Fluid?attenuated inversion recovery diffusion?weighted imaging (DWI) for evaluating chemotherapy response in patients with acute leukemia: Comparison with conventional DWI

Background: At present, the diagnosis and efficacy evaluation of acute leukemia (AL) are assessed by bone marrow aspiration, which is invasive and subject to sampling errors. Therefore, there is a pressing need to develop a noninvasive and accurate imaging method to evaluate bone marrow changes in patients with AL. This study aimed to compare the apparent diffusion coefficient (ADC) values obtained from fluid?attenuated inversion recovery diffusion?weighted imaging (FLAIR?DWI) and conventional DWI in the lumbar bone marrow of patients with AL and to investigate their performance for evaluating response to induction chemotherapy. Methods: A total of 28 patients with newly diagnosed AL and 25 patients with AL after induction chemotherapy underwent MRI scans at 1.5 Tesla using a conventional DWI and a FLAIR?DWI sequence on sagittal planes covering the lumbar bone marrow. Further, the ADC values from these two sequences, denoted as ADCCON and ADCFLAIR, were measured on multiple vertebrae. The percentage of leukemia cells in bone marrow was recorded, and bone marrow aspiration was performed on treated patients to determine complete remission (CR) and nonremission (NR). Results: ADCFLAIR [(0.453 ± 0.103) × 10?3 mm2/s] was significantly lower than ADCCON [(0.486 ± 0.096) × 10?3 mm2/s] in the 28 untreated patients (t = 3.051, P = 0.005). In the 25 treated patients, ADCFLAIR and ADCCON values [(0.566 ± 0.239) × 10?3 mm2/s] and [(0.716 ± 0.235) × 10?3 mm2/s], respectively, were higher compared with the untreated patients. The ADCCON values showed a nonsignificant difference between the CR (n = 18) and NR (n = 7) groups (t = 1.409, P = 0.305). However, the ADCFLAIR values exhibited statistically significant difference (t = 2.542, P = 0.018) between the two groups. In a receiver operator characteristic (ROC) analysis, the area under the curve (AUC) using ADCFLAIR (0.770) was larger than that of ADCCON (0.611) in distinguishing the CR and NR patients following the chemotherapy. Conclusion: Although both ADCCON and ADCFLAIR are sensitive to tissue changes induced by chemotherapy, FLAIR?DWI outperformed conventional DWI in separating AL patients with CR from NR after chemotherapy. A possible mechanism is that FLAIR?DWI suppresses signals from free water, making the ADC measurement more sensitive to structural changes in the bone marrow

External validation of chemotherapy response score system for histopathological assessment of tumor regression after neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma / 부인종양

OBJECTIVE: The chemotherapy response score (CRS) system based on histopathological examination has been recently proposed for tubo-ovarian high-grade serous carcinoma (HGSC) to assess response to neoadjuvant chemotherapy (NAC). This study was aimed at validating the CRS system in an external cohort of tubo-ovarian HGSC patients. METHODS: This study included 110 tubo-ovarian HGSC patients who underwent NAC followed by interval debulking surgery. The 3-tiered CRS of the omental and adnexal tissue sections was determined by 3 independent pathologists. Differences in patient outcomes according to CRS were analyzed. RESULTS: The CRS system was highly reproducible among the 3 pathologists. Fleiss' kappa value and Kendall's coefficient of concordance for the omental CRS were 0.656 and 0.669, respectively. The omental CRS significantly predicted progression-free survival (PFS). The median PFS of patients whose tumors exhibited the omental CRS 1–2 (15 months) was significantly shorter than that of patients with an omental CRS of 3 (19 months; p=0.016). In addition, after adjusting for age, stage, and debulking status, the omental CRS was an independent prognostic factor for PFS of tubo-ovarian HGSC patients who were treated with NAC (adjusted hazard ratio [HR]=1.74; 95% confidence interval [CI]=1.05–2.87). CONCLUSION: The CRS system for assessing NAC response was a reproducible prognostic tool in our cohort. The application of the CRS system after NAC can improve survival estimation in HGSC patients.

The feasibility research of ADC value in dynamic monitoring to chemotherapy response of advanced gastric carcinoma / 实用放射学杂志

Objective To evaluate the value of DWI and ADC value in monitoring the chemotherapy response of advanced gastric carcinoma dynamically.Methods 42 advanced gastric carcinoma patients who were confirmed by histopathology underwent T2 WI and DWI examinations at pre-chemotherapy,post-chemotherapy 3 d,7 d,30 d and 60 d respectively.The longest diameters of tumor pre-chemotherapy and post-chemotherapy 60 d were measured on axial T2 WI,meanwhile the ADC values at different time points were calculated.The mean ADC value among pre-and post-chemotherapy of each group (PR and SD)was compared.Results The ADC value of PR group increased gradually.The mean ADC value before therapy was statistically lower than those at differ-ent time points post-chemotherapy (P < 0.05).The ADC value of SD group increased gradually from pre-chemotherapy to post-chemotherapy 30 d,and then the ADC value decreased at post-chemotherapy 60 d.The differences of the mean ADC values in differ-ent time points were statistically significant (P < 0.05).Conclusion DWI and ADC value can dynamically,quantitatively and early detect and monitor the chemotherapy response of advanced gastric carcinoma.

Association between Chemotherapy-Response Assays and Subsets of Tumor-Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study

PURPOSE: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. MATERIALS AND METHODS: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. RESULTS: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. CONCLUSIONS: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.

Predictive Value of In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay in Advanced Gastric Cancer Patients Who Received Oral 5-Fluorouracil after Curative Resection / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To assess the usefulness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results in advanced gastric cancer patients receiving adjuvant chemotherapy. MATERIALS AND METHODS: Sixty-two patients underwent curative surgical resection between January, 2006 and December, 2008. Their highly purified surgical specimens were evaluated by ATP-CRAs. Of the 62, 49 had successful assay results and they received either oral 5-fluorouracil or other chemotherapies. We retrospectively analyzed data for 24 patients who were treated with oral 5-fluorouracil and whose assays were successful. RESULTS: The median observation time was 24.6 months (range, 10.1 to 40.9 months). The median treatment time was 11.2 months (range, 1.2 to 17.7 months). The median age was 66 years (range, 30 to 81 years). Patients were grouped into sensitive- and resistant-groups according to adenosine triphosphate-based chemotherapy response results for fluorouracil. The sensitive-group showed a significantly longer time to relapse (not reached in the sensitive-group vs. 24.8 months in the resistant-group, p=0.043) and longer overall survival compared to the resistant-group (not reached in the sensitive-group vs. 35.7 months in the resistant-group, p=0.16, statistically insignificant). CONCLUSION: Patients who receive curative surgical resection significantly benefit from sensitive adjuvant chemotherapy according to ATP-CRA results for time to relapse.

Heterogeneity of Adenosine Triphosphate-Based Chemotherapy Response Assay in Colorectal Cancer - Secondary Publication

PURPOSE: Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is a well-documented and validated technology that can individualize chemotherapy for patients with lung, stomach, or breast cancer. This study explored the feasibility of ATP-CRA as a chemosensitivity test in patients with colorectal cancer. MATERIALS AND METHODS: A total of 118 patients who underwent surgical resection for colorectal adenocarcinoma were analyzed for chemosensitivity to 6 anticancer drugs using ATP-CRA. We calculated the cell death rate (CDR) by measuring intracellular ATP levels of drug-exposed cells and untreated controls. RESULTS: Interpretable results were available for 85.5% (118/138) of patients. The mean coefficient of variation for triplicate ATP measurements was 9.2%. The highest CDR was observed in irinotecan (34.0%) and the lowest CDR in etoposide (21.0%). Paclitaxel had the broadest range of CDR (0-86.7%) and 5-FU had the narrowest range of CDR (0-56.8%). The overall highest responsiveness was seen most prevalently in irinotecan (24.7%, 23/93 patients). Irinotecan had the greatest responsiveness in patients with well differentiated and moderately differentiated carcinoma. CONCLUSION: Our study suggests that ATP-CRA could be used to identify patients with colorectal cancer who might benefit from treatment with a specific chemotherapeutic agent.

Preliminary Study of the Clinical Features of the Chemosensitivity Test in Colorectal Cancer

PURPOSE: Colorectal cancers have been known to be refractory to chemotherapy in the past decades. Recently, novel agents have been developed and various data have shown an improved response rate and a survival benefit. However, considerable heterogeneity exists between cancers of the same tissue type, including colorectal cancer. Thus, Individualized chemotherapy that is tailored specifically to the characteristics of the tumor is necessary for an improved clinical outcome. RESULTS: We evaluate the chemosensitivity of colorectal cancer to standard drugs (5-FU, oxaliplatin, and irinotecan) and to drugs used for other cancers (mitomycin, paclitaxel, and gemcitabine) by using Adenosine-triphosphate-based chemotherapy response assay (ATP-CRA). RESULTS: The degree of in-vitro response to a single anticancer medication was highest for 5-FU. According to stages, 5-FU is the most sensitive chemotherapeutic agent in Duke's B, irinotecan in Duke's C, and 5-FU in Duke's D patients. With tumor location, irinotecan is most sensitive in colon cancers and 5-FU in rectal cancers. The effect of treatment is superior in the test-guided therapy group in Duke's D colorectal cancer patients. CONCLUSIONS: Chemosensitivity tests may be useful in selecting optimum drugs for patient who require chemotherapy. However, the results of this study do not strongly support the usefulness of this assay; further studies with a sufficient number of cases and an extended observation period are ongoing.

The Results of the ATP Based Chemotherapy Response Assay in Gastric Cancer Tissues

PURPOSE: Recently, chemosensitivity tests have become widely used for the selection of effective drugs in gastric cancer patients. In this study, a chemosensitivity test was performed to select agents to increase the effectiveness of adjuvant chemotherapy. MATERIALS AND METHODS: Chemosensitivity testing was performed in 81 gastric cancer patients that received a gastrectomy at the Yeungnam University Hospital. An ATP (adenosine triphosphate) based chemotherapy response assay was used. Clinicopatholgical factors such as sex, age, expression of tumor markers (CEA and CA19-9 levels), location of the tumor, morphology of advanced cancer, histological type, cell differentiation, depth of invasion, Lauren classification, Ming classification, lymphatic invasion, vascular invasion, neural invasion, lymph node metastasis and TNM stage were used to correlate the chemosensitivity and clinicopathological factors. RESULTS: The most effective antitumor agents in gastric cancer patients were (in order of effectiveness) 5-FU, Epirubicin, Irinotecan and Oxaliplatin in our series. The chemosensitivity test showed a significant difference in susceptibility according to clinicopathological factors. CONCLUSION: Further studies on multidrug therapy are needed to evaluate synergistic effects of drugs. Therefore, for effective chemotherapy, it is more efficacious to select a chemosensitive drug than continue to use the same drug regimen.

The Relationship between MDR1 Polymorphisms and the Response to Etoposide/Cisplatin Combination Chemotherapy in Small Cell Lung Cancer / 결핵및호흡기질환

No abstract available.

Multidrug resistance-associated protein (MRP) and multidrug resistance (MDR1) gene expression in osteosarcoma and their prognostic significance / 대한정형외과학회잡지

PURPOSE: The purpose of this study is to evaluate the correlations between the multidrug resistance-associated protein (MRP) and multidrug resistance (MDR1) gene in osteosarcoma, and their prognostic significances by RT-PCR method. MATERIALS AND METHODS: We isolated RNA from 34 fresh deep-frozen primary osteosarcoma tissue specimens and evaluated the expression level of MRP and MDR1 m-RNA using RT-PCR method. GAPDH was used as the housekeeping gene for the experiment. RESULTS: The average MRP/GAPDH m-RNA ratio was 0.550 and the average MDR1/GAPDH m-RNA ratio was 0.419. There were moderate degree of correlations between MRP/GAPDH m-RNA and MDR1/GAPDH m-RNA ratio (p<0.05). There was significant correlations between the chemotherapy response and the MDR1/GAPDH m-RNA ratio (p<0.05), but not with the MRP/GAPDH ratio. Multivariate analysis for the correlation between the MRP and MDR1 gene expression and the chemotherapy response revealed that only the MDR1/GAPDH m-RNA ratio was significantly related to it (p<0.05). CONCLUSION: There was a moderate degree of correlation between the expressions of MRP and MDR1 genes. However, the chemotherapy response showed significant correlations with the expression of MDR1 gene, but not with MRP gene.

Prognostic factors affecting response to chemotherapy and survival duration in Korean patients with multiple myeloma / 대한내과학회지

BACKGROUND: New therapeutic modalities such as high dose chemotherapy and stem cell support have been tried to prolong the survival period of the patients with multiple myeloma. However, little is known about the criteria for the application of those new therapies. There are only a few reports for the prognostic factors of multiple myeloma in Korea. The purpose of this study is to analyze the prognostic factors affecting chemotherapy response and survival in patients with multiple myeloma. METHODS: We retrospectively analysed the clinical records of 122 patients who were newly diagnosed as multiple myeloma by SWOG criteria, between November, 1989 and April, 1997 at Asan Medical Center. RESULTS: 1) The peak incidence was the 7th decade and male to female ratio was 1.3:1. The most common presenting symptom at first diagnosis was bone pain. 2) Initial clinical stage was as followed: stage I in 17.2% , stage II in 16.4% and 66.4% in III. The immunoglobulin classes were IgG in 51.6%, light chain only in 25.4%, IgA in 16.4%, IgD in 4.1%, and non-secretory type in 2.5%. Plasma cell types in bone marrow were classified as plasmablastic type in 45.9%, plasmacytic type in 54.1%. 3) Eighty two patients who recieved chemotherapy more than 3 cycles were evaluable for chemotherapy response. Overall response rate was 69.5%. Factors affecting response to chemotherapy were serum creatinine level, plasma cell type, total plasma cell percentage and plasmablast percentasge of total nucleated cells in bone marrow. 4) For total 122 patients, overall median survival period was 21 months, and estimated 5 year survival rate was 23.5%. Factors affecting survival were serum creatinine, corrected calcium, albumin, beta2-microglobulin level, response to chemotherapy, total plasma cell percentage and plasmablast percentage in bone marrow. CONCLUSION: Bone marrow findings at initial diagnosis are significantly associated with response to chemotherapy and survival duration.