J Penagaricano

A prospective cohort study of microvascular decompression and Gamma Knife surgery in patients with trigeminal neuralgia

OBJECT The aim of this study was to analyze 1 surgeons 4-year experience with microvascular decompression ([MVD], 36 patients) and Gamma Knife surgery ([GKS], 44 patients) in 80 consecutive patients with trigeminal neuralgia (TN). METHODS The authors conducted a prospective cohort study from March 1999 to December 2003 with an independent clinical assessment of the results and serial patient satisfaction surveys. All patients completed a 2004 patient satisfaction survey (0.5-5 years postoperative), and 70% of surviving patients completed the same survey in 2007 (3.9-8.5 years postoperative). Follow-up was undertaken in 100% of the patients (mean 3.4 +/- 2.14 years, range 0.17-8.5 years). RESULTS Respective initial and latest follow-up raw pain-free rates were 100 and 80.6% for MVD and 77.3 and 45.5% for GKS. The median time to the maximal benefit after GKS was 4 weeks (range 1 week-6 months). Respective initial, 2-, and 5-year actuarial pain-free rates were 100, 88, and 80% for MVD and 78, 50, and 33% for GKS (p = 0.0002). The relative risk of losing a pain-free status by 5 years posttreatment was 3.35 for patients in the GKS group compared with the MVD group. Initial and 5-year actuarial rates for >or= 50% pain relief after GKS were 100 and 80%, respectively. The respective rates of permanent mild and severe sensory loss were 5.6 and 0% for patients in the MVD group, as opposed to 6.8 and 2.3% for patients in the GKS group. Anesthesia dolorosa did not occur during the study. Both procedures enjoyed a high degree of early patient satisfaction (95-100%). Microvascular decompression maintained the same rate of patient satisfaction, but satisfaction with GKS decreased to 75% as pain control waned. Twenty-three patients (29%) died of causes unrelated to the TN or the surgical intervention during the follow-up, and their pain status was known at the time of death. Statistically significant intergroup differences for the MVD versus GKS cohorts were age (median 54 years, range 36-70 years vs median 74 years, range 48-92 years, respectively), preoperative symptom duration (median 2.58 years, range 0.33-15 years vs median 7.5, range 0.6-40 years, respectively), and the presence of major comorbidities (2.8 vs 58.3%, respectively). CONCLUSIONS In this nonrandomized prospective cohort trial of selected patients with potentially relevant intergroup differences, MVD was significantly superior to GKS in achieving and maintaining a pain-free status in those with TN and provided similar early and superior longer-term patient satisfaction rates compared with those for GKS. The complications of wound cerebrospinal fluid leakage, hearing loss, and persistent diplopia (1 case each in the MVD group) were not seen after GKS.

Pediatric Craniospinal Axis Irradiation With Helical Tomotherapy: Patient Outcome and Lack of Acute Pulmonary Toxicity

PURPOSE To present the patient outcomes and risk of symptomatic acute radiation pneumonitis (ARP) in 18 pediatric patients treated with helical tomotherapy to their craniospinal axis for a variety of neoplasms. METHODS AND MATERIALS A total of 18 patients received craniospinal axis irradiation with helical tomotherapy. The median age was 12 years (range, 2.5-21). The follow-up range was 3-48 months (median, 16.5). Of the 18 patients, 15 received chemotherapy in the neoadjuvant, adjuvant, or concomitant setting. Chemotherapy was tailored to the particular histologic diagnosis; 10 of 18 patients underwent surgical removal of the gross primary tumor. The patients were followed and evaluated for ARP starting at 3-6 months after completion of craniospinal axis irradiation. ARP was graded using the Common Toxicity Criteria, version 3. RESULTS At the last follow-up visit, 14, 2, and 2 patients were alive without disease, alive with disease, and dead of disease, respectively. The cause-specific survival rate was 89% (16 of 18), disease-free survival rate was 78% (14 of 18), and overall survival rate was 89% (16 of 18). No patient had treatment failure at the cribriform plate. No patient developed symptoms of ARP. CONCLUSION Craniospinal axis irradiation using helical tomotherapy yielded encouraging patient outcomes and acute toxicity profiles. Although large volumes of the lung received low radiation doses, no patient developed symptoms of ARP during the follow-up period.

Dosimetric comparison of Helical Tomotherapy and Gamma Knife Stereotactic Radiosurgery for single brain metastasis

BackgroundHelical Tomotherapy (HT) integrates linear accelerator and computerized tomography (CT) technology to deliver IMRT. Targets are localized (i.e. outlined as gross tumor volume [GTV] and planning target volume [PTV]) on the planning kVCT study while daily MVCT is used for correction of patients set-up and assessment of inter-fraction anatomy changes. Based on dosimetric comparisons, this study aims to find dosimetric equivalency between single fraction HT and Gamma Knife® stereotactic radiosurgery (GKSRS) for the treatment of single brain metastasis.MethodsThe targeting MRI data set from the GKSRS were used for tomotherapy planning. Five patients with single brain metastasis treated with GKSRS were re-planned in the HT planning station using the same prescribed doses. There was no expansion of the GTV to create the PTV. Sub-volumes were created within the PTV and prescribed to the maximum dose seen in the GKSRS plans to imitate the hot spot normally seen in GKSRS. The PTV objective was set as a region at risk in HT planning using the same prescribed dose to the PTV periphery as seen in the corresponding GKSRS plan. The tumor volumes ranged from 437–1840 mm3.ResultsConformality indices are inconsistent between HT and GKSRS. HT generally shows larger lower isodose line volumes, has longer treatment time than GKSRS and can treat a much larger lesion than GKSRS. Both HT and GKSRS single fraction dose-volume toxicity may be prohibitive in treating single or multiple lesions depending on the number and the sizes of the lesions.ConclusionBased on the trend for larger lower dose volumes and more constricted higher dose volumes in HT as compared to GKSRS, dosimetric equivalency was not reached between HT and GKSRS.

Evaluation of Spatially Fractionated Radiotherapy (GRID) and Definitive Chemoradiotherapy With Curative Intent for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Initial Response Rates and Toxicity

PURPOSE To present results and acute toxicity in 14 patients with bulky (>or=6 cm) tumors from locally advanced squamous cell carcinoma of the head and neck who received spatially fractionated radiotherapy (GRID) therapy to the bulky mass followed by concomitant chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT). METHODS AND MATERIALS GRID therapy to the GTV was delivered by creating one treatment field with a checkerboard pattern composed of open-closed areas using a multileaf collimator. The GRID prescription was 20 Gy in one fraction. Chemotherapy started the day of GRID therapy and continued throughout the course of SIB-IMRT. The SIB-IMRT prescription was 66, 60, and 54 Gy to the planning target volume (PTV), intermediate-risk PTV, and low-risk PTV, respectively, in 30 fractions. RESULTS With a median follow-up of 19.5 months (range, 2-38 months), the overall control rate of the GRID gross tumor volume was 79% (11 of 14). The most common acute skin and mucosal toxicities were Grade 3 and 2, respectively. CONCLUSION For the treatment of locally advanced neck squamous cell carcinoma of the head and neck, GRID followed by chemotherapy and SIB-IMRT is well tolerated and yields encouraging clinical and pathologic responses, with similar acute toxicity profiles as in patients receiving chemoradiotherapy without GRID.

Spatially Fractionated Radiation Induces Cytotoxicity and Changes in Gene Expression in Bystander and Radiation Adjacent Murine Carcinoma Cells

Radiation-induced bystander effects have been extensively studied at low doses, since evidence of bystander induced cell killing and other effects on unirradiated cells were found to be predominant at doses up to 0.5 Gy. Therefore, few studies have examined bystander effects induced by exposure to higher doses of radiation, such as spatially fractionated radiation (GRID) treatment. In the present study, we evaluate the ability of GRID treatment to induce changes in GRID adjacent (bystander) regions, in two different murine carcinoma cell lines following exposure to a single irradiation dose of 10 Gy. Murine SCK mammary carcinoma cells and SCCVII squamous carcinoma cells were irradiated using a brass collimator to create a GRID pattern of nine circular fields 12 mm in diameter with a center-to-center distance of 18 mm. Similar to the typical clinical implementation of GRID, this is approximately a 50:50 ratio of direct and bystander exposure. We also performed experiments by irradiating separate cultures and transferring the medium to unirradiated bystander cultures. Clonogenic survival was evaluated in both cell lines to determine the occurrence of radiation-induced bystander effects. For the purpose of our study, we have defined bystander cells as GRID adjacent cells that received approximately 1 Gy scatter dose or unirradiated cells receiving conditioned medium from irradiated cells. We observed significant bystander killing of cells adjacent to the GRID irradiated regions compared to sham treated controls. We also observed bystander killing of SCK and SCCVII cells cultured in conditioned medium obtained from cells irradiated with 10 Gy. Therefore, our results confirm the occurrence of bystander effects following exposure to a high-dose of radiation and suggest that cell-to-cell contact is not required for these effects. In addition, the gene expression profile for DNA damage and cellular stress response signaling in SCCVII cells after GRID exposure was studied. The occurrence of GRID-induced bystander gene expression changes in significant numbers of DNA damage and cellular stress response signaling genes, providing molecular evidence for possible mechanisms of bystander cell killing.

Evaluation of Integral Dose in Cranio-spinal Axis (CSA) Irradiation with Conventional and Helical Delivery:

In cranio-spinal axis (CSA) irradiation, patients are usually treated in the prone position with junctions between cranial and spinal fields. Collimator angle and pedestal rotations are introduced to obtain coplanar alignment of the matched junction. Furthermore, daily moving junctions are commonly used to feather out the junctional dose as additional safe-guards to avoid radiation myelopathy. Helical tomotherapy integrates linear accelerator and CT technology capable of delivering CSA treatment without geometric matches or feathering of junctions. The patient is treated with helical beams in the supine position. Since CSA is used mainly in the pediatric population, the potential increase in integral dose to structures or the whole body from linac- or tomotherapy-based IMRT raises concerns of increased rates of secondary malignancies. In this study, we will present an integral dose comparison between conventional CSA (3D) and helical delivery to the CSA (TOMO) utilizing the Tomotherapy Hi-ART system for three pediatric patients. Integral dose was calculated for organ at risk (OAR), two targets (PTV-BRAIN and PTV-SPINE), entire planning CT data set and to the healthy tissue (entire CT-DATA SET minus the PTV). Overall integral dose was 8% higher in the TOMO plans for Patients #1 and #3, but 2% lower in Patient #2. DVH analysis shows that TOMO plans give lower doses to larger volumes and higher doses to smaller volumes of tissue in all three cases. The advantages of the TOMO plans are minimization of matched junctions and better sparing of most OARs. With increased computational and memory power in the tomotherapy planning station, the excess integral dose to the healthy tissue can be re-distributed within the patient and in turn the total integral dose can be same or lower than in conventional delivery. The impact of a small increase in overall integral dose and the associated risks of secondary malignancies are unknown. Long-term follow-up is needed to answer this question.

Comparison of IMRT Treatment Plans Between Linac and Helical Tomotherapy Based on Integral Dose and Inhomogeneity Index

Intensity modulated radiotherapy (IMRT) is an advanced treatment technology for radiation therapy. There are several treatment planning systems (TPS) that can generate IMRT plans. These plans may show different inhomogeneity indices to the planning target volume (PTV) and integral dose to organs at risk (OAR). In this study, we compared clinical cases covering different anatomical treatment sites, including head and neck, brain, lung, prostate, pelvis, and cranio-spinal axis. Two treatment plans were developed for each case using Pinnacle(3) and helical tomotherapy (HT) TPS. The inhomogeneity index of the PTV and the non-tumor integral dose (NTID) were calculated and compared for each case. Despite the difference in the number of effective beams, in several cases, NTID did not increase from HT as compared to the step-and-shoot delivery method. Six helical tomotherapy treatment plans for different treatment sites have been analyzed and compared against corresponding step-and-shoot plans generated with the Pinnacle(3) planning system. Results show that HT may produce plans with smaller integral doses to healthy organs, and fairly homogeneous doses to the target as compared to linac-based step-and-shoot IMRT planning in special treatment site such as cranio-spinal.

Present and Future Technology for Simultaneous Superficial Thermoradiotherapy of Breast Cancer

This paper reviews systems and techniques to deliver simultaneous thermoradiotherapy of breast cancer. It first covers the clinical implementation of simultaneous delivery of superficial (microwave or ultrasound) hyperthermia and external photon beam radiotherapy, first using a Cobalt-60 teletherapy unit and later medical linear accelerators. The parallel development and related studies of the Scanning Ultrasound Reflector Linear Arrays System (SURLAS), an advanced system specifically designed and developed for simultaneous thermoradiotherapy, follows. The performance characteristics of the SURLAS are reviewed and power limitation problems at high acoustic frequencies (>3 MHz) are discussed along with potential solutions. Next, the feasibility of simultaneous SURLAS hyperthermia and intensity modulated radiation therapy/image-guided radiotherapy (IMRT/IGRT) is established based on published and newly presented studies. Finally, based on the encouraging clinical results thus far, it is concluded that new trials employing the latest technologies are warranted along with further developments in treatment planning.

Clinical feasibility of TBI with helical tomotherapy.

Our purpose was to present the clinical feasibility of TBI with helical tomotherapy (HT) in four patients with AML. Treatment planning, delivery, dose verification and summation, toxicity and patient outcomes for each patient are presented. TBI prescription was set in such a manner that 80% of the clinical target volume received 12 Gy in six fractions, at two fractions per day. Dose reconstruction was carried out by recontouring the regions of interest in the daily pretreatment megavoltage computed tomography of each individual fraction and calculating its corresponding dose. A deformable registration model was used for dose summation of all individual fractions. Differences between planned and delivered doses were calculated. Average planned and delivered doses to the regions of interest differed by up to 2.7%. TBI toxicity was limited to radiotherapy oncology group grade 1 dermatitis in all patients and grade 1 headache in one patient. Two patients are alive with no evidence of disease and no GVHD. Two patients died of GVHD, but there was no evidence of disease at the time of death. We conclude that HT simplifies the process of TBI. Dose verification is possible with HT showing small differences between plan and delivered doses.

High dose bystander effects in spatially fractionated radiation therapy

Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments.