Methotrexate distribution within the subarachnoid space after intraventricular and intravenous administration

Purpose: Intrathecal methotrexate achieves high concentrations in cerebrospinal fluid (CSF), but drug distribution throughout the subarachnoid space after an intralumbar dose is limited. The objective of this study was to quantify methotrexate distribution in CSF after intraventricular and intravenous administration and to identify factors that influence CSF distribution. Methods: Nonhuman primates (Macaca mulatta) with permanently implanted catheters in the lateral and fourth ventricles received methotrexate by bolus injection (0.5 mg) and infusion (0.05 to 0.5 mg/day over 24 to 168 h) into the lateral ventricle, as well as intravenous infusions. CSF was sampled from the lumbar space, fourth ventricle and the subarachnoid space at the vertex. Methotrexate in CSF and plasma was measured with the dihydrofolate reductase inhibition assay. Results: After bolus intraventricular injection, methotrexate exposure in lumbar CSF ranged from 11% to 69% of that achieved in the fourth ventricle. During continuous intraventricular infusions, methotrexate steady-state concentrations (C_ss) in lumbar CSF and CSF from the vertex were only 20% to 25% of the ventricular CSF C_ss. The dose, duration of infusion, and infusate volume did not influence drug distribution to the lumbar CSF, but probenicid increased the lumbar to ventricular C_ss ratio, suggesting the involvement of a probenicid-sensitive transport pump in the efflux of MTX from the CSF. During the intravenous infusions, the ventricular methotrexate C_ss was lower than the lumbar C_ss and the C_ss in CSF from the vertex. Conclusion: Methotrexate CSF distribution after intraventricular injection was uneven, and at steady-state CSF methotrexate concentrations were lower at sites that were more distant from the injection site. Received: 20 April 1999 / Accepted: 28 July 1999     

Effect of probenecid on ventricular cerebrospinal fluid methotrexate pharmacokinetics after intralumbar administration in nonhuman primates

PURPOSE: Intrathecal methotrexate (MTX) achieves high concentrations in the cerebrospinal fluid (CSF) following intralumbar administration. However, peak ventricular CSF MTX concentrations are highly variable and are < 10% of those achieved with intraventricular dosing. The objectives of this study were to evaluate the effect of intralumbar and intravenous probenecid on ventricular CSF MTX concentrations after intralumbar administration of MTX, and to compare the pharmacokinetics of MTX after intralumbar and intraventricular administration. METHODS: Nonhuman primates (Macaca mulatta) with permanently implanted catheters in the lateral and fourth ventricles received 0.5 mg intraventricular (lateral ventricle) MTX, or 0.5 mg intralumbar MTX with and without intralumbar or intravenous probenecid. Animals were kept prone for 1 h after MTX administration, and ventricular CSF was sampled up to 48 h from a fourth ventricular Ommaya reservoir. MTX concentrations were measured using the dihydrofolate reductase enzyme inhibition assay. Area under the ventricular CSF MTX concentration-time curve (AUC) was used as a measure of MTX exposure. RESULTS: Peak ventricular CSF MTX concentrations and AUCs were highly variable after intralumbar MTX administration. Ventricular CSF MTX AUCs increased by a mean of 3.2-fold after the addition of intralumbar probenecid. Intravenous administration of probenecid did not result in an increase in ventricular CSF MTX AUCs. Asymptomatic pleocytosis was observed in all animals after intralumbar probenecid administration. Ventricular CSF MTX concentrations and AUCs were less variable after intraventricular administration of MTX. CONCLUSION: The administration of intralumbar but not intravenous probenecid increases the ventricular CSF MTX exposure after intralumbar MTX administration.     

Comparative estimation of percentage breast tissue density for digital mammography, digital breast tomosynthesis, and magnetic resonance imaging

Given the increasingly important role of breast density as an independent risk factor for breast cancer, and the variable breast imaging tests that potentially provide measures for density. We compared breast tissue density on digital mammography (FFDM), digital breast tomosynthesis (DBT), and magnetic resonance imaging (MRI) using semi-automated automated software. These three imaging modalities have not been previously directly compared for estimating breast tissue density. Following informed consent from all participating women, FFDM, DBT, and MRI were performed. Breast percentage density was calculated with semi-automated software, and compared, for all three imaging modalities. 48 patients (mean age, 41 years; range, 35–67 years) underwent FFDM, DBT, and MRI. Percent FFDM, DBT, and MRI breast density measures showed a positive linear correlation, (r = 0.95 for MRI and DBT, P < 0.0001; r = 0.97, P < 0.0001 for FFDM and DBT; r = 0.87 for FFDM and MRI). Linear regression analysis related to MRI and DBT had a high r ² = 0.89 (95 % CI = 0.88–0.99, P < 0.001). FFDM overestimated breast density in 15.1 % in comparison to DBT and in 16.2 % in comparison to MRI, or conversely each of DBT and MRI underestimated density (relative to FFDM) by 15.1 or 16.2 %, respectively. Differences in percentage breast density between FFDM and DBT, and between FFDM and MRI, were highly significant (P < 0.0001). Differences in percentage breast density between DBT and MRI were not significant (P > 0.05). Breast density measures using FFDM, DBT, or MRI were generally well-correlated, although differences were noted between estimates when comparing FFDM and DBT, and for estimates comparing FFDM and MRI. No signficant differences in percentage density were observed when comparing DBT and MRI. Our work highlight that differences between FFDM, DBT, and MRI should be considered when measuring percentage breast density.     

Diagnostic performance of breast-specific gamma imaging in the assessment of residual tumor after neoadjuvant chemotherapy in breast cancer patients

To evaluate the diagnostic performance of breast-specific gamma imaging (BSGI) in the assessment of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer patients, female breast cancer patients who underwent NAC, preoperative ^99mTc-sestamibi BSGI, and subsequent definitive breast surgery were enrolled retrospectively. The accuracy of BSGI in the assessment of residual tumor presence and residual tumor size was evaluated and compared to that of magnetic resonance imaging (MRI) using pathology results as the gold standard. The sensitivity and specificity of BSGI for residual tumor detection in 122 enrolled patients were 74.0 and 72.2 %, respectively, and were comparable to those of MRI (81.7 and 72.2 %; P > 0.100). The residual tumor size was significantly underestimated by BSGI in the luminal subtype (P = 0.008) and by MRI in the luminal (P < 0.001) and HER2 subtypes (P = 0.032), with a significantly lesser degree of underestimation by BSGI than MRI in both subtypes. In the triple-negative subtype, both BSGI and MRI generated accurate tumor size measurements. The residual cellularity of triple-negative tumors was significantly higher than that of the non-triple-negative tumors (P = 0.017). The diagnostic performance of BSGI in the assessment of residual tumor is comparable to that of MRI in breast cancer patients. The assessment of residual tumor extent by BSGI depends on the molecular subtype, but BSGI may be more accurate than MRI. Underestimation of tumor size in the luminal and/or HER2 subtypes by BSGI and MRI may be due to low-residual cellularity.     

Evaluation of Multifocality and Multicentricity With Breast Magnetic Resonance Imaging in Each Breast Cancer Subtype

Introduction

The purpose of this study was to evaluate whether diagnostic performance of breast magnetic resonance imaging (MRI) for detection of multifocality and multicentricity (MFMC) of breast cancer (BC) can be influenced by different histotypes or immunophenotypes in newly diagnosed patients with breast cancer.

A study of circulating anti-CD25 antibodies in non-small cell lung cancer

Purpose

Tumors can trigger specific immune response to tumor-associated antigens but the precise mechanism remains unclear. Since regulatory T-lymphocytes (Treg) play a crucial role in controlling autoimmune responses, the present work was undertaken to test whether dysfunction of Treg cells could be involved in developing autoimmunity in patients with lung cancer.

Methods

In this study, we developed an in-house enzyme-linked immunosorbent assay to test circulating anti-CD25 autoantibodies among 272 patients with non-small cell lung cancer (NSCLC) and 226 control subjects matched in age, gender and smoking history.

Results

Mann–Whitney U test showed that the anti-CD25 IgG level was significantly higher in patients with NSCLC than control subjects (Z = ?7.48, P < 0.001) while the anti-CD25 IgA level was not significantly changed in the patient group as compared with the control group (Z = ?1.34, P = 0.181). Spearman correlation analysis failed to reveal a significant correlation between the levels of anti-CD25 IgG and IgA either in patients with NSCLC (r = ?0.034, P = 0.578) or in control subjects (r = 0.055, P = 0.429). ROC analysis showed an AUC of 0.70 for anti-CD25 IgG, in which NSCLC at stage III had the highest AUC (0.75). The sensitivity against a specificity of >90 % was 35.0 % for anti-CD25 IgG assay with an inter-assay deviation of 9.4 %, and 4.0 % for anti-CD25 IgA assay with an inter-assay deviation of 13.0 %.

Conclusions

Circulating anti-CD25 IgG antibody may be a useful biomarker for prognosis of lung cancer.     

Pharmacokinetics of intrathecal gemcitabine in nonhuman primates.

PURPOSE: Gemcitabine is an excellent candidate for regional therapy. We quantified cerebrospinal fluid (CSF) and plasma concentrations of gemcitabine and its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), in nonhuman primates given intrathecal gemcitabine. EXPERIMENTAL DESIGN: Three nonhuman primates received 5 mg of gemcitabine via lateral ventricle. CSF was sampled from the fourth ventricle in all of the animals and the lumbar space in one, and one had plasma sampled. One animal had ventricular CSF sampled after receiving 5 mg intralumbar gemcitabine. Gemcitabine and dFdU were measured by high-performance liquid chromatography. Three additional animals had 5 mg intralumbar gemcitabine administered weekly for 4 weeks and were monitored for toxicity. RESULTS: At 37 degrees C in vitro, gemcitabine was stable in CSF. Ventricular delivery of gemcitabine produced peak ventricular CSF gemcitabine concentrations of 297 +/- 105 microg/ml. After 6 h, the concentrations were <0.03 microg/ml. Intrathecal gemcitabine was rapidly and extensively converted to dFdU. CSF dFdU concentrations increased to 82 microg/ml at 1 h and then declined to very low values by 24 h. After intraventricular administration, CSF gemcitabine and dFdU area(s) under the curve (AUC) were 251 +/- 85 and 249 +/- 88 microg/ml x h. Intralumbar gemcitabine produced lower ventricular CSF gemcitabine and dFdU concentrations than did intraventricular gemcitabine. The plasma gemcitabine AUC associated with 5 mg of intraventricular gemcitabine was 2 mg/ml x h, which was >200-fold lower than the CSF gemcitabine AUC in the same animal. Transient CSF pleocytosis was the only toxicity observed. CONCLUSIONS: Our results demonstrate a large pharmacokinetic advantage of intrathecal gemcitabine and support a planned Phase I clinical trial of this dosing strategy.     

Identifying the survival subtypes of glioblastoma by quantitative volumetric analysis of MRI

This study was to project a powerful volumetric-related parameter on magnetic resonance imaging (MRI) for classifying patients with glioblastoma multiforme (GBM) into distinct subgroups objectively. The preoperative MRIs of 147 patients with primary GBM were analyzed. Volumetric-related parameters, including V1 (tumor volume), V2 (peritumoral T2/FLAIR hyperintense volume) and V2/V1 (the volume ratio), were estimated by an ellipsoid model. Log-rank analysis and Cox regression methods were used to compare Kaplan–Meier plots and identified prognostic parameters. Log-rank analysis revealed that V1 and V2 were correlated with survival, but the P value was marginally significant (P = 0.082, P = 0.091, for progression-free survival [PFS]; P = 0.120, P = 0.073, for overall survival [OS], respectively). V2/V1 was a potential prognostic factor for both PFS and OS (P < 0.001 and P < 0.001, respectively). Cox regression analysis documented that higher V2/V1 (ratio ≥ 7.0) was independent unfavorable prognostic factor. The odd ratio (OR) of higher V2/V1 was 2.662 (95 % confidence interval [CI], 1.782–3.975; P < 0.001) for PFS and 3.450 (95 % CI, 2.079–5.725; P < 0.001) for OS, respectively. The volumetric-related parameters of V1, V2 and V2/V1 were helpful for predicting the prognosis of patients with GBM. V2/V1 was a more comprehensive and systematic prognostic factor in GBM patient, especially for those with small tumor but large peritumoral T2 hyperintense or large tumor but small peritumoral T2 hyperintense.     

Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study

The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) catheter positioning in relation to imaging features and (2) to examine the potential impact of catheter positioning, overall catheter placement and imaging features on long term clinical outcome in the PRECISE study. Catheter positioning and overall catheter placement were scored and used as a surrogate of adequate placement. Imaging studies obtained on day 43 and day 71 after resection were each retrospectively reviewed. Catheter positioning scores, catheter overall placement scores, local tumor control and imaging change scores were reviewed and correlated using Generalized Linear Mixed Models. Cox PH regression analysis was used to examine whether these imaging based variables predicted overall survival (OS) and progression free survival (PFS) after adjusting for age and KPS. Of 180 patients in the CED group, 20 patients did not undergo gross total resection. Of the remaining 160 patients only 53% of patients had fully conforming catheters in respect to overall placement and 51% had adequate catheter positioning scores. Better catheter positioning scores were not correlated with local tumor control (P = 0.61) or imaging change score (P = 0.86). OS and PFS were not correlated with catheter positioning score (OS: P = 0.53; PFS: P = 0.72 respectively), overall placement score (OS: P = 0.55; PFS: P = 0.35) or imaging changes on day 43 MRI (P = 0.88). Catheter positioning scores and overall catheter placement scores were not associated with clinical outcome in this large prospective trial.     

Polysomy of chromosomes 1 and 19: an underestimated prognostic factor in oligodendroglial tumors

The clinical significance of chromosomes 1 and 19 deletion was well established in oligodendroglial tumors (ODGs). This study was designed to evaluate the prognostic implication of chromosomes 1 and 19 polysomy in gliomas. 584 patients with histological diagnosis of primary gliomas enrolled in the study. Chromosomes 1 and 19 status was detected with fluorescence in situ hybridization (FISH). Of the 584 cases, the frequency of 1q and 19p polysomy in mixed gliomas was significantly higher than ODGs or astrocytic tumors (1q P = 0.032 and P = 0.044; 19p P = 0.024 and P = 0.027); the frequency of 1q and 19p polysomy in low-grade gliomas (WHO II) was relatively lower compared with WHO III or WHO IV (1q P = 0.097 and P = 0.026; 19p P = 0.04 and P = 0.002). 1q, 19p and co-polysomy were confirmed as risk factors conveyed unfavorable outcomes, which has been further validated in both anaplastic oligodendroglial tumors (AOGs) (P = 0.07, P = 0.028 and P = 0.054 for PFS; P = 0.007, P = 0.001 and P = 0.002 for OS, respectively) and glioblastomas with oligodendroglioma component (GBMOs) (P = 0.005, P < 0.001 and P < 0.001 for PFS; P = 0.136, P = 0.006 and P = 0.051 for OS, respectively). Based on chromosomes 1/19 co-deletion and co-polysomy, AOGs and GBMOs could be divided into three subgroups which harbored distinct prognosis (AOGs P < 0.001 for PFS and P < 0.001 for OS; GBMOs P < 0.001 for PFS and P = 0.012 for OS). Chromosomes 1/19 polysomy are potential prognostic factors which confer unfavorable outcomes. The molecular prognostic grouping model based on chromosomes 1/19 co-polysomy and co-deletion better predicts prognosis and provides a more reliable information for treatment decision-making.     

The efficacy and limitations of stereotactic radiosurgery as a salvage treatment after failed whole brain radiotherapy for brain metastases

The aim of the present study was to evaluate the efficacy and limitations of repeat stereotactic radiosurgery (SRS) salvage for patients with recurrence of brain metastases (BM) after whole brain radiotherapy (WBRT). This is a retrospective, observational, single-center trial analyzing 77 consecutive patients with recurrent BM who were treated primarily with WBRT. All patients underwent SRS as salvage treatment. Median age was 62 years, and median Karnofsky performance status (KPS) was 80. The median interval between the starting date of WBRT and radiosurgery was 10.6 months. One, two and more than two SRS sessions were required in 42, 13 and 22 patients, respectively. The median total planning target volume (PTV) was 8.1 mL and the median dose prescribed was 20 Gy. The median follow-up was 7.7 months. 1- and 2-year neurological death-free survival (NS) rates were 87 and 78 %, respectively. Competing risk analysis demonstrated active extra-central nervous system (CNS) disease [Hazard ratio (HR) 0.236, P = 0.041] and total PTV on initial SRS (≥5 mL) (HR 4.22, P = 0.033) to be associated with the NS rate. 1- and 2-year overall survival (OS) rates were 41 and 11 %, respectively. The median OS time was 8.2 months. Active extra-CNS disease (HR 1.94, P = 0.034) and high KPS (≥90) (HR 0.409, P = 0.006) were associated with the OS rate. In total, 798 tumors (75 %) in 66 patients (86 %) with sufficient radiological follow-up data were evaluated. 1- and 2-year metastasis local control rates were 76.6 and 57.9 %, respectively. Prescribed dose (≥20 Gy) (HR 0.326, P < 0.001), tumor volume (≥2 mL) (HR 1.98, P = 0.007) and metastases from breast cancer (HR 0.435, P < 0.001) were independent predictive factors for local tumor control. Repeat salvage SRS for recurrent BM after WBRT appeared to be a safe and effective treatment. In the majority of patients, even those with numerous BM, neurological death could be delayed or even prevented.     

Short-interval estimation of proliferation rate using serial diffusion MRI predicts progression-free survival in newly diagnosed glioblastoma treated with radiochemotherapy

Cell invasion, motility, and proliferation level estimate (CIMPLE) mapping is a new imaging technique that provides parametric maps of microscopic invasion and proliferation rate estimates using serial diffusion MRI data. However, a few practical constraints have limited the use of CIMPLE maps as a tool for estimating these dynamic parameters, particularly during short-interval follow-up times. The purpose of the current study was to develop an approximation for the CIMPLE map solution for short-interval scanning involving the assumption that net intervoxel tumor invasion does not occur within sufficiently short time frames. Proliferation rate maps created using the “no invasion” approximation were found to be increasingly similar to maps created from full solution during increasingly longer follow-up intervals (3D cross correlation, R ² = 0.5298, P = 0.0001). Results also indicate proliferation rate maps from the “no invasion” approximation had significantly higher sensitivity (82 vs. 64 %) and specificity (90 vs. 80 %) for predicting 6 month progression free survival and was a better predictor of time to progression during standard radiochemotherapy compared to the full CIMPLE solution (log-rank; no invasion estimation, P = 0.0134; full solution, P = 0.0555). Together, results suggest the “no invasion” approximation allows for quick estimation of proliferation rate using diffusion MRI data obtained from multiple scans obtained daily or biweekly for use in quantifying early treatment response.     

Radiological Kinetics of Brain Metastases and Clinical Implications for Patients Treated With Stereotactic Radiosurgery

Aims

Select patients with brain metastases receive stereotactic radiosurgery (SRS) with the objective of improving survival and intracranial disease control. Brain metastases number and volume are prognostic factors used to inform patient selection. The aim of this study was to assess the rate of change of brain metastases size and number (growth kinetics) between the diagnostic and day of SRS magnetic resonance imaging (MRI) scans.

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate: A study from the EORTC childrens' leukemia cooperative group

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m² of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10⁻⁶ M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 ± 33.11 μM; the mean CSF MTX level was 1.47 ± 1.1 μM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 ± 0.027. CSF drug concentrations greater than or equal to 10⁻⁶ M were achieved in 81% of the courses. The highest level was 8.4 × 10⁻⁶ M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.     

Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized,double-blind,placebo-controlled trial

Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen, Denmark. Women, 30–75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI. The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly lower with melatonin than with placebo (3 [11 %] of 27 vs. 9 [45 %] of 20; relative risk 0.25 [95 % CI 0.077–0.80]), giving a NNT of 3.0 [95 % CI 1.7–11.0]. No significant differences were found between AUC for the subjective parameters. No differences in side effects were found (P = 0.78). Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery.     

A single-center analysis of the survival benefits of adjuvant gemcitabine chemotherapy for biliary tract cancer

Background

Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC.

Methods

We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m². Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m² in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders.

Results

Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28–0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07–0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02–0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01–0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03–0.85; interaction, P = 0.13).

Conclusions

Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.     

大剂量甲氨蝶呤化疗的脑脊液药代动力学研究

Objective: To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate (HD-MTX) and provide a solid fundament for clinical practice. Methods: MTX at a high dose ranging from 1.0 to 3.0 g per course was intravenously administered to 30 patients with malignant tumors. Blood and CSF samples were consecutively collected up to 36 h after the initiation of infusion (6 h). MTX concentrations were measured by using a reversed phase high-performance liquid chromatography (RP-HPLC) assay. Results: CSF MTX concentrations were (1.65±1.52)×10^-6, (4.3±3.34)×10^-7, (1.46±1.10)×10^-7 and (3.19±4.38)×10^-8 mol/L, respectively, at 0, 6, 12 and 24 h post infusion, and became undetectable at 36 h post infusion. The concentration-time curve of CSF MTX closely resembled that of the plasma MTX and fitted with the following linear regression equation: Ŷ=0.057 97+0.010 82X (Ŷ: CSF MTX concentration, X: Plasma MTX concentration, r=0.8357). Conclusion: CSF MTX was metabolized in a linear two-compartment model. Additionally, pharmacokinetic analysis of MTX levels indicated a positive correlation between CSF MTX and plasma MTX levels.     

Detectability comparison of modes in dual-mode digital breast tomosynthesis

Background

The objectives of this study were: (1) to evaluate the detectability of full-field digital mammography (FFDM) plus dual-mode digital breast tomosynthesis (DBT) and compare it with that of FFDM alone and (2) to compare the detectability of high-resolution-mode (HR mode used with 40°-angle imaging, 100-µm pixel size, and higher dose) DBT with that of standard-mode (ST mode used with 15°-angle imaging, 150-µm pixel size, and lower dose) DBT for diagnostic evaluation.

Materials

The local Institutional Review Board approved this retrospective study of two different sets of cases. All participants gave written informed consent. FFDM and DBT images of 471 women who were recalled were acquired between August 2013 and October 2014. HR mode and ST mode were applied to 155 breasts and 157 breasts, respectively. The cases of both modes were selected randomly. Eight radiologists interpreted the images. The detectability for recall cases and for follow cases, and area under the receiver operating characteristic curve (AUC) were calculated.

Results

Adding DBT to FFDM significantly increased the detectability for recall cases and AUC relative to those of FFDM alone (HR mode 8.9 %; 95 % confidence interval (CI) 5.7, 15.0 %; P = 0.013 and 4.9 %; 95 % CI 2.1, 7.7 %; P = 0.001; ST mode 8.3 %; 95 % CI 4.1, 12.1 %; P = 0.007 and 2.9 %; 95 % CI 0.5, 5.3 %; P = 0.02), whereas the detectability for follow cases did not significantly differ. The AUC increase was significantly higher in HR mode than in ST mode (1.5 %; 95 % CI 0.5, 3.7 %; P = 0.023).

Conclusion

Adding HR-mode or ST-mode DBT to FFDM significantly improved the detectability for diagnostic evaluation case.