Hyun Ae Jung

Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS) treated with anthracycline-containing chemotherapy

BackgroundPeripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with poor treatment outcomes. The aim of this study was to evaluate whether lymphopenia at diagnosis would have an adverse effect on survival in patients with PTCL-NOS treated with anthracycline-containing chemotherapy.MethodsA total of 118 patients with PTCL-NOS treated with anthracycline-containing chemotherapy from 4 Korean institutions were included.ResultsThirty-six patients (30.5%) had a low absolute lymphocyte count (ALC, < 1.0 × 109/L) at diagnosis. Patients with lymphopenia had shorter overall survival (OS) and progression-free survival (PFS) rates compared with patients with high ALCs (P = 0.003, P = 0.012, respectively). In multivariate analysis, high-intermediate/high-risk International Prognostic Index (IPI) scores and lymphopenia were both associated with shorter OS and PFS. Treatment-related mortality was 25.0% in the low ALC group and 4.8% in the high ALC group (P = 0.003). In patients considered high-intermediate/high-risk based on IPI scores, lymphopenia was also associated with shorter OS and PFS (P = 0.002, P = 0.001, respectively).ConclusionThis study suggests that lymphopenia could be an independent prognostic marker to predict unfavorable OS and PFS in patients with PTCL-NOS treated with anthracycline-containing chemotherapy and can be used to further stratify high-risk patients using IPI scores.

High-throughput profiling identifies clinically actionable mutations in salivary duct carcinoma

BackgroundSalivary duct carcinoma (SDC) is a highly aggressive subtype of salivary gland cancers and there is no established standard therapy for this disease. Thus, development of molecular markers for SDC will be important to guide the diagnosis and therapy of this aggressive tumor.MethodsWe performed next-generation sequencing using the Ion Torrent AmpliSeq cancer panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes, and we analyzed copy number variations (CNVs) of 21 genes by NanoString nCounter for 37 patients with SDC. Fluorescent in situ hybridization was also conducted to confirm ERBB2 gene amplification. Clinical records and tumor histopathology of the patients were retrospectively reviewed.ResultsGenetic alterations were detected in 29 of 37 (78.3%) tumors, including mutations in PIK3CA (N = 9, 24.3%), ERBB2 (N = 4, 10.8%), and EGFR (N = 4, 10.8%). To our knowledge, this is the first time that ERBB2 mutations have been reported in this tumor type. Both PIK3CA and ERBB2 mutation status were associated with poor overall survival, but without statistical significance. ERBB2 amplification was strong and common in SDC and almost all cases also exhibited EGFR and ERBB3 amplifications.ConclusionsThis study reports the largest and most comprehensive analysis of DNA aberrations in SDC. Our results show that PIK3CA and/or ERBB2 alterations in the development of SDC might be a useful diagnostic tool and could serve as a potential therapeutic target.

Effect of paclitaxel/carboplatin salvage chemotherapy in noncutaneous versus cutaneous metastatic melanoma.

Little is known about the efficacy of salvage chemotherapy for patients with metastatic, noncutaneous melanoma after the failure of dacarbazine-based chemotherapy. Because of the high incidence of noncutaneous melanoma in Korea, we assessed the outcomes of paclitaxel/carboplatin (PC) salvage chemotherapy in patients with noncutaneous metastatic melanoma. We retrospectively analyzed patients with metastatic melanoma who received intravenous paclitaxel (175 mg/m2) plus intravenous carboplatin (area under the curve 5) on day 1 of a 21-day cycle as salvage chemotherapy at Samsung Medical Center (SMC) between February 2009 and February 2012. The overall response rate, overall survival, and progression-free survival were evaluated. Thirty-two patients with a median age of 54 years (range 24–72 years) received PC as salvage chemotherapy. All patients had been pretreated with a median of three systemic chemotherapies. Of the 32 patients, 10 (31.3%) had cutaneous melanoma, eight (25%) had acral melanoma, 10 (31.3%) had mucosal melanoma, and two (6.3%) had ocular melanoma. In response to treatment, seven of the 32 patients (21.9%) achieved partial response and 11 (34.4%) had stable disease. The median progression-free survival was 2.53 months for all patients, 4.3 months for patients with controlled disease (partial response and stable disease), and 1.37 months for patients with progressive disease (P=0.0001). The median overall survival was 5.2 months. No significant difference was noted between patients with noncutaneous and cutaneous metastatic melanoma (P=0.75). PC salvage chemotherapy may be a reasonable therapeutic option for heavily pretreated metastatic melanoma patients. Salvage therapy with this combination had definite clinically meaningful benefits in patients with metastatic melanoma, including those with noncutaneous melanoma.

Comparison of the Freiburg and Charlson comorbidity indices in predicting overall survival in elderly patients with newly diagnosed multiple myeloma.

Multiple myeloma occurs primarily in elderly patients. Considering the high prevalence of comorbidities, comorbidity is an important issue for the management of myeloma. However, the impact of comorbidity on clinical outcomes has not been fully investigated. We retrospectively analyzed patients with newly diagnosed myeloma. Comorbidities were assessed based on the Charlson comorbidity index (CCI) and the Freiburg comorbidity index (FCI). The CCI is a summary measure of 19 comorbid conditions. FCI is determined by performance status, renal impairment, and lung disease. This study included 127 patients with a median age of 71 years. Approximately half of the patients had additional disorders at the time of diagnosis, and diabetes mellitus was the most frequent diagnosis (18.9%). The most significant factors for prognosis among patient-related conditions were a history of solid cancer and performance status (ECOG ≥ 2). The FCI score was divided into 3 groups (0, 1, and 2-3), and the CCI score was divided into 2 groups (2-3 and ≥4). FCI was a strong prognostic tool for OS (P > 0.001) and predicted clinical outcome better than CCI (P = 0.059). In conclusion, FCI was more useful than CCI in predicting overall survival in elderly patients with myeloma.

The BIM Deletion Polymorphism and its Clinical Implication in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors

Introduction: A germline BIM deletion polymorphism has been proposed to predict poor treatment response to certain kinase inhibitors. The purpose of this study was to explore whether the BIM deletion polymorphism predicts treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in Korean patients with EGFR-mutant non–small-cell lung cancer (NSCLC). Methods: Peripheral blood samples from a total of 205 patients with EGFR-mutant NSCLC who were treated with EGFR TKIs between July 2008 and April 2013 were included. The incidence of BIM deletions in these samples was detected by polymerase chain reaction. We compared the clinical outcomes in patients with and without the polymorphism after treatment with EGFR TKIs (gefitinib or erlotinib). Results: The BIM deletion polymorphism was present in 15.6% (32 of 205) of patients. One patient was homozygous for the deletion, and the remaining 31 had heterozygous deletions. The majority of patients were younger than 65 years (74%), female (68%), never smokers (76%), and had stage IV NSCLC (67%). There were no associations between the BIM deletion polymorphism and clinicopathological features including gender, age, smoking status, histology, stage, and number of metastasis sites. Patients with and without the BIM deletion polymorphism had similar objective response rates (91 vs. 84%, p = 0.585). Progression-free survival and overall survival did not differ significantly between patients with and without the BIM deletion polymorphism (median progression-free survival 12 vs. 11 months, p = 0.160; median overall survival 31 vs. 30 months, p = 0.452). Multivariate analysis identified significantly predictive markers for clinical outcomes of EGFR TKIs including Eastern Cooperative Oncology Group performance status 0–1, adenocarcinoma histology, recurrent disease, and EGFR mutation type. The results were validated in an independent cohort of 69 NSCLC patients. Conclusions: It remains to be determined whether the BIM deletion polymorphism provides intrinsic resistance or decreased sensitivity to EGFR TKIs in EGFR-mutant NSCLC patients.

Prognostic relevance of pretreatment quality of life in diffuse large B-cell lymphoma patients treated with rituximab-CHOP: results from a prospective cohort study.

The self-reported quality of life (QoL) has been used as an index of general health status. Thus, we evaluated the significance of pretreatment QoL in predicting survival outcome of patients with diffuse large B cell lymphoma (DLBCL). Two hundred sixty-three patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were enrolled to this prospective cohort study, and their QoL was evaluated. The pretreatment QoL was significantly associated with increased serum lactate dehydrogenase, extranodal involvement, and stage III/IV. Patients scoring poorly on the global health and function scale and high on the symptom/sign scale completed treatment at a significantly lower rate than patients with good scale. The treatment-related mortality was also more frequent in patients with poor QoL. The univariate analysis showed a prognostic relevance of pretreatment QoL, so the poor QoL group showed a worse survival outcome than the good QoL group. This pretreatment QoL also independently predicted overall survival in the multivariate analysis. Thus, the pretreatment assessment of QoL may be a valid prognostic marker for DLBCL patients treated with R-CHOP.

Changes in the mean corpuscular volume after capecitabine treatment are associated with clinical response and survival in patients with advanced gastric cancer.

Purpose Capecitabine is known to increase mean corpuscular volume (MCV). To define the incidence of capecitabine-induced macrocytosis and its association with chemotherapy outcomes, we investigated data of 89 patients with advanced gastric cancer (AGC) who were enrolled in a randomized chemotherapy trial involving capecitabine. Materials and Methods Chemotherapy-naïve AGC patients were treated with capecitabine (1,000 mg/m2/day on days 1-14) plus cisplatin (75 mg/m2 on day 1), with or without epirubicin (50 mg/m2 on day 1). Complete blood counts including MCV were measured at baseline and on day 1 of each 3-week chemotherapy course. Macrocytosis was defined as a MCV increase > 10 fL from baseline. Multivariate Cox proportional hazards models were used for analysis of the impact of clinical and MCV values on chemotherapy outcomes. Results At baseline, the mean MCV was 88.2 fL (normal range, 80 to 100 fL). During chemotherapy, MCV increased in a dose-dependent manner with a mean increase of 11.3 fL. MCV elevation after capecitabine treatment in 74 patients (90%) and 44 patients (42%) developed macrocytosis. Results of multivariate analysis showed that development of macrocytosis was independent of baseline hemoglobin level, liver metastasis, performance status, or liver function. The number of chemotherapy cycles showed strong association with development of macrocytosis and hematologic adverse events. In addition, a significant association was observed between macrocytosis and clinical response or survival. Conclusion Macrocytosis developed with more frequent and prolonged use of capecitabine. It is possible that association with treatment outcomes warrants further investigation.

Nomogram to predict treatment outcome of fluoropyrimidine/platinum-based chemotherapy in metastatic esophageal squamous cell carcinoma.

Purpose The degree of benefit from palliative chemotherapy differs widely among patients with metastatic esophageal squamous cell carcinoma (MESCC). The purpose of this study was to develop and validate a prognostic nomogram to predict survival and aid physicians and patients in the decision-making process regarding treatment options. Materials and Methods Clinicopathologic variables and treatment outcomes of 239 patients who were diagnosed with MESCC and received either fluorouracil/cisplatin (FP) or capecitabine/cisplatin (XP) as first-line chemotherapy were reviewed. A nomogram was developed as a prognostic scoring system incorporating significant clinical and laboratory variables based on a multivariate Cox proportional hazards regression model. An independent series of 61 MESCC patients treated with FP served as an independent data set for nomogram validation. Results No difference in response rate was observed between the FP group (44.8%) and the XP group (54.2%). Similarly, no significant differences in median progression-free survival and median overall survival were observed between regimen groups. Multivariate analysis showed that poor performance status (Eastern Cooperative Oncology Group [ECOG] status≥2), weight loss (10% of the weight loss for 3 months), low albumin level (≤3.5 g/dL), and absence of previous esophagectomy at the time of chemotherapy were significantly associated with low OS in both groups (p<0.05). Based on these findings, patients were classified into favorable (score, 0 to 90), intermediate (91-134), and poor (>135) prognostic groups. The median survival for those with a favorable ECOG was 13.8 months (95% confidence interval [CI], 10.8 to 18.6 months), for intermediate 11.2 months (95% CI, 8.7 to 11.9 months), and for poor, 7.0 months (95% CI, 3.6 to 10.0 months). External validation of the nomogram in a different patient cohort yielded significantly similar findings. Conclusion The nomogram described here predicts survival in MESCC patients and could serve as a guide for the use of FP/XP chemotherapy in MESCC patients.

Treatment Outcome and Relevance of Palliative Chemotherapy in Urachal Cancer

Background: Urachal cancer is a rare malignancy that accounts for <1% of bladder cancers. There is currently no consensus on the diagnosis and management of urachal cancer and there are very few reports on palliative chemotherapy for unresectable disease. We delineate the clinical features and treatment outcome of urachal cancer, in particular the relevance of palliative chemotherapy in recurrent, metastatic disease. Methods: The clinicopathologic variables and treatment outcome of patients who were treated for urachal cancer were retrospectively reviewed. Results: Among 28 eligible patients, 25 had localized disease and 3 had metastatic disease at initial diagnosis. All patients with localized disease underwent curative resection and there was disease recurrence in 10. Out of 13 patients with metastatic disease either at initial diagnosis or during follow-up, the lung was the most common metastatic site (n = 5), followed by the liver, bone and peritoneum. Ten patients received palliative chemotherapy. A total of 24 chemotherapeutic regimens were administered; regimens with a base of fluoropyrimidine (5-FU), taxane and gemcitabine were the most common. The overall response rate of all chemotherapeutic regimens was 16.7%. The 5-FU-based regimens showed a good response, with 2 of 4 patients who received these showing a partial response. One tumor with a partial small-cell component showed a partial response to both an etoposide-based regimen and a taxane-based regimen. Conclusions: In urachal cancer, curative surgery is still the recommended treatment with respect to overall survival. A 5-FU-based chemotherapy regimen could be considered for metastatic recurrent disease.

Characterization of Durable Responder for Capecitabine Monotherapy in Patients With Anthracycline- and Taxane-Pretreated Metastatic Breast Cancer.

BACKGROUND The purpose of this study was to evaluate predictive factors and the clinical characteristics of durable responders to capecitabine monotherapy in heavily-treated patients with metastatic breast cancer (MBC). PATIENTS AND METHODS Between December 2000 and May 2012, a total of 236 evaluable patients with MBC who had been treated with second- or greater-line palliative capecitabine monotherapy after a previous treatment regimen with anthracycline and taxane were included. Capecitabine (1250 mg/m(2) twice daily) was administered for 2 weeks followed by a 1-week rest period. RESULTS The response rate was 23.3% and median progression-free survival (PFS) was 4.7 months (95% confidence interval, 4.0-5.5). Among 236 patients, 33 patients (14.0%) showed durable response (>12 months) to capecitabine monotherapy. Patients with durable response showed significantly greater incidence of estrogen receptor (ER) positivity (81.8% vs. 59.1%; P = .012), single-organ metastasis (51.5% vs. 32.0%; P = .047), and absence of lymph node metastasis (75.8% vs. 54.2%; P = .023), compared with patients without durable response. In multivariate analysis, ER positivity and single-organ metastasis retained a significant association with better PFS to capecitabine monotherapy (hazard ratio [HR], 0.51; P < .001 and HR, 0.62; P = .004). CONCLUSION Our data suggest that ER positivity and single-organ metastasis can be useful predictive markers for better PFS to second- or greater-line palliative capecitabine monotherapy in anthracycline- and taxane-pretreated MBC patients.