Evaluation of the peripheral dose in stereotactic radiotherapy and radiosurgery treatments.

PURPOSE: The main purpose of this work was to compare peripheral doses absorbed during stereotactic treatment of a brain lesion delivered using different devices. These data were used to estimate the risk of stochastic effects. METHODS: Treatment plans were created for an anthropomorphic phantom and delivered using a LINAC with stereotactic cones and a multileaf collimator, a CyberKnife system (before and after a supplemental shielding was applied), a TomoTherapy system, and a Gamma Knife unit. For each treatment, 5 Gy were prescribed to the target. Measurements were performed with thermoluminescent dosimeters inserted roughly in the position of the thyroid, sternum, upper lung, lower lung, and gonads. RESULTS: Mean doses ranged from of 4.1 (Gamma Knife) to 62.8 mGy (LINAC with cones) in the thyroid, from 2.3 (TomoTherapy) to 30 mGy (preshielding CyberKnife) in the sternum, from 1.7 (TomoTherapy) to 20 mGy (preshielding CyberKnife) in the upper part of the lungs, from 0.98 (Gamma Knife) to 15 mGy (preshielding CyberKnife) in the lower part of the lungs, and between 0.3 (Gamma Knife) and 10 mGy (preshielding CyberKnife) in the gonads. CONCLUSIONS: The peripheral dose absorbed in the sites of interest with a 5 Gy fraction is low. Although the risk of adverse side effects calculated for 20 Gy delivered in 5 Gy fractions is negligible, in the interest of optimum patient radioprotection, further studies are needed to determine the weight of each contributor to the peripheral dose.

Image-guided robotic radiosurgery as salvage therapy for locally recurrent prostate cancer after external beam irradiation: retrospective feasibility study on six cases.

AIMS AND BACKGROUND: Technological advances in treatment planning and execution are providing new potential opportunities in the treatment of recurrent prostate cancer. This study was conducted to evaluate the feasibility and safety of reirradiation with image-guided radiosurgery using CyberKnife, a robotic arm-driven compact linear accelerator, for intraprostatic recurrence after external beam radiotherapy (EBRT). METHODS: Between September 2007 and May 2008, 6 patients diagnosed with locally recurrent prostate cancer after EBRT were treated using the CyberKnife system. The total reirradiation dose was 30 Gy in five fractions. Prior to radiosurgery four patients were treated with androgen-deprivation therapy. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and the Houston-Phoenix definition (PSA nadir + 2 ng/mL) were used for toxicity and biochemical failure evaluation, respectively. RESULTS: After a median follow-up of 11.2 months (range, 9.6-18.6 months), all patients are alive with no evidence of severe urinary or rectal acute morbidity. Local control cannot be exactly determined due to the short follow-up and the bias of the use of androgen ablation. Four patients had biochemical failure, three of them with clinical failure evidence (lymph node, bone and lung metastasis, respectively): none of these patients had clinical evidence of tumor persistence in the prostate. CONCLUSIONS: Salvage radiosurgery with CyberKnife after irradiation is feasible with low urinary and rectal morbidity. A longer follow-up and a larger number of patients are necessary to evaluate its effectiveness and optimal patient selection criteria.

Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study.

BACKGROUND: Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics. METHODS: Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors. RESULTS: The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm3, and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm3 were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4-2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ2 = 5.02, p = 0.019; low vs. high: log-rank test, χ2 = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis. CONCLUSIONS: The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.

Paragangliomas of head and neck: a treatment option with CyberKnife radiosurgery.

Paragangliomas are highly vascular and predominantly benign neoplasms that have traditionally been treated by surgery, embolization and/or external beam radiotherapy (EBRT). The aim of this study is to evaluate the short-term local tumor control and safety of CyberKnife radiosurgery for these lesions. Nine patients, eight with jugular glomus paragangliomas and one with a carotid body paraganglioma, were treated. The target contouring was performed on merged CT and MR images. Eight patients were treated with doses ranging from 11 to 13 Gy (mean 12.5 Gy) in a single fraction and one with 24 Gy in three fractions prescribed to 72-83% isodose line. The mean follow-up was 20 months. One patient died from unrelated causes. There were no local recurrences. All eight patients also demonstrated neurological stability or improvement. Neither cranial nerve palsies have arisen, nor has deterioration beyond baseline been observed. In conclusion, CyberKnife radiosurgery appears to be both safe and effective in the treatment of skull base paragangliomas. Determining whether long-term complications will arise will require further investigation.

Cyberknife Radiosurgery for Trigeminal Neuralgia.

Introduction Image-guided robotic radiosurgery is an emerging minimally-invasive treatment option for trigeminal neuralgia (TN). Our group has treated 560 cases up to date, and report here the clinical outcomes of 387 treatments with three years follow-up. This study represents the largest single-center experience on CyberKnife radiosurgery for the treatment of TN so far reported. Methods CyberKnife radiosurgery treatment was offered to patients with drug-resistant TN, after the failure of other treatments or refusal of invasive procedures. A second treatment was offered to patients with a poor response after the first treatment or with recurrent pain. Treatment protocol required the non-isocentric delivery of 60 Gy prescribed to the 80% isodose to a 6 mm retrogasserian segment of the affected trigeminal nerve. Retreatments typically received 45 Gy, again prescribed to the 80% isodose. The final plan was developed accordingly to individual anatomy and dose distribution over the trigeminal nerve, gasserian ganglion, and brainstem. Clinical outcomes such as pain control and hypoesthesia/numbness have been evaluated after 6, 12, 24, and 36 months.  Results Our group has treated 527 patients with Cyberknife radiosurgery at Centro Diagnostico Italiano (CDI), Milan, Italy, during the last decade. A minimum follow-up of six months was available on 496 patients. These patients received 560 treatments: 435 patients (87.7%) had a single treatment, 60 patients (12.1%) had two treatments, and one patient (0.2%) had five treatments (two on the right side, three on the left side). Twenty four patients had multiple sclerosis (4.8%). Four hundred and forty-three patients (84%) received the treatment without previous procedures, while 84 patients (16%) underwent radiosurgery after the failure of other treatments. A neurovascular conflict was identified in 59% of the patients. Three hundred and forty-three patients (receiving a total of 387 treatments) had a minimum of 36 months follow up. Pain relief rate at 6, 12, 18, 24, 30 and 36 months was respectively 92, 87, 87, 82, 78 and 76%. Forty-four patients out of 343 (12.8%) required a second treatment during the observed period. At 36 months post-treatment, 21 patients (6,1%) reported the presence of bothering facial hypoesthesia. Eighteen patients out of 21 (85.7%) developed this complication after a repeated treatment.  Conclusions Frameless image-guided robotic radiosurgery in experienced hands is a safe and effective procedure for the treatment of TN, providing excellent pain control rates in the absence of major neurological complications. Repeated treatments due to recurrent pain are associated with restored pain control but at the price of a higher rate of sensory complications.

Localization accuracy of robotic radiosurgery in 1-view tracking.

PURPOSE: When a lung lesion is detected by only one couple of X-ray tube and image detector integrated with CyberKnife®, the fiducial-less tracking is limited to 1-view (34% of lung treatments at Centro Diagnostico Italiano). The aim of the study was mainly to determine the margin needed to take into account the localization uncertainty along the blind view (out-of-plane direction). METHODS: 36 patients treated in 2-view tracking modality (127 fractions in total) were included in the study. The actual tumor positions were determined retrospectively through logfile analysis and were projected onto 2D image planes. In the same plots the planned target positions based on biphasic breath-hold CT scans were represented preserving the metric with respect to the imaging center. The internal margin necessary to cover in out-of-plane direction the 95% of the target position distribution in the 95% of cases was calculated by home-made software in Matlab®. A validation test was preliminarily performed using XLT Phantom (CIRS) both in 2-view and 1-view scenarios. RESULTS: The validation test proved the reliability of the method, in spite of some intrinsic limitations. Margins were estimated equal to 5 and 6 mm for targets in upper and lower lobe respectively. Biphasic breath-hold CT led to underestimate the target movement in the hypothetical out-of-plane direction. The inter-fractional variability of spine-target distance was an important source of uncertainty for 1-view treatments. CONCLUSION: This graphic comparison method preserving metric could be employed in the clinical workflow of 1-view treatments to get patient-related information for customized margin definition.

Image-Guided Robotic Radiosurgery for Trigeminal Neuralgia.

BACKGROUND: Frameless, non-isocentric irradiation of an extended segment of the trigeminal nerve introduces new concepts in stereotactic radiosurgery for medically resistant trigeminal neuralgia (TN). OBJECTIVE: To report the results of the largest single-center experience about image-guided robotic radiosurgery for TN. METHODS: A cohort of 138 patients treated with CyberKnife® (Accuray Incorporated, Sunnyvale, California) radiosurgery with a minimum follow-up of 36 mo were recruited. Pain relief, medications, sensory disturbances, rate and time of pain recurrence were prospectively analyzed. RESULTS: Median follow-up was 52.4 mo; median dose 75 Gy; median target length 5.7-mm; median target volume 40 mm³; median prescription dose 60 Gy (80% isodose line). Actuarial pain control rate (Barrow Neurological Institute [BNI] class I-IIIa) at 6, 12, 24, and 36 mo were 93.5%, 85.8%, 79.7%, and 76%, respectively. Overall, 33 patients (24%) required a second treatment. Overall, 18.1% developed sensory disturbances after 16.4 ± 8.7 mo. One patient (0.7%) developed BNI grade IV dysfunction; 6 (4.3%) developed BNI grade III (somewhat bothersome) hypoesthesia after retreatment; BNI grade II (not bothersome) hypoesthesia was reported by 18 patients (11 after retreatment). Shorter nerve length (<6 mm vs 6 mm), smaller nerve volume (<30 mm3 vs >30 mm3), and lower prescription dose (<58 vs >58 Gy) were associated with treatment failure (P = .01, P = .02, P = .03, respectively). Re-irradiation independently predicted sensory disturbance (P < .001). CONCLUSION: Targeting a 6-mm segment of the trigeminal nerve with a prescribed dose of 60 Gy appears safe and effective. Persistent pain control was achieved in most patients with acceptable risk of sensory complications, which were typically found after re-irradiation.

Staged Image-guided Robotic Radiosurgery and Deferred Chemotherapy to Treat a Malignant Glioma During and After Pregnancy.

A 26-year-old pregnant woman with a fast-growing malignant deep-seated brain glioma was offered a therapeutic abortion to allow subsequent surgical resection. This option was refused by the mother, but the fast tumor growth placed the life of both mother and child at risk. A staged CyberKnife radiosurgery treatment was then planned, aiming to provide at least temporary tumor growth control and allow a safe delivery while keeping the doses received by the fetus well below the allowed doses. Growth control and the safe delivery of a healthy child were achieved after this first treatment. An intensive chemotherapy program based on the combination of Avastin, irinotecan, and Temodal was then started. Recurring tumor growth was treated with a second CyberKnife procedure while continuing the above chemotherapy protocol. At 43 months after the second CyberKnife procedure, the tumor had disappeared on magnetic resonance imaging. Neither mother nor child showed the neurological sequelae. Staged radiosurgery and deferred chemotherapy proved to be a safe and effective treatment to allow the delivery of a healthy child and the long-term control of an aggressive brain glioma.

Increased migration of a human glioma cell line after in vitro CyberKnife irradiation.

A human glioblastoma multiforme cell line (U87) and its derived-spheroids were irradiated either using a conventional irradiation (CIR) or a CK-like irradiation (IIR) in which the 8 Gy was delivered intermittently over a period of 40 minutes. The ability of glioma cells to migrate into a matrigel matrix was evaluated on days 1-8 from irradiation. Irradiation with CK-driven IIR significantly increased the invasion potential of U87 cells in a matrigel-based assay. In contrast to CIR, IIR was associated with increased levels of TGF-ß at four days (Real time PCR), ß1-integrin at 4-5 days (real-time PCR and western blot) and no elevation in phosphorylated AKT at days 4 and 5 (western blot). Our data suggests that glioma cell invasion as well as elevations of TGF-ß and ß1-integrin are associated with IIR and not CIR.

Multisession radiosurgery for optic nerve sheath meningiomas--an effective option: preliminary results of a single-center experience.

BACKGROUND: Traditional treatment options for optic nerve sheath meningiomas (ONSMs) include observation, surgery, and radiotherapy, but to date none of these has become the clear treatment of choice. OBJECTIVE: To evaluate the effectiveness and safety of multisession radiosurgery for ONSMs. METHODS: From May 2004 to June 2008, 21 patients with ONSMs were treated by radiosurgery using the frameless CyberKnife system. Patient age ranged from 36 to 73 years (mean, 54 years). All patients were treated using multisession radiosurgery, with 5 fractions of 5 Gy each to a total dose of 25 Gy prescribed to the 75% to 85% isodose line. Patients were evaluated for tumor growth control and visual function. RESULTS: The median pretreatment tumor volume was 2.8 mL (range, 0.3-23 mL). The mean follow-up was 30 months (range, 11-68 months). All patients tolerated treatment well, with only 1 patient in whom a mild optic neuropathy developed (which remitted after systemic steroid therapy). No other acute or late radiation-induced toxicities were observed. No patients showed ONSM progression on follow-up magnetic resonance imaging. Two patients (10%) had a partial response. No patients had worsening of visual function; visual function was stable in 65% and improved in 35% of patients. CONCLUSION: Multisession radiosurgery for ONSMs was found to be safe and effective. The preliminary results from this study, in terms of growth control, visual function improvement, and toxicity, are quite promising. Further investigations are warranted.