Hyeong Su Kim

Excision repair cross‐complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin‐based chemotherapy

Kim KH, Do I‐G, Kim HS, Chang MH, Kim HS, Jun HJ, Uhm J, Yi SY, Lim DH, Ji SH, Park MJ, Lee J, Park SH, Kwon GY, Lim HY. Excision repair cross‐complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin‐based chemotherapy. APMIS 2010; 118: 941–8.

Clinical Impact of Phosphorylated Signal Transducer and Activator of Transcription 3, Epidermal Growth Factor Receptor, p53, and Vascular Endothelial Growth Factor Receptor 1 Expression in Resected Adenocarcinoma of Lung by Using Tissue Microarray

The signal transducer and activator of transcription 3 (STAT3) play a key role in the downstream pathway of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer and promote cell proliferation, invasion, and angiogenesis. The clinical significance of phosphorylated STAT3 (pSTAT3), EGFR, p53, and vascular endothelial growth factor receptor 1 (VEGFR‐1) expression in patients with completely resected lung adenocarcinoma was evaluated to determine the effects of pSTAT3 in tumor angiogenesis and proliferation.

Clinical Comparisons of Two Free Light Chain Assays to Immunofixation Electrophoresis for Detecting Monoclonal Gammopathy

Free light chains (FLCs) are useful biomarkers for the diagnosis and monitoring of various plasma cell dyscrasias. One hundred fifty-seven samples from 120 patients for screening or monitoring of monoclonal gammopathy (MG) were included. The new N Latex FLC assays (Siemens Healthcare Diagnostics GmbH, Germany) were compared with the Freelite FLC assays (The Binding Site Ltd., UK) and the results were analyzed with those of immunofixation electrophoresis (IFE). The Freelite FLC assay showed significantly wider assay ranges than the N Latex FLC assay. The correlation coefficients of the two FLC kappa (κ) assays, lambda (λ) assays, and the κ/λ ratio were 0.9792, 0.8264, and 0.9064, respectively. The concordance rate was 84.7% for the FLC κ assays, 79.6% for FLC λ, and 89.2% for the κ/λ ratio. The clinical sensitivity and specificity of the κ/λ ratios were 72.2% and 93.6% for the Freelite assay and 64.6% and 100% for the N Latex FLC assay. Two FLC assays showed good correlations and concordance. However, the clinical sensitivity of the κ/λ ratio was higher in the Freelite FLC assays; clinical specificity was higher in the N Latex FLC assay. Both FLC assays seem to have limited clinical utility in detecting MG in certain clinical settings.

Variations in dose distribution and optical properties of GafchromicTM EBT2 film according to scanning mode

PURPOSE The authors aim was to investigate the effects of using transmission and reflection scanning modes, the film orientation during scanning, and ambient room light on a dosimetry system based on the Gafchromic(TM) EBT2 film model. METHODS For calibration, the films were cut to 3 × 3 cm(2) and irradiated from 20 to 700 cGy at the depth of maximum dose using 6 and 10 MV photon beams in a 10 × 10 cm(2) field size. Absolute dose calibration of the linear accelerator was done according to the TRS398 protocol. An FG65-G ionization chamber was used to monitor the dose while irradiating the films in solid water. The film pieces were scanned with an EPSON Expression 1680 Pro flatbed scanner in transmission and reflection modes. Authors investigated the effect of orientation on films and examined the optical properties of EBT2 film using an ellipsometer and an ultraviolet (UV)/visible spectrometer to explain the dosimetric dependence of the film on orientation during the scanning process. To investigate the effect of ambient room light, films were preirradiated in 6 and 10 MV photon beams with intensity-modulated radiotherapy (IMRT) quality assurance (QA) plans, and then exposed to room light, either directly for 2 days in a workroom or for 2 months in a film box. Gamma index pass criteria of (3%, 3 mm) were used. RESULTS The dose response curves based on net optical density (NOD) indicated that the reflection scanning mode can provide a better dose sensitivity than the transmission scanning mode, whereas the standard deviation of the dose is greater in reflection mode than in transmission mode. When the film was rotated 90° from the portrait orientation, the average dose of the EBT2 film decreased by 11.5-19.6% in transmission mode and by 1.5-2.3% in reflection mode. Using an ellipsometer, variation of the refractive index of EBT2 film-the birefringence property-was found to be the largest between 45° (1.72 and 1.71) and 135° (1.8 and 1.77) for 300 and 800 cGy. Absorption spectra of EBT2 films measured with spectrometer were the function of film orientation. The readings in reflection scanning mode were more stable against room light than those in transmission scanning mode, although dose readings increased in both modes after the films were exposed to room light. CONCLUSIONS The transmission scanning mode exhibited a strong dependence on film orientation during scanning and a change in optical density resulting from room light exposure, so a constant scanning orientation and minimal exposure to light can reduce uncertainty in the measured dose (23 ± 3%). The angular dependence was analyzed using Jones matrices and optical properties of EBT2 film were obtained using an ellipsometer and an UV/visible spectrometer. The reflection scanning mode has relatively good stability with respect to room light and film orientation on a scanner, although the large standard deviation of dose is a disadvantage in measurements of absolute dose. Reflection scanning mode can offer a potential advantage for film dosimetry in radiotherapy, although transmission scanning mode is still recommended for dosimetry as it provides better uncertainty results.

A phase II study of pemetrexed and carboplatin as a salvage therapy for platinum-pretreated patients with non-small cell lung cancer

BACKGROUND Although platinum-based doublet chemotherapy is considered as standard of care for patients with advanced non-small cell lung cancer (NSCLC), most of them are eventually supposed to experience disease progression. Pemetrexed, docetaxel, erlotinib, and gefitinib have been shown to be active as monotherapy for pretreated patients. In this study, the efficacy of pemetrexed and carboplatin as a salvage therapy for patients with advanced NSCLC is evaluated. PATIENTS AND METHODS From March 2007 to February 2009, 32 patients who were diagnosed with inoperable NSCLC and treated with one or more prior cisplatin-based chemotherapies were enrolled. Treatment consisted of pemetrexed 500 mg/m(2) over a 10-min intravenous infusion and carboplatin at an AUC 5 mg/mL/min over a 30-min intravenous infusion on Day 1 of a 21-day cycle. All patients were supplemented with folic acid and vitamin B12 to reduce the hematological toxicity of pemetrexed. RESULTS There were one (3.1%) complete response and five partial (15.6%) responses. The overall response rate was 18.8% and the median response duration was 4.4 months. Among the responders, four patients had adenocarcinoma and two had squamous cell carcinoma. Nine patients had stable disease, and the disease control rate was 46.9%. With a median follow up duration of 9.4 months, the median time to progression was 2.3 months and the median OS was 9.4 months. Seven patients (21.9%) experienced grade 3 and 4 hematologic toxicities; one anemia (3.1%), six neutropenia (18.8%), and six thrombocytopenia (18.8%). Two patients experienced grade 4 febrile neutropenia with infection. Four patients (12.5%) experienced grade 3 non-hematologic toxicities; four asthenia (12.5%), two anorexia (6.3%), and one stomatitis (3.1%). Grade 1-2 peripheral neuropathy developed in 13 patients (40.6%). CONCLUSION The combination of pemetrexed and carboplatin showed favorable toxicity profiles and activity in the pretreated patients with advanced NSCLC. It is suggested that this regimen can be a good chemotherapeutic option as a salvage therapy for patients with NSCLC.

Comparison of RECIST version 1.0 and 1.1 in assessment of tumor response by computed tomography in advanced gastric cancer

OBJECTIVE Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0 (RECIST 1.0) was proposed as a new guideline for evaluating tumor response and has been widely accepted as a standardized measure. With a number of issues being raised on RECIST 1.0, however, a revised RECIST guideline version 1.1 (RECIST 1.1) was proposed by the RECIST Working Group in 2009. This study was conducted to compare CT tumor response based on RECIST 1.1 vs. RECIST 1.0 in patients with advanced gastric cancer (AGC). METHODS We reviewed 61 AGC patients with measurable diseases by RECIST 1.0 who were enrolled in other clinical trials between 2008 and 2010. These patients were retrospectively re-analyzed to determine the concordance between the two response criteria using the κ statistic. RESULTS The number and sum of tumor diameters of the target lesions by RECIST 1.1 were significantly lower than those by RECIST 1.0 (P<0.0001). However, there was excellent agreement in tumor response between RECIST 1.1 and RECIST 1.0 (κ=0.844). The overall response rates (ORRs) according to RECIST 1.0 and RECIST 1.1 were 32.7% (20/61) and 34.5% (20/58), respectively. One patient with partial response (PR) based on RECIST 1.0 was reclassified as stable disease (SD) by RECIST 1.1. Of two patients with SD by RECIST 1.0, one was downgraded to progressive disease and the other was upgraded to PR by RECIST 1.1. CONCLUSIONS RECIST 1.1 provided almost perfect agreement with RECIST 1.0 in the CT assessment of tumor response of AGC.

Retrospective analyses of cisplatin-based doublet combination chemotherapy in patients with advanced gastric cancer

BackgroundsCisplatin-based chemotherapy, in combination with fluoropyrimidines or taxanes, have demonstrated efficacy against advanced gastric cancer (AGC). This retrospective study was performed with the data obtained from our cancer chemotherapy registry and eight another cancer centers.MethodsIn 2008, a total of 283 AGC patients were treated with cisplatin-based doublet chemotherapy in the first-line setting: capecitabine plus cisplatin (XP, n = 77), S-1 plus cisplatin (SP, n = 97), taxanes (docetaxel, paclitaxel) plus cisplatin (TP, n = 72), and 5-fluorouracil plus platinum (FP, n = 37). The primary endpoint of this study was overall survival (OS) and the secondary endpoints were safety, response rate and progression-free survival (PFS).ResultsThe median age was 54 years with a range of 28-78 years and median delivered number of chemotherapy cycles were XP: 4, SP: 5, TP: 5 and FP: 5, respectively. Objective tumor responses (38%; 95% CI, 32-43%) were 40% for XP, 42% for SP, 36% for DP, and 24% for FP. The estimated median PFS was 4.5 months (95% CI, 3.6-5.4 months) and the median OS was 12.3 months (95% CI, 10.8-13.7 months). No statistically significant difference was found between each regimen used as first-line chemotherapy. At multivariate analysis, independent prognostic parameters for OS were prior gastrectomy, peritoneal dissemination, performance status and hemoglobin levelConclusionAll of the cisplatin-based doublet chemotherapy regimens appear to be active as first-line chemotherapy for AGC. With better patient selection according to clinical parameters and molecular markers, clinical outcomes of AGC patients in first-line setting can be improved.

Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review

Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option in the fight against advanced non-small-cell lung cancer (NSCLC). KRAS is the most frequently mutated oncogene in NSCLC. We performed this meta-analysis to investigate if KRAS mutation status affects survival benefits of ICIs in patients with advanced NSCLC. Electronic databases were searched for eligible studies. We included randomized trials with the data of overall survival stratified by KRAS mutation status. From 3 eligible studies, 138 patients with KRAS mutant NSCLC and 371 with KRAS wild-type tumor were included in the meta-analysis. Compared to chemotherapy with docetaxel, ICIs improved overall survival in patients with previously treated KRAS mutant NSCLC (hazard ratio = 0.64 [95% confidence interval, 0.43–0.96], P = 0.03). For patients with KRAS wild-type NSCLC, however, ICIs did not prolong overall survival over that with chemotherapy (hazard ratio = 0.88 [95% confidence interval, 0.68–1.13], P = 0.30). In conclusion, ICIs as a salvage therapy improved overall survival over that with docetaxel in advanced NSCLC patients with KRAS mutation, but not in those with KRAS wild-type tumor. These results suggest that KRAS mutation status may be a potential biomarker for survival benefits to ICIs.

Chemotherapy in Elderly Patients with Gastric Cancer

Gastric cancer (GC) is one of the most frequent malignant diseases in the elderly. Systemic chemotherapy showed an improvement of quality of life and survival benefit compared to supportive care alone in patients with advanced GC. Because comorbidities or age-related changes in pharmacokinetics and pharmacodynamics may lead to higher toxicity, however, many oncologists hesitate to recommend elderly patients to receive chemotherapy. Available data suggest that elderly patients with GC are able to tolerate and benefit from systemic chemotherapy to the same extent as younger patients. The age alone should not be the only criteria to preclude effective chemotherapy. However, proper patient selection is extremely important to deliver effective treatment safely. A comprehensive geriatric assessment (CGA) is a useful method to assess life expectancy and risk of morbidity in older patients and to guide providing optimal treatment. Treatment should be personalized based on the nature of the disease, the life expectancy, the risk of complication, and the patients preference. Combination chemotherapy can be considered for older patients with metastatic GC who are classified as non-frail patients by CGA. For frail or vulnerable patients, however, monotherapy or only symptomatic treatment may be desirable. Targeted agents seem to be promising treatment options for elderly patients with GC considering their better efficacy and less toxicity.

Comparison of RECIST 1.0 and RECIST 1.1 in Patients with Metastatic Cancer: A Pooled Analysis

Background:We conducted this pooled analysis to investigate the impact of RECIST 1.1 on the selection of target lesions and classification of tumor response, in comparison with RECIST 1.0. Methods: We searched MEDLINE and EMBASE for articles with terms of RECIST 1.0 or RECIST 1.1. We looked into all abstracts and virtual meeting presentations from the conferences of ASCO and ESMO between 2009 and 2013. Results: There were six articles in the literature comparing the clinical impacts of RECIST 1.0 and RECIST 1.1 in patients with metastatic cancer. A total of 359 patients were recruited from the six trials; 217 with non-small cell lung cancer, 61 with gastric cancer, 58 with colorectal cancer, and 23 with thyroid cancer. The number of target lesions by RECIST 1.1 was significantly lower than that by RECIST 1.0 (P<0.001). Because of new lymph node criteria, fourteen patients (3.1%) had no target lesions when adopting RECIST 1.1. RECIST 1.1 showed high concordance with RECIST 1.0 in the assessment of tumor responses (k = 0.903). Sixteen patients (4.8%) showed disagreement between the two criteria. Conclusion: This pooled study demonstrated that RECIST 1.1 showed a highly concordant response assessment with RECIST 1.0 in patients with metastatic cancer.