Antonio Pontoriero

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme

Glioblastoma multiforme (GBM) is a devastating malignant brain tumor characterized by resistance to available therapeutic approaches and relentless malignant progression that includes widespread intracranial invasion, destruction of normal brain tissue, progressive disability, and death. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are increasingly used in patients with recurrent GBM to complement traditional treatments such as resection, conventional external beam radiotherapy, and chemotherapy. Both SRS and fSRT are powerful noninvasive therapeutic modalities well suited to treat focal neoplastic lesions through the delivery of precise, highdose radiation. Although no randomized clinical trials have been performed, a variety of retrospective studies have been focused on the use of SRS and fSRT for recurrent GBMs. In addition, state-of-the-art neuroimaging techniques, such as MR spectroscopic imaging, diffusion tensor tractography, and nuclear medicine imaging, have enhanced treatment planning methods leading to potentially improved clinical outcomes. In this paper the authors reviewed the current applications and efficacy of SRS and fSRT in the treatment of GBM, highlighting the value of these therapies for recurrent focal disease.

Integration of functional neuroimaging in CyberKnife radiosurgery: feasibility and dosimetric results

OBJECT The integration of state-of-the-art neuroimaging into treatment planning may increase the therapeutic potential of stereotactic radiosurgery. Functional neuroimaging, including functional MRI, navigated brain stimulation, and diffusion tensor imaging-based tractography, may guide the orientation of radiation beams to decrease the dose to critical cortical and subcortical areas. The authors describe their method of integrating functional neuroimaging technology into radiosurgical treatment planning using the CyberKnife radiosurgery system. METHODS The records of all patients who had undergone radiosurgery for brain lesions at the CyberKnife Center of the University of Messina, Italy, between July 2010 and July 2012 were analyzed. Among patients with brain lesions in critical areas, treatment planning with the integration of functional neuroimaging was performed in 25 patients. Morphological and functional imaging data sets were coregistered using the Multiplan dedicated treatment planning system. Treatment planning was initially based on morphological data; radiation dose distribution was then corrected in relation to the functionally relevant cortical and subcortical areas. The change in radiation dose distribution was then calculated. RESULTS The data sets could be easily and reliably integrated into the Cyberknife treatment planning. Using an inverse planning algorithm, the authors achieved an average 17% reduction in the radiation dose to functional areas. Further gain in terms of dose sparing compromised other important treatment parameters, including target coverage, conformality index, and number of monitor units. No neurological deficit due to radiation was recorded at the short-term follow-up. CONCLUSIONS Radiosurgery treatments rely on the quality of neuroimaging. The integration of functional data allows a reduction in radiation doses to functional organs at risk, including critical cortical areas, subcortical tracts, and vascular structures. The relative simplicity of integrating functional neuroimaging into radiosurgery warrants further research to implement, standardize, and identify the limits of this procedure.

Protecting venous structures during radiosurgery for parasagittal meningiomas

Symptomatic edema is a potential complication of meningioma radiosurgery. Parasagittal meningiomas are at a particular risk for symptomatic edema, suggesting a role for a venous occlusive complication. The authors sought to develop a strategy to optimize CyberKnife stereotactic radiosurgical treatment parameters to reduce the irradiation of the peritumoral venous system. Multislice CT venography with 3D reconstructions was performed and coregistered with thin-section, contrast-enhanced, volumetric MR images. The tumor and critical volumes were contoured on the MR images. Venous anatomical details obtained from the CT venographic study were then exported onto the MR imaging and fused MR imaging-CT study. Target and critical structure volumes and dosimetric parameters obtained with this method were analyzed. The authors found that reducing the irradiation of veins that course along the surface of the meningioma, which may be at risk for radiation-induced occlusion, is feasible in parasagittal meningioma radiosurgery without compromising other treatment parameters including conformality, homogeneity, and target coverage. Long-term follow-up is needed to assess the clinical validity of this treatment strategy.

Integration of Three-Dimensional Rotational Angiography in Radiosurgical Treatment Planning of Cerebral Arteriovenous Malformations

PURPOSE Accuracy in delineating the target volume is a major issue for successful stereotactic radiosurgery for arteriovenous malformations. The aim of the present study was to describe a method to integrate three-dimensional (3D) rotational angiography (3DRA) into CyberKnife treatment planning and to investigate its potential advantages compared with computed tomography angiography (CTA) and magnetic resonance angiography. METHODS AND MATERIALS A total of 20 patients with a diagnosis of cerebral arteriovenous malformation were included in the present study. All patients underwent multislice computed tomography and 3D-volumetric CTA, 3DRA, and 3D magnetic resonance angiography. The contouring of the target and critical volumes was done separately using CTA and thereafter directly using 3DRA. The composite, conjoint, and disjoint volumes were measured. RESULTS The use of CTA or 3DRA resulted in significant differences in the target and critical volumes. The target volume averaged 3.49 ± 3.01 mL measured using CTA and 3.26 ± 2.93 mL measured using 3DRA, for a difference of 8% (p < .05). The conjoint and disjoint volume analysis showed an 88% volume overlap. The qualitative evaluation showed that the excess volume obtained using CTA was mostly tissue surrounding the nidus and venous structures. The mean contoured venous volume was 0.67 mL measured using CTA and 0.88 mL (range, 0.1-2.7) measured using 3DRA (p < .05). CONCLUSIONS 3DRA is a volumetric angiographic study that can be integrated into computer-based treatment planning. Although whether 3DRA provides superior accuracy has not yet been proved, its high spatial resolution is attractive and offers a superior 3D view. This allows a better 3D understanding of the target volume and distribution of the radiation doses within the volume. Additional technical efforts to improve the temporal resolution and the development of software tools aimed at improving the performance of 3D contouring are warranted.

Usefulness of four dimensional (4D) PET/CT imaging in the evaluation of thoracic lesions and in radiotherapy planning: Review of the literature

In the past decade, Positron Emission Tomography (PET) has become a routinely used methodology for the assessment of solid tumors, which can detect functional abnormalities even before they become morphologically evident on conventional imaging. PET imaging has been reported to be useful in characterizing solitary pulmonary nodules, guiding biopsy, improving lung cancer staging, guiding therapy, monitoring treatment response and predicting outcome. This review focuses on the most relevant and recent literature findings, highlighting the current role of PET/CT and the evaluation of 4D-PET/CT modality for radiation therapy planning applications. Current evidence suggests that gross tumor volume delineation based on 4D-PET/CT information may be the best approach currently available for its delineation in thoracic cancers (lung and non-lung lesions). In our opinion, its use in this clinical setting is strongly encouraged, as it may improve patient treatment outcome in the setting of radiation therapy for cancers of the thoracic region, not only involving lung, but also lymph nodes and esophageal tissue. Literature results warrants further investigation in future prospective studies, especially in the setting of dose escalation.

Diarrhoea in irradiated patients: a prospective multicentre observational study.

AIMS To determine the incidence of cancer treatment-induced diarrhoea in patients submitted to irradiation. METHODS Forty-five Italian radiation oncology departments took part in this prospective observational study and a total of 1020 patients were enrolled. The accrual lasted three consecutive weeks; evaluation was based on diary cards filled in daily by patients during radiotherapy and one week after cessation. Diary cards recorded both the onset and intensity of diarrhoea. RESULTS A total of 1004 patients were eligible for this analysis. 147/1004 (14.6%) patients had diarrhoea. The median minimum number of daily events was 1 (range 1-7) with a median maximum events of 3 (range 1-23). 82/147 patients (56.2%) had a drug prescription for diarrhoea. In the evaluation of the onset of diarrhoea, in multivariate analysis, we found the following factors to be statistically significant predictors of an increased likelihood of diarrhoea: primitive tumour site, therapeutic purpose and field size. CONCLUSIONS Patients with abdominal-pelvic cancer, treated with curative purpose and using large field sizes are at high risk of cancer treatment-induced diarrhoea. Diarrhoea was also observed in patients treated at other sites. In this population group there is the need for more stringent monitoring during the delivery of radiation therapy.

External beam irradiation in the palliation of bone metastases: a practice analysis among Sicilian Departments of Radiation Oncology.

Background In the treatment of bone metastases, the choice of radiation fractionation, total radiation dose, delivery technique, and imaging studies before treatment varies among radiation oncologists. Surveys on this issue, using case scenarios, have been published by groups from Europe, North America, and Australia-New Zealand. Our objective was to analyze retrospectively the “real” practice in nine radiotherapy centers located in Sicily. Method A questionnaire including 17 items was distributed to 30 practicing radiation oncologists working in seven departments of four Sicilian cities (Messina, Catania, Ragusa and Palermo) during a meeting of the Sicilian Division of the Associazione Italians Radioterapia Oncologica (AIRO). Participants were asked to answer the questions using a card for every patient treated with external beam irradiation from 1 January to 31 December, 2000. Results Six centers returned the questionnaires; 332 cards were valuable for a total of 5644 responses. All six responding departments used linear accelerators for treatment delivery. The most common dose fractionation was 30 Gy in 10 fractions and the most common technique used was opposed parallel local fields. Before the start of irradiation a bone scan was performed in 325 of the 332 (98%) patients treated and CT and/or MRI was performed in 320 (96%); surprisingly, standard roentgenograms were used in only 142 of 332 patients (42.8%). Conclusion The “real” radiation practice for bone metastases in the region of Sicily confirms the results of the previously reported international surveys: there is a clear preference for fractionated treatment and local field therapy. The results of randomized studies, which demonstrated both the efficacy and the feasibility of a single 6–8 Gy fraction in the palliation of bone metastases, have little or no impact on the pattern of practice.

Frameless stereotactic radiosurgery for the treatment of multiple sclerosis-related trigeminal neuralgia

BACKGROUND Trigeminal neuralgia (TN) affects 7% of patients with multiple sclerosis (MS). In such patients, TN is difficult to manage either pharmacologically and surgically. Radiosurgical rhizotomy is an effective treatment option. The nonisocentric geometry of radiation beams of CyberKnife introduces new concepts in the treatment of TN. Its efficacy for MS-related TN has not yet been demonstrated. METHODS Twenty-seven patients with refractory TN and MS were treated. A nonisocentric beams distribution was chosen; the maximal target dose was 72.5 Gy. The maximal dose to the brainstem was <12 Gy. Effects on pain, medications, sensory disturbance, rate, and time of pain recurrence were analyzed. RESULTS Median follow-up was 37 (18-72) months. Barrow Neurological Institute pain scale score I-III was achieved in 23/27 patients (85%) within 45 days. Prescription isodose line (80%) accounting for a dose of 58 Gy incorporated an average of 4.85 mm (4-6 mm) of the nerve and mean nerve volume of 26.4 mm3 (range 20-38 mm3). Seven out of 27 patients (26%) had mild, not bothersome, facial numbness (Barrow Neurological Institute numbness score II). The rate of pain control decreased progressively after the first year, and only 44% of patients retained pain control 4 years later. CONCLUSIONS Frameless radiosurgery can be effectively used to perform retrogasserian rhizotomy. Pain relief was satisfactory and, with our dose/volume constraints, no sensory complications were recorded. Nonetheless, long-term pain control was possible in less than half of the patients. This is a limitation that CyberKnife radiosurgery shares with other techniques in MS patients.

Post-Treatment Edema after Meningioma Radiosurgery is a Predictable Complication.

Symptomatic post-treatment edema (PTE) causing seizures, focal deficits, and intracranial hypertension is a rather common complication of meningioma radiosurgery. Factors associated to the occurrence of PTE still needs to be clarified. We retrospectively analyzed our patients’ data to identify factors associated with the development of symptomatic PTE. Supposed risk factors were systematically analyzed. Between July 2007 and March 2014, 245 meningiomas in 229 patients were treated by a single fraction or multisession radiosurgery (2-5 fractions) or hypofractionated stereotactic radiotherapy (6-15 fractions) using the CyberKnife system (Accuray Inc., Sunnyvale, CA) at the University Hospital of Messina, Italy. Local tumor control was achieved in 200 of 212 patients with World Health Organization (WHO) Grade I meningiomas (94%) at a mean follow-up of 62 months. Symptomatic PTE on MRI was diagnosed in 19 patients (8.3%) causing seizure (n=17, 89%), aggravating headache (n=12, 63%), or focal deficits (n=13, 68%). Four variables were found to be associated with the likelihood of edema development, including tumor volume > 4.5 mL, non-basal tumor location, tight brain/tumor interface, and atypical histology. Nonetheless, when multivariate logistic regression analysis was performed, only tumor volume and brain-tumor interface turned out to be independent predictors of PTE development. Our results suggest that the factor associated with the risk of developing PTE is associated to characteristics of meningioma rather than to the treatment modality used. Accordingly, an appropriate patient selection is the way to achieve safe treatment and long-term disease control.

High-Dose Robotic Stereotactic Body Radiotherapy in the Treatment of Patients With Prostate Cancer Preliminary Results in 26 Patients

Background: Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in patients with localized prostate cancer (LpC). The primary end point was the evaluation of both acute and late toxicities; secondary end point was the observation of prostate-specific antigen (PSA) nadir. Patients and Methods: Patients with LpC having prostate volume ≤90 cm3 were enrolled in the present study. Patients were treated with SBRT alone or in combined modality (SBRT + EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated, Sunnyvale, California) and fiducial tracking system. Results: From February 2008 to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled. Androgen deprivation therapy (ADT) was administered in 16 of the 26 patients. The median pretreatment PSA was 9.4 (range, 4.5-14.3) ng/mL. All patients completed the planned therapy. Acute Grade 1 toxicity was observed in 18 patients, genitourinary (GU) in 12 / 26 patients, and gastrointestinal (GI) in 6 / 26 patients. Acute Grade 2 GU toxicity was reported in 1 / 26 patients, and Grade 2 GI toxicity was observed in 2 / 26 patients. The median PSA nadir was 0.15 (range, 0.02 = 1.4) ng/mL. Late toxicities were observed in 5 / 26 patients: Grade 1 GU (3 of 26), Grade 2 GU (1 of 26), and Grade 1 GI (1 of 26). Median follow-up was 21.5 (range, 8-65) months. Conclusions: Our preliminary results of SBRT “simulating” HDR for LpC confirm a minimal toxicity and an optimal PSA response. The PSA nadirs appear comparable with HDR-BRT.