Thomas Tichler

Early Detection of Response to Radiation Therapy in Patients With Brain Malignancies Using Conventional and High b-Value Diffusion-Weighted Magnetic Resonance Imaging

PURPOSE To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. PATIENTS AND METHODS Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. RESULTS One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. CONCLUSION The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

The protective role of the immunomodulator AS101 against chemotherapy‐induced alopecia studies on human and animal models

The immunomodulator AS101 has been demonstrated to exhibit radioprotective and chemoprotective effects in mice. Following phase‐I studies, preliminary results from phase‐II clinical trials on non‐small‐cell‐lung‐cancer patients showed a reduction in the severity of alopecia in patients treated with AS101 in combination with chemotherapy. To further substantiate these findings, the present study was extended to include 58 patients treated either with the optimal dose of 3 mg/m2 AS101 combined with carboplatin and VP‐16, or with chemotherapy alone. As compared with patients treated with chemotherapy alone, there was a significant decrease in the level of alopecia in patients receiving the combined therapy. The newly developed rat model was used to elucidate the protective mechanism involved in this effect. We show that significant prevention of chemotherapy‐induced alopecia is obtained in rats treated with Ara‐C combined with AS101, administered i.p. or s.c. or applied topically to the dorsal skin. We show that this protection by AS101 is mediated by macrophage‐derived factors induced by AS101. Protection by AS101 can be ascribed, at least in part, to IL‐1, since treatment of rats with IL‐1RA largely abrogated the protective effect of AS101. Moreover, we demonstrate that in humans there is an inverse correlation between the grade of alopecia and the increase in IL‐1α. In addition, protection by AS101 could be related to PGE2 secretion, since injection of indomethacin before treatment with AS101 and Ara‐C partly abrogated the protective effect of AS101. To assess the ability of AS101 to protect against chemotherapy‐induced alopecia, phase‐II clinical trials have been initiated with cancer patients suffering from various malignancies.

Bone marrow-sparing and prevention of alopecia by AS101 in non-small-cell lung cancer patients treated with carboplatin and etoposide.

PURPOSE The aim of this study was to evaluate the ability of the immunomodulator AS101 to prevent chemotherapy-induced neutropenia and thrombocytopenia and thus allow patients to receive full-dose antineoplastic agents according to protocol design. We also aimed to determine the production level of various hematopoietic growth factors in treated patients. PATIENTS AND METHODS This study of 44 unresectable or metastatic non-small-cell lung cancer (NSCLC) patients was an open-label prospective randomized study of standard chemotherapy alone versus chemotherapy plus AS101. Each patient received carboplatin (300 mg/m2 intravenously [IV] on day 1 of a 28-day cycle, and etoposide (VP-16) (200 mg/m2 orally) on days 3, 5, and 7 of each cycle. AS101 was administered at 3 mg/m2 three times per week starting 2 weeks before chemotherapy. RESULTS AS101, which manifested no major toxicity, significantly reduced neutropenia and thrombocytopenia and thus allowed all treated patients to receive full-dose antineoplastic agents, in contrast to only 28.5% of the control group. Continuous treatment with AS101 significantly reduced the number of days per patient of thrombocytopenia and neutropenia and did not provide protection to tumor cells as reflected by the higher overall response rate compared with the chemotherapy-alone arm. Interestingly, AS101 treatment also significantly prevented chemotherapy-induced alopecia. These effects correlate with the ability of AS101-treated patients to increase significantly the production of colony-stimulating factors (CSFs) interleukin-1 alpha (IL-1 alpha) and IL-6. CONCLUSION AS101 has significant bone marrow (BM)-sparing effects and prevents hair loss in chemotherapy-treated patients, with minimal overall toxicity. These effects are probably due to increased production of IL-1 alpha, IL-6, and granulocyte-macrophage (GM)-CSF.

Malignant fibrous histiocytoma of the anterior mediastinum: a rare case with 19 years survival

We report here in an additional case, which is the second MFH occurring in the anterior mediastinum, and in contrast to other cases, had a prolonged survival

Early non-invasive detection of brain tumor response to radiation using diffusion weighted MRI

patient ranged from 0.5cm to 2.6 cm, with a median of 1.6 cm. This difference was not related to patient’s AP and right-left dimensions. The lateral distances from the anterior midline are: 3.5 ,-0.4; 2.9 ,-0.4; 2.5 ,-0.4; 2.9 ,-2.7;, and 2.7 ,-0.7 cm, at the 1st, 2nd, 3rd, 4th, and 5th intercostal spaces respectively. Although the IM lateral positions varied from patient to patient, they were relatively consistent in respect to the lateral border of sternum, all located maximally less than 1 cm laterally at 2nd, 3rd, 4th, and 5th intercostal spaces, and 0.5 cm medially of the 1st intercostal space. Distances from the most lateral border of AXN and the most medial border of HH were -2.1 ,-1.3, 0.7 ,-0.5, and 2.9 ,-1.5 cm at levels of HH head, coracoid process and lateral end of clavicle respectively (negative value indicates overlapping). AXN frequently overlapped HH anteriorly when the arm was angled more than 90 degree, but did not when the arm is placed 90 degree or less. The gantry angle of the SCV port also effected HH sparing. The larger the angle, the less HH could be spared. DVHs of IMC, AXN, and HH at different conventional beam settings were also analyzed and showed significant variation of node coverage and HH sparing.