Chong Hyun Suh

Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation

Non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation shows good and rapid response to EGFR tyrosine kinase inhibitors (TKIs). We prospectively evaluated the efficacy of EGFR TKI for metastatic brain tumors in NSCLC patients harboring EGFR mutation. This was an open-label, single-institution, phase II study. Patients diagnosed with NSCLC harboring EGFR mutation and measurable metastatic brain tumors were eligible. They received either erlotinib or gefitinib once a day. Out of total 28 patients enrolled, 23 patients (83%) showed a partial response (PR) and 3 patients (11%) did stable disease (SD), giving a disease control rate of 93%. Median progression free survival (PFS) and overall survival (OS) were 6.6 months (95% CI, 3.8-9.3 months) and 15.9 months (95% CI, 7.2-24.6 months), respectively. There was no difference in PFS and OS according to EGFR TKIs used. After discontinuation of the treatment, 14 patients (50%) received local therapy for metastatic brain tumors during their disease course, either whole brain radiotherapy or radiosurgery, giving a local therapy-free interval of 12.6 months (95% CI, 7.6-17.6 months). EGFR TKI therapy might be the treatment of choice for metastatic brain tumors in NSCLC patients harboring an activating EGFR mutation.

Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment

BACKGROUND Both gefitinib and erlotinib are reversible epidermal growth factor receptor tyrosine kinase inhibitors, but they have somewhat different pharmacological properties. We conducted a phase II study of erlotinib after failure of gefitinib treatment in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with advanced/metastatic NSCLC who had shown disease progression on gefitinib treatment were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity. RESULTS Between September 2006 and January 2008, a total of 23 patients were enrolled and all were assessable for response and toxicity. All patients were never smokers and all but one had adenocarcinoma. Of these 23 patients, one had a partial response and one stable disease, resulting in an objective response rate of 4.3% and a disease control rate of 8.7%. These two patients benefited from erlotinib for 6.2 months and 7.8 months, respectively; both had also benefited from prior gefitinib therapy. The most common toxic effects were skin rash and diarrhea. CONCLUSION Erlotinib should not be given routinely after failure of gefitinib treatment, but can be an option for more highly selected subsets, especially those who had benefited from prior gefitinib treatment. Identification of molecular markers in tumors is important to understand and overcome acquired resistance to gefitinib.

Prediction of Pseudoprogression in Patients with Glioblastomas Using the Initial and Final Area Under the Curves Ratio Derived from Dynamic Contrast-Enhanced T1-Weighted Perfusion MR Imaging

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced T1-weighted perfusion MR imaging is much less susceptible to artifacts, and its high spatial resolution allows accurate characterization of the vascular microenvironment of the lesion. The purpose of this study was to test the predictive value of the initial and final area under the time signal-intensity curves ratio derived from dynamic contrast-enhanced perfusion MR imaging to differentiate pseudoprogression from early tumor progression in patients with glioblastomas. MATERIALS AND METHODS: Seventy-nine consecutive patients who showed new or enlarged, contrast-enhancing lesions within the radiation field after concurrent chemoradiotherapy were assessed by use of conventional and dynamic contrast-enhanced perfusion MR imaging. The bimodal histogram parameters of the area under the time signal-intensity curves ratio, which included the mean area under the time signal-intensity curves ratio at a higher curve (mAUCRH), 3 cumulative histogram parameters (AUCR50, AUCR75, and AUCR90), and the area under the time signal-intensity curves ratio at mode (AUCRmode), were calculated and correlated with the final pathologic or clinical diagnosis. The best predictor for differentiation of pseudoprogression from early tumor progression was determined by receiver operating characteristic curve analyses. RESULTS: Seventy-nine study patients were subsequently classified as having pseudoprogression (n=37, 46.8%) or early tumor progression (n=42, 53.2%). There were statistically significant differences of mAUCRH, AUCR50, AUCR75, AUCR90, and AUCRmode between the 2 groups (P < .0001, each). Receiver operating characteristic curve analyses showed the mAUCRH to be the best single predictor of pseudoprogression, with a sensitivity of 90.1% and a specificity of 82.9%. AUCR50 was found to be the most specific predictor of pseudoprogression, with a sensitivity of 87.2% and a specificity of 83.1%. CONCLUSIONS: A bimodal histogram analysis of the area under the time signal-intensity curves ratio derived from dynamic contrast-enhanced perfusion MR imaging can be a potential, noninvasive imaging biomarker for monitoring early treatment response in patients with glioblastomas.

Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma

To understand the prognostic value of lymphocyte recovery after autologous peripheral blood stem cell transplantation (APBSCT), we performed a retrospective study of 59 newly diagnosed multiple myeloma (MM) patients who underwent frontline APBSCT. Conditioning regimens were melphalan 100 mg/m2 for 2 days. Following APBSCT, all patients showed complete or partial response. Median follow-up time was 29.57 months and median recovery of absolute lymphocyte count (ALC) ⩾1000/mm3 was 23 days. Univariate analysis revealed that significant predictors of overall survival (OS) included bone marrow (BM) plasma cells ⩽40% at diagnosis (P=0.0243) and recovery of ALC ⩾1000/mm3 by day +23 (P=0.0156). Positive predictors for progression-free survival (PFS) were BM plasma cells ⩽40% at diagnosis (P=0.0134) and recovery of ALC ⩾1000/mm3 by day +23 (P=0.0243). Absolute neutrophil count ⩾1000/mm3 on day +12 was marginally significant for OS and PFS (P=0.0821 and P=0.1153, respectively). Multivariate analysis showed that ALC ⩾1000/mm3 on day +23 independently predicted OS (P=0.031) and prolonged PFS (P=0.011), and that serum β2-microglobulin was marginally significant for prolonged OS (P=0.066). In conclusion, ALC recovery was an independent predictor of both OS and PFS in MM.

Histogram Analysis of Intravoxel Incoherent Motion for Differentiating Recurrent Tumor from Treatment Effect in Patients with Glioblastoma: Initial Clinical Experience

BACKGROUND AND PURPOSE: Intravoxel incoherent motion can simultaneously measure diffusion and perfusion characteristics. Our aim was to determine whether the perfusion and diffusion parameters derived from intravoxel incoherent motion could act as imaging biomarkers for distinguishing recurrent tumor from treatment effect in patients with glioblastoma. MATERIALS AND METHODS: Fifty-one patients with pathologically confirmed recurrent tumor (n = 31) or treatment effect (n = 20) were assessed by means of intravoxel incoherent motion MR imaging. The histogram cutoffs of the 90th percentiles for perfusion and normalized CBV and the 10th percentiles for diffusion and ADC were calculated and correlated with the final pathology results. A leave-one-out cross-validation was used to evaluate the diagnostic performance of our classifiers. RESULTS: The mean 90th percentile for perfusion was significantly higher in the recurrent tumor group (0.084 ± 0.020) than in the treatment effect group (0.040 ± 0.010) (P < .001). The 90th percentile for perfusion provided a smaller number of patients within an overlap zone in which misclassifications can occur, compared with the 90th percentile for normalized CBV. The mean 10th percentile for diffusion was significantly lower in the recurrent tumor group than in the treatment effect group (P = .006). Receiver operating characteristic curve analyses showed the 90th percentile for perfusion to be a significant predictor for differentiation, with a sensitivity of 87.1% and a specificity of 95.0%. There was a significant positive correlation between the 90th percentiles for perfusion and normalized CBV (r = 0.674; P < .001). CONCLUSIONS: A histogram analysis of intravoxel incoherent motion parameters can be used as a noninvasive imaging biomarker for differentiating recurrent tumor from treatment effect in patients with glioblastoma.

Successful Publication of Systematic Review and Meta-Analysis of Studies Evaluating Diagnostic Test Accuracy

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Lymphocyte recovery as a positive predictor of prolonged survival after autologous peripheral blood stem cell transplantation in T-cell non-Hodgkin's lymphoma

Summary:We performed a retrospective study on recovery and survival of patients with T-cell NHL after autologous peripheral blood stem cell transplantation (APBSCT). Of a total of 39 patients with high-risk T-cell NHL, 33 were analyzed. Six patients who experienced early treatment mortality without full lymphocyte recovery were excluded. We chose absolute lymphocyte count (ALC) recovery as 1000 cells/μl as a cutoff value. ALC recovery day was defined as the first of 3 consecutive days with ALC above 1000 cells/μl. Univariate analysis revealed that age younger than 45 years, good international prognostic index, chemosensitive disease prior to APBSCT, and early ALC recovery (1000 cells/μl within 25 days of APBSCT) were predictors of prolonged survival. Multivariate analyses confirmed that chemosensitive disease prior to APBSCT and early ALC recovery were strongly associated with better overall survival (OS) (P=0.005 and 0.011, respectively) and progression-free survival (PFS) (P<0.001 and P=0.013, respectively). Our finding, that ALC recovery ⩾1000 cells/μl is an independent predictor of OS and PFS in T-cell NHL after APBSCT, suggests that earlier immune recovery may contribute to longer survival.

Atypical Imaging Features of Primary Central Nervous System Lymphoma That Mimics Glioblastoma: Utility of Intravoxel Incoherent Motion MR Imaging

PURPOSE To determine the utility of intravoxel incoherent motion (IVIM)-derived perfusion and diffusion parameters for differentiation of atypical primary central nervous system lymphoma (PCNSL) from glioblastoma in patients who do not have acquired immunodeficiency syndrome. MATERIALS AND METHODS The institutional review board approved this retrospective study and waived the informed consent requirement. Sixty patients with either pathologic analysis-confirmed atypical PCNSLs (n = 19) or glioblastomas (n = 41) were assessed by using maximum IVIM-derived perfusion fraction (f) and minimum true IVIM diffusion parameter (D). Two readers independently calculated IVIM parameters and maximum normalized cerebral blood volume (nCBV) and minimum apparent diffusion coefficient. Leave-one-out cross-validation and intraclass correlation coefficients were assessed to determine reliability and reproducibility of the parameters, respectively. RESULTS Mean maximum f was significantly higher in the glioblastoma group than in the atypical PCNSL group (reader 1, 0.101 ± 0.016 [standard deviation] vs 0.021 ± 0.010; P < .001; reader 2: 0.107 ± 0.024 vs 0.027 ± 0.015; P < .001). Mean minimum D did not significantly differ between the two groups (reader 1, P = .202; reader 2, P = .091). By using maximum f as a discriminative index, respective sensitivity and specificity were 89.5% and 95.1% for reader 1 and 84.2% and 95.1% for reader 2. There was a significant positive correlation between maximum f and the corresponding nCBV (r = 0.68; P < .001). The intraclass correlation coefficient between readers was highest for measurement of maximum f (intraclass correlation coefficient, 0.92). CONCLUSION IVIM imaging can be used as a noninvasive imaging method to differentiate malignant brain tumors that show similar conventional MR imaging features.

Diagnostic Performance of Prostate Imaging Reporting and Data System Version 2 for Detection of Prostate Cancer: A Systematic Review and Diagnostic Meta-analysis

CONTEXT In 2015, the updated Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) for the detection of prostate cancer (PCa) was established. Since then, several studies assessing the value of PI-RADSv2 have been published. OBJECTIVE To review the diagnostic performance of PI-RADSv2 for the detection of PCa. EVIDENCE ACQUISITION MEDLINE and EMBASE databases were searched up to December 7, 2016. We included diagnostic accuracy studies that used PI-RADSv2 for PCa detection, using prostatectomy or biopsy as the reference standard. The methodological quality was assessed by two independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity of all studies were calculated. Results were pooled and plotted in a hierarchical summary receiver operating characteristic plot with further exploration using meta-regression and multiple subgroup analyses. Head-to-head comparison between PI-RADSv1 and PI-RADSv2 was performed for available studies. EVIDENCE SYNTHESIS Twenty-one studies (3857 patients) were included. The pooled sensitivity was 0.89 (95% confidence interval [CI] 0.86-0.92) with specificity of 0.73 (95% CI 0.60-0.83) for PCa detection. Proportion of patients with PCa, magnetic field strength, and reference standard were significant factors affecting heterogeneity (p<0.01). Multiple subgroup analyses showed consistent results. In six studies performing head-to-head comparison, PI-RADSv2 demonstrated higher pooled sensitivity of 0.95 (95% CI 0.85-0.98) compared with 0.88 (95% CI 0.80-0.93) for PI-RADSv1 (p=0.04). However, the pooled specificity was not significantly different (0.73 [95% CI 0.47-0.89] vs 0.75 [95% CI 0.36-0.94], respectively; p=0.90). CONCLUSIONS PI-RADSv2 shows good performance for the detection of PCa. PI-RADSv2 has higher pooled sensitivity than PI-RADSv1 without significantly different specificity. PATIENT SUMMARY We reviewed all previous studies using Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) for prostate cancer detection. We found that the updated PI-RADSv2 shows significant improvement compared with the original PI-RADSv1.

Determination of Normal Hepatic Elasticity by Using Real-time Shear-wave Elastography

PURPOSE To determine normal reference values of liver elasticity and measurement reliability by using real-time shear-wave elastography (SWE) in patients with a range of ages and body mass index (BMI) measurements, with presence or absence of hepatic steatosis. MATERIALS AND METHODS The institutional review board approved this study, and informed consent was waived because of the retrospective nature of the study. Two hundred thirty-eight patients who underwent SWE and ultrasonography-guided liver biopsies on the same day were identified retrospectively. The median kilopascal value of three consecutive measurements was used as a representative value for each subject. One hundred ninety-six patients who were potential donors for living-donor liver transplantation and had biopsy-proven normal (123 nonsteatotic and 73 steatotic) livers as the only histologic abnormality were included in the study. Reference ranges of normal hepatic elasticity were calculated by using lower and upper limits at the 2.5 and 97.5 percentiles. With the upper value of the reference range as a cutoff value, the sensitivity and specificity for the diagnosis of hepatic fibrosis were calculated. Measurement reliability was evaluated by using the intraclass correlation coefficient (ICC). To investigate the effects of potential confounding factors (age, hepatic steatosis, and BMI) on liver elasticity, the Pearson correlation test and the Student t test were performed. RESULTS The reference range of normal hepatic elasticity was 2.6-6.2 kPa. With 6.2 kPa as a cutoff value, the sensitivity and specificity for the diagnosis of hepatic fibrosis were 91% (20 of 22 subjects) and 95.9% (188 of 196 subjects), respectively. The overall ICC for the elasticity measurements was 0.924. The potential confounding factors that we considered had negligible effects on the elasticity values. CONCLUSION Hepatic elasticity values measured with SWE in histologically proven normal livers ranged from 2.6 to 6.2 kPa, with high measurement reliability. The effect of the potential confounding factors on liver elasticity was negligible.