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Background Prostate magnetic resonance imaging (MRI) is increasingly used in the detection, image-guided biopsy, and active surveillance of prostate cancer. The accuracy of prostate MRI may differ based on factors including imaging technique, patient population, and reader experience. Objective To determine whether the accuracy of prostate MRI varies with reader experience. Design, setting, and participants We rescored regions of interest from 194 consecutive patients who had undergone MRI/ultrasonography fusion biopsy. Original prostate MRI scans had been interpreted by one of 33 abdominal radiologists (AR group). More than 14 mo later, rescoring was performed by two blinded, prostate MRI radiologists (PR group). Likert scoring was used for both original MRI reports and rescoring. Outcome measurements and statistical analysis Test performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of prostate MRI was defined for the AR and PR groups. A Likert score of 4–5 was considered test positive and clinically significant prostate carcinoma (csPCa; Gleason grade group [GGG] ≥2) was considered outcome positive. Results and limitations MRI-positive lesions (Likert 4–5) scored by the PR group resulted in csPCa more frequently than those scored by the AR group (64.9% vs 39.3%). MRI-negative lesions (Likert 2–3) were more likely to result in a clinically insignificant biopsy (benign pathology or GGG 1) when scored by the PR versus the AR group (91.8% vs 76.6%). Sensitivity and specificity of MRI to detect csPCa were higher for the PR group than for the AR group (sensitivity 85.9% vs 70.7%; specificity 77.3% vs 46.8%). Overall diagnostic accuracy was higher for the PR group than for the AR group (80.1% vs 54.6%). Conclusions Sensitivity, specificity, PPV, and NPV of prostate MRI were higher for the PR group than for the AR group. Patient summary We examined the accuracy of prostate magnetic resonance imaging (MRI) in two groups of radiologists. Experienced radiologists were more likely to detect clinically significant prostate cancer on MRI., Take Home Message The utility of prostate magnetic resonance imaging to accurately detect clinically significant prostate cancer depends on the radiologist’s experience. Both histopathological feedback and volume of interpretations are likely important for the development of expertise.

PURPOSE: To report long term follow-up of the efficacy of subtotal prostate ablation using a “hockey-stick” template, including oncologic control and quality of life (QoL) impact. METHODS: We performed a prospective controlled trial to evaluate the efficacy of subtotal prostate ablation in selected men with baseline and confirmatory biopsy showing grade group (GG) 1–2 prostate cancer. “Hockey-stick” cryoablation that included the ipsilateral hemi-gland and contralateral anterior prostate was performed. Prostate biopsies and QOL queries were performed at 6, 18 and 36 months following regional ablation, and follow-up was updated to include subsequent clinic visits. RESULTS: Between August 2009 and January 2012, 72 men were screened for eligibility and 47 opted to undergo confirmatory biopsy. Of these, 23 were deemed eligible and treated with regional cryoablation. Median age was 64 years. Median follow-up was 74 months. A single patient had

INTRODUCTION AND OBJECTIVE:Organ preserving therapies are of particular interest in the treatment of localized prostate cancer (PC) with a goal of decreasing morbidity associated with radical treat...

The purpose of this study is to compare the prognostic value of various solid tumor response criteria as well as the additive value of clinical risk factors in patients with advanced renal cell carcinoma (RCC).Two sets of CT scans (pretreatment scans and scans obtained 1-3.5 months after treatment) were reviewed for 57 patients with metastatic RCC treated with pazopanib in the salvage setting. Tumor response on the posttherapy scan was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and Choi, modified Choi (mChoi), MASS (Morphology, Attenuation, Size, and Structure), and 10% threshold criteria. In addition, combined Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors plus imaging criteria were used to define response groups. Response evaluations using these criteria were correlated with overall survival (OS) and progression-free survival (PFS), with use of the log-rank test.Patients classified as having progressive disease (PD) on the basis of RECIST, mChoi, and MASS criteria had a significantly worse OS than patients with stable disease (SD) and partial response (PR). With the addition of MSKCC risk factors, all groups with PD defined by combined criteria had significantly worse OS. For 37 patients with no or one MSKCC risk factor, response groups defined by Choi, mChoi, MASS, and 10% threshold criteria did not differ in PFS or OS. However, among 20 patients with two to three MSKCC risk factors, those classified as having PR had longer PFS than did those with SD and had longer OS than did those with PD.For patients with advanced RCC for which prior therapies have failed, the prognostic value of various imaging-based tumor response criteria differs on the basis of the MSKCC clinical risk status.

ObjectiveThe purpose was to validate the prognostic value of an early optimal morphological response on CT in patients treated with bevacizumab-containing chemotherapy for unresectable colorectal cancer liver metastases (CLM). It also evaluated the prognostic value of size-based criteria and the association of optimal morphological response with the receipt of bevacizumab.Design141 patients treated first using bevacizumab and 142 patients from a randomised study evaluating the addition of bevacizumab to oxaliplatin-based chemotherapy were retrospectively analysed. Radiologists evaluated pretreatment and restaging CT scans using morphological response criteria. Responses were also assessed with size-based criteria: Response Evaluation Criteria in Solid Tumors (RECIST), early tumour shrinkage (ETS) and deepness of response (DpR). The ability of each criterion to predict progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) was determined using a univariate Cox proportional hazards model.ResultsIn both populations, median PFS was significantly longer for patients achieving an optimal morphological response (10.4 vs 6.8 months, p=0.03; and 8.3 vs 4.9 months, pConclusionIn patients with unresectable CLM, early morphological response may be a better predictor of PFS than size-based response. The addition of bevacizumab improves morphological response rate.

The obesity epidemic has significantly increased the incidence and severity of hepatic steatosis in liver surgery patients and liver donors, potentially impacting postoperative liver regeneration and function. Development of a non-invasive means to quantify hepatic steatosis would facilitate selection of candidates for liver resection and transplant donation.An IRB-approved protocol prospectively enrolled 28 patients with liver tumors requiring hepatic resection. In all patients, fast dual-echo gradient-echo MR images were acquired using 2-Point Dixon technique in 2D and 3D. The degree of steatosis was quantified by percent fat fraction (%FF) from in- and out-of-phase, and water-only and fat-only images. The technique-specific %FFs were compared to intraoperative and histopathological findings.For patients with30% steatosis by histology, the mean %FF was 22% (SD ± 5.2%) compared to a mean %FF of 5.0% (SD ± 2.1%, p = 0.0001) in patients with30% steatosis. Using scaled values for the MR-calculated %FF, all patients with30% pathologic steatosis could be identified preoperatively.Quantitative MRI identified patients with clinically-relevant steatosis with 100% accuracy. These findings could have significant impact on the management of liver resection patients and transplant donors.

Purpose: Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients.Patients and methods: A retrospective cohort study was conducted in PDGFRA exon 18 mutation GIST patients treated in six expert centres in the Netherlands and the United States. Two independent radiologists assessed radiological response to imatinib according to Choi's criteria in all patients with measurable disease treated with imatinib in neo-adjuvant or palliative intent.Results: Seventy-one patients with PDGFRA exon 18 mutation were identified of whom 48 patients (69%) had a D842V mutation. Twenty-two (45.8%) D842V-mutated GIST patients received imatinib treatment, 16 had measurable disease. Fourteen out of the 23 (60.9%) patients with non-D842V mutations received imatinib treatment, eight had measurable disease. Two out of 16 (12.5%) D842V-mutated GIST patients had partial response, 3 patients (18.8%) had stable disease and 9 patients (56.3%) had progressive disease as best response. Two patients did not have follow-up computed tomography scans to assess response. Six out of 8 (75%) patients with non-D842V exon 18 mutations had partial response and two (25%) had stable disease as best response.Conclusion: Patients with D842V-mutated GISTs can occasionally respond to imatinib. In the absence of better therapeutic options, imatinib should therefore not be universally withheld in patients with this mutation. (C) 2017 Elsevier Ltd. All rights reserved.

This study investigated changes in quality and sensory characteristics of soy sauce (Kanjang) with added Astragalus membranaceus (AK) to develop a new soy sauce product with improved sensory characteristics. The pure salinity slowly increased, but AK 10% decreased. The pH was a constant in all samples. The soluble solid content (Brix) increased after 2 months, but AK 10% decreased. With increased addition of Astragalus membranaceus (AM), the optical density increased after 4 months. The amino nitrogen increased in soy sauce with AK 5%. The total free amino acid content gradually increased in soy sauce with AK 5% aged for 6 months. As the addition of AM increased, the crude protein level decreased, but there was no difference between AK 0% and 5%. The sensory tests of AK 5% after 6 months showed higher acceptance. According to the aging period, the acceptability of AK 5% was the best. The results showed that soy sauce with of AK 5% and aged for 6 months exhibits greatly enhanced quality and sensory characteristics. Therefore, it is expected to be used as a natural resources in seasoning area.

Highlights • We evaluated the added value of a USPIO agent (Ferumoxtran-10) to MRI evaluation of LN metastasis in loco-regionally advanced cervical cancer in a multicenter trial. • There was no significant difference in the accuracy of f-10 MRI as compared to standard MRI to detect LN metastasis in advanced cervical cancer (P > 0.05). • F-10 MRI increased sensitivity of MRI to detect metastasis in small (, Rationale and objectives To assess if ferumoxtran-10 (f-10) improves accuracy of MRI to detect lymph node (LN) metastasis in advanced cervical cancer. Materials and methods F-10 MRI component of an IRB approved HIPAA compliant ACRIN/GOG trial was analyzed. Patients underwent f-10 MRI followed by extra-peritoneal or laparoscopic pelvic and abdominal lymphadenectomy. F-10-sensitive sequences were T2* GRE sequences with TE of 12 and 21. Seven independent blinded readers reviewed f-10-insensitive sequences and all sequences in different sessions. Region correlations were performed between pathology and MRI for eight abdomen and pelvis regions. Sensitivity and specificity were calculated at participant level. Reference standard is based on pathology result of surgically removed LNs. Results Among 43 women enrolled in the trial between September 2007 and November 2009, 33 women (mean age 49 ± 11 years old) with advanced cervical cancer (12 IB2, 3 IIA, 15 IIB and 3 IIIB, 29 squamous cell carcinomas, 32 grade 2 or 3) were evaluable. Based on histopathology, LN metastasis was 39% in abdomen and 70% in pelvis. Sensitivity of all sequence review in pelvis, abdomen, and combined were 83%, 60%, and 86%, compared with 78%, 54%, and 80% for f-10 insensitive sequences (P: 0.24, 0.44 and 0.14, respectively). Mean diameter of the largest positive focus on histopathology was 13.7 mm in abdomen and 18.8 mm in pelvis (P = 0.018). Specificities of all sequence review in pelvis, abdomen, and combined were 48%, 75%, and 43%, compared with 75%, 83%, and 73% (P: 0.003, 0.14, 0.002 respectively) for f-10 insensitive sequences. Conclusion Addition of f-10 increased MRI sensitivity to detect LN metastasis in advanced cervical cancer. Increased sensitivity did not reach statistical significance and was at the expense of lower specificity.

To report the efficacy, physician-reported toxicity, and patient-reported outcomes of men with intermediate-risk prostate cancer after brachytherapy in a prospective phase 2 trial.This prospective phase 2 trial involved 300 patients with previously untreated prostate cancer treated from 2006 through 2013. Eligible patients had ≤cT2b (T3 excluded according to magnetic resonance imaging), Gleason score (GS) 6 with prostate-specific antigen (PSA) level 10-15 ng/mL, or GS 7 with PSA10 ng/mL, and were treated with prostate brachytherapy (without hormonal therapy).Median patient age was 64.9 years; 3.7% had GS 6, 78.7% had GS 7 (3+4), and 17.7% had GS 7 (4+3). Median follow-up time was 5.1 years. Median PSA at 5 years was 0.01 ng/mL (range, 0-6.0 ng/mL). Ten biochemical failures occurred, for a 5-year freedom from biochemical failure rate of 97.3% (95% confidence interval [CI], 95.1-99.5), and 16 patients died, only 1 from prostate cancer, for 5-year rates of overall and biochemical progression-free survival of 94.9% (95% CI, 92.1-97.9) and 92.7% (95% CI, 89.3-96.2%). Four patients had late grade 3 genitourinary toxicity, and 2 patients had late grade 3 rectal toxicity; no grade 4 or 5 toxicity was observed. Rates of "moderate or big problems" at 4 years were 7.4% for urinary (vs 0.4% at baseline), 2.9% bowel (vs 0.4%), and 29.7% sexual function (vs 19.7%). Most men were "satisfied or extremely satisfied" (91% at 2 years after treatment and 93% at 4 years).Brachytherapy monotherapy is safe and effective and leads to good quality of life for some men with localized intermediate-risk prostate cancer.

Endometrial and cervical cancer are the most common gynecologic malignancies in the world. Accurate staging of cervical and endometrial cancer is essential to determine the correct treatment approach. The current International Federation of Gynecology and Obstetrics (FIGO) staging system does not include modern imaging modalities. However, magnetic resonance (MR) imaging has proved to be the most accurate noninvasive modality for staging endometrial and cervical carcinomas and often helps with risk stratification and making treatment decisions. Multiparametric MR imaging is increasingly being used to evaluate the female pelvis, an approach that combines anatomic T2-weighted imaging with functional imaging (ie, dynamic contrast material-enhanced and diffusion-weighted imaging). MR imaging helps guide treatment decisions by depicting the depth of myometrial invasion and cervical stromal involvement in patients with endometrial cancer and tumor size and parametrial invasion in those with cervical cancer. However, its accuracy for local staging depends on technique and image quality, namely thin-section high-resolution multiplanar T2-weighted imaging with simple modifications, such as double oblique T2-weighting supplemented by diffusion weighting and contrast enhancement.

This patient had congenital absent portal vein and hepatic adenomatosis combined with malignant transformation to well-differentiated hepatocellular carcinoma.

BACKGROUND: Hemangiopericytomas and malignant solitary fibrous tumors (HPC/SFT) are rare, closely related sarcomas with unpredictable behavior that respond infrequently to chemotherapy. An optimal systemic treatment strategy for advanced HPC/SFT has not yet been identified. METHODS: We retrospectively analyzed the records of 14 patients with histopathologically confirmed HPC/SFT who were treated at The University of Texas MD Anderson Cancer Center between May 2005 and June 2007. All patients were treated with temozolomide 150 mg/m2 orally on days 1-7 and days 15-21 and bevacizumab 5 mg/kg intravenously on days 8 and 22, repeated at 28-day intervals. Computed tomography assessment of tumor size and density (Choi criteria) was used to determine the best response to therapy. The Kaplan–Meier method was used to estimate progression-free survival. RESULTS: The median follow-up period was 34 months. Eleven patients (79%) achieved a Choi partial response, with a median time to response of 2.5 months. Two patients (14%) had stable disease as the best response, and 1 patient (7%) had Choi progressive disease as the best response. The estimated median progression-free survival was 9.7 months, with a 6-month progression-free rate of 78.6%. The most frequently observed toxic effect was myelosuppression. CONCLUSION: Combination therapy with temozolomide and bevacizumab is a generally well-tolerated and clinically beneficial regimen for HPC/SFT patients. Additional investigation in a controlled, prospective trial is warranted. Cancer 2011;. © 2011 American Cancer Society.

Gastrointestinal stromal tumor (GIST) is the most common sarcoma arising in the gastrointestinal (GI) tract. Imatinib mesylate (imatinib) is efficacious in treating advanced and metastatic GIST. Patients undergoing resection of GIST realize a highly variable median disease-free survival (DFS). In the absence of prospective data, we conducted a randomized, phase II study to assess the safety and efficacy of preoperative and postoperative imatinib for the treatment of GIST. Nineteen GIST patients undergoing surgical resection were randomized to receive 3, 5, or 7 days of preoperative imatinib (600 mg daily). Patients received postoperative imatinib for 2 years. Perioperative adverse events were compared with those in an imatinib-naïve historical control. The efficacy of imatinib was assessed by (18)fluorodeoxyglucose positron emission tomography ((18)FDG-PET), dynamic computed tomography (dCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and DFS. Imatinib did not affect surgical morbidity as compared with an imatinib-naïve cohort (p/= 0.1). Most patients responded to preoperative imatinib by (18)FDG-PET and dCT (69% and 71%, respectively). Tumor cell apoptosis increased by an average of 12% (range 0-33%) and correlated with the duration of preoperative imatinib (p = 0.04). Median DFS of patients treated with surgery and imatinib was 46 months (range 10-46 months). Tumor size was a predictor of recurrence after postoperative imatinib (p = 0.02). Imatinib appears to be safe and may be considered for patients undergoing surgical resection of their GIST. Radiographic response and tumor cell apoptosis occur within the first week of imatinib therapy.

Activating mutation in KIT or platelet-derived growth factor-alpha can lead to gastrointestinal stromal tumors (GISTs). Eighty-four cases from two institutes were analyzed. Of them, 62 (74%) harbored KIT mutations, 7 of which are previously unreported. One exhibited duplication from both intron 11 and exon 11, which has not been reported in KIT in human cancer. A homozygous/hemizygous KIT-activating mutation was found in 9 of the 62 cases (15%). We identified three GIST patients with heterozygous KIT-activating mutations at initial presentation, who later recurred with highly aggressive clinical courses. Molecular analysis at recurrence showed total dominance of homozygous (diploid) KIT-activating mutation within a short period of 6-13 months, suggesting an important role of oncogene homozygosity in tumor progression. Topoisomerase II is active in the S- and G(2) phases of cell cycle and is a direct and accurate proliferative indicator. Cellular and molecular analysis of serial tumor specimens obtained from consecutive surgeries or biopsy within the same patient revealed that these clones that acquired the homozygous KIT mutation exhibited an increased mitotic count and a striking fourfold increase in topoisomerase II proliferative index (percentage cells show positive topoisomerase II nuclear staining compared to the heterozygous counterpart within the same patient. KIT forms a homodimer as the initial step in signal transduction and this may account for the quadruple increase in proliferation. Using SNPs for allelotyping on the serial tumor specimens, we demonstrate that the mechanism of the second hit resulting in homozygous KIT-activating mutation and loss of heterozygosity is achieved by mitotic nondisjunction, contrary to the commonly reported mechanism of mitotic recombination.

The objective of this study was to develop a quantitative image feature model to predict non-small cell lung cancer (NSCLC) volume shrinkage from pre-treatment CT images. 64 stage II-IIIB NSCLC patients with similar treatments were all imaged using the same CT scanner and protocol. For each patient, the planning gross tumor volume (GTV) was deformed onto the week 6 treatment image, and tumor shrinkage was quantified as the deformed GTV volume divided by the planning GTV volume. Geometric, intensity histogram, absolute gradient image, co-occurrence matrix, and run-length matrix image features were extracted from each planning GTV. Prediction models were generated using principal component regression with simulated annealing subset selection. Performance was quantified using the mean squared error (MSE) between the predicted and observed tumor shrinkages. Permutation tests were used to validate the results. The optimal prediction model gave a strong correlation between the observed and predicted tumor shrinkages with r=0.81 and MSE=8.60×10(-3). Compared to predictions based on the mean population shrinkage this resulted in a 2.92 fold reduction in MSE. In conclusion, this study indicated that quantitative image features extracted from existing pre-treatment CT images can successfully predict tumor shrinkage and provide additional information for clinical decisions regarding patient risk stratification, treatment, and prognosis.

Purpose To develop a fast T1-weighted, fat-suppressed three-dimensional dual echo Dixon technique and to demonstrate its use in contrast agent enhanced MRI. Materials and Methods A product fast three-dimensional gradient echo pulse sequence was modified to acquire dual echoes after each RF excitation with water and fat signals in-phase (IP) and opposed-phase (OP), respectively. An on-line reconstruction algorithm was implemented to automatically generate separate water and fat images. The signal to noise ratio (SNR) of the new technique was compared to that of the product technique in phantom. In vivo abdomen and breast images of cancer patients were acquired at 1.5 Tesla using both techniques before and after intravenous administration of gadolinium contrast agent. Results In phantom, the new technique yields a close to the theoretically predicted 41% increase in SNR in comparison to the product technique without fat suppression (FS). In vivo images of the new technique show noticeably improved FS and image quality in comparison to the images acquired of the same patients using the product technique with FS. Conclusion The three-dimensional dual echo Dixon technique provides excellent image quality and can be used for T1-weighted, fat-suppressed imaging with contrast agent injection. J. Magn. Reson. Imaging 2006. © 2005 Wiley-Liss, Inc.

KIT gain of function mutations play an important role in the pathogenesis of gastrointestinal stromal tumors (GISTs). Imatinib is a selective tyrosine kinase inhibitor of ABL, platelet-derived growth factor receptor (PDGFR), and KIT and represents a new paradigm of targeted therapy against GISTs. Here we report for the first time that, after imatinib treatment, an additional specific and novel KIT mutation occurs in GISTs as they develop resistance to the drug. We studied 12 GIST patients with initial near-complete response to imatinib. Seven harbored mutations in KIT exon 11, and 5 harbored mutations in exon 9. Within 31 months, six imatinib-resistant rapidly progressive peritoneal implants (metastatic foci) developed in five patients. Quiescent residual GISTs persisted in seven patients. All six rapidly progressive imatinib-resistant implants from five patients show an identical novel KIT missense mutation, 1982T→C, that resulted in Val654Ala in KIT tyrosine kinase domain 1. This novel mutation has never been reported before, is not present in pre-imatinib or post-imatinib residual quiescent GISTs, and is strongly correlated with imatinib resistance. Allelic-specific sequencing data show that this new mutation occurs in the allele that harbors original activation mutation of KIT.

The magnetic resonance spectroscopic imaging (MRSI) is the only technique that is currently available in the clinical practice to provide the metabolic status of prostate tissue at the cellular level with a great potential to improve the clinical patient care. Increasing the field strength from 1.5 to 3 T can theoretically provide proportionately higher signal-to-noise ratio (SNR) and improve spectral separation between prostatic metabolite peaks. The technique, however, has been limited to a few academic institutions that are equipped with a team of experts primarily due to due to serious technical challenges in optimizing the spectral quality. High quality shimming is key to the successful MRSI acquisition. Without optimization of the increased field inhomogeneity and radiofrequency (RF) dielectric effect at 3 T, the spectral peak broadening and residual signal from the periprostatic fat tissue may render the overall spectra non-diagnostic. The purpose of this technical note is to present the practical steps of successful acquisition of 3 T MRSI and to address several important technical challenges in minimizing the effect of the increased magnetic field and RF field inhomogeneity in order to obtain highest possible spectral quality based on our initial experience in using 3 T MRSI prototype software.

Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patient's lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patient's own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinib's effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response. Interim analysis of eight patients demonstrated significant induction of IFN-γ-producing-CD8(+), -CD4(+), -NK cell, and IFN-γ-producing-tumor-infiltrating-lymphocytes, signifying significant Th1 response and NK cell activation. After a median follow-up of 3.6 years, complete response (CR) + partial response (PR) = 100%, overall survival = 100%, one patient died of unrelated illness while in remission, six of seven evaluable patients are either in continuing PR/CR (5 patients) or have progression-free survival (PFS, 1 patient) exceeding the upper limit of the 95% confidence level of the genotype-specific-PFS of the phase III imatinib-monotherapy (CALGB150105/SWOGS0033), demonstrating highly promising clinical outcomes. The current trial is closed in preparation for a larger future trial. We conclude that combination of targeted therapy and immunotherapy is safe and induced significant Th1 response and NK cell activation and demonstrated highly promising clinical efficacy in GIST, thus warranting development in other tumor types.

High-resolution magnetic resonance (MR) imaging plays a pivotal role in the pretreatment assessment of primary rectal cancer. The success of this technique depends on obtaining good-quality high-resolution T2-weighted images of the primary tumor; the mesorectal fascia, peritoneal reflection, and other pelvic viscera; and superior rectal and pel vic sidewall lymph nodes. Although orthogonal axial high-resolution T2-weighted MR images are the cornerstone for the staging of primary rectal cancer, high-resolution sagittal and coronal images provide additional value, particularly in tumors that arise in a redundant tortuous rectum. Coronal high-resolution T2-weighted MR images also improve the assessment of nodal morphology, particularly for superior rectal and pelvic sidewall nodes, and of the relationship between advanced-stage tumors and adjacent pelvic structures. Rectal gel should be used in MR imaging examinations conducted for the staging of polypoid tumors, previously treated lesions, and small rectal tumors. However, it should not be used in examinations performed to stage large or low rectal tumors. Diffusion-weighted imaging is useful for identifying nodes and, occasionally, the primary tumor when the tumor is difficult to visualize with other sequences. Three-dimensional T2-weighted imaging provides multiplanar capability with a superior signal-to-noise ratio compared with two-dimensional T2-weighted imaging.

The goal of this study is to demonstrate a practical magnetic resonance imaging technique for quantifying a wide range of hepatic iron concentration (HIC) for hematologic oncology patients with transfusion iron overload in a routine clinical setting. To cover a wide range of T(2)* values from hematologic patients, we used a dual-acquisition method with two clinically available acquisition protocols on a 1.5T MRI scanner with different ΔTEs to acquire data in two breath-holds. An in-house image postprocessing software tool was developed to generate T(2)*, iron maps, and water and fat images, when fat is presented in the liver. The resulting iron maps in DICOM format are transferred to the institutional electronic medical record system for review by radiologists. The measured liver T(2)* values for 28 patients ranged from 0.56 ± 0.13 to 25.0 ± 2.1 milliseconds. These T(2)* values corresponded to HIC values ranging from 1.2 ± 0.1 mg/g to 45.0 ± 10.0 mg/g (dry weight). A moderate correlation between overall serum ferritin levels and R(2)* was found with a correlation coefficient of 0.83. Repeated phantom scans confirmed that the precision of this method is better than 4% for T(2)* measurements. The dual- acquisition method also improved the ability to quantify HIC of the patients with hepatic steatosis.

Hemangiopericytomas and malignant solitary fibrous tumors (HPC/SFT) are rare, closely related sarcomas with unpredictable behavior that respond infrequently to chemotherapy. An optimal systemic treatment strategy for advanced HPC/SFT has not yet been identified.We retrospectively analyzed the records of 14 patients with histopathologically confirmed HPC/SFT who were treated at The University of Texas MD Anderson Cancer Center between May 2005 and June 2007. All patients were treated with temozolomide 150 mg/m(2) orally on days 1-7 and days 15-21 and bevacizumab 5 mg/kg intravenously on days 8 and 22, repeated at 28-day intervals. Computed tomography assessment of tumor size and density (Choi criteria) was used to determine the best response to therapy. The Kaplan-Meier method was used to estimate progression-free survival.The median follow-up period was 34 months. Eleven patients (79%) achieved a Choi partial response, with a median time to response of 2.5 months. Two patients (14%) had stable disease as the best response, and 1 patient (7%) had Choi progressive disease as the best response. The estimated median progression-free survival was 9.7 months, with a 6-month progression-free rate of 78.6%. The most frequently observed toxic effect was myelosuppression.Combination therapy with temozolomide and bevacizumab is a generally well-tolerated and clinically beneficial regimen for HPC/SFT patients. Additional investigation in a controlled, prospective trial is warranted.

Clinical management of patients with gastrointestinal stromal tumors (GISTs) has dramatically changed with the introduction of novel therapeutics, such as imatinib mesylate. This has created a need to re-evaluate the existing criteria used to assess treatment response. The current Response Evaluation Criteria in Solid Tumors are based on unidimensional tumor size, and do not take into account changes in responding GISTs such as a decrease in tumor density and decrease in the number of intratumoral vessels with computed tomography (CT). Positron emission tomography (PET) has been found to be highly sensitive in detecting early response, and to be useful in predicting long-term response to imatinib in patients with metastatic GIST; however, widespread use of PET is limited because of a lack of scanner availability and cost constraints. Modified CT criteria using a combination of tumor density and tumor size are promising in early response evaluation, and have excellent prognostic value. Identifying appropriate treatment response criteria is essential to optimize treatment for patients with GIST.

BACKGROUND. The therapy for gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (IM). It is unknown whether the levels of KIT expression or the presence of CD34, smooth muscle actin (SMA), desmin, or S-100 protein predicts patient outcome from IM therapy. In the current study, the prognostic effects for KIT and other proteins (CD34, SMA, desmin, S-100) were analyzed in a series of GISTs in which protein expression was evaluated by immunohistochemical analysis (IHC). METHODS. The cases of 106 patients with GIST who were uniformly treated with IM at the study institution between December 15, 2000, and January 13, 2002 were evaluated retrospectively. The association between KIT intensity, CD34, desmin, SMA, S-100 protein, and progression-free survival (PFS) was studied. Kaplan-Meier analysis and the Cox proportional hazards regression model were used for statistical analysis. RESULTS. The majority of tumors arose from the stomach (37%), small intestine (35%), and colorectum (14%). KIT expression as determined by IHC was categorized as weak (10%), intermediate (32%), or strong (58%). Patient tumors expressed CD34 (75%), SMA (56%), desmin (1%), and S-100 protein (32%). Patients whose GIST had weak, intermediate, or strong KIT expression were found to have an 18-month PFS rate of 80%, 84%, and 69%, respectively (P = .30). The presence or absence of CD34, SMA, desmin, or S-100 protein did not appear to correlate with PFS after IM. CONCLUSIONS. Patients with the appropriate clinical presentation and KIT-positive GIST tumors appear to benefit from IM independent of the level of KIT or the expression of CD34, SMA, desmin, or S-100 protein by IHC. Cancer 2006. © 2006 American Cancer Society.

Gastrointestinal stromal tumors (GISTs), which arise from the interstitial cells of Cajal, are the most common nonepithelial tumors of the gastrointestinal tract. It is now well known that imatinib, a new molecularly targeted tyrosine kinase receptor blocker, results in a dramatic response and markedly improved long-term survival in patients with GISTs. The increasing recognition of GISTs and the prolonged survival have made imaging increasingly important not only for diagnosis but also for monitoring the effects of treatment and detecting tumor progression. Computed tomography (CT) is the imaging modality of choice for these purposes. The imaging findings at initial presentation, during treatment, and at tumor progression were studied in 113 patients with primary and advanced GISTs before and up to 37 months after imatinib treatment. GISTs occur anywhere along the gastrointestinal tract, most commonly in the stomach and small bowel. At contrast material-enhanced CT, localized primary GISTs are typically exophytic, large, hypervascular masses. When the tumors respond to treatment, the changes in tumor size may initially vary; however, GISTs typically become homogeneous and hypoattenuating, with disappearance of enhancing tumor nodules and tumor vessels in the early posttreatment period. Development of a nodule within the treated tumor is unique to GISTs and indicates recurrence regardless of changes in tumor size.

BACKGROUND The natural history of gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (imatinib) therapy. Before imatinib, Bcl-2 expression in GIST was associated with a worse prognosis or added no additional prognostic value. To the authors' knowledge, the current study is the first to evaluate Bcl-2 expression in pre-imatinib GIST tissue samples as a prognostic marker of progression-free survival (PFS) time in patients treated with imatinib. METHODS The cases of 81 patients with GIST who were evaluated between December 15, 2000 and September 1, 2001 were retrospectively reviewed. Clinicopathologic variables were reviewed. GIST cell morphology and patterns of Bcl-2 expression were described. The methods of Kaplan–Meier and the Cox proportional hazards regression model were used for statistical analysis. RESULTS Sixty-one (75%) patients had tumors that expressed Bcl-2, and 20 (25%) patients had tumors that were negative for Bcl-2. All epithelioid tumors (n = 12) expressed Bcl-2 and tumors with mixed morphology exhibited Bcl-2 expression in the epithelioid component. A trend toward longer PFS for patients whose tumors expressed Bcl-2 at a greater immunohistochemical intensity was observed (20.6 mos for no Bcl-2 expression; 28.3 mos for 1++Bcl-2 expression; 31.9 mos for 1.5++Bcl-2 expression; 40.8 mos for 2++Bcl-2 expresssion; and 35.9 mos for 3++Bcl-2 expression). CONCLUSIONS In contrast to studies performed in the preimatinib era, in which Bcl-2 was found to be a negative prognostic indicator, the current study suggests a trend toward better PFS with increasing Bcl-2 expression level in GISTs from patients subsequently treated with imatinib. Larger studies may help elucidate the influence of Bcl-2 expression on PFS after therapy with imatinib. Cancer 2006. © 2006 American Cancer Society.

The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future.A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN).Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure.Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.

A burgeoning number of direct intratumoral therapies are being used to treat human solid tumors. One of the most common sites of application of these tumor-directed treatments has been the liver. The liver is second only to lymph nodes as a common site of metastasis from nonhepatic malignancies.1 Primary liver cancer, specifically hepatocellular carcinoma (HCC), is 1 of the most common human solid malignancies worldwide, with an annual incidence of over 1 million new diagnoses.2 A proportion of patients with primary or secondary hepatic malignancies with disease confined to the liver will derive long-term survival benefit from surgical resection of their disease. Unfortunately, less than 10%–30% of patients with primary or secondary hepatic malignancies are candidates for surgical resection because of the number of tumors, location of tumors that preclude a margin-negative resection, or because of coexistent chronic liver dysfunction producing an unacceptable risk of liver failure after partial hepatectomy.3–7 Patients with liver-only malignant disease who are not candidates for resection may be offered a rapidly evolving menu of direct tumor cytodestructive treatments. The in situ destruction of unresectable primary and secondary hepatic malignancies can potentially improve the median survival of patients and provide palliative relief of symptoms. The latter is particularly true in patients with pain related to tumor displacement of the hepatic capsule or in patients with symptoms related to excess hormone production from metastatic neuroendocrine tumors. Destruction of unresectable hepatic tumors has been performed by direct intratumoral injection of cytotoxic substances, including absolute ethanol, acetic acid, heated hypertonic saline, or chemotherapy agents; by intratumoral placement of cryoprobes to freeze tumors; or more recently by intratumoral placement of needles or fibers that generate heat with radiofrequency electrical current, microwaves, or laser to produce thermal tissue necrosis. An ideal direct in situ antitumor therapy would produce complete destruction of all malignant cells with no significant side effects or complications. Clearly, no such treatment exists and all in situ cytodestructive treatments must be evaluated based on improvements in patient survival rates, local tumor control rates, and complications associated with treatment. Thermal ablation techniques, particularly radiofrequency ablation (RFA), to treat primary and secondary hepatic malignancies have gained widespread availability and use over the past 5 years.8–11 The local control and complication rates associated with microwave and laser ablation have been reported rarely; thus, it is difficult to assess the treated tumor control efficacy and risk to patients using these treatment modalities.8 Treatment-related complications are not always reported in hepatic tumor RFA studies and the complication types and incidence rates in a large, prospective series of patients have not been previously reported.10–12

Purpose To demonstrate a new hybrid magnetic resonance imaging (MRI) technique capable of simultaneously generating water-specific and silicone-specific images in a single acquisition. Materials and Methods This technique combines short TI inversion-recovery (STIR) technique for robust fat suppression with an efficient fast spin-echo-based three-point Dixon technique for robust separation of remaining water and silicone in the presence of field inhomogeneities. Images demonstrating the feasibility of the technique were acquired with a 1.5-Tesla scanner in a phantom and in a volunteer with both saline and silicone implants in vivo. Results The new technique provided water-specific and silicone-specific images of diagnostic quality. Separation of the water and silicone chemical species was complete and satisfactory. Compared with a chemical shift-selective technique, the new technique does not rely heavily on field homogeneity and requires the same or even less scan time to acquire images with similar scan parameters, resolution, and signal-to-noise ratio (SNR). Conclusion The feasibility and potential application of the new technique were demonstrated via imaging a phantom and a silicone breast prosthesis in vivo, and it may be used for more consistent imaging of the silicone implants without compromising the image quality or overall scan time. J. Magn. Reson. Imaging 2004;19:298–302. © 2004 Wiley-Liss, Inc.

Purpose: For nonsmall cell lung cancer (NSCLC) patients, quantitative image features extracted from computed tomography (CT) images can be used to improve tumor diagnosis, staging, and response assessment. For these findings to be clinically applied, image features need to have high intra and intermachine reproducibility. The objective of this study is to identify CT image features that are reproducible, nonredundant, and informative across multiple machines. Methods: Noncontrast-enhanced, test-retest CT image pairs were obtained from 56 NSCLC patients imaged on three CT machines from two institutions. Two machines (“M1” and “M2”) used cine 4D-CT and one machine (“M3”) used breath-hold helical 3D-CT. Gross tumor volumes (GTVs) were semiautonomously segmented then pruned by removing voxels with CT numbers less than a prescribed Hounsfield unit (HU) cutoff. Three hundred and twenty eight quantitative image features were extracted from each pruned GTV based on its geometry, intensity histogram, absolute gradient image, co-occurrence matrix, and run-length matrix. For each machine, features with concordance correlation coefficient values greater than 0.90 were considered reproducible. The Dice similarity coefficient (DSC) and the Jaccard index (JI) were used to quantify reproducible feature set agreement between machines. Multimachine reproducible feature sets were created by taking the intersection of individual machine reproducible feature sets. Redundant features were removed through hierarchical clustering based on the average correlation between features across multiple machines. Results: For all image types, GTV pruning was found to negatively affect reproducibility (reported results use no HU cutoff). The reproducible feature percentage was highest for average images (M1 = 90.5%, M2 = 94.5%, M1∩M2 = 86.3%), intermediate for end-exhale images (M1 = 75.0%, M2 = 71.0%, M1∩M2 = 52.1%), and lowest for breath-hold images (M3 = 61.0%). Between M1 and M2, the reproducible feature sets generated from end-exhale images were relatively machine-sensitive (DSC = 0.71, JI = 0.55), and the reproducible feature sets generated from average images were relatively machine-insensitive (DSC = 0.90, JI = 0.87). Histograms of feature pair correlation distances indicated that feature redundancy was machine-sensitive and image type sensitive. After hierarchical clustering, 38 features, 28 features, and 33 features were found to be reproducible and nonredundant for M1∩M2 (average images), M1∩M2 (end-exhale images), and M3, respectively. When blinded to the presence of test-retest images, hierarchical clustering showed that the selected features were informative by correctly pairing 55 out of 56 test-retest images using only their reproducible, nonredundant feature set values. Conclusions: Image feature reproducibility and redundancy depended on both the CT machine and the CT image type. For each image type, the authors found a set of cross-machine reproducible, nonredundant, and informative image features that would be useful for future image-based models. Compared to end-exhale 4D-CT and breath-hold 3D-CT, average 4D-CT derived image features showed superior multimachine reproducibility and are the best candidates for clinical correlation.

Response evaluation in Oncology has relied primarily on change in tumor size. Inconsistent results in the prediction of clinical outcome when size based criteria are used and the increasing role of targeted and loco-regional therapies have led to the development of new methods of response evaluation that are unrelated to change in tumor size. The goals of this review are to expose briefly the size based criteria and to present the non-size based approaches that are currently applicable in the clinical setting. Other paths that are still being explored are not discussed in details.