Treatment-induced remission of medulloblastoma using a chemotherapeutic regimen devoid of vincristine in a child with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (cmt) disease is the most common form of inherited neuropathy. Core features include peripheral neuropathy and secondary axonal degeneration, with a noted distal predominance of limb-muscle wasting, weakness, and sensory loss. Given the significant prevalence of cmt, superimposed neoplastic disease can be encountered within this patient population. Malignancies that are treated with vincristine (a microtubule-targeting agent), even at low doses as part of standard treatment, pose a significant challenge for patients with cmt. Here, we present the case of a child with cmt who was successfully treated for medulloblastoma without vincristine, a standard drug used for treatment of that disease, to avoid the risk of severe debilitating neuropathy. This report is the first of a patient successfully treated for medulloblastoma without vincristine.

Implementation of talairach atlas based automated brain segmentation for radiation therapy dosimetry.

Radiotherapy for brain cancer inevitably results in irradiation of uninvolved brain. While it has been demonstrated that irradiation of the brain can result in cognitive deficits, dose-volume relationships are not well established. There is little work correlating a particular cognitive deficit with dose received by the region of the brain responsible for the specific cognitive function. One obstacle to such studies is that identification of brain anatomy is both labor intensive and dependent on the individual performing the segmentation. Automatic segmentation has the potential to be both efficient and consistent. Brains2 is a software package developed by the University of Iowa for MRI volumetric studies. It utilizes MR images, the Talairach atlas, and an artificial neural network (ANN) to segment brain images into substructures in a standardized manner. We have developed a software package, Brains2DICOM, that converts the regions of interest identified by Brains2 into a DICOM radiotherapy structure set. The structure set can be imported into a treatment planning system for dosimetry. We demonstrated the utility of Brains2DICOM using a test case, a 34-year-old man with diffuse astrocytoma treated with three-dimensional conformal radiotherapy. Brains2 successfully applied the Talairach atlas to identify the right and left frontal, parietal, temporal, occipital, subcortical, and cerebellum regions. Brains2 was not successful in applying the ANN to identify small structures, such as the hippocampus and caudate. Further work is necessary to revise the ANN or to develop new methods for identification of small structures in the presence of disease and radiation induced changes. The segmented regions-of-interest were transferred to our commercial treatment planning system using DICOM and dose-volume histograms were constructed. This method will facilitate the acquisition of data necessary for the development of normal tissue complication probability (NTCP) models that assess the probability of cognitive complications secondary to radiotherapy for intracranial and head and neck neoplasms.

Effect of multileaf collimator leaf width on physical dose distributions in the treatment of CNS and head and neck neoplasms with intensity modulated radiation therapy.

The purpose of this work is to examine physical radiation dose differences between two multileaf collimator (MLC) leaf widths (5 and 10 mm) in the treatment of CNS and head and neck neoplasms with intensity modulated radiation therapy (IMRT). Three clinical patients with CNS tumors were planned with two different MLC leaf sizes, 5 and 10 mm, representing Varian-120 and Varian-80 Millennium multileaf collimators, respectively. Two sets of IMRT treatment plans were developed. The goal of the first set was radiation dose conformality in three dimensions. The goal for the second set was organ avoidance of a nearby critical structure while maintaining adequate coverage of the target volume. Treatment planning utilized the CadPlan/Helios system (Varian Medical Systems, Milpitas CA) for dynamic MLC treatment delivery. All beam parameters and optimization (cost function) parameters were identical for the 5 and 10 mm plans. For all cases the number of beams, gantry positions, and table positions were taken from clinically treated three-dimensional conformal radiotherapy plans. Conformality was measured by the ratio of the planning isodose volume to the target volume. Organ avoidance was measured by the volume of the critical structure receiving greater than 90% of the prescription dose (V(90)). For three patients with squamous cell carcinoma of the head and neck (T2-T4 N0-N2c M0) 5 and 10 mm leaf widths were compared for parotid preservation utilizing nine coplanar equally spaced beams delivering a simultaneous integrated boost. Because modest differences in physical dose to the parotid were detected, a NTCP model based upon the clinical parameters of Eisbruch et al. was then used for comparisons. The conformality improved in all three CNS cases for the 5 mm plans compared to the 10 mm plans. For the organ avoidance plans, V(90) also improved in two of the three cases when the 5 mm leaf width was utilized for IMRT treatment delivery. In the third case, both the 5 and 10 mm plans were able to spare the critical structure with none of the structure receiving more than 90% of the prescription dose, but in the moderate dose range, less dose was delivered to the critical structure with the 5 mm plan. For the head and neck cases both the 5 and 10 x 2.5 mm beamlets dMLC sliding window techniques spared the contralateral parotid gland while maintaining target volume coverage. The mean parotid dose was modestly lower with the smaller beamlet size (21.04 Gy v 22.36 Gy). The resulting average NTCP values were 13.72% for 10 mm dMLC and 8.24% for 5 mm dMLC. In conclusion, five mm leaf width results in an improvement in physical dose distribution over 10 mm leaf width that may be clinically relevant in some cases. These differences may be most pronounced for single fraction radiosurgery or in cases where the tolerance of the sensitive organ is less than or close to the target volume prescription.

3D conformal radiation therapy (3DCRT) for high grade prostate cancer: a multi-institutional review.

PURPOSE: To evaluate the results of 3DCRT and the effect of higher than traditional doses in patients with high grade prostate cancer, we compiled data from three institutions and analyzed the outcome of this relatively uncommon subset of prostate cancer patients. METHODS AND MATERIALS: The 180 patients with Gleason score 8- 10 adenocarcinoma of the prostrate were treated with 3DCRT at the Univer sity of Michigan Health System, University of California-San Francisco, or Fox Chase Cancer. Eligible patients had T1-T4 NO or NX MO adenocarci noma with a pretreatment PSA. Pretreatment characteristics included: me dian age 72 years, 60.6% Gleason score 8 tumors, 57.6% T1-T2, and median pretreatment PSA 17.1 ng/ml (range 0.3-257.1). The total dose received was <70 Gy in 30%, 70-75 Gy in 37%, and >75 Gy in 33%, 27% received adju vant or neoadjuvant hormonal therapy. The median follow-up was 3.0 years for all patients and 16% of patients were followed up for at least 5 years. RESULTS: The 5-year freedom from PSA failure was 62.5% for all patients and 79.3% in T1-T2 patients. Univariate analysis revealed that T-stage (T1-T2 vs. T3-T4), pretreatment PSA, and RT dose predicted for freedom from PSA failure. A 5-year overall survival for all patients was 67.3%. Only RT dose was predictive of 5-year overall survival on univariate analysis. Because a significant association was seen between T-stage and RT dose, the Cox proportional hazards model was performed separately for T1-T2 and T3-T4 tumors. None of the prognostic factors reached statistical significance for overall survival or freedom from PSA failure in T3-T4 patients or for overall survival in T1-T2 patients. Lower RT dose and higher pretreatment PSA predicted for PSA failure on multivariate analysis in T1-T2 patients. CONCLUSION: This retrospective study from three institutions with experience in dose escalation suggests a dose effect for PSA control above 70 Gy in patients with T1-T2 high grade prostate cancer. These results are superior to surgery and emphasize the need for dose escalation in treating Gleason 8-10 prostate cancer.

Effects of pelvic rotation and needle angle on pubic arch interference during transperineal prostate implants.

PURPOSE: Pubic arch interference due to an enlarged prostate gland or a narrow pubic arch is often a limiting factor in adequate prostate coverage during transperineal brachytherapy. The purpose of this study was to evaluate the effects of both pelvic rotation and needle angles on pubic arch interference using CT-based 3-D information. METHODS AND MATERIALS: Seven patients had CT imaging in both supine and lithotomy positions and 3-D treatment planning was performed with three needle angles (20 downward, 0, 20 upward). The pubic arch interference was then measured and comparisons were made for each needle trajectory and pelvic position. RESULTS: Increasing pelvic rotation from supine to lithotomy position shows less pubic arch interference. Directing the needle tip upward shows less pubic arch interference in both supine and lithotomy positions when compared to needle tips directed downward. CONCLUSIONS: Both pelvic position and needle angles are important factors influencing pubic arch interference. Preplanning CT-based 3-D information may assist for individualized treatment planning in patients with a significant bony interference, thus avoiding pubic arch interference during implantation.