Role of dynamic contrast-enhanced sonography for characterization and monitoring of extramedullary myeloma: comparison with serologic data.

OBJECTIVE: To measure blood perfusion in extramedullary myeloma by contrast-enhanced sonography, correlate it with specific hematologic parameters, and determine their utility for local and systemic response monitoring. METHODS: Twenty-five consecutive patients (14 male and 11 female; median age, 68 years) with extramedullary myeloma were included. After intravenous administration of 2.4 mL of sulfur hexafluoride, extramedullary myeloma masses were examined for 60 seconds. All patients underwent contrast-enhanced sonography at baseline, and 15 were monitored additionally (3 weeks during therapy). Average peak perfusion, regional blood flow (RBF), and regional blood volume (RBV) were calculated. Baseline perfusion parameters were compared with short-term follow-up sonographic data and serologic biomarkers (M gradient). For validation of extramedullary myeloma and systemic myeloma, patients underwent midterm (<3 months) imaging and serologic diagnosis. RESULTS: Patients with baseline ß2-microglobulin (B2M) greater than 3.5 mg/L (n = 17) showed higher perfusion parameters compared with baseline B2M less than 3.5 mg/L (n = 8). At short-term follow-up, patients were classified by serologic criteria as responders (n = 9) and nonresponders (n = 6) and by sonographic criteria as responders (n = 10) and nonresponders (n = 5). In sonographic responders, mean peak, RBV, and RBF dropped from 59.13, 1446.09, and 71.52 (artificial units) at baseline to 29.30, 364.19, and 34.64 at follow-up (P < .05), whereas in nonresponders, perfusion parameters increased from 33.18, 789.82, and 36.92 at baseline to 51.14, 1491.06, and 65.34 at follow-up (P > .05). Prediction of a midterm course of systemic myeloma using serologic data yielded sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.66, 0.77, 0.66, and 0.77, whereas sonographic results (judged by RBV) yielded values of 0.66, 0.55, 0.5, and 0.71. Separate prediction of a local (extramedullary myeloma) response by sonography yielded sensitivity, specificity, PPV, and NPV of 0.8, 1.0, 1.0, and 0.71. CONCLUSIONS: Contrast-enhanced sonography is a valuable tool for short-term monitoring of the treatment response in extramedullary myeloma.

Diffuse alveolar hemorrhage in patients with hematological malignancies: HRCT patterns of pulmonary involvement and disease course.

OBJECTIVE: To analyze high-resolution computed tomography (HRCT) patterns of lung involvement and disease course in patients with hematological malignancies experiencing diffuse alveolar hemorrhage (DAH) after chemotherapy ± allogeneic stem cell transplantation (allo-SCT). MATERIALS AND METHODS: Sixteen patients experiencing DAH after chemotherapy ± allo-SCT were enrolled. A total of 74 computed tomography (CT) scans obtained before, during, and after onset of DAH were evaluated retrospectively. RESULTS: CT features of DAH are each, by oneself, nonspecific. However, conjoint bilateral, diffuse, and dependent ground glass opacity ± crazy paving, accompanied by airspace bronchograms, should suggest this complication. The HRCT course comprises a wide range of trends that are not predictive for patient's outcome, but progression of parenchymal consolidations at follow up was more often detrimental.

Perfusion and flow extraction product as potential discriminators in untreated follicular and diffuse large B cell lymphomas using volume perfusion CT with attempt at histopathologic explanation.

OBJECTIVE: The purpose of this article is to measure perfusion parameters, including transit constant (K(trans)), in untreated follicular and diffuse large B cell lymphoma using volume perfusion CT, to establish their discriminating role and to search for a possible histopathologic background. SUBJECTS AND METHODS: Between January 2010 and June 2011, 46 consecutive patients with untreated histologically confirmed follicular lymphoma (n = 16) or diffuse large B cell lymphoma (n = 30) were enrolled. A 40-second volume perfusion CT of the tumor bulk using 6.9-cm z-axis coverage and a total of 26 volume measurements was performed. Blood flow (BF), blood volume (BV), and K(trans) were determined. Tumor size was recorded as the product of long- and short-axis diameters. In 13 of 46 patients, pathologic specimens of an appropriate size were available for assessment of microvessel density (MVD) and microvascular luminal diameter for comparison with volume perfusion CT measurements. RESULTS: Mean BF, BV, and K(trans) values were significantly higher in follicular lymphoma than in diffuse large B cell lymphoma, even after controlling for patient age and tumor size (p < 0.05, respectively). Although MVD was slightly, but not significantly, higher in follicular lymphoma versus diffuse large B cell lymphoma (p > 0.05), microvascular luminal diameter was significantly larger in follicular lymphoma than in diffuse large B cell lymphoma (p < 0.05). We defined cutoff values for BF, BV, and K(trans). If the cutoff points are met for all three parameters, the overall accuracy for correctly identifying diffuse large B cell lymphoma and follicular lymphoma was 90.5% and 87.5%, respectively. CONCLUSION: Volume perfusion CT allows assessment of differences in vascularity of follicular and diffuse large B cell lymphomas, reflecting vascular luminal variability and histopathologic anatomy.

Evaluation of response in malignant tumors treated with the multitargeted tyrosine kinase inhibitor sorafenib: a multitechnique imaging assessment.

OBJECTIVE: The purpose of this article is to illustrate the characteristic changes induced in different tumor types by the multitargeted tyrosine kinase inhibitor sorafenib. CONCLUSION: Sorafenib reduces tumor perfusion and thereby induces necrosis and often hemorrhage. Malignant tumors treated with sorafenib undergo both morphologic and functional changes; however, the morphologic changes are less frequent and inadequate for early evaluation of response. Therefore, imaging tools accurately assessing hemorrhage and decrease in tumor perfusion with subsequent necrosis should be the mainstay in monitoring targeted therapy agents.

Marginal zone B-cell non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue type: imaging findings.

OBJECTIVE: The aim of this essay is to describe the imaging features of marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type throughout various organs. CONCLUSION: Awareness of the expected locations of MALT lymphoma combined with knowledge of the incidence and imaging findings leads to accurate diagnosis of lesions suspicious for this disorder and helps to differentiate this disease from other abnormalities.

Gefitinib in combination with oxaliplatin and 5-fluorouracil in irinotecan-refractory patients with colorectal cancer: a phase I study of the Arbeits gemeinschaft Internistische Onkologie (AIO).

BACKGROUND: The aim of the study was to establish the recommended dose and to evaluate the safety of gefitinib plus FUFOX regimen in irinotecan-refractory colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients with advanced CRC progressing on fluoropyrimidine/irinotecan-based chemotherapy and with an ECOG performance level 0-2 were enrolled. Four dose levels with sequential dose escalation of oral gefitinib and FUFOX were tested. Each cycle consisted of 5 weeks with gefitinib given daily to weekly FUFOX x4 to be repeated at day 36. RESULTS: Eighteen patients were enrolled. No dose-limiting toxicity (DLT) was observed at the dose levels L1-L3. At L4 diarrhea was the major DLT requiring treatment interruption in 3 patients. Other grade 3/4 toxicities were observed with skin rash, paresthesia, anemia, and nausea/vomiting (n = 1 each). Grade 1/2 toxicities consisted of diarrhea (n = 9), mucositis (8), skin rash (10), paresthesia (10), nausea (7) as well as leukopenia (2) and fever (1). Clinical benefit was seen in 11 of 16 evaluable patients (69%): 4 patients showed partial response (25%), 7 stable disease (44%). Median time to progression was 219 days (range 50-387 days). CONCLUSION: Gefitinib at a dose of 250 mg daily in combination with weekly 5-fluorouracil at 2,000 mg/m(2) or gefitinib at a dose of 500 mg daily with 5-fluorouracil at 1,600 mg/m(2) plus oxaliplatin has an acceptable safety profile.

Bendamustine hydrochloride in patients with refractory soft tissue sarcoma: a noncomparative multicenter phase 2 study of the German sarcoma group (AIO-001).

BACKGROUND: For patients with advanced soft tissue sarcoma (STS), no standard treatment is established after previous chemotherapy with anthracyclines and ifosfamide. Bendamustine hydrochloride is a bifunctional alkylating agent that is not cross-resistant to other DNA-interacting substances including anthracyclines and oxazaphosphorines. It has shown single-agent activity in refractory lymphoma, myeloma, and some solid tumors. A phase 2 study was initiated to evaluate the efficacy of bendamustine in previously treated patients. METHODS: Thirty-six of 44 screened patients were included and received a total of 101 cycles (median, 2 cycles; range, 1-8 cycles), 21 as second-line treatment and 15 as third-line treatment. The median age was 55 years (range, 18-79 years). Bendamustine was given as an intravenous infusion over 30 minutes at a dose of 100 mg/m(2) on 2 consecutive days and repeated every 28 days. Eighty-eight percent of cycles could be given without dose or schedule modification. RESULTS: The toxicity profile was mild, consisting of National Cancer Institute Common Toxicity Criteria (CTC) grade 3 neutropenia in 11% and grade 3 anemia in 9% of patients. Nonhematologic toxicities were noticed with CTC grade 3 fever in 3% of patients. No other grade 3 toxicity and no treatment-related toxic deaths were observed. The best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria was 1 partial remission (3%) and disease stabilizations in 31% of patients. Six of 15 patients (40%) with leiomyosarcoma histology achieved stable disease. The estimated 3-month and 6-month progression-free survival rates were 35.3% and 23.5%, respectively, for all histologic subtypes included. CONCLUSIONS: In patients with refractory STS, bendamustine is well tolerated and appears moderately effective, particularly in patients with leiomyosarcoma histology.

Mitomycin C plus infusional 5-fluorouracil in platinum-refractory gastric adenocarcinoma: an extended multicenter phase II study.

OBJECTIVE: To assess the toxicity and activity of bolus mitomycin C (MMC) in combination with a 24-hour continuous infusion of 5-fluorouracil (5-FU) in gastric cancer patients who had received at least one prior chemotherapy regimen. PATIENTS AND METHODS: Patients were treated with MMC (10 mg/m(2)) on days 1 and 22, 5-FU (2.6 g/m(2)) as a 24-hour infusion, and folinic acid 500 mg/m(2) weekly for 6 weeks. RESULTS: Thirty-four patients with gastric cancer, 16 after failure of first-line chemotherapy and 18 after failure of at least two prior chemotherapies, were included. In the intent-to-treat analysis, 9 (26.5%) of the 34 patients had a partial response and 10 (29.4%) a disease stabilization (disease control rate 56%). The median time to progression was 3.3 months (CI95: 2.8-3.7), and the median overall survival was 7.2 months (CI95: 5.9-8.4). Grade III/IV thrombocytopenia occurred in 14.7% of patients (n = 5), while the most frequent nonhematological grade III/IV toxicities were mucositis and diarrhea, each affecting 9% of patients. CONCLUSIONS: As the tested regimen was generally safe and well tolerated by the patients, MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen for patients with advanced gastric cancer.

Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease--a long-term follow-up.

OBJECTIVE: We and others have reported the use of tacrolimus in refractory inflammatory bowel disease (IBD). Little is known about its long-term efficacy and safety. METHODS: In this retrospective, observational single center study the charts of 53 adult patients with steroid-dependent (n = 18) or steroid-refractory (n = 35) IBD, Crohn's disease (CD) (n = 11), ulcerative colitis (UC) (n = 40), or pouchitis (PC) (n = 2) were reviewed. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in all and initially intravenously in 2 patients (0.01 mg/kg body weight per day), aiming for serum trough levels of 4-8 ng/mL. Forty-one of 53 (77.1%) patients were receiving concomitant azathioprine. The mean treatment duration was 25.2 +/- 4.6 SD months (0.43-164 months). Patients were followed for a mean of 39 +/- 4.1 SD months (5-164 months). Response was evaluated using a modified clinical activity index (M-CAI). RESULTS: Thirty-one UC (78%), 10 CD (90.1%), and both PC (100%) patients experienced an immediate clinical response or went into remission at 30 days. A statistically significant drop on the M-CAI was documented for UC and CD patients. Nine UC patients (22.5%) underwent colectomy between 1.6 and 41.3 months following initiation. Mean colectomy-free survival was 104.8 +/- 15.5 (95% CI 74.4-135.2) months (limited to 164.4 months). Cumulative colectomy-free survival was estimated 56.5% at 43.8 months. Steroids were reduced or discontinued in 40 of 45 UC and CD patients (90%) taking steroids. Side effects included a temporary rise of creatinine (n = 4, 7.6%), tremor or paresthesias (n = 5, 9.4%), hyperkalemia (n = 1, 1.9%), hypertension (n = 1, 1.9%), and opportunistic infections (n = 2, 3.8%). CONCLUSION: Long-term tacrolimus therapy appears safe and effective in refractory IBD.