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PURPOSE:We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model.METHODS:VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy.RESULTS:The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE.CONCLUSION:SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity.

Background The hierarchical organization of hematopoiesis with unidirectional lineage determination has become a questionable tenet in view of the experimental evidence of reprogramming and transdifferentiation of lineage-determined cells. Clinical examples of hematopoietic lineage plasticity are rare. Here we report on a patient who presented with an acute B-lymphoblastic leukemia and developed a Langerhans’ cell sarcoma 9 years later. We provide evidence that the second neoplasm is the result of transdifferentiation.Design and Methods B-cell acute lymphoblastic leukemia was diagnosed in an 11-year old boy in 1996. Treatment according to the ALL-BFM-1995 protocol resulted in a complete remission. Nine years later, in 2005, Langerhans’ cell sarcoma was diagnosed in a supraclavicular lymph node. Despite treatment with different chemotherapy protocols the patient had progressive disease. Finally, he received an allogeneic peripheral blood stem cell transplant and achieved a continuous remission. Molecular studies of IGH- and TCRG-gene rearrangements were performed with DNA from the Langerhans’ cell sarcoma and the cryopreserved cells from the acute B-lymphoblastic leukemia. The expression of PAX5 and ID2 was analyzed with real-time reverse transcriptase polymerase chain reaction.Results Identical IGH-rearrangements were demonstrated in the acute B-lymphoblastic leukemia and the Langerhans’ cell sarcoma. The key factors required for B-cell and dendritic cell development, PAX5 and ID2, were differentially expressed, with a strong PAX5 signal in the acute B-lymphoblastic leukemia and only a weak expression in the Langerhans’ cell sarcoma, whereas ID2 showed an opposite pattern.Conclusions The identical IGH-rearrangement in both neoplasms indicates transdifferentiation of the acute B-lymphoblastic leukemia into a Langerhans’ cell sarcoma. Loss of PAX5 and the acquisition of ID2 suggest that these key factors are involved in the transdifferentiation from a B-cell phenotype into a Langerhans’/dendritic cell phenotype. (Clinical trial registration at: Deutsches KrebsStudienRegister, http://www.studien.de, study-ID:8)

Purpose:  To compare local tumor control after percutaneous tumor ablation by interstitial laser therapy (ILT) or CT-guided brachytherapy (CTGB). Patients and Methods:  In a matched pair analysis including 18 patients with 36 liver metastases of colorectal primary, both ILT and CTGB were performed in different lesions. The following matching factors were considered: (i) tumor size ≤ 5 cm, and (ii) execution of chemotherapy after tumor ablation. Primary endpoint was local tumor control. Results:  Treated lesions were identical in terms of tumor size and all matching criteria were fulfilled in all patients except for the performance of adjuvant chemotherapy. Median follow-up was 14 months (3–24 months) for both groups. Only five of 18 patients (28%) demonstrated local tumor progression after CTGB, whereas in ten of 18 patients (56%) tumor progression was found after ILT. Differences encountered were significant for all patients (p = 0.04), whereas in those who fulfilled all matching criteria (n = 14) the level of statistical significance was not reached (p = 0.23). Conclusion:  CTGB demonstrated superior local tumor control compared to ILT in long-term follow-up. [ABSTRACT FROM AUTHOR]

Purpose:  To assess differences in delineated target volumes of liver metastases using contrast-enhanced CT and different MRI sequences for radiation treatment planning. Patients and Methods:  25 patients with 43 colorectal liver metastases were recruited. Tumor margins were defined by two experienced radiologists. The resulting D90 was assessed and the CT-based 3-D dose distribution merged with the according MRI dataset by employing image fusion. A theoretical D90 as a result of MRI-based treatment planning was assessed for various MRI sequences individually. Results:  In venous phase contrast-enhanced CT, the mean tumor volume was 20 ml; T1-weighted (T1w) MRI, 27 ml; contrast-enhanced T1w 42 ml; T2w 65 ml. The difference between the target volumes as assessed by either CT or MRI was 181% for T1w images, 178% for contrast-enhanced T1w, and 246% for T2w sequences. All differences were statistically significant (p The analysis of the dose-volume histograms revealed statistically significant differences (i.e., for the D90) for the different target volumes specified by CT and MRI: mean D90 on CT, 18 Gy; plain T1w, 16 Gy; contrast-enhanced T1w, 15.5 Gy; T2w, 12 Gy. Hence, delineation of a larger target volume in T2w MRI compared to contrast-enhanced CT resulted in a smaller D90. The mean differences of tumor volumes assessed by CT and plain T1w were significantly higher in the group of patients showing local tumor recurrences as compared to patients with long-term local tumor control (p = 0.002). Conclusion:  For treatment planning of liver metastases, the use of either plain T1w or T2w sequences is recommended to delineate the clinical target volume as completely as possible and not to miss potential tumor cell congregations in the surroundings as in CT. [ABSTRACT FROM AUTHOR]