Advances in technology for intracranial stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) refers to a single radiation treatment delivering a high dose to an intra-cranial target localized in three-dimensions by CT and/or MRI imaging. Traditionally, immobilization of the patient's head has been achieved using a rigid stereotactic head frame as the key step in allowing for accurate dose delivery. SRS has been delivered by both Cobalt-60 (Gamma Knife) and linear accelerator (linac) technologies for many decades. The focus of this review is to highlight recent advances and major innovations in SRS technologies relevant to clinical practice and developments allowing for non-invasive frame SRS.

Stereotactic radiotherapy in the treatment of juxtapapillary choroidal melanoma: 2-year follow-up.

OBJECTIVE: To evaluate the efficacy and complications of stereotactic radiotherapy in the management of patients with juxtapapillary choroidal melanoma. DESIGN: Retrospective review. PARTICIPANTS: 64 patients with juxtapapillary choroidal melanoma. METHODS: Consecutive patients with juxtapapillary choroidal melanomas located within 2 mm of the optic nerve, treated with stereotactic radiotherapy at Princess Margaret Hospital from October 1998 to January 2006, were reviewed for treatment effect and complication rates. RESULTS: Median age was 63 years. Median tumor height was 4.2 mm, and median maximum tumor diameter was 9.8 mm. The prescribed radiation dose was 70 Gy in 5 fractions over 10 days, and the median follow-up was 26 months. After treatment, there was local tumor recurrence in 3 patients, and in 8 patients there was systemic progression. Actuarial rates of local tumor control, metastases, and survival at 26 months were 94%, 12%, and 94%, respectively. Rates of radiation-induced neovascular glaucoma, cataract, retinopathy, and optic neuropathy at 26 months were 28%, 45%, 80%, and 52%, respectively. Enucleation was necessary for 7 patients. CONCLUSIONS: Stereotactic radiotherapy offers a noninvasive alternative with acceptable ocular toxicity rates to enucleation and brachytherapy in the management of juxtapapillary choroidal melanoma.

EDR2 film dosimetry for IMRT verification using low-energy photon filters.

Recently the EDR2 (extended dose range) film has been introduced commercially for applications in radiation therapy dosimetry. In addition to characterizing the wide dynamic range, several authors have reported a reduced energy dependence of this film compared to that of X-Omatic Verification (XV) films for megavoltage photon beams. However, those investigations were performed under limited geometrical conditions. We have investigated the dosimetric performance of EDR2 film for the verification of IMRT fields at more clinically relevant conditions by comparing the film doses with the doses measured with an ion chamber and XV films. The effects of using a low energy scattered photon filter on EDR2 film dosimetry was also studied. In contrast to previous reports our results show that EDR2 film still exhibits considerable energy dependence (a maximum discrepancy of 9%, compared with an ion chamber) at clinically relevant conditions (10 cm depth for IMRT fields). However, by using the low-energy filters the discrepancy is reduced to within 3%. Therefore, EDR2 film, in combination with the filters, is found to be a promising two-dimensional dosimeter for verification of IMRT treatment fields.

Dosimetric comparison between two MLC systems commonly used for stereotactic radiosurgery and radiotherapy: a Monte Carlo and experimental study.

In this work dosimetric parameters of two multi-leaf collimator (MLC) systems, namely the beam modulator (BM), which is the MLC commercial name for Elekta "Synergy S" linear accelerator and Radionics micro-MLC (MMLC), are compared using measurements and Monte Carlo simulations. Dosimetric parameters, such as percentage depth doses (PDDs), in-plane and cross-plane dose profiles, and penumbras for different depths and field sizes of the 6 MV photon beams were measured using ionization chamber and a water tank. The collimator leakages were measured using radiographic films. MMLC and BM were modeled using the EGSnrc-based BEAMnrc Monte Carlo code and above dosimetric parameters were calculated. The energy fluence spectra for the two MLCs were also determined using the BEAMnrc and BEAMDP. Dosimetric parameters of the two MLCs were similar, except for penumbras. Leaf-side and leaf-end 80-20% dose penumbras at 10 cm depth for a 10×10 cm(2) field size were 4.8 and 5.1mm for MMLC and 5.3 mm and 6.3 mm for BM, respectively. Both Radionics MMLC and Elekta BM can be used effectively based on their dosimetric characteristics for stereotactic radiosurgery and radiotherapy, although the former showed slightly sharper dose penumbra especially in the leaf-end direction.

Dosimetric and late radiation toxicity comparison between iodine-125 brachytherapy and stereotactic radiation therapy for juxtapapillary choroidal melanoma.

PURPOSE: To compare the dose distributions and late radiation toxicities for (125)I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. METHODS: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log-rank test compared the estimates. RESULTS: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. CONCLUSIONS: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

A comparison between ¹²5Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma.

AIMS: To compare the treatment efficacy and radiation complications between (125)Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma. METHODS: Consecutive juxtapapillary melanoma patients treated with radiotherapy were included. Patients were divided into two cohorts: patients treated with (125)Iodine brachytherapy and patients with stereotactic radiotherapy. Comparison included the rates postradiotherapy local recurrence, secondary enucleation, metastasis and radiotherapy complications. Kaplan-Meier estimates were used to determine the actuarial rates, and logrank test to compare between the estimates. RESULTS: We included 94 patients with juxtapapillary melanoma treated with radiotherapy. The brachytherapy cohort included 30 patients and stereotactic radiotherapy was 64. The median follow-up was 46 months in both cohorts. No statistically significant differences existed between the two cohorts on comparing pretreatment clinical data and tumour characteristics. On comparing treatment efficacy, the actuarial rates at 50 months for tumour recurrence were 11% and 7% (p=0.61), secondary enucleation was 11% and 21% (p=0.30) and for metastasis were 4% and 16% (p=0.11), respectively. On comparing treatment complications, the actuarial rates at 50 months for cataracts were 62% and 75% (p=0.1), for neovascular glaucoma 8% and 47% (p=0.002), for radiation retinopathy 59% and 89% (p=0.0001), and for radiation papillopathy 39% and 74% (p=0.003), respectively. CONCLUSIONS: Both (125)Iodine brachytherapy and stereotactic radiotherapy demonstrate comparable efficacy in the management of juxtapapillary choroidal melanoma. However, stereotactic radiotherapy shows statistically significant higher radiation-induced ocular morbidities at 4 years postradiotherapy.

Predicting nonauditory adverse radiation effects following radiosurgery for vestibular schwannoma: a volume and dosimetric analysis.

PURPOSE: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. METHODS: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. RESULTS: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. CONCLUSIONS: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

Neovascular glaucoma after stereotactic radiotherapy for juxtapapillary choroidal melanoma: histopathologic and dosimetric findings.

PURPOSE: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. METHODS AND MATERIALS: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. RESULTS: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. CONCLUSIONS: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

Simultaneous infield boost with helical tomotherapy for patients with 1 to 3 brain metastases.

OBJECTIVE: We sought to model the feasibility of a simultaneous in field boost (SIB) to individual brain metastases during a course of whole brain radiotherapy (WBXRT) using helical tomotherapy (HT) intensity-modulated radiation therapy. PATIENTS AND METHODS: Planning computed tomography data from 14 patients with 1 to 3 brain metastases were used to model an intralesional SIB delivery that yielded a total intralesional dose of 60 Gy with a surrounding whole brain dose of 30 Gy (designed to be isoeffective to WBXRT of 30 Gy with an 18 Gy in 1 fraction radiosurgery boost). Accuracy of treatment of a phantom on the HT unit was measured. Comparisons of HT delivery versus a conventional stereotactic radiotherapy technique for a particularly challenging simulated anatomy were made. RESULTS: In all cases, SIB to 60 Gy with WBXRT to 30 Gy was possible while maintaining critical structures below assigned dose limits. Estimated radiation delivery time for the SIB treatment was approximately 10 minutes per fraction. Planning and treatment of the head phantom was associated with an overall accuracy of 2 mm. Comparison to conventional noncoplanar arc fractionated stereotactic radiotherapy plan demonstrated similar target coverage and improved critical tissue sparing even for a challenging anatomy with multiple lesions in the same plane as the optic apparatus. CONCLUSIONS: Based on this study, use of an image guided SIB using HT seemed feasible and a phase I trial initiated at our institution is described. Potential advantages of this approach include frameless stereotaxis through daily megavoltage computed tomography localization, more efficient use of resources and exploitation of radiobiologic advantages of fractionation.

Fractionated stereotactic radiotherapy for acoustic neuroma: single-institution experience at The Princess Margaret Hospital.

BACKGROUND: The clinical outcome and toxicity of fractionated stereotactic radiotherapy (FSRT) was assessed for acoustic neuroma in 60 patients treated in a single institution. METHODS: Between October 1996 and February 2005, 60 patients received FSRT for acoustic neuroma (AN). The mean total dose applied was 50 Gy in single daily 2-Gy fractions over 5 weeks. The median irradiated tumor volume was 4.9 cm(3) (range, 0.3-49.0 cm(3)). The median follow-up period was 31.9 months. RESULTS: FSRT was well tolerated in all patients. The 5-year actuarial local control rate was 96.2% (95% CI: 91.1%-100.0%). Five-year actuarial progression-free survival was 92.8% (95% CI: 84.8%-100.0%). The overall hearing preservation rate was 77.3%. Five of 6 patients with initial cranial nerve V (CNV) numbness remained stable post-FSRT. Two of 3 patients with baseline trigeminal neuralgia improved with the remaining patient stable. All 3 patients with nonsurgically related facial nerve weakness either improved or achieved stability in function. There were no cases of new cranial nerve toxicity post-FSRT. CONCLUSIONS: FSRT for the treatment of AN is safe, effective, and well tolerated. FSRT should thus be considered as an effective alternative treatment modality when compared with microsurgical resection or single fraction stereotactic radiosurgery.

A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk.

BACKGROUND: Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. METHODS: Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. RESULTS: Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. CONCLUSION: The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment.

Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma.

BACKGROUND: Estimates of radiation-related second cancer risk among Hodgkin lymphoma survivors are largely based on radiation therapy (RT) fields and doses no longer in use, and these estimates do not account for differences in normal tissue dose among individual patients. This study gives individualized estimates for the risks of lung and female breast cancer expected with contemporary involved-field RT and low-dose (20 Gy) RT for mediastinal Hodgkin lymphoma. METHODS: Three RT plans were constructed for 37 consecutive patients with mediastinal Hodgkin lymphoma: 35 Gy mantle RT, 35 Gy involved-field RT (IFRT), and 20 Gy IFRT. For each of the 111 RT plans, individual-level dosimetry data were incorporated into a cell initiation/inactivation/proliferation model to estimate the excess relative risk (ERR) and cumulative incidence of radiation-induced second cancer. RESULTS: ERR estimates were compatible with results of epidemiological studies. Compared with 35 Gy mantle radiation therapy, 35 Gy IFRT was predicted to reduce the 20-year ERRs of breast and lung cancer by 63% and 21%, respectively, primarily because of lower normal tissue doses with the omission of axillary RT. Low-dose (20 Gy) IFRT was associated with a 77% and 57% decrease in these ERRs. Patient-specific differences in normal tissue dose with IFRT led to 11-fold and 3.6-fold variations among individual's estimates of breast and lung cancer ERR, respectively. CONCLUSIONS: Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient-specific counseling and the development of more effective RT techniques.