The Tofts tracer kinetic models are often used to analyze dynamic contrast-enhanced MRI data. They are derived from a general two-compartment exchange model (2CXM) but assume negligible plasma mean transit time. The 2CXM estimates tissue plasma perfusion and capillary permeability-surface area; the Tofts models estimate the transfer constant K trans , which reflects a combination of these two parameters.The aims of this study were to compare the 2CXM and Tofts models and report microvascular parameters in patients with cervical cancer. Thirty patients were scanned pretreatment using a dynamic contrast-enhanced MRI protocol with a 3 sec temporal resolution and a total scan duration of 4 min. Whole-tumor parameters were estimated with both models. The 2CXM provided superior fits to the data for all patients (all 30 P values < 0.005), and significantly different parameter estimates were obtained (P < 0.01). K trans (mean 5 0.35 6 0.26) did not equal absolute values of tissue plasma perfusion (mean 5 0.65 6 0.56 mL/mL/min) or permeability-surface area (mean 5 0.14 6 0.09 mL/mL/min) but correlated strongly with tissue plasma perfusion (r 5 0.944; P 5 0.01). Average plasma mean transit time, calculated with the 2CXM, was 22 6 16 sec, suggesting the assumption of negligible plasma mean transit time is not appropriate in this dataset and the 2CXM is better suited for its analysis than the Tofts models. The results demonstrate the importance of selecting an appropriate tracer kinetic model in dynamic contrastenhanced MRI. Magn Reson Med 63:691-700,

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Twenty-nine patients underwent magnetic resonance (MR) imaging for investigation of müllerian duct anomalies (MDAs). The anomalies evaluated were uterine agenesis (n = 2), uterine hypoplasia (n = 5), unicornuate uterus (n = 5), uterus didelphys (n = 5), bicornuate uterus (n = 10), and septate uterus (n = 2). The MR imaging interpretation was correlated with results of laparotomy (n = 18), hysterosalpingography (HSG) (n = 5), laparoscopy (n = 2), hysteroscopy (n = 1), HSG and laparotomy (n = 2), and HSG and laparoscopy (n = 1). MR imaging enabled correct classification of the anomaly in each patient and identification of coincidental gynecologic disease in 10 patients (34%). MR imaging results influenced clinical treatment in six (24%) of 25 patients referred prospectively. Of particular value was the ability to characterize septal tissue (myometrium versus fibrous tissue), identify the patients in whom the septum of bicornuate uteri had both fibrous and myometrial components, and establish that suspected adnexal lesions were actually components of obstructed MDAs.

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These observations suggest that inhibition of PDGFR-beta might improve delivery of a concurrently administered therapy. However, in cancer patients, further exploration of the dosing regimen of CDP860 is required to dissociate adverse effects from beneficial effects. The findings challenge the view that inhibition of PDGF alone is beneficial, and confirm that effects of PDGFR kinase inhibition mediate, to some extent, the fluid retention observed in patients treated with mixed tyrosine kinase inhibitors.

Background:Penis cancer is rare and clinical trial evidence on which to base treatment decisions is limited. Case reports suggest that the combination of docetaxel, cisplatin and 5-flurouracil (TPF) is highly active in this disease.Methods:Twenty-nine patients with locally advanced or metastatic squamous carcinoma of the penis were recruited into a single-arm phase II trial from nine UK centres. Up to three cycles of chemotherapy were received (docetaxel 75 mg m−2 day 1, cisplatin 60 mg m−2 day 1, 5-flurouracil 750 mg m−2 per day days 1–5, repeated every 3 weeks). Primary outcome was objective response (assessed by RECIST). Fourteen or more responses in 26 evaluable patients were required to confirm a response rate of 60% or higher (Fleming-A'Hern design), warranting further evaluation. Secondary endpoints included toxicity and survival.Results:10/26 evaluable patients (38.5%, 95% CI: 20.2–59.4) achieved an objective response. Two patients with locally advanced disease achieved radiological complete remission. 65.5% of patients experienced at least one grade 3/4 adverse event.Conclusion:Docetaxel, cisplatin and 5FU did not reach the pre-determined threshold for further research and caused significant toxicity. Our results do not support the routine use of TPF. The observed complete responses support further investigation of combination chemotherapy in the neoadjuvant setting.

Magnetic resonance (MR) imaging features of pelvic radiation change were assessed in 51 patients and were correlated with tumor and critical tissue radiation dose, time after treatment, and clinical symptoms. The severity of MR tissue changes was graded. Radiation tissue toxicity increased significantly when the dose exceeded 4,500 cGy, with the incidence of marked bladder and rectal changes rising from 8% to 51% and from 24% to 48%, respectively. Similar dose-related changes were seen in other pelvic organs. All grades of tissue change were seen in the bladder and rectum regardless of the time from start of therapy. All patients who exhibited clinical grade 2 or 3 bladder and rectal changes showed moderate or severe changes on MR images. In asymptomatic patients, minimal MR changes were seen in the bladder (47%) and in the rectum (33%). The accuracy of MR imaging in differentiating between radiation damage and residual/recurrent tumor varied with the primary tumor site, being excellent for recurrent cervical cancer and less so for rectal carcinoma.

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