patients. Chemotherapy-naive patients with advanced NSCLC (IIIB/IV) who were elderly (65

We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m2 per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m2 per day times 3 days) in addition to cytarabine (200 mg/m2 per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P = .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P = .030; EFS, 40.8% vs 28.4%, P = .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio [HR], 1.802, P = .024; OS, HR, 0.739, P = .032; EFS, HR, 0.774, P = .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.gov as #NCT00474006.

Introduction Diffuse large B cell lymphoma (DLBCL) of primary nodal (PN) or primary extranodal (PEN) origin may differ immunophenotypically, in that PEN lymphoma cells may originate from activated rather than germinal center B (GCB) cells. We evaluated the relationship between DLBCL clinicopathological features, including expression of B-cell differentiation markers, and primary tumor site. Patients and Methods Expression of CD10, Bcl-6, Bcl-2, and MUM1 was determined in paraffin-embedded tissues from 123 patients with DLBCL. Results Of the 123 patients with DLBCL, 40 (32.5%) had the GCB and 83 (67.5%) had the non-GCB phenotype. Fifty-one patients (42%) showed disease involvement at PEN sites, including 29 with disease in the gastrointestinal (GI) tract (14 in the stomach, 15 in the intestine). Of these 51 patients, 16 (31.4%) were classified with the GCB and 35 (68.5%) with the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes among primary sites. Of the 72 patients with PN DLBCL, 22 (31%) had the GCB and 50 (69%) had the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes between patients with PN and PEN DLBCL. Although lactate dehydrogenase (LDH) concentration > normal, stage >II, and rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) treatment were independent predictors of overall survival (OS), GCB subtype, and presence of PEN disease failed to predict survival upon multivariate analysis. Conclusion There was no difference in GCB and non-GCB phenotypes between patients with PN and PEN DLBCLs. Additional studies are needed to further assess molecular differences between the two groups.

The present study was conducted to evaluate the efficacy and safety of a combination regimen of S-1, paclitaxel plus cisplatin in patients with advanced gastric cancer.Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 80 mg/m² plus cisplatin 30 mg/m² on days 1, 8 and S-1 35 mg/m² orally twice daily on days 1-14 based on a 3-week cycle.Forty-four patients were enrolled in the current study, among whom 38 were assessable for efficacy and all assessable for toxicity. Two complete response and 24 partial responses were confirmed, giving an overall response rate of 59.1%. At a median follow-up of 11.4 months, the median time to progression and median overall survival was 9.4 (95% CI 6.8-12.1) months and 11.2 (95% CI 7.6-14.8) months, respectively. Grade 3/4 neutropenia occurred in 45 events (20.9%) and febrile neutropenia was observed in five events (2.3%). The common non-hematologic toxicity was nausea (grade 1/2, 27.2%) and diarrhea (grade 1/2, 9.0%).The combination of S-1, paclitaxel and cisplatin was found to be well tolerated and effective in patients with advanced gastric cancer.

We conducted a phase 2 study with bortezomib, doxorubicin, and dexamethasone (PAD) followed by thalidomide and dexamethasone (TD) in patients with relapsed multiple myeloma (MM). Forty patients were enrolled between November 2005 and October 2007, with follow-up continuing until January 2009. Efficacy could be assessed in 37 patients. The overall response rate to PAD followed by TD was 83.6%: complete response 51.4%, near-complete response 13.4%, very good partial remission 5.4%, and partial response 13.4%. The median follow-up was 27 months (range 13-39). The median progression-free survival (PFS) from the start of treatment was 18 months (95% CI, 9.7-26.2 months), with a 1-year PFS rate of 56.9% and 3-year PFS rate of 25.7%. Median overall survival was 35.1 months (95% CI, 18.5-51.7), with a 1-year survival rate of 75% and 3-year survival rate of 27.3%. One hundred seventy-eight PAD cycles (median 6, range 1-6) in 38 patients were assessable for safety. The most common hematologic toxicity was thrombocytopenia, with grade 3-4 in 35.8%. Sensory neuropathy occurred at grade 2 in 26.3% and grade 3 in 10.3%. Two hundred TD treatment cycles (median 4, range 0-12 cycles) were administered. Most adverse events were of mild degree and manageable. PAD followed by TD in patients with relapsed MM is very effective and tolerable.

The present study analyzed the polymorphisms of DNA repair genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer.A total of 94 patients with recurrent or metastatic colorectal cancer treated with oxaliplatin-based combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 16 DNA repair genes were determined using a PCR-RFLP assay.During the median follow-up duration of 15.9 (2.1-53.0) months, 67 (71.3%) progressions and 29 (30.9%) deaths were observed. Among the 60 patients assessable for response, response to the oxaliplatin-based regimens was found in 27 (45%) patients (9 CR and 18 PR). In a logistic regression analysis adjusted to age, sex, primary site, disease status, and regimen, the POLR2C rs4937 and MSH2 rs3732183 polymorphisms were statistically associated with the response to the oxaliplatin-based chemotherapy. A multivariate survival analysis showed that the TT genotype of the MGMT (rs1625649) -535GT polymorphism was found to correlate with a worse progression-free survival (PFS) than the combined GG + GT genotypes (HR = 3.137; 95% CI = 1.423-6.914; P = 0.005), which was also observed among the 60 evaluable patients (HR = 2.653; 95% CI = 1.101-6.392; P = 0.030) For the clinical parameters, curative resection was the most significant prognostic factor in a Cox model for PFS and overall survival (HR = 0.229 and 0.205; P0.001 and 0.001, respectively).The MGMT -535GT polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy.

Objective This prospective multicenter study conducted by the Korean Cancer Study Group evaluated the efficacy and safety of pemetrexed in Korean patients with advanced non-small cell lung cancer (NSCLC) who had prior chemotherapy. Patients and methods: Patients with stage IIIB or IV NSCLC in whom prior chemotherapy failed received pemetrexed 500mg/m 2 every 3 weeks with folic acid and vitamin B12 supplementation until disease progression or the development of intolerable toxicity. Eighty-one patients were enrolled. Results The overall response rate for 78 evaluable patients was 5.1% [95% confidence interval (CI) 1.4–12.6; partial response 4/78, no complete response]. The disease control rate including complete, partial response and stable disease was 46.2% (36/78, 95% CI 34.8–57.8). With a median 8.7 months follow-up, the median time to progression was 3.1 months (95% CI 1.17–5.03) and the median overall survival (OS) was 7.8 months (95% CI 5.19–10.35). The median OS for patients with adenocarcinoma histology was 18.7 months compared to 6.1 months for non-adenocarcinoma. In a multivariate analysis, Eastern Cooperative Oncology Group performance status 0–1 [hazards ratio (HR)=0.331, 95% CI 0.135–0.814] and adenocarcinoma (HR=0.504, 95% CI 0.283–0.899) were independent factors for prolongation of overall survival.Conclusions Pemetrexed monotherapy has promising efficacy in patients with advanced NSCLC as a second-line therapy with less hematologic and non-hematologic toxicity, especially in those with adenocarcinoma histology.

The objective of this study was to evaluate the efficacy and toxicity of docetaxel and cisplatin combination chemotherapy in patients with metastatic esophageal cancer.Patients with untreated metastatic squamous cell esophageal cancer, which was histologically proven with at least one measurable lesion, were eligible for the study. Docetaxel 70 mg/m(2) and cisplatin 70 mg/m(2) were intravenously given on day 1 of 21 days schedule.From December 2004 to December 2007, total of 39 patients (M/F = 39/0) were enrolled. The median age was 65 years. Thirty-four patients were evaluable for response. There were 3 (7.7%) complete remission, 10 (25.6%) partial remission, 11 (28.2%) stable disease, and 10 (25.6%) progression disease. The objective tumor response rate was 33.3% in intention-to-treat (ITT). Median PFS was 5.0 months and median survival was 8.3 months. Median number of cycles administered was 3. The relative dose intensity of docetaxel and cisplatin was 92 and 91%, respectively. This treatment was comparatively tolerated with grade 3/4 neutropenia in 20.5%/10.3%, grade 3 infection in 2.6% of patients.Docetaxel plus cisplatin combination chemotherapy showed promising antitumor activity with manageable toxicities in patients with metastatic squamous esophageal cancer.

The frequency of thromboembolic events (TE) in Caucasian patients with multiple myeloma (MM) receiving thalidomide as the initial treatment has been reported to be 10~58% without prophylactic anticoagulation. Korean MM patients treated with thalidomide were studied to determine the frequency of TE and associated risk factors. A retrospective medical record review of the Korean MM registry from 25 centers in Korea between 2003 and 2007 was performed. We assessed the incidence of arterial and venous TE and the associated clinical parameters. Three hundred and sixty MM patients (median age 61 years, range 32-88 years) received thalidomide treatment. Fourteen patients (3.9%) developed TE: 12 had venous and two had arterial locations. The sites for the venous TE included lungs (seven), lower extremities (four), upper extremities (one), and neck (one). Arterial TE developed in cerebral and peripheral arteries each. No single clinical parameter such as prerequisite for the metabolic syndrome, disease status, and treatment regimen were predictive for the development of TE. The frequency of TE in patients who received thalidomide as initial therapy (7/155) was not different from those who received thalidomide for progressive or relapsed disease (7/205, p = 0.592). The frequency of TE during thalidomide treatment in Korean patients with MM was low. No significant clinical factor was found to be a risk factor. The subgroup requiring thromboprophylaxis among the Korean patients with MM, receiving thalidomide, needs to be clarified.

Upfront high-dose myeloablative chemotherapy followed by a single autologous stem cell transplantation (ASCT) is the standard therapy for patients under the age of 65 years with newly diagnosed multiple myeloma (MM). Because disease status after induction chemotherapy is variable, we evaluated the prognostic effect of disease status before ASCT, especially in patients who were initially chemosensitive. We retrospectively analyzed the initially chemosensitive MM patients (≥ partial remission [PR]) enrolled in the Korean Multiple Myeloma Working Party Web-based registration system (www.myeloma.or.kr). Between November 1996 and January 2007, 197 MM patients (median age 53 years) were treated with induction chemotherapy followed by a single ASCT. All patients received peripheral blood stem cell (PBSC) support after conditioning with melphalan (Mel) alone. We considered those patients with no detectable M-protein regardless of the result of immunofixation to be in complete remission (CR) in this study. The median follow-up times were 29.2 months (range, 5.4 to 103.8 months) from the day of diagnosis and 22.4 months (range, 0.4 to 96.0 months) from the day of ASCT. Before ASCT, 63 patients (32%) were in CR and 134 (68%) were in partial remission (PR). The patients in CR had significantly longer overall survival (OS) from the day of ASCT compared with those in PR (P = .0015). Among the patients who received induction chemotherapy with vincristine, adriamycin, and dexamethasone (n = 162), the same difference in OS was seen between those in CR and those in PR before ASCT (P = .0016). CR after ASCT also predicted longer OS (P = .0135); however, patients with continued CR after ASCT had significantly higher OS after ASCT compared with patient with induced CR after ASCT who were in PR before ASCT (P = .0178). Multivariate analysis indicated that remission status pre-ASCT (CR vs PR) is a significant prognostic factor for predicting OS after ASCT (P = .012, Cox proportional hazard analysis; odds ratio = 2.83; 95% confidence interval = 1.25 to 6.37). We conclude that patients with MM who are in CR before ASCT have a better OS than those in PR before ASCT. Continued CR after ASCT may be an important prognostic factor as well. Our findings suggest that the development of more effective induction regimens, including novel antimyeloma agents to improve initial response, should be pursued to enhance clinical benefits post-ASCT.

Aim: The Korean Multiple Myeloma Working Party performed a nationwide registration of multiple myeloma patients via a web-based data bank system. Methods: We retrospectively analyzed registered data from 3,209 patients since 1999. Results: The median overall survival (OS) was 50.13 months (95% confidence interval: 46.20–54.06 months). Patients ≤40 years demonstrated a longer OS than patients >65 years of age (median OS 71.13 vs. 36.73 months, p < 0.001). Patients who received novel agents at any time during their treatments showed a longer OS than patients who did not (median OS 42.23 vs. 55.50 months, p < 0.001). Response to treatment was associated with OS, with tandem autologous stem cell transplantation (SCT) producing longer OS than single autologous SCT. Conclusions: We demonstrated associations between survival outcomes and treatment modalities as well as baseline disease characteristics in a registry of multiple myeloma patients using a web-based data analysis.

Primary retroperitoneal mucinous cystadenocarcinoma is a rare tumor. Only about 30 such cases have been reported in the worldwide literature, and a few Korean cases have been reported. The pathogenesis is not clear, and coelomic metaplasia of the retroperitoneal mesothelium has gained wide support. There is no consensus on the appropriate treatment, but surgical exploration is needed for the diagnosis and treatment, and adjuvant chemotherapy may be recommended following complete surgical excision. The long-term prognosis has not been established. We report here on a 32-year-old woman who was diagnosed as having a retroperitoneal mucinous cystadenocarcinoma with mural nodules of sarcomatoid change. Tumor excision and adjuvant chemotherapy were done and the patient is doing well without any evidence of recurrence at 42 months postoperatively.

Background The standard sunitinib schedule, 4 weeks on, followed by 2 weeks off (4/2 schedule), is associated with troublesome toxicities, and maintenance of adequate sunitinib dosing and drug levels, which are essential for achieving an optimal treatment outcome, is challenging. The objective of this study was to investigate the efficacy and safety of an alternative sunitinib dosing schedule of 2 weeks on and 1 week off (2/1 schedule) compared with the standard sunitinib schedule of 4 weeks on and 2 weeks off (4/2 schedule). Patients and methods In this multicenter, randomized, open-label, phase II trial, treatment-naive patients with clear-cell type metastatic renal cell carcinoma (mRCC) were randomly assigned to 4/2 or 2/1 schedules after stratification by Memorial Sloan Kettering Cancer Center risk group and the presence or absence of measurable lesions. The primary end point was the 6-month failure-free survival (FFS) rate, determined by intention-to-treat analysis. Results From November 2007 to February 2014, 76 patients were accrued, and 74 were eligible. FFS rates at 6 months were 44% with the 4/2 schedule (N = 36) and 63% with the 2/1 schedule (N = 38). Neutropenia (all grades, 61% versus 37%; grade 3–4, 28% versus 11%) and fatigue (all grades, 83% versus 58%) were more frequently observed with schedule 4/2. There was a strong tendency toward a lower incidence of stomatitis, hand–foot syndrome, and rash with schedule 2/1. Objective response rates (ORRs) were 47% in schedule 2/1 and 36% in schedule 4/2. With a median follow-up of 30.0 months, the median time to progression (TTP) was 12.1 months in schedule 2/1 and 10.1 months in schedule 4/2. Conclusion Sunitinib administered with a 2/1 schedule is associated with less toxicity and higher FFS at 6 months than a 4/2 schedule, without compromising the efficacy in terms of ORR and TTP (NCT00570882).

The objective of this study was to review the natural history of extrapulmonary small cell carcinoma (EPSCC) with specific emphasis on clinical features, response to treatment and survival. The records of all patients (n=34) with EPSCC treated at Yeungnam University Medical Center and Catholic University of Daegu Medical Center between 1998 and 2005 were retrieved and reviewed. The primary sites of tumor were the esophagus and thymus in 6 patients (17.6%) each, pancreas and stomach in 5 patients each (14.7%); other sites included were the cervix, abdominal lymph nodes, abdominal wall, bladder, colon, maxillary sinus, nasal cavity, ovary, parotid gland and liver. Twenty three patients out of 34 had limited disease. The median survival of all patients was 14 months. Independent prognostic factors included stage and primary tumor location. The prognosis for the patients with extensive disease and in the gastrointestinal group was unfavorable. EPSCC is a non homogeneous disease entity. As a result of its frequent recurrence, multimodal therapy has a better outcome even in cases of limited disease. Combination chemotherapy plays a central role for treatment of extensive disease in EPSCC. Further multicenter studies are now needed to determine more details regarding disease sub-class and optimal treatment modality.

TNF-alpha mediated apoptosis of the hematopoietic cells has been thought to contribute to the ineffective hematopoiesis observed in myelodysplastic syndrome (MDS). The combination of pentoxifylline (P) and ciprofloxacin (C) has been shown to reduce the serum levels of TNF-alpha, and an earlier trial of P and C with dexamethasone (D) provided good palliation for patients with MDS. The purpose of this study is to assess the hematologic response to PCD therapy for patients suffering with MDS. 21 of 25 patients who completed at least of 12 weeks of treatment were evaluable for the treatment efficacy. At baseline, the patient's median age was 60 yr (range: 18-75 yr). The diagnoses according to WHO classification included: RA (n=5), RCMD (n=10), RARS (n=1), RCMD/RS (n=1), RAEB (3), and CMML (n=1). 11 patients (52%) had at least single lineage response. 3 patients (11%) showed improvement of triple lineage cytopenia. There were no differences in the response rates between the FAB subtypes. The median time to response was 4 weeks (range: 2-12 weeks), and it is interesting that 9 of 11 patients who had a response remained without relapse for a median of 177 days (range: 78-634 days). These preliminary results indicate that anti-cytokine therapy with PCD is an effective and well tolerated palliative treatment for patients with MDS.

Thrombotic thrombocytopenic purpura (TTP) is a disseminated form of thrombotic micro-angiopathy. Although most cases are held to be idiopathic, its association with malignancy iswellrecognizedanditusuallyoccursattheterminalstageofcancer.Bonemarrownecrosis(BMN)is another rare disorder defined pathologically as the necrosis of myeloid tissue and medullarystromawithpreservationofbone.Whilehematologicmalignancyisthemostcommonunderlyingdisease associated with BMN, it can also be caused by solid tumors. Neither TTP nor BMNassociated with colon cancer has been reported. We describe here a patient with the rare asso-ciation of TTP and BMN displayed as the first manifestation of an advanced colon cancer. Theanemia and thrombocytopenia responded not to plasma exchange but to the combinationchemotherapy. This case indicates that metastatic cancer should be included in the differentialdiagnosis of TTP and BMN, and that the chemotherapy may improve the detrimental clinicalcourse.Key words: thrombotic thrombocytopenic purpura – bone marrow necrosis – colon cancer –microangiopathic hemolytic anemia

PURPOSE This study was conducted to evaluate the efficacy and safety of combination chemotherapy, with docetaxel and cisplatin, as a first line treatment for advanced non-small cell lung cancer. MATERIALS AND METHODS Between March 1998 and December 2001, 35 patients with advanced non-small cell lung cancer were enrolled in this study. The patients were treated at 3-week intervals, with one course of a regimen consisting of docetaxel (75 mg/m2 IV for 1 hours) on day 1 and cisplatin (60 mg/m2 IV) on day 2. RESULTS The median age of the patients was 60.3 years. Of the 35 patients, 20 and 15 had stage IIIb and stage IV diseases, respectively. A complete response was observed in 1 patient and partial response in 15, with an overall response rate of 46%. The overall median survival duration was 40.3+/-25.2 weeks. The median time to progression and response duration were 21.6+/-5.5 and 15.1+/-5.9 weeks, respectively. The survival duration was statistically significantly longer in the response group (50.6 weeks) than in the non-response group (31.6 weeks) (p

Background: Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key suppressors of the cytotoxic immune response. PD-L1 expression on tumor cells may be induced by the immune microenvironment, resulting in immune escape, and an adverse prognosis in many malignancies. In colorectal carcinoma the response to PD-1/PD-L1 inhibition is correlated with microsatellite instability. However, little is known about the clinicopathologic, molecular, and prognostic characteristics of colorectal carcinoma with PD-L1 expression. In surgically resected colorectal adenocarcinoma, micrometastasis should be crucial for recurrence, and micrometastasis may be related to PD-L1. The aim of this study is to assess the PD-L1 expression and its association with clinicopathologic manifestations. Methods: PD-L1 expression was evaluated in 176 resected colorectal adenocarcinomas using tissue microarrays. Immunohistochemical staining was performed to evaluate the expression of PD-L1. The relationship of clinicopathologic manifestations and PD-L1 expression in colorectal cancer were evaluated by chi-squared test, Kaplan-Meier survival and Cox regression test. Results: High PD-L1 expression was present in 52.8% colorectal adenocarcinoma and was not related pathologic T or N stage. High PD-L1 expression was associated with decreased recurrence rate (p < 0.001), better disease-free survival (p < 0.001). Cox regression analysis revealed that pathologic N stage and High PD-L1 expression was an independent prognostic factors of disease-free survival (p < 0.001). Conclusion: High PD-L1 expression is an independent prognostic factor, such as pathologic stage in colorectal adenocarcinoma. PD-L1 expression is independent prognostic factor, relating immune response to micrometastasis and immune suppression by PD-L1 may not be effective in micrometastasis of colorectal adenocarcinoma. Key words: PD-L1, colon, cancer, immunology, micrometastasis Citation Format: Ilseon Hwang, Keon Uk Park, Jin Young Kim, Hun-Mo Ryoo, Yun-Han Lee. Programmed cell death ligand 1 expression in resected colorectal adenocarcinomas: association with micrometastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3927. doi:10.1158/1538-7445.AM2017-3927

e21540 Background: Full geriatric assessment is time-consuming and labor intensive, and most screening tools were developed in Western countries, which cannot reflect differences in some domains such as nutrition deficit, in Asians. Methods: This prospective study to validate a novel geriatric screening tool, the Korean Cancer Study Group Geriatric Score (KG)-7, was conducted as a substudy of a multicenter study for the prediction tool of toxicity in older cancer patients receiving 1st line chemotherapy (KCSG PC13-09). Abnormal GA was defined as deficits in at least 2 out of 6 domains [activities of daily living (ADL), Korean-instrument ADL (K-IADL), Mini-Mental Status Examination in the Korean version of the Consortium (MMSE-KC), Short-Form Geriatric Depression Scale (SGDS), the Mini Nutritional Assessment (MNA), Timed Get Up and Go test (TGUG)]. KG-7 questionnaire was answered before full GA. We compared the performance of KG-7 with G-8 score, obtained from MNA, by calculating AUC of accuracy, and also sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV). Results: Baseline GA and KG-7 results of 301 patients were collected. Median age was 75 years old (range 70-93). Eighty six (28.6%) and 124 patients (41.2%) showed dependent ADL and IADL, respectively. Impairment for domains of MMSE, SGDS, MNA, and TGUG was identified in 166 (55.1%), 132 (43.9%), 230 (76.4%), and 52 patients (17.3%), respectively. Abnormal GA was documented in 221 patients (73.4%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, the AUC was 0.741 (95% CI, 0.683-0.800), and the SE, SP, PPV, and NPV were 75.6%, 58.7%, 84.3%, and 44.9%, respectively. Abnormal KG-7 score was shown in 198 patients (66.9%). With the ≤ 14 cut-off value of G-8 for abnormal GA, the G-8 showed a SE, SP, PPV, and NPV of 93.6%, 28.0%, 79.2%, and 60.0% with AUC of 0.766 (95% CI, 0.703-0.829). Abnormal G-8 score was shown in 260 patients (88.1%). Conclusions: KG-7 could identify patients with abnormal GA with comparable performance with G-8 and can be a useful screening tool for Asian countries with limited resources and high patient volume.

e21539 Background: Older adults have increased risk of developing chemotherapy toxicity. Currently available prediction tools do not provide information on cumulative risk and none are from Asia. Methods: Patients with histologically confirmed solid cancer aged ≥70 years were prospectively enrolled from 17 centers and underwent geriatric assessment before starting their 1st line chemotherapy. Chemotherapy toxicity prediction model was built for adverse events (AEs) ≥G3, among geriatric assessment, laboratory and clinical variables. Model discrimination values were evaluated using c-statistics compared with actual cumulative incidence of AE ≥G3 in each cycle. Results: 301 patients were enrolled with a median age of 75 years (range 70-93). Primary site included colorectal (28.9%), lung (24.6%), hepato-biliary-pancreatic (22.3%), stomach (10.6%) and others (13.6%). Median chemotherapy cycle was 4 (2-7 cycles). During first line chemotherapy, 53.8% of patients experienced AEs ≥G3. Six variables significantly associated with occurrence of AEs ≥ G3 were serum protein < 6.7 g/dL, no dose reduction at first cycle, suffering from psychological stress or acute disease in the past 3 months, water consumption of less than 3 cups per day, not being able to obey command of 'Grab a piece of paper in your hand', and self-perception of ‘not in good health’. Model with all six variables was selected with the highest mean value of c statistics (0.646) and prediction tool indicated score ranging from 0 to 8 points. Patients were classified to 4 risk groups; 61 (21.0%), 143 (49.3%), 66 (22.8%), and 20 (6.9%) in low (0, 1 point), medium-low (2, 3), medium-high (4, 5), and high risk group (6, 7, 8). Predicted cumulative incidence of AEs ≥G3 was discriminated according to risk groups; low risk group: 13%, 19%, 27%, 30%, 30% in cycle 1, cycle 2, cycle 3, cycle 4, cycle 5, medium-low risk: 17%, 37%, 48%, 56%, 60%, medium-high risk: 26%, 44%, 50%, 68%, 75%, and high risk: 45%, 62%, 87%, 94%, 94%. Conclusions: Novel prediction tool could identify those at high risk of developing AEs ≥G3 after chemotherapy, which provided information on cumulative incidence in each cycle.

ObjectiveTo collect preliminary data on the effects of Saam acupuncture with regard to the immunity in cancer patients.MethodsTen cancer patients were analyzed for improvements in immunity. Acupuncture was applied at the 5 acupuncture points, Jingqu (LU 8), Zutonggu (BL 66), Yanggu (SI 5), Yangchi (TE 4), and Zhongwan (CV 12) for 2 weeks with 4 sessions. We assessed the effect of Korean Saam acupuncture on the immune system in cancer patients by measuring particular blood cell subsets, including CD3+, CD4+, CD8+, CD19+, and CD56+ cells, as well as total white blood cell count, absolute neutrophil count, and fatigue score. The measurement was performed before and after acupuncture and at a 2-week follow-up.ResultsThere was a statistically significant increase in the number of CD3+ (P=0.023) and CD8+ cells (P

The practical usefulness of Helicobacter pylori eradication for immune thrombocytopenia (ITP) patients is still controversial. However, some ITP patients respond to H. pylori eradication. We conducted a multi-center, open label, prospective phase II study to define the efficacy and toxicities of H. pylori eradication as the first line treatment for persistent or chronic ITP patients with moderate thrombocytopenia. Patients with persistent or chronic ITP showing moderate thrombocytopenia (30 × 10(9)/L ≤ platelet count ≤ 70 × 10(9)/L) and positive C(13)-urea breath test (UBT) were selected. Medication consisted of lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg orally twice daily for a week. Complete response (CR) rate at 4 weeks, 3 months, 6 months, 12 months, and maximal response was 19.2, 50.0, 50.0, 26.9, and 65.4%, respectively. Overall response rate (ORR) at 4 weeks, 3 months, 6 months, 12 months, and maximal response was 19.2, 57.7, 65.4, 30.8, and 69.2%, respectively. Median maximal platelet count during the first 3 months was 110 × 10(9)/L (range, 40-274). Median time to CR was 8 weeks (95% CI = 5.429-10.571). Median time to ORR was 4 weeks (95% CI = 1.228-6.772). Only per-protocol population was a response predictor for ORR at 3 months (70.0%, p = 0.054) and maximal ORR (80.0%, p = 0.051), but not for CR at 3 months (60.0%, p = 0.160). Therefore, eradication of H. pylori is an effective and durable first line treatment for persistent or chronic ITP with moderate thrombocytopenia with high ORR and rapid onset in this study.