Novel unconventional radiotherapy techniques: Current status and future perspectives - Report from the 2nd international radiation oncology online seminar.

•Improvement of therapeutic ratio by novel unconventional radiotherapy approaches.•Immunomodulation using high-dose spatially fractionated radiotherapy.•Boosting radiation anti-tumor effects by adding an immune-mediated cell killing.

Virtual bronchoscopy-guided lung SAbR: dosimetric implications of using AAA versus Acuros XB to calculate dose in airways.

In previous works, we showed that incorporating individual airways as organs-at-risk (OARs) in the treatment of lung stereotactic ablative radiotherapy (SAbR) patients potentially mitigates post-SAbR radiation injury. However, the performance of common clinical dose calculation algorithms in airways has not been thoroughly studied. Airways are of particular concern because their small size and the density differences they create have the potential to hinder dose calculation accuracy. To address this gap in knowledge, here we investigate dosimetric accuracy in airways of two commonly used dose calculation algorithms, the anisotropic analytical algorithm (AAA) and Acuros-XB (AXB), recreating clinical treatment plans on a cohort of four SAbR patients. A virtual bronchoscopy software was used to delineate 856 airways on a high-resolution breath-hold CT (BHCT) image acquired for each patient. The planning target volumes (PTVs) and standard thoracic OARs were contoured on an average CT (AVG) image over the breathing cycle. Conformal and intensity-modulated radiation therapy plans were recreated on the BHCT image and on the AVG image, for a total of four plan types per patient. Dose calculations were performed using AAA and AXB, and the differences in maximum and mean dose in each structure were calculated. The median differences in maximum dose among all airways were ≤0.3Gy in magnitude for all four plan types. With airways grouped by dose-to-structure or diameter, median dose differences were still ≤0.5Gy in magnitude, with no clear dependence on airway size. These results, along with our previous airway radiosensitivity works, suggest that dose differences between AAA and AXB correspond to an airway collapse variation ≤0.7% in magnitude. This variation in airway injury risk can be considered as not clinically relevant, and the use of either AAA or AXB is therefore appropriate when including patient airways as individual OARs so as to reduce risk of radiation-induced lung toxicity.

Tissue-specific features of microglial innate immune responses.

As tissue-resident macrophages of the brain, microglia are increasingly considered as cellular targets for therapeutical intervention. Innate immune responses in particular have been implicated in central nervous system (CNS) infections, neuro-oncology, neuroinflammatory and neurodegenerative diseases. We here review the impact of 'nature and nurture' on microglial innate immune responses and summarize documented tissue-specific adaptations. Overall, such adaptations are associated with regulatory processes rather than with overt differences in the expressed repertoire of activating receptors of different tissue-resident macrophages. Microglial responses are characterized by slower kinetics, by a more persistent nature and by a differential usage of downstream enzymes and accessory receptors. We further consider factors like aging, previous exposure to inflammatory stimuli, and differences in the microenvironment that can modulate innate immune responses. The long-life span of microglia in the metabolically active CNS renders them susceptible to the phenomenon of 'inflammaging', and major challenges lie in the unraveling of the factors that underlie age-related alterations in microglial behavior.

Functionally weighted airway sparing (FWAS): a functional avoidance method for preserving post-treatment ventilation in lung radiotherapy.

Recent changes to the guidelines for screening and early diagnosis of lung cancer have increased the interest in preserving post-radiotherapy lung function. Current investigational approaches are based on spatially mapping functional regions and generating regional avoidance plans that preferentially spare highly ventilated/perfused lung. A potentially critical, yet overlooked, aspect of functional avoidance is radiation injury to peripheral airways, which serve as gas conduits to and from functional lung regions. Dose redistribution based solely on regional function may cause irreparable damage to the 'supply chain'. To address this deficiency, we propose the functionally weighted airway sparing (FWAS) method. FWAS (i) maps the bronchial pathways to each functional sub-lobar lung volume; (ii) assigns a weighting factor to each airway based on the relative contribution of the sub-volume to overall lung function; and (iii) creates a treatment plan that aims to preserve these functional pathways. To evaluate it, we used four cases from a retrospective cohort of SAbR patients treated for lung cancer. Each patient's airways were auto-segmented from a diagnostic-quality breath-hold CT using a research virtual bronchoscopy software. A ventilation map was generated from the planning 4DCT to map regional lung function. For each terminal airway, as resolved by the segmentation software, the total ventilation within the sub-lobar volume supported by that airway was estimated and used as a function-based weighting factor. Upstream airways were weighted based on the cumulative volumetric ventilation supported by corresponding downstream airways. Using a previously developed model for airway radiosensitivity, dose constraints were determined for each airway corresponding to a <5% probability of airway collapse. Airway dose constraints, ventilation scores, and clinical dose constraints were input to a swarm optimization-based inverse planning engine to create a 3D conformal SAbR plan (CRT). The FWAS plans were compared to the patients' prescribed CRT clinical plans and the inverse-optimized clinical plans. Depending on the size and location of the tumour, the FWAS plan showed superior preservation of ventilation due to airflow preservation through open pathways (i.e. cumulative ventilation score from the sub-lobar volumes of open pathways). Improvements ranged between 3% and 23%, when comparing to the prescribed clinical plans, and between 3% and 35%, when comparing to the inverse-optimized clinical plans. The three plans satisfied clinical requirements for PTV coverage and OAR dose constraints. These initial results suggest that by sparing pathways to high-functioning lung subregions it is possible to reduce post-SAbR loss of respiratory function.

Inverse 4D conformal planning for lung SBRT using particle swarm optimization.

A critical aspect of highly potent regimens such as lung stereotactic body radiation therapy (SBRT) is to avoid collateral toxicity while achieving planning target volume (PTV) coverage. In this work, we describe four dimensional conformal radiotherapy using a highly parallelizable swarm intelligence-based stochastic optimization technique. Conventional lung CRT-SBRT uses a 4DCT to create an internal target volume and then, using forward-planning, generates a 3D conformal plan. In contrast, we investigate an inverse-planning strategy that uses 4DCT data to create a 4D conformal plan, which is optimized across the three spatial dimensions (3D) as well as time, as represented by the respiratory phase. The key idea is to use respiratory motion as an additional degree of freedom. We iteratively adjust fluence weights for all beam apertures across all respiratory phases considering OAR sparing, PTV coverage and delivery efficiency. To demonstrate proof-of-concept, five non-small-cell lung cancer SBRT patients were retrospectively studied. The 4D optimized plans achieved PTV coverage comparable to the corresponding clinically delivered plans while showing significantly superior OAR sparing ranging from 26% to 83% for D max heart, 10%-41% for D max esophagus, 31%-68% for D max spinal cord and 7%-32% for V 13 lung.

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk.

The clinical applications of stereotactic body radiotherapy or stereotactic ablative radiotherapy (SABR) for the treatment of primary and metastatic tumours of different organ sites have been expanding rapidly in the recent decade. SABR requires advanced technology in radiotherapy planning and image guidance to deliver a highly conformal ablative dose precisely to targets (or tumours) in the body. Although this treatment modality has shown promising results with regard to tumour control, some serious complications have been observed and reported. In order to achieve a favourable therapeutic ratio, strategies to mitigate the risk of complications must be in place. This overview will summarise the reported serious complications caused by SABR and strategies to mitigate the risk will be discussed.

SU-E-T-451: Optimization of Normalized Prescription Isodose Selection for Stereotactic Radiation Therapy: Conventional Vs. Robotic Linac.

PURPOSE: To determine the optimal prescription isodose line that minimizes normal tissue irradiation for stereotactic radiation therapy comparing conventional linear accelerator and robotic delivery. METHODS: A computer based digital torso phantom which has the capability to simulate respiratory and cardiac motion were used in this study. Spherical targets were constructed in lung and liver, with diameter of 20mm, 30mm, and 40mm. Two concentric 5mm shells, from the target surface extending 5mm radially and from 5mm to 10mm, were identified/contoured. Non-coplanar, non- opposing 3D conformal beams were designed for linac planning. Variable prescription isodose lines were achieved by varying the block margin. 4D dose calculation was used for moving target and surrounding tissue. After linac planning, the CT images and contours were transferred for Cyberknife® planning. Variable prescription isodose lines were achieved by inverse planning technique. Doses of 60Gy in 3 fractions were prescribed to cover exactly 95% of target tumor with each technology. gEUD (generalized effective uniform dose) with different formulations for parallel and serial tissues was used for comparison between different plans. RESULTS: For linac plans, the optimal prescription isodose line yielding maximum normal tissue sparing occurs between 50% and 70% for the lung tumor and 60% and 90% for liver tumor. The gEUD difference between plans with optimum and arbitrarily chosen prescription isodose line may be up to 20% of prescription dose. For Cyberknife plans, the optimal prescription isodose line is approximately 50% for tissues displaying either parallel or serial behavior. These results are similar for different tumor sizes. CONCLUSIONS: Both conventional linac and Cyberknife® delivery can provide conformal tumor coverage with normal tissue sparing. By carefully choosing the optimal prescription isodose line, the gEUD of the surrounding normal tissue can be reduced by up to 20% of prescription dose.

SU-E-T-190: Design, Development, and Evaluation of a Modified, Anthropomorphic, Head, Quality Assurance Phantom for Use in Stereotactic Radiosurgery.

PURPOSE: To develop and evaluate a modified anthropomorphic head phantom for evaluation of stereotactic radiosurgery (SRS) dose planning and delivery. METHODS: A phantom was constructed from a water equivalent, plastic, head-shaped shell. The original phantom design, with only a spherical target, was modified to include a nonspherical target (pituitary) and an adjacent organ at risk (OAR) (optic chiasm), within 2 mm, simulating the anatomy encountered when treating acromegaly. The target and OAR spatial proximity provided a more realistic treatment planning and dose delivery exercise. A separate dosimetry insert contained two TLD for absolute dosimetry and radiochromic film, in the sagittal and coronal planes, for relative dosimetry. The prescription was 25Gy to 90% of the GTV with >= 10% of the OAR volume receiving >= 8Gy. The modified phantom was used to test the rigor of the treatment planning process, dosimeter reproducibility, and measured dose delivery agreement with calculated doses using a Gamma Knife, CyberKnife, and linear accelerator based radiosurgery systems. RESULTS: TLD results from multiple irradiations using either a CyberKnife or Gamma Knife agreed with the calculated target dose to within 4.7% with a maximum coefficient of variation of+/-2.0%. Gamma analysis in the coronal and sagittal film planes showed an average passing rate of 99.3% and 99.5% using +/-5%/3mm criteria, respectively. A treatment plan for linac delivery was developed meeting the prescription guidelines. Dosimeter reproducibility and dose delivery agreement for the linac is expected to have results similar to the results observed with the CyberKnife and Gamma Knife. CONCLUSIONS: A modified anatomically realistic SRS phantom was developed that provided a realistic clinical planning and delivery challenge that can be used to credential institutions wanting to participate in NCI funded clinical trials. Work supported by PHS CA010953, CA081647, CA21661 awarded by NCI. DHHS.

Pulmonary hilar stereotactic body radiation therapy in the rat.

Stereotactic Body Radiation therapy (SBRT) is an emerging modality of treatment for early stage non-small cell lung carcinoma. Concerns have arisen related to increased toxicities for medial tumors. We have developed a model of high dose, hypofractionated radiotherapy to the pulmonary hilum using the Leksell Gamma-Knife. Sprague-Dawley rats received hypofractionated SBRT to the unilateral lung hilum using a custom immobilization device on the Gamma Knife. Each animal was individually scanned, treatment planned, and treated with either two 4 mm or one 8 mm collimated shots at escalating doses of 20, 40, and 80 Gy to the 50% isodose volume, encompassing the right mainstem bronchus. All animals were carefully followed post-treatment and imaged by plain film and CT. In addition, histopathological analysis of all rats was performed at selected time points. Animals treated with 4 mm collimated shots demonstrated no appreciable changes on plain films or sequential, follow-up CT scans, or histopathologically. Animals irradiated with the 8 mm collimator were less active, gained weight at a reduced rate, and demonstrated histopathological changes in 7/34 animals six months post-irradiation. Cellular atypia and interstitial pneumonitis were found, three of the seven of the animals showed clear bronchial damage and two showed vascular damage. Significant volume and time effects were found. Utilizing a novel Gamma Knife based animal model to study SBRT toxicity, it was found that the bronchus will tolerate small volumes of very high dose radiotherapy. It was postulated that radiation of the surrounding support stroma and normal tissue are important in the etiology of bronchial or hilar damage.

Children and young adults in a prolonged unconscious state after severe brain injury: long-term functional outcome as measured by the DRS and the GOSE after early intensive neurorehabilitation.

OBJECTIVE: To investigate the long-term (2-15 years) functional outcome of children and young adults who received an early intensive neurorehabilitation programme (EINP) after a prolonged period of unconsciousness due to severe brain injury; to differentiate between traumatic brain injury (TBI) and non-traumatic brain injury (nTBI); and to compare the results on two different outcome scales: the Disability Rating Scale (DRS) and the Glasgow Outcome Scale Extended (GOSE). SUBJECTS: One hundred and forty-five patients, who were admitted to EINP between December 1987 and January 2001. OUTCOME MEASURES: The Post-Acute Level of Consciousness scale (PALOC-s), the DRS, including categorized scores (DRScat), and the GOSE. RESULTS: The long-term functional level of 90 patients could be determined, of whom 25 were deceased. The mean DRS-score of the surviving patients was 6.8 (SD = 6.6); the mean score on the GOSE was 4.5 (SD = 1.7). There was a significant difference in the outcome amongst traumatic and non-traumatic patients (t88 = 4.21; p < 0.01). The correlation between the DRS and the GOSE was high (Spearman rho = 0.85; p < 0.01), as well as the correlation between the categorized scores of the DRS and the GOSE (Spearman rho = 0.81; p < 0.01). The distribution of outcome scores on the DRScat is more diverse than on the GOSE. Especially item 7 of the DRS, measuring functional independence, showed considerable variance in discriminating between different outcome levels. CONCLUSIONS: More patients with TBI than expected reached a (semi-) independent level of functioning, indicating a possible effect of EINP. Patients suffering from nTBI did not demonstrate these outcome levels. Only a few patients stayed in a vegetative state for more than a couple of years. In this cohort of severe brain-injured young people, the DRS offered the best investigative possibilities for long-term level of functioning.

Which MR imaging sequences are necessary in determining the need for radiation therapy for cord compression? A prospective study.

BACKGROUND AND PURPOSE: To determine which MR imaging sequences are necessary to assess for spinal metastases. METHODS: Hypothetical MR imaging interpretations and management plans were made prospectively for consecutive adult cases acquired retrospectively. Standardized MR imaging protocols were independently interpreted by 2 neuroradiologists. MR imaging protocol types varied: 1) T1-weighted images only; 2) T1-weighted and T2-weighted images; 3) T1-weighted and postcontrast T1-weighted images; and 4) T1- and T2-weighted images and postcontrast T1-weighted images. Hypothetical management plans were created by 2 radiation oncologists. Logit model was used to investigate the effect of MR imaging protocol type on the probability of recommending radiation therapy (RT). Mixed effect models were used to investigate whether median spinal level or total number of spinal levels of planned RT was associated with MR imaging protocol type. RESULTS: Thirty-one subjects were evaluated, each with multiple scan interpretations. Logit model showed that neither MR imaging protocol type nor neuroradiologist reader affected the probability that the oncologist would recommend RT (all P > .50). Mixed models showed that neither ML nor NL was affected by MR imaging protocol type or by neuroradiologist reader (all P > .12). CONCLUSION: Although MR imaging is known to be the most useful diagnostic test in suspected spinal cord compression, which particular MR images are necessary remain unclear. Compared with T1-weighted images alone, the additional use of T2-weighted and/or postcontrast T1-weighted sequences did not significantly affect the probability that RT would be recommended or the levels that would be chosen for RT in our study. Our data suggest that unenhanced T1-weighted images may be sufficient for evaluation of possible cord compression.

Bench- and pilot-scale sludge electrodewatering in a diaphragm filter press.

Electrodewatering is a technique in which pressure dewatering is combined with electrokinetic effects to realize an improved solid/liquid separation and hence increased filter cake dry matter contents. In order to be energy efficient, it is shown that sludge should be dewatered by pressure dewatering to a high extent prior to electric field application, and a sufficient contact time for the electric field must be guaranteed. In order to realize these goals, a bench- and pilot-scale diaphragm filter press suited for electrodewatering were constructed for treatment of sewage and other types of sludges. It was shown that electrodewatering of sludge is a feasible technique, especially for biological sludge types. Other types of sludge are less suited for electrodewatering because of the restricted improvements that can be realized in cake dry matter content and the high electric energy consumption. Furthermore, it was shown in pilot-scale tests that the use of a diaphragm filter press with electrodewatering facilities was very well suited to deliver dry filter cakes of sewage sludge at a moderate energy consumption. Depending on local market prices for investment, operating and sludge disposal costs, this technology may therefore lead to important savings in the sludge management process.

An eight-year follow-up to a randomized clinical trial of participant satisfaction with three types of mandibular implant-retained overdentures.

Studies have shown that mandibular implant overdentures significantly increase satisfaction and quality of life of edentulous elders. Improved chewing ability appears to have a positive impact on nutritional state. Therefore, it is important to determine the best design of this prosthesis over the long term. In this randomized controlled trial, three groups of edentulous participants with atrophic mandibles wore 3 types of implant overdentures. During an eight-year follow-up, only seven of the 110 participants had dropped out of this study. Almost all participants were still satisfied with their overdentures. Participant satisfaction concerning retention and stability of the mandibular overdenture had decreased significantly in the two-implant ball attachment group, whereas the opinion of participants in the single- and triple-bar groups was still at the same level. The long-term results suggest that a mandibular overdenture retained by 2 implants with a single bar may be the best treatment strategy for edentulous people with atrophic ridges.

Quantitative analysis of three-dimensional conformal radiotherapy techniques for posterior fossa treatment in children.

Numerous beam directions using 3-D conformal techniques can be employed in treating tumors in the posterior fossa, each with characteristic normal tissue exposure along the entrance and exit trajectory. A representative variety of beam configurations were modeled in a modern computer planning system initially with the entire posterior fossa as the target. These beams were quantitatively scored using criteria based on integral doses for both low dose and high dose effects encompassing a variety of critical normal structures, thus identifying strengths and weaknesses of each beam. By blocking portions of a particular beam accounting for unfavorable scores, a map of "zones" within the posterior fossa ideally treated by a certain beam or beams could be constructed. No universally ideal photon beam arrangement for the entire posterior fossa target could be identified. However, using single beam analysis, the strengths and weaknesses of particular strategies could be quantified. For example, vertex beams treating the cerebellar hemispheres allow the greatest sparing of cochlea and hypothalamus but at the cost of increased low to moderate dose to the supratentorial brain. Using the constructed maps identifying "zones" appropriately treated by a given beam or beams, three-dimensional conformal treatment plans with favorable dose-volume statistics can be designed based on previously defined normal tissue tolerance considerations. It is shown how this approach can be individualized based on specific patient characteristics (e.g., age). We conclude that radiotherapy directed to the posterior fossa can be optimized based on systematic assessment of individual beam contributions to normal tissues. This technique allows fast selection of treatment beams based on known normal tissue anatomical and tolerance information. Further studies will be required regarding long term effects of various radiation doses on specific volumes of normal tissue in order to individualize beam selection. When treating children, knowledgeable consideration of these beam characteristics can help avoid late effects.

Contamination dose from photoneutron processes in bodily tissues during therapeutic radiation delivery.

Dose to the total body from induced radiation resulting from primary exposure to radiotherapeutic beams is not detailed in routine treatment planning though this information is potentially important for better estimates of health risks including secondary cancers. This information can also allow better management of patient treatment logistics, suggesting better timing, sequencing, and conduct of treatment. Monte Carlo simulations capable of taking into account all interactions contributing to the dose to the total body, including neutron scattering and induced radioactivity, provide the most versatile and accurate tool for investigating these effects. MCNPX code version 2.2.6 with full IAEA library of photoneutron cross sections is particularly suited to trace not only photoneutrons but also protons and heavy ion particles that result from photoneutron interactions. Specifically, the MCNPX code is applied here to the problem of dose calculations in traditional (non-IMRT) photon beam therapy. Points of calculation are located in the head, where the primary irradiation has been directed, but also in the superior portion of the torso of the ORNL Mathematical Human Phantom. We calculated dose contributions from neutrons, protons, deutrons, tritons and He-3 that are produced at the time of photoneutron interactions in the body and that would not have been accounted for by conventional radiation oncology dosimetry.

Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival.

BACKGROUND: As screening central nervous system (CNS) imaging is not routinely performed, the incidence and clinical relevance of occult CNS metastases in advanced breast cancer is unknown. PATIENTS AND METHODS: All patients screened for participation in one of four clinical trials were included; each of the trials excluded patients with known CNS involvement and required screening CNS imaging. A cohort of breast cancer patients with symptomatic CNS metastases was identified from the IU Cancer Center Tumor Registry for comparison. RESULTS: From November 1998 to August 2001, 155 screening imaging studies were performed. Twenty-three patients (14.8%) had occult CNS metastases. HER-2 overexpression (P = 0.02) and number of metastatic sites (P = 0.03) were predictive of CNS involvement by multivariate analysis. Median survival from time of metastasis (1.78 versus 2.76 years; P <0.0001) and from screening (4.67 versus 10.4 months; P = 0.0013) was shorter in patients with than without occult CNS metastasis. Survival among patients with occult CNS metastasis was similar to patients with symptomatic CNS disease. CONCLUSIONS: Patients with CNS involvement, whether occult or symptomatic, have an impaired survival. Occult CNS metastasis is relatively common, but impact on survival of treating occult CNS disease in patients with progressive systemic metastases is questionable.

How should we describe the radioblologic effect of extracranial stereotactic radlosurgery: equivalent uniform dose or tumor control probability?

Extracranial stereotactic radiosurgery (ESR) is now undergoing clinical investigation at numerous institutions as a treatment for solitary malignant lesions. Because there is no standard ESR technique, the same minimum dose might be applied through widely variable target dose-volume histograms. For multicenter trials of ESR or interinstitutional comparisons, a reliable index of radiobiological dose equivalency might facilitate the evaluation of dose-response relationships. Equivalent uniform dose (EUD) and tumor control probability (TCP) were considered for this application. While EUD appears more robust for the prospective description of ESR, TCP is expected to remain more valuable for a post hoc estimation of radiosensitivity parameters.

Radioablación estereotáctica extracraneal. Revisión de las bases biológicas, técnica y experiencia clínica preliminar / Extracranial stereotactic radioablation. Review of biological basis, technique and preliminary clinical experience

La radioablación estereotáctica extracraneal es una nueva y estimulante modalidad de tratamiento en la que se administran dosis grandes hipofraccionadas de irradiación a los tumores extracraneales. En el presente artículo revisamos brevemente el razonamiento, las implicaciones biológicas del hipofraccionamiento “extremo” la técnica de tratamiento y los datos publicados. Además se presentarán los datos de un ensayo clínico fase I en pacientes con cáncer de pulmón de células no pequeñas (NSCLC) inoperable, estadio clínico I, realizado en la Indiana University (AU)

Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases.

PURPOSE: Motexafin gadolinium is a magnetic resonance imaging (MRI)--detectable redox active drug that localizes selectively in tumor cells and enhances the effect of radiation therapy. This phase Ib/II trial of motexafin gadolinium, administered concurrently with 30 Gy in 10 fractions whole-brain radiation therapy (WBRT), was conducted to determine maximum-tolerated dose (MTD), dose-limiting toxicity, pharmacokinetics, and biolocalization in patients with brain metastases. Additional endpoints were radiologic response rate and survival. PATIENTS AND METHODS: Motexafin gadolinium was administered before each radiation treatment in this open-label, multicenter, international trial. In phase Ib, drug dose was escalated until the MTD was exceeded. In phase II, drug was evaluated in a narrow dose range. RESULTS: In phase Ib, the motexafin gadolinium dose was escalated in 39 patients (0.3 mg/kg to 8.4 mg/kg). In phase II, 22 patients received 5 mg/kg to 6.3 mg/kg motexafin gadolinium. Ten once-daily treatments were well tolerated. The MTD was 6.3 mg/kg, with dose-limiting reversible liver toxicity. Motexafin gadolinium's tumor selectivity was established using MRI. The radiologic response rate was 72% in phase II. Median survival was 4.7 months for all patients, 5.4 months for recursive partitioning analysis (RPA) class 2 patients, and 3.8 months for RPA class 3 patients. One-year actuarial survival for all patients was 25%. CONCLUSION: Motexafin gadolinium was well tolerated at doses up to 6.3 mg/kg, was selectively accumulated in tumors, and, when combined with WBRT of 30 Gy in 10 fractions, was associated with a high radiologic response rate.

Preliminary experience in the treatment of choroidal melanoma with gamma knife radiosurgery.

OBJECT: The authors report their early results from an ongoing experience treating patients with choroidal melanoma by using gamma knife radiosurgery (GKS). METHODS: Between September 1998 and March 2000, 11 patients were treated for choroidal melanoma. Treatment was facilitated with specialized frame placement. Eye immobilization was accomplished with supra- and infraorbital nerve block and tethering sutures to the periorbital tissue. Magnetic resonance imaging was performed to localize the tumor for treatment planning. Plugging patterns were used to steer fall-off radiation away from the fovea, optic nerve, or lens. Tumor volume, tumor location relative to critical structures, and dose to critical structures were determined using GammaPlan. Tumor response was determined using ultrasonography. Toxicity was determined by clinical assessment, visual acuity testing, and ophthalmoscopy. All 11 patients successfully completed the treatment. In every case, 40 Gy was prescribed to the 50% isodose, which completely encompassed all visible tumor. Tumor height ranged from 2.9 to 7 mm. The tumor diameter ranged from 6 to 13 mm. The range of follow up was 2 to 19 months. No tumor has progressed. One patient had improvement in vision because of improvement in retinal detachment. Two patients experienced visual decline. One patient's visual decline was due to a vitreous hemorrhage, and the other's was due to hard exudates encroaching on the macula. One patient has developed a dry eye that is managed effectively with topical eye lubricants. CONCLUSIONS: This preliminary experience demonstrates that GKS is a feasible treatment option for small- to medium-sized choroidal melanomas. Longer follow up and additional patients will be required to improve the assessment and the ultimate tumor control and toxicity in this ongoing series.