Repeat gamma knife stereotactic radiosurgery in the treatment of trigeminal neuralgia: A single-center experience and focused review of the literature.

OBJECTIVES: Repeat Gamma Knife stereotactic radiosurgery (GKSR) for refractory trigeminal neuralgia (TGN) is an increasingly common practice. Prior studies have reported varying success rates and incidence of trigeminal nerve dysfunction following repeated GKSR. We report treatment outcomes and toxicity in patients following repeat GKSR for TGN at the University of Alabama at Birmingham (UAB) with a focused review of the literature. METHODS: We retrospectively reviewed medical records of 55 TGN patients re-treated with radiosurgery using the Leksell Gamma Knife® at the University of Alabama at Birmingham between 1996 and 2012. Outcomes were defined using the Modified Marseille Scale. Demographics, prior treatments and symptom duration were correlated with outcomes. RESULTS: Eighteen patients (33%) achieved Marseille Class I or II, 14 (25%) Class III or IV, and 23 (42%) Class V at a mean follow-up of 14.4 months. Twenty-five patients (45%) developed new trigeminal nerve dysfunction after re-treatment. Of these, four (16%) did not develop dysfunction until subsequent microvascular decompression (MVD) for inadequate symptom relief. CONCLUSIONS: Although more than half of the patients undergoing repeat GKSR for refractory TGN maintained excellent or good outcomes (Marseille classes I-IV) at an average follow-up of 14.4 months, neither age, gender, nor pre-treatment duration of symptoms or interval between treatments had a statistically significant effect on outcomes. Following repeat GKSR, patients have increased risk for new-onset trigeminal nerve dysfunction and those undergoing MVD after repeat GKSR may have an increased risk for new-onset trigeminal nerve dysfunction.

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.

Multi-institutional competing risks analysis of distant brain failure and salvage patterns after upfront radiosurgery without whole brain radiotherapy for brain metastasis.

Background: In this study, we use a competing risks analysis to assess factors predictive of early-salvage whole brain radiotherapy (WBRT) and early death after upfront stereotactic radiosurgery (SRS) alone for brain metastases in an attempt to identify populations that benefit less from upfront SRS. Patients and methods: Patients from eight academic centers were treated with SRS for brain metastasis. Competing risks analysis was carried out for distant brain failure (DBF) versus death prior to DBF as well as for salvage SRS versus salvage WBRT versus death prior to salvage. Linear regression was used to determine predictors of the number of brain metastases at initial DBF (nDBF). Results: A total of 2657 patients were treated with upfront SRS alone. Multivariate analysis (MVA) identified an increased hazard of DBF associated with increasing number of brain metastases (P < 0.001), lowest SRS dose received (P < 0.001), and melanoma histology (P < 0.001), while there was a decreased hazard of DBF associated with increasing age (P < 0.001), KPS < 70 (P < 0.001), and progressive systemic disease (P = 0.004). MVA for first salvage SRS versus WBRT versus death prior to salvage revealed an increased hazard of first salvage WBRT seen with increasing number of brain metastases (P < 0.001) and a decreased hazard with widespread systemic disease (P = 0.002) and increasing age (P < 0.001). Variables associated with nDBF included age (P = 0.02), systemic disease status (P = 0.03), melanoma histology (P = 0.05), and initial number of brain metastases (P < 0.001). Conclusions: Patients with a higher initial number of brain metastases were more likely to experience DBF, have a higher nDBF, and receive early-salvage WBRT, while patients who were older, had lower KPS, or had more systemic disease were more likely to experience death prior to DBF or salvage WBRT.

SU-E-T-631: Beam Geometry Selection Using Sequential Beam Addition.

PURPOSE: To investigate a beam geometry selection algorithm based on sequential addition of beams. METHODS: The sequential beam addition algorithm (SBA) requires an objective function (score) and a set of candidate beam geometries (pool). The optimal score is determined for each beam in the pool and the best beam selected. Scores are then calculated for the selected beam in combination with each member of the pool. The pair with the best score is selected and the score again determined in combination with each beam in the pool. The process is repeated until the desired number of beams is reached. We selected 3 treatment sites, breast, lung, and brain, and determined beam arrangements for up to 11 beams from a pool comprised of 25 equi-angular transverse beams. For the brain, arrangements were additionally selected from a pool of 22 non-coplanar beams. Scores were determined for geometries comprised of equi-angular transverse beams (EQA), as well as two tangential beams for the breast case. RESULTS: In all cases, SBA resulted in scores superior to EQA. The breast case had the strongest dependence on beam geometry, for which only 7 beam EQA had a score better than the tangential beams, whereas all SBA geometries with more than two beams were superior. For the lung case, for both EQA and SBA the scores monotonically improved with increasing number of beams; however, SBA required fewer beams to achieve scores equivalent to EQA. For the brain case, SBA with a coplanar pool was equivalent to EQA, while the non-coplanar pool resulted in slightly better scores; however, the dose-volume histograms demonstrated that the differences were not clinically significant. CONCLUSIONS: For situations in which beam geometry has a significant effect on the objective function, SBA can identify arrangements equivalent to equi-angular geometries but using fewer beams. Varian Medical Systems.

TU-E-BRB-11: End-To-End Positioning Quality Assurance for Image-Guided Radiosurgery of Multiple Targets Using a Single-Isocenter.

PURPOSE: Using a single isocenter significantly reduces delivery times in radiosurgery involving multiple targets. However, because not every target can be placed at isocenter with this type of treatment, a conventional Winston-Lutz test cannot be used. We describe a novel Winston-Lutz like mulitarget test (MTT) for verifying accurate positioning. METHODS: A target phantom, comprised of an acrylic plate with recesses for three 3/4″ spheres was constructed and a high-resolution (0.5×0.5×0.8 mm) CT scan obtained with PTFE spheres placed in the recesses. The scan was imported into a commercial treatment planning system and multiple beams were prepared, having their isocenter at the centroid of the arrangement of spheres. Every beam incorporated three MLC-defined rectangular apertures that circumscribed the spheres. Custom software selected setup parameters (table, gantry and collimator angle, MLC openings) such that the spheres were centered as precisely as possible within their respective MLC fields, considering the discrete width of collimator leaves. The phantom, with the PTFE replaced by steel spheres, was placed on the treatment couch and imaged using stereoscopic x-ray beams. A 6 degree-of-freedom robotic couch applied translations and rotations to reproduce the CT position. A MV EPID rendered images of the spheres within their respective apertures, allowing identification of sphere and aperture centers. Any error upstream would manifest itself as inaccurate centering of a sphere. RESULTS: Eight beams with table angle 0 and two beams each with table angles 49.7, 89.8, 272.3, and 310.1 were selected. The maximum calculated distance between any sphere and the respective aperture center was 0.07 mm. The median difference measured from the MV images ranged from 0.1 mm to 1.4 mm with a median of 0.8 mm. CONCLUSIONS: The MTT is a practical end-to-end test for quality assurance of the entire positioning process in multitarget radiosurgery, from CT scanning to beam delivery.

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.

Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases.

BACKGROUND: Merkel cell carcinoma (MCC) is an unusual and potentially aggressive cancer of the skin. There is no consensus regarding the optimal therapeutic approach, and the relative roles of surgery, radiotherapy, and chemotherapy still are controversial The aim of this study is to analyze the roles of these therapeutic options. METHODS: The medical records of 16 patients with a diagnosis of localized, primary MCC treated at the University of Alabama at Birmingham were reviewed. An extensive review of the English-language literature also was performed. The Kaplan-Meier method was used to develop the survival curves. Comparisons were made using Fisher's exact test. Significance was defined as P < .05. RESULTS: MCC presented primarily in Caucasians (98.3%) with a median age of 69 years. Immunosuppressive therapy appeared to play a role in the development of this cancer. In the UAB experience, 3-year actuarial survival was 31%. The only factor significantly associated with overall survival was the stage of disease at presentation: median survivals were 97 vs. 15 months for stages I and II, respectively (log-rank, P = .02). From the literature review, adjuvant radiotherapy was associated with a reduced risk of local recurrence (P < .00001). CONCLUSIONS: MCC is an aggressive cancer, with a high tendency for local recurrence and distant spread. Surgery and adjuvant radiotherapy appear to provide optimal local control. The role of chemotherapy remains to be defined.

Effect of Foley catheters on seed positions and urethral dose in (125)I and (103)Pd prostate implants.

PURPOSE: To estimate the perturbation of seed position and urethral dose, subsequent to withdrawal of urethral catheters. METHODS AND MATERIALS: A mathematical model based on the volume incompressibility of tissues was used to compute seed positions and doses following removal of the Foley. The model assumed that the central axis of the urethra remains stationary, and that prostate tissue and seeds move radially toward the center of the urethra to fill the void left by the catheter. Seed motion has also been measured using transrectal ultrasound. RESULTS: Based on the computations, seeds located originally close to the urethra travel relatively large distances toward the urethra upon Foley removal, whereas seeds located further away move substantially less. This seed motion leads to higher urethral doses than shown in a standard treatment plan. Dose enhancements increase with catheter size, decrease with increasing prostate volume, are more pronounced for (103)Pd than for (125)I, and range between 3.5% and 32.4%. Postimplant dosimetry is equally affected if images are taken with urethral catheters in place, showing lower urethral doses than actually delivered. Preliminary ultrasound based measurements of seed motion agree with the theory. CONCLUSION: During the implantation procedure, 12 fr or smaller urethral catheters are preferable to larger diameter catheters if urine drainage is sufficient. Treatment planners should avoid planning seeds at 5 mm or closer from the urethra. Special caution is indicated in prostates having about 20 cm(3) or smaller volumes, and when (103)Pd is used. Postimplant dosimetry is susceptible to the same errors.

In vivo urethral dose measurements: a method to verify high dose rate prostate treatments.

Radiation doses delivered in high dose rate (HDR) brachytherapy are susceptible to many inaccuracies and errors, including imaging, planning and delivery. Consequently, the dose delivered to the patient may deviate substantially from the treatment plan. We investigated the feasibility of using TLD measurements in the urethra to estimate the discrepancy in treatments for prostate cancer. The dose response of the 1 mm diam, 6 mm long LiF rods that we used for the in vivo measurements was calibrated with the 192Ir HDR source, as well as a 60Co teletherapy unit. A train of 20 rods contained in a sterile plastic tube was inserted into the urethral (Foley) catheter for the duration of a treatment fraction, and the measured doses were compared to the treatment plan. Initial results from a total of seven treatments in four patients show good agreement between theory and experiment. Analysis of any one treatment showed agreement within 11.7% +/- 6.2% for the highest dose encountered in the central prostatic urethra, and within 10.4% +/- 4.4% for the mean dose. Taking the average over all seven treatments shows agreement within 1.7% for the maximum urethral dose, and within 1.5% for the mean urethral dose. Based on these initial findings it seems that planned prostate doses can be accurately reproduced in the clinic.

A prospective evaluation of the timing of postoperative radiotherapy for preventing heterotopic ossification following traumatic acetabular fractures.

PURPOSE: Preoperative and immediate postoperative irradiation of traumatic acetabular fractures (TAF), although known to reduce heterotopic ossification (HO), can cause significant organizational and logistic difficulties. We sought to determine an acceptable time interval between surgery and radiation without compromising control, as well as to update our large experience and to further validate our treatment philosophy. METHODS AND MATERIALS: Beginning in June 1995, we began a prospective study, irradiating 152 patients on postoperative days 1, 2, or 3. There were also 17 patients delayed further secondary to medical difficulties. RESULTS: All patients treated since June 1995 received 700 cGy/1 fx. Fifty-eight patients received radiation within 24 hours of surgery, 41 within 2 days, 53 within 3 days, 13 within 4 days, and 4 were delayed further. Delaying irradiation for up to 4 days postoperatively caused no statistical increase in HO (p = 0.625). Of 263 patients in our retrospective cohort, HO occurred in 5.3% of patients who received irradiation versus 60% of patients who did not. CONCLUSION: In our prospective study, we noted no perceptible increase in HO with up to a 3-day interval between surgery and radiotherapy. This allows a more structured treatment schedule and allows the patient more time to heal and recover. Updated results from our overall series continue to demonstrate that adjuvant radiation decreases the incidence and severity of HO after TAF.

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.

Controversies in the management of stage I seminoma.

Current controversies in the treatment of stage I seminoma center on the relative roles of surveillance, adjuvant radiotherapy (RT), and adjuvant single-agent chemotherapy. Surveillance has been studied in over 800 patients, 17.1% of whom have relapsed. There is no evidence that surveillance compromises survival in properly selected, compliant patients. The economic benefit of treating only those patients who relapse is offset by the cost of screening diagnostic studies and salvage therapy, and by issues of patient anxiety and compliance. Other methods of reducing the toxicity of RT include reductions in RT dose and volume. A randomized trial has shown that omission of the pelvic field produces relapse-free survival equivalent to that achieved with pelvic plus para-aortic RT. A similar study is currently evaluating a reduction in RT dose from 30 to 20 Gy. Early results from nonrandomized studies of one or two cycles of single-agent chemotherapy demonstrate efficacy comparable to RT in the adjuvant treatment of stage I seminoma. A randomized trial is underway to determine the equivalence of adjuvant carboplatin (Paraplatin) and RT. Long-term follow-up from these studies will provide information not only on the relative efficacy of these alternative strategies but also on the late effects of therapy, including infertility and second malignancy.

Urologic aspects of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma can present initially as urologic disease. The 15 reported cases in the literature are analyzed and 5 cases, featuring ureteral obstruction, renal artery compression, abdominal bruit, positive urinary cytology, varicocele, renal mass and hematuria as the initial presentation of this disease, are added. The diagnosis and management are reviewed.