Pharmacokinetics of Ferumoxytol in the Abdomen and Pelvis: A Dosing Study with 1.5- and 3.0-T MRI Relaxometry.

Background The off-label use of ferumoxytol (FE), an intravenous iron preparation for iron deficiency anemia, as a contrast agent for MRI is increasing; therefore, it is critical to understand its pharmacokinetics. Purpose To evaluate the pharmacokinetics of FE in the abdomen and pelvis, as assessed with quantitative 1.5- and 3.0-T MRI relaxometry. Materials and Methods R2*, an MRI technique used to estimate tissue iron content in the abdomen and pelvis, was performed at 1.5 and 3.0 T in 12 healthy volunteers between April 2015 and January 2016. Volunteers were randomly assigned to receive an FE dose of 2 mg per kilogram of body weight (FE2mg) or 4 mg/kg (FE4mg). MRI was repeated at 1.5 and 3.0 T for each volunteer at five time points: days 1, 2, 4, 7, and 30. A radiologist experienced in MRI relaxometry measured R2* in organs of the mononuclear phagocyte system (MPS) (ie, liver, spleen, and bone marrow), non-MPS anatomy (kidney, pancreas, and muscle), inguinal lymph nodes (LNs), and blood pool. A paired Student t test was used to compare changes in tissue R2*. Results Volunteers (six female; mean age, 44.3 years ± 12.2 [standard deviation]) received either FE2 mg (n = 5) or FE4 mg (n = 6). Overall R2* trend analysis was temporally significant (P < .001). Time to peak R2* in the MPS occurred on day 1 for FE2mg and between days 1 and 4 for FE4mg (P < .001 to P < .002). Time to peak R2* in non-MPS anatomy, LNs, and blood pool occurred on day 1 for both doses (P < .001 to P < .09). Except for the spleen (at 1.5 T) and liver, MPS R2* remained elevated through day 30 for both doses (P = .02 to P = .03). Except for the kidney and pancreas, non-MPS, LN, and blood pool R2* returned to baseline levels between days 2 and 4 at FE2mg (P = .06 to P = .49) and between days 4 and 7 at FE4mg (P = .06 to P = .63). There was no difference in R2* change between non-MPS and LN R2* at any time (range, 1-71 sec-1 vs 0-50 sec-1; P = .06 to P = .97). Conclusion The pharmacokinetics of ferumoxytol in lymph nodes are distinct from those in mononuclear phagocyte system (MPS) organs, parallel non-MPS anatomy, and the blood pool. © RSNA, 2019 Online supplemental material is available for this article.

Collagen organization of renal cell carcinoma differs between low and high grade tumors.

BACKGROUND: The traditional pathologic grading for human renal cell carcinoma (RCC) has low concordance between biopsy and surgical specimen. There is a need to investigate adjunctive pathology technique that does not rely on the nuclear morphology that defines the traditional grading. Changes in collagen organization in the extracellular matrix have been linked to prognosis or grade in breast, ovarian, and pancreatic cancers, but collagen organization has never been correlated with RCC grade. In this study, we used Second Harmonic Generation (SHG) based imaging to quantify possible differences in collagen organization between high and low grades of human RCC. METHODS: A tissue microarray (TMA) was constructed from RCC tumor specimens. Each TMA core represents an individual patient. A 5 µm section from the TMA tissue was stained with standard hematoxylin and eosin (H&E). Bright field images of the H&E stained TMA were used to annotate representative RCC regions. In this study, 70 grade 1 cores and 51 grade 4 cores were imaged on a custom-built forward SHG microscope, and images were analyzed using established software tools to automatically extract and quantify collagen fibers for alignment and density assessment. A linear mixed-effects model with random intercepts to account for the within-patient correlation was created to compare grade 1 vs. grade 4 measurements and the statistical tests were two-sided. RESULTS: Both collagen density and alignment differed significantly between RCC grade 1 and RCC grade 4. Specifically, collagen fiber density was greater in grade 4 than in grade 1 RCC (p < 0.001). Collagen fibers were also more aligned in grade 4 compared to grade 1 (p < 0.001). CONCLUSIONS: Collagen density and alignment were shown to be significantly higher in RCC grade 4 vs. grade 1. This technique of biopsy sampling by SHG could complement classical tumor grading approaches. Furthermore it might allow biopsies to be more clinically relevant by informing diagnostics. Future studies are required to investigate the functional role of collagen organization in RCC.

Granulocyte colony-stimulating factor utilization postautologous hematopoietic stem cell transplant in multiple myeloma patients: Does one size fit all?

PURPOSE: To evaluate a single institution's experience with granulocyte colony-stimulating factor after autologous hematopoietic stem cell transplant in myeloma patients to identify populations that benefit most from granulocyte colony-stimulating factor administration. METHODS: Retrospective chart reviews were conducted on patients 18+ years with multiple myeloma that underwent autologous hematopoietic stem cell transplant at UW Health from January 2012 to May 2016. Data collection included demographics, length of stay, time to engraftment, Eastern Cooperative Oncology Group performance status score, and hematopoietic cell transplantation-comorbidity index. The primary outcome was days from transplant to engraftment, defined as absolute neutrophil count > 500/mm3 for two consecutive days or absolute neutrophil count > 1000/mm3 once. A subset analysis was performed on patients whose date of engraftment was known. RESULTS: In total, 216 individual patients were included in the full cohort and 122 patients included in the subset analysis. Median time to engraftment between patients administered granulocyte colony-stimulating factor and the nongranulocyte colony-stimulating factor group was 12 versus 19 days (P < 0.001) in the full cohort and 12 versus 14 days (P < 0.001) in the subset analysis. The average length of stay posthematopoietic stem cell transplant in the granulocyte colony-stimulating factor group was 15 days versus 17 days in the nongranulocyte colony-stimulating factor group (P = 0.026) in the subset analysis. Additionally, no difference in time to engraftment was seen when stratified by age, Eastern Cooperative Oncology Group performance status score, or hematopoietic cell transplantation-comorbidity index. CONCLUSION: Our study supports use of granulocyte colony-stimulating factor posthematopoietic stem cell transplant in myeloma patients to decrease time to engraftment and length of stay. Consideration should be given to utilization in all patients in this population posthematopoietic stem cell transplant. Further research is needed to identify the populations that benefit most from granulocyte colony-stimulating factor administration.

Detection of pediatric musculoskeletal pathology using the fluid-sensitive sequence.

BACKGROUND: Musculoskeletal complaints are common among children, and magnetic resonance (MR) is increasingly used to supplement the clinical assessment. The validation of a short triage protocol could reduce the number of unnecessary contrast-enhanced MR studies that sometimes also require the need for sedation. OBJECTIVE: To compare the diagnostic accuracy between fluid-sensitive sequence and contrast-enhanced MR study in the detection of musculoskeletal pathology in the pelvis and the appendicular skeleton in children older than 2 years. MATERIALS AND METHODS: We performed a retrospective review between Feb. 1, 2016, and Oct. 31, 2016, and identified 99 studies from 96 patients (48 boys and 48 girls; mean age ± standard deviation, 11.1±4.6 years) without syndromic deformity, recent trauma, a history of infectious or inflammatory arthropathy, prior instrumentation or incomplete records. Two radiologists reviewed each study twice, at least 1 month apart, first using only the fluid-sensitive sequences (triage study) and later using the contrast-enhanced study. Readers rated the presence or absence of pathology independently and generated final impressions in consensus. We used Cohen's kappa (κ) and percentage agreement to compare agreement between readers and between studies, respectively. RESULTS: Inter-reader agreement was overall higher for the contrast-enhanced studies (κ range = 0.91-1) than for the triage studies (κ range = 0.49-1). Percentage agreement between studies was high for the detection of pathology (97-100%) and for the impressions (93%). Clinical diagnoses were stress reaction or overuse in 31%, infection in 21%, space-occupying process in 17%, normal in 15%, inflammatory in 14%, and both inflammatory and overuse in 1%. The full study increased diagnostic confidence in five studies and accuracy in two but did not alter management. CONCLUSION: The fluid-sensitive sequence had a near-perfect percentage of agreement with the contrast-enhanced study in the detection of musculoskeletal pathology and could possibly be used to screen children who need a contrast-enhanced MR study.

Juvenile Osteochondritis Dissecans: Cartilage T2 Mapping of Stable Medial Femoral Condyle Lesions.

Purpose To determine whether a T2 mapping sequence could depict early changes in the composition and microstructure of cartilage overlying stable lesions of the medial femoral condyle in patients with juvenile osteochondritis dissecans (JOCD). Materials and Methods This retrospective study analyzed a sagittal T2 mapping sequence performed between September 1, 2015, and March 31, 2017, on 16 patients (10 boys and six girls; median age, 11.5 years) with 18 stable medial femoral condyle JOCD lesions and 18 age-, sex-, and skeletal maturation-matched control participants (11 boys and seven girls; median age, 11.5 years). Cartilage T2 values were quantitatively measured within regions of interest placed around the cartilage within and overlying the JOCD lesion in patients with JOCD and around the cartilage on the weight-bearing medial femoral condyle in patients with JOCD and controls. Wilcoxon signed rank and Wilcoxon rank sum tests were used to compare T2 values. Results T2 values were significantly higher (P < .001) for cartilage within the JOCD lesion than for cartilage overlying the JOCD lesion in patients with JOCD. However, there were no significant differences in T2 values between cartilage overlying the JOCD lesion and cartilage on the weight-bearing medial femoral condyle in patients with JOCD (P = .67) or in T2 values of the cartilage on the weight-bearing medial femoral condyle between patients with JOCD and controls (P = .30). Conclusion There were no significant quantifiable differences in T2 values of cartilage overlying stable JOCD lesions and normal cartilage on the medial femoral condyle, suggesting no substantial changes in cartilage composition and microstructure.

Maturation-Related Changes in T2 Relaxation Times of Cartilage and Meniscus of the Pediatric Knee Joint at 3 T.

OBJECTIVE: The objective of our study was to use a T2 mapping sequence performed at 3 T to investigate changes in the composition and microstructure of the cartilage and menisci of the pediatric knee joint during maturation. MATERIALS AND METHODS: This retrospective study was performed of MRI examinations of 76 pediatric knees without internal derangement in 72 subjects (29 boys [mean age, 12.5 years] and 43 girls [mean age, 13.0 years]) who were evaluated with a sagittal T2 mapping sequence. T2 relaxation time values were quantitatively measured in eight cartilage subregions and in the medial and lateral menisci. Wilcoxon rank sum and Kruskal-Wallis tests were used to analyze the relationship between cartilage and meniscus T2 relaxation time values and sex and skeletal maturation, respectively. A multivariate linear regression model was used to investigate the independent association between cartilage T2 relaxation time values and age, weight, and body mass index (BMI [weight in kilograms divided by the square of height in meters]). RESULTS: There were no significant sex differences (p = 0.26-0.91) in T2 relaxation time values for cartilage or meniscus. T2 relaxation time values in each individual cartilage subregion significantly decreased (p < 0.001) with progressive maturation. T2 relaxation time values in the lateral meniscus significantly increased (p = 0.001) with maturation, whereas T2 relaxation time values in the medial meniscus did not significantly change (p = 0.82). There was a significant association (p < 0.001) between cartilage T2 relaxation time values and age independent of weight and BMI, but no significant association between cartilage T2 relaxation time values and weight (p = 0.06) and BMI (p = 0.20) independent of age. CONCLUSION: Cartilage T2 relaxation time values significantly decreased in all cartilage subregions and meniscus T2 relaxation time values significantly increased in the lateral meniscus during maturation. These changes in T2 relaxation time values reflect age-related changes in tissue composition and microstructure.

Stereotactic body radiation therapy (SBRT) improves local control and overall survival compared to conventionally fractionated radiation for stage I non-small cell lung cancer (NSCLC).

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been adopted as the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC), with local control rates consistently >90%. However, data directly comparing the outcomes of SBRT with those of conventionally fractionated radiotherapy (CONV) is lacking. MATERIAL AND METHODS: Between 1990 and 2013, 497 patients (525 lesions) with early-stage NSCLC (T1-T2N0M0) were treated with CONV (n = 127) or SBRT (n = 398). In this retrospective analysis, five endpoints were compared, with and without adjusting for clinical and dosimetric factors. Competing risks analysis was performed to estimate and compare the cumulative incidence of local failure (LF), nodal failure (NF), distant failure (DF) and disease progression. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by the Cox regression model. Propensity score (PS) matched analysis was performed based on seven patient and clinical variables: age, gender, Karnofsky performance status (KPS), histology, T stage, biologically equivalent dose (BED), and history of smoking. RESULTS: The median dose delivered for CONV was 75.6 Gy in 1.8-2.0 Gy fractions (range 60-90 Gy; median BED = 89.20 Gy) and for SBRT 48 Gy in four fractions (45-60 Gy in three to five fractions; median BED = 105.60 Gy). Median follow-up was 24.4 months, and 3-year LF rates were 34.1% with CONV and 13.6% with SBRT (p < .001). Three-year OS rates were 38.9 and 53.1%, respectively (p = .018). PS matching showed a significant improvement of OS (p = .0497) for SBRT. T stage was the only variable correlating with all five endpoints. CONCLUSION: SBRT compared to CONV is associated with improved LF rates and OS. Our data supports the continued use and expansion of SBRT as the standard of care treatment for inoperable early-stage NSCLC.

Do Headache Patients Require More Care in Between Visits Than Other Neurology Outpatients?

BACKGROUND: There is evidence that time spent in patient care in between patient visits is increasing and a contributor to physician burnout. The extent of this work on providers in the field of headache medicine is unknown. OBJECTIVES: To establish whether headache outpatients require a high level of care in addition to clinic visits, based on the quantity of remote encounters per patient (phone calls and secure email communication to the clinics), in comparison to other neurologic clinics. METHODS: In an academic referral clinic, a total of 3164 established patients were included in this retrospective analysis, 275 from the headache clinic, the remainder from various other neurology clinics (2 physician providers per clinic except 3 physician providers in the headache clinic). Patients presenting for a follow-up visit between January 2014 and April 2016 were observed for a 12-month period during which the number of a) telephone and b) secure email (MyChart) encounters per patient was recorded, and in addition, the number of entries related to each of these encounters. This analysis did not require IRB approval as per institutional guidelines. RESULTS: Headache clinic patients required a high frequency of remote encounters (composite of both telephone and email messages) per patient, second only to the MS clinic patients. Use of secure email messaging (MyChart) per patient was much higher in the headache clinic compared to all other clinics. CONCLUSION: Patients in a headache clinic in an academic tertiary care setting require a high intensity of remote outpatient care, more so than patients in other neurology subspecialty clinics and general neurology clinic, with the exception of the neuroimmunology/MS clinic. This is to a large extent secondary to the very frequent use of secure email linked to the electronic medical record by headache patients.

Role of Early Pulmonary Hypertension as a Risk Factor for Late Pulmonary Hypertension in Extremely Preterm Infants.

OBJECTIVE: The evidence on the role of early pulmonary vascular disease (PVD) in the development of late pulmonary hypertension (PH) in the extremely preterm infants is limited. Objectives were to determine the incidence of early and late PH in extreme preterm infants and to evaluate the role of early PH as a risk factor for development of clinically detected late PH. METHODS: It was a retrospective analysis of early echocardiograms (day of life 5-14) in preterm infants, 22 to 27 weeks' gestation, admitted to the University of Iowa NICU between July 01, 2012 to June 30, 2015. Late echocardiograms performed for clinical suspicion of PH were also analyzed. RESULTS: A total of 154 infants were included in the study. Early PH was diagnosed in 31 (20%) infants. Twenty-four (16%) infants were evaluated for clinically suspected PH. Eight (5%) infants were diagnosed with late PH. Infants with early PH had echocardiograms performed earlier than infants without the evidence of early PH. Early PH was not associated with the development of late PH (p = 0.99). CONCLUSION: Early PH is common among extremely preterm infants (20%). Five percent of infants had clinically detected late PH. Infants with early PH had echocardiograms performed earlier than infants without the evidence of early PH. Early PH was not associated with the development of clinically detected late PH.

Outcomes of primary refractory diffuse large B-cell lymphoma (DLBCL) treated with salvage chemotherapy and intention to transplant in the rituximab era.

Rituximab-containing salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant (ASCT) in chemosensitive patients remains the standard of care for patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, its role in those patients achieving less than a complete response to first-line therapy (primary refractory disease) in the rituximab era is not well defined. We reviewed the outcomes of 82 transplant-eligible patients with primary refractory DLBCL who underwent salvage therapy with the intent of administering high-dose therapy and ASCT to patients achieving chemosensitive remission. The estimated 3-year overall and progression-free survival for all patients was 38% and 29%, respectively, and 65% and 60% respectively for patients proceeding to stem cell transplant. Long-term remission was achieved in 45% of patients achieving a partial response (PR) to initial induction therapy and <20% of patients with stable or progression of disease following initial therapy. These results suggest that salvage chemotherapy with the intent of subsequent high-dose therapy and ASCT remains a feasible strategy in certain patients with primary refractory DLBCL, particularly for those achieving a PR to frontline therapy. The primary barrier to curative therapy in patients with primary refractory disease is resistance to salvage therapy, and future studies should be aimed towards increasing the response rate in this population.

Long-term Survival Based on the Surgical Approach to Lobectomy For Clinical Stage I Nonsmall Cell Lung Cancer: Comparison of Robotic, Video-assisted Thoracic Surgery, and Thoracotomy Lobectomy.

OBJECTIVE: To compare the long-term outcomes among robotic, video-assisted thoracic surgery (VATS), and open lobectomy in stage I nonsmall cell lung cancer (NSCLC). BACKGROUND: Survival comparisons between robotic, VATS, and open lobectomy in NSCLC have not yet been reported. Some studies have suggested that survival after VATS is superior, for unclear reasons. METHODS: Three cohorts (robotic, VATS, and open) of clinical stage I NSCLC patients were matched by propensity score and compared to assess overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed to identify factors associated with the outcomes. RESULTS: From January 2002 to December 2012, 470 unique patients (172 robotic, 141 VATS, and 157 open) were included in the analysis. The robotic approach harvested a higher number of median stations of lymph nodes (5 for robotic vs 3 for VATS vs 4 for open; P < 0.001). Patients undergoing minimally invasive approaches had shorter median length of hospital stay (4 d for robotic vs 4 d for VATS vs 5 d for open; P < 0.001). The 5-year OS for the robotic, VATS, and open matched groups were 77.6%, 73.5%, and 77.9%, respectively, without a statistically significant difference; corresponding 5-year DFS were 72.7%, 65.5%, and 69.0%, respectively, with a statistically significant difference between the robotic and VATS groups (P = 0.047). However, multivariate analysis found that surgical approach was not independently associated with shorter OS and DFS. CONCLUSIONS: Minimally invasive approaches to lobectomy for clinical stage I NSCLC result in similar long-term survival as thoracotomy. Use of VATS and robotics is associated with shorter length of stay, and the robotic approach resulted in greater lymph node assessment.

Unification of favourable intermediate-, unfavourable intermediate-, and very high-risk stratification criteria for prostate cancer.

OBJECTIVE: To improve on the existing risk-stratification systems for prostate cancer. PATIENTS AND METHODS: This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P < 0.001), distant metastasis-free survival (DMFS, P < 0.001), prostate cancer-specific mortality (PCSM, P < 0.001), and overall survival (OS, P < 0.001) compared with patients with favourable-intermediate-risk (FIR) prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P < 0.001), DMFS (P < 0.001), and PCSM (P = 0.001) compared with patients with standard high-risk (SHR) prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. RESULTS: Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. CONCLUSION: Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR with SHR patients, results in modestly improved prediction of outcomes, potentially allowing better personalisation of therapeutic recommendations.

Treatment outcomes and secondary cancer incidence in young patients with hairy cell leukaemia.

Repeated therapy of hairy cell leukaemia (HCL) with treatments that have potential long-term toxicities has raised concerns regarding increased risk for younger patients. We compared clinical outcomes and disease complications in 63 patients with HCL aged ≤40 years at diagnosis with 268 patients >40 years treated at Memorial Sloan Kettering Cancer Center. The rate of complete remission following initial therapy was 87% and 83% (P = 0·71) and estimated 10-year overall survival was 100% and 82% (P = 0·25) in younger and older patients, respectively. Younger patients required therapy earlier and had a significantly shorter time between first and second therapy (median: 63 months vs. 145 months) (P = 0·008). Younger patients required significantly more lines of therapy during follow-up. The 10-year cumulative incidence of secondary malignancies in young and old patients was 0·205 and 0·287, respectively (P = 0·22). The incidence of secondary cancers in patients aged >40 years at diagnosis increased with the number of treatments for HCL (P = 0·018). These results highlight that young patients with HCL have shorter responses to treatment and require more lines of therapy to maintain disease control, while attaining similar long-term survival. This has implications in the design of future clinical trials given our findings that secondary malignancies increase with more chemotherapy exposure.

Brain Tumors: The Influence of Tumor Type and Routine MR Imaging Characteristics at BOLD Functional MR Imaging in the Primary Motor Gyrus.

Purpose To evaluate the effects of histologic features and anatomic magnetic resonance (MR) imaging characteristics of brain tumors on the functional MR imaging signal in the primary motor cortex (PMC), as false-negative blood oxygen level-dependent (BOLD) functional MR imaging activation can limit the accurate localization of eloquent cortices. Materials and Methods Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant retrospective study. It comprised 63 patients referred between 2006 and 2014 for preoperative functional MR imaging localization of the Rolandic cortex. The patients had glioblastoma multiforme (GBM) (n = 20), metastasis (n = 21), or meningioma (n = 22). The volumes of functional MR imaging activation were measured during performance of a bilateral hand motor task. Ratios of functional MR imaging activation were normalized to PMC volume. Statistical analysis was performed for the following: (a) differences between hemispheres within each histologic tumor type (paired Wilcoxon test), (b) differences across tumor types (Kruskal-Wallis and Fisher tests), (c) pairwise tests between tumor types (Mann-Whitney U test), (d) relationships between fast fluid-attenuated inversion recovery (FLAIR) data and enhancement volume with activation (Spearman rank correlation coefficient), and (e) differences in activation volumes by tumor location (Mann-Whitney U test). Results A significant interhemispheric difference was found between the activation volumes in GBMs (mean, 511.43 voxels ± 307.73 [standard deviation] and 330.78 voxels ± 278.95; P < .01) but not in metastases (504.68 voxels ± 220.98 and 460.22 voxels ± 276.83; P = .15) or meningiomas (424.07 voxels ± 247.58 and 415.18 voxels ± 222.36; P = .85). GBMs showed significantly lower activation ratios (median, 0.49; range, 0.04-1.15) than metastases (median, 0.79; range, 0.28-1.66; P = .043) and meningiomas (median, 0.91; range, 0.52-2.05; P < .01). There was a moderate correlation with the volumes of FLAIR abnormality in metastases (ρ = -0.50) and meningiomas (ρ = -0.55). Enhancement volume (ρ = -0.11) and tumor distance from the PMC (median, 0.73 and range, 0.04-2.05 for near and median, 0.82 and range, 0.39-1.66 for far; P = .14) did not influence activation. Conclusion BOLD functional MR imaging activation in the ipsilateral PMC is influenced by tumor type and is significantly reduced in GBMs. FLAIR abnormality correlates moderately with the activation ratios in metastases and meningiomas. © RSNA, 2016 Online supplemental material is available for this article.

Multiparametric MRI in the assessment of response of rectal cancer to neoadjuvant chemoradiotherapy: A comparison of morphological, volumetric and functional MRI parameters.

PURPOSE: To compare morphological and functional MRI metrics and determine which ones perform best in assessing response to neoadjuvant chemoradiotherapy (CRT) in rectal cancer. MATERIALS AND METHODS: This retrospective study included 24 uniformly-treated patients with biopsy-proven rectal adenocarcinoma who underwent MRI, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after completion of CRT. On all MRI exams, two experienced readers independently measured longest and perpendicular tumour diameters, tumour volume, tumour regression grade (TRG) and tumour signal intensity ratio on T2-weighted imaging, as well as tumour volume and apparent diffusion coefficient on DW-MRI and tumour volume and transfer constant Ktrans on DCE-MRI. These metrics were correlated with histopathological percent tumour regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC). RESULTS: For both readers, post-treatment DW-MRI and DCE-MRI volumetric tumour assessments were significantly associated with %TR; DCE-MRI volumetry showed better inter-reader agreement (CCC=0.700) than DW-MRI volumetry (CCC=0.292). For one reader, mrTRG, post-treatment T2 tumour volumetry and assessments of volume change made with T2, DW-MRI and DCE-MRI were also significantly associated with %TR. CONCLUSION: Tumour volumetry on post-treatment DCE-MRI and DW-MRI correlated well with %TR, with DCE-MRI volumetry demonstrating better inter-reader agreement. KEY POINTS: • Volumetry on post-treatment DCE-/DW-MRI sequences correlated well with histopathological tumour regression. • DCE-MRI volumetry demonstrated good inter-reader agreement. • Inter-reader agreement was higher for DCE-MRI volumetry than for DW-MRI volumetry. • DCE-MRI volumetry merits further investigation as a metric for evaluating treatment response.

Development of a risk stratification system to guide treatment for female germ cell tumors.

OBJECTIVE: Due to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer. METHODS: Chart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome. RESULTS: Of 93 patients, 92 (99%) underwent primary surgery and 85 (92%) received chemotherapy. Modified IGCCCG classification was significantly associated with progression-free survival (PFS) and overall survival (OS), both when applied preoperatively and pre-chemotherapy (p<0.001 for all four analyses). Progression after initial chemotherapy (n=29) was detected by imaging in 14 (48%) patients, by serum tumor markers in 6 (21%) patients, and by multiple methods in the rest. Seven (29%) of 24 patients treated with salvage chemotherapy achieved long-term PFS, including 4/6 who received high-dose chemotherapy (HDCT) as initial salvage versus 3/16 treated with other initial salvage regimens. The estimated 3-year OS rate was 84% (95% CI, 76-92%), with a trend favoring dysgerminoma over non-dysgerminoma histologies (p=0.12). CONCLUSIONS: Modified IGCCCG classification was prognostic for female GCT patients in this cohort and identified a poor-risk group who may benefit from more intensive first-line chemotherapy. Both imaging and tumor marker evaluation were important in identifying relapses after first-line chemotherapy. The majority of long-term remissions with salvage therapy were achieved with initial salvage HDCT.

Combined gadoxetic acid and gadobenate dimeglumine enhanced liver MRI: a parameter optimization study.

PURPOSE: To demonstrate the feasibility of combined delayed-phase gadoxetic acid (GA) and gadobenate dimeglumine (GD) enhanced liver MRI for improved detection of liver metastases, and to optimize contrast agent dose, timing, and flip angle (FA). METHODS: Fourteen healthy volunteers underwent liver MRI at 3.0T at two visits during which they received two consecutive injections: 1. GA (Visit 1 = 0.025 mmol/kg; Visit 2 = 0.05 mmol/kg) and 2. GD (both visits = 0.1 mmol/kg) 20 min after GA administration. Two sub-studies were performed: Experiment-1 Eight subjects underwent multi-phase breath-held 3D-fat-saturated T1-weighted spoiled gradient echo (SGRE) imaging to determine the optimal imaging window for the combined GA + GD protocol to create a homogeneously hyperintense liver and vasculature ("plain-white-liver") with maximum contrast to muscle which served as a surrogate for metastatic lesions in both experiments. Experiment-2 Six subjects underwent breath-held 3D-fat-saturated T1-weighted SGRE imaging at three different FA to determine the optimal FA for best image contrast. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated. RESULTS: Experiment-1 The combined GA + GD protocol created a homogeneously hyperintense liver and vasculature with maximum CNR liver/muscle at approximately 60-120 s after automatic GD-bolus detection. Experiment-2 Flip angles between 25° and 35° at a dose of 0.025 mmol/kg GA provided the best combination that minimized liver/vasculature CNR, while maximizing liver/muscle CNR. CNR performance to achieve a "plain-white-liver" was superior with 0.025 mmol/kg GA compared to 0.05 mmol/kg. CONCLUSION: Combined GA + GD enhanced T1-weighted MRI is feasible to achieve a homogeneously "plain-white-liver". Future studies need to confirm that this protocol can improve sensitivity of liver lesion detection in patients with metastatic liver disease.

Decitabine induction with myeloablative conditioning and allogeneic hematopoietic stem cell transplantation in high-risk patients with myeloid malignancies is associated with a high rate of infectious complications.

Patients with high-risk myelodysplastic syndrome or acute myeloid leukemia have an increased risk of death following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases, and post-transplant cyclophosphamide (PTCy) has reduced rates of graft-versus-host-disease (GVHD). We hypothesized that decitabine induction with allo-HSCT and PTCy would improve outcomes in a high-risk myeloid disease population. We performed a phase-II trial of decitabine at 20 mg/m2 for 10 days followed by allo-HSCT using a myeloablative regimen of fludarabine, IV busulfan and 4 Gy total body irradiation with PTCy for GVHD prophylaxis. Twenty patients underwent decitabine induction and 17 patients proceeded to transplant per protocol. Median overall survival from decitabine induction was 210 days (95 % CI 122-not reached). All patients developed grade 4 neutropenia after decitabine, eleven patients (55 %) developed grade 3-4 infections, and 5 cases were fatal. There were 5/20 (25 %) long-term survivors with a median follow-up of 3.6 years. Decitabine induction followed by myeloablative allo-HSCT in a high-risk population was associated with a high risk of infection and mortality related to enhanced immunosuppression. Further exploration of decitabine conditioning on reduced intensity platforms and improved infectious prophylaxis and screening may better mitigate toxicity (ClinicalTrials.gov (NCT01707004)).

Procedure-Specific Risk Prediction for Recurrence in Patients Undergoing Lobectomy or Sublobar Resection for Small (≤2 cm) Lung Adenocarcinoma: An International Cohort Analysis.

INTRODUCTION: This work was performed to develop and validate procedure-specific risk prediction for recurrence following resection for early-stage lung adenocarcinoma (ADC) and investigate risk prediction utility in identifying patients who may benefit from adjuvant chemotherapy (ACT). METHODS: In patients who underwent resection for small (≤2 cm) lung ADC (lobectomy, 557; sublobar resection, 352), an association between clinicopathologic variables and risk of recurrence was assessed by a competing risks approach. Procedure-specific risk prediction was developed based on multivariable regression for recurrence. External validation was conducted using cohorts (N = 708) from Japan, Taiwan, and Germany. The accuracy of risk prediction was measured using a concordance index. We applied the lobectomy risk prediction approach to a propensity score-matched cohort of patients with stage II-III disease (n = 316, after matching) with or without ACT and compared lung cancer-specific survival between groups among low- or high-risk scores. RESULTS: Micropapillary pattern, solid pattern, lymphovascular invasion, and necrosis were involved in the risk prediction following lobectomy, and micropapillary pattern, spread through air spaces, lymphovascular invasion, and necrosis following sublobar resection. Both internal and external validation showed good discrimination (concordance index in lobectomy and sublobar resection: internal, 0.77 and 0.75, respectively; and external, 0.73 and 0.79, respectively). In the stage II-III propensity score-matched cohort, among high-risk patients, ACT significantly reduced the risk of lung cancer-specific death (subhazard ratio 0.43, p = 0.001), but not among low-risk patients. CONCLUSIONS: Procedure-specific risk prediction for patients with resected small lung ADC can be used to better prognosticate and stratify patients for further interventions.

Quantitating whole lesion tumor biology in rectal cancer MRI: taking a lesson from FDG-PET tumor metrics.

PURPOSE: To determine the value of novel whole tumor metrics in DWI-MRI and DCE-MRI of rectal cancer treatment assessment. MATERIALS AND METHODS: This retrospective study included 24 uniformly treated patients with rectal adenocarcinoma who underwent MRI including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after chemoradiotherapy. Two experienced readers independently measured tumor volume and apparent diffusion coefficient (ADC) on DWI-MRI and tumor volume and transfer constant K trans on DCE-MRI. In addition, we explored and defined Total Lesion Diffusion (TLD) as Total DWI tumor volume multiplied by mean volumetric ADC and Total Lesion Perfusion (TLP) as the total DCE tumor volume multiplied by the mean volumetric K trans. These metrics were correlated with histopathologic percent tumor regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC). RESULTS: For both readers, post-treatment TLP revealed comparable correlations with %TR compared with K trans (reader 1; Spearman's rho = - 0.36 vs. - 0.32, reader 2; Spearman's rho = - 0.32 vs. - 0.28). In addition, TLP afforded the highest inter-reader agreement at post-treatment among TLP, DCE vol, and K trans (CCC: 0.64 vs. 0.36 vs. 0.35). Post-treatment TLD showed similar correlation with %TR as DWI volume in reader 1 and superior correlation with %TR for reader 2 (reader 1; Spearman's rho - 0.56 vs. - 0.57, reader 2; Spearman's rho - 0.59 vs. - 0.45). CONCLUSION: The novel tumor metrics TLD and TLP revealed similar results to established metrics for correlation with tumor response with equivalent or superior inter-reader agreements and we recommend that these be studied in larger trials.