Re-irradiation for recurrent intracranial meningiomas: Analysis of clinical outcomes and prognostic factors.

PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/ß = 2 for brain tissue and α/ß = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis. RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.

Automation of pencil beam scanning proton treatment planning for intracranial tumours.

PURPOSE: To evaluate the feasibility of comprehensive automation of an intra-cranial proton treatment planning. MATERIALS AND METHODS: Class solution (CS) beam configuration selection allows the user to identify predefined beam configuration based on target localization; automatic CS (aCS) will then explore all the possible CS beam geometries. Ten patients, already used for the evaluation of the automatic selection of the beam configuration, have been also employed to training an algorithm based on the computation of a benchmark dose exploit automatic general planning solution (GPS) optimization with a wish list approach for the planning optimization. An independent cohort of ten patients has been then used for the evaluation step between the clinical and the GPS plan in terms of dosimetric quality of plans and the time needed to generate a plan. RESULTS: The definition of a beam configuration requires on average 22 min (range 9-29 min). The average time for GPS plan generation is 18 min (range 7-26 min). Median dose differences (GPS-Manual) for each OAR constraints are: brainstem -1.60 Gy, left cochlea -1.22 Gy, right cochlea -1.42 Gy, left eye 0.55 Gy, right eye -2.33 Gy, optic chiasm -1.87 Gy, left optic nerve -4.45 Gy, right optic nerve -2.48 Gy and optic tract -0.31 Gy. Dosimetric CS and aCS plan evaluation shows a slightly worsening of the OARs values except for the optic tract and optic chiasm for both CS and aCS, where better results have been observed. CONCLUSION: This study has shown the feasibility and implementation of the automatic planning system for intracranial tumors. The method developed in this work is ready to be implemented in a clinical workflow.

Multidisciplinary Management of Craniopharyngiomas in Children: A Single Center Experience.

BACKGROUND: Craniopharyngioma (CP) is a rare brain tumor involving the sellar region. The best management is still debated. Gross total resection (GTR) is considered the best option to improve recurrence-free survival, but considerable long-term sequelae with a significant impact on quality of life have been reported. Subtotal resection followed by radiotherapy achieves similar disease control compared to GTR with less complications. METHODS: We retrospectively reviewed 10 pediatric patients affected by CP treated with partial resection and subsequent proton therapy (PBT). We reviewed visual, endocrinological, and neuropsychological data at baseline, after surgery, and after radiation for all patients. RESULTS: At the time of diagnosis, visual impairment was detected in 70% of patients and endocrinological abnormalities in 50%. All patients were subject to one or more surgical procedures. Surgery had no impact on visual status; however, it caused a worsening of endocrine function in half of patients. After surgery, all patients underwent PBT, achieving a partial response in 7 out of 10 patients (70%), while stable disease was observed in the other three patients (30%) at a median follow-up of 78 months from the end of PBT. Both visual and endocrine deficits were stable after PBT, with neurocognitive performance scores unchanged from baseline. CONCLUSIONS: A conservative surgical approach followed by PBT represents a safe and effective strategy to manage CP and limit long-term sequelae.

Is it beneficial to use apertures in proton radiosurgery with a scanning beam? A dosimetric comparison in neurinoma and meningioma patients.

PURPOSE: To assess the dosimetric advantages of apertures in intracranial single fraction proton radiosurgery. MATERIALS AND METHODS: Six neuroma and 10 meningioma patients were investigated. For each patient, six plans were computed, with two spot spacing and three aperture settings (no apertures, 5 and 8 mm margin between aperture and clinical target volume [CTV]). All plans were optimized on the CTV with the same beam arrangement and the same single-field robust optimization (2 mm setup errors, 3.5% range uncertainties). Robustness analysis was performed with 0.5 and 1.0 mm systematic setup errors and 3.5% range uncertainties. CTV coverage in the perturbed scenarios and healthy brain tissue sparing in the surrounding of the CTV were compared. RESULTS: Meningiomas were larger and at a shallow depth than neuromas. In neuromas, spot spacing did not affect OAR doses or the robustness of CTV coverage and the apertures reduced brain dose without any significant impact on CTV robustness. In meningiomas, smaller spot spacing produced a reduction in brain V5Gy and improved robustness of CTV coverage; in addition, an 8 mm margin aperture reduced low and medium brain tissue doses without affecting robustness in the 0.5 mm perturbed scenario. A 5 mm margin aperture caused a reduction of plan robustness. CONCLUSION: The optimal use of apertures is a trade-off between sparing of low and medium dose to the healthy brain and robustness of target coverage, also depending on size and depth of the lesion.

Predict Treatment Response by Magnetic Resonance Diffusion Weighted Imaging: A Preliminary Study on 46 Meningiomas Treated with Proton-Therapy.

OBJECTIVE: a considerable subgroup of meningiomas (MN) exhibit indolent and insidious growth. Strategies to detect earlier treatment responses based on tumour biology rather than on size can be useful. We aimed to characterize therapy-induced changes in the apparent diffusion coefficient (ADC) of MN treated with proton-therapy (PT), determining whether the pre- and early post-treatment ADC values may predict tumour response. METHODS: Forty-four subjects with MN treated with PT were retrospectively enrolled. All patients underwent conventional magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) at baseline and each 3 months for a follow-up period up to 36 months after the beginning of PT. Mean relative ADC (rADCm) values of 46 MN were measured at each exam. The volume variation percentage (VV) for each MN was calculated. The Wilcoxon test was used to assess the differences in rADCm values between pre-treatment and post-treatment exams. Patients were grouped in terms of VV (threshold -20%). A p < 0.05 was considered statistically significant for all the tests. RESULTS: A significant progressive increase of rADCm values was detected at each time point when compared to baseline rADCm (p < 0.05). Subjects that showed higher pre-treatment rADCm values had no significant volume changes or showed volume increase, while subjects that showed a VV < -20% had significantly lower pre-treatment rADCm values. Higher and earlier rADCm increases (3 months) are related to greater volume reduction. CONCLUSION: In MN treated with PT, pre-treatment rADCm values and longitudinal rADCm changes may predict treatment response.

Multicomponent T2 relaxometry reveals early myelin white matter changes induced by proton radiation treatment.

PURPOSE: To investigate MRI myelin water imaging (MWI) by multicomponent T2 relaxometry as a quantitative imaging biomarker for brain radiation-induced changes and to compare it with DTI. METHODS: Sixteen patients underwent fractionated proton therapy (PT) receiving dose to the healthy tissue because of direct or indirect (base skull tumors) irradiation. MWI was performed by a multi-echo sequence with 32 equally spaced echoes (10-320 ms). Decay data were processed to identify 3 T2 compartments: myelin water (Mw) below 40 ms, intra-extracellular water (IEw) between 40 and 250 ms, and free water (CSFw) above 250 ms. Both MWI and DTI scans were acquired pre (pre)-treatment and immediately at the end (end) of PT. After image registration, voxel-wise difference maps, obtained by subtracting MWI and DTI pre from those acquired at the end of PT, were compared with the corresponding biological equivalent dose (BED). RESULTS: Mw difference showed a positive correlation and IEw difference showed a negative correlation with BED considering end-pre changes (P < .01). The changes in CSFw were not significantly correlated with the delivered BED. The changes in DTI data, considering end-pre acquisitions, showed a positive correlation between fractional anisotropy and the delivered BED. CONCLUSION: MWI might detect early white matter radiation-induced alterations, providing additional information to DTI, which might improve the understanding of the pathogenesis of the radiation damage.

Magnetic Resonance Imaging during Proton Therapy Irradiation Allows for the Early Response Assessment of Pediatric Chordoma.

Chordoma in pediatric patients is very rare. Proton therapy has become a gold standard in the treatment of these neoplasms, as high dose escalation can be achieved regarding the target while maximizing the sparing of the healthy tissues near the tumor. The aim of the work was to assess the evolution of morphological sequences during treatment using T1/T2-weighted magnetic resonance imaging (MRI) for the early response assessment of a classic chordoma of the skull base in a pediatric patient who had undergone surgical excision. Our results demonstrated a significant quantitative reduction in the residual nodule component adhered to the medullary bulb junction, with an almost complete recovery of normal anatomy at the end of the irradiation treatment. This was mainly shown in the T2-weighted MRI. On the other hand, the classic component of the lesion was predominantly present and located around the tooth of the axis. The occipital condyles were morphologically and dimensionally stable for the entire irradiation period. In conclusion, the application of this type of monitoring methodology, which is unusual during the administration of a proton treatment for chordoma, highlighted the unexpected early response of the disease. At the same time, it allowed the continuous assessment of the reliability of the treatment plan.

Quantitative Multicomponent T2 Relaxation Showed Greater Sensitivity Than Flair Imaging to Detect Subtle Alterations at the Periphery of Lower Grade Gliomas.

PURPOSE: To demonstrate that quantitative multicomponent T2 relaxation can be more sensitive than conventional FLAIR imaging for detecting cerebral tissue abnormalities. METHODS: Six patients affected by lower-grade non-enhancing gliomas underwent T2 relaxation and FLAIR imaging before a radiation treatment by proton therapy (PT) and were examined at follow-up. The T2 decay signal obtained by a thirty-two-echo sequence was decomposed into three main components, attributing to each component a different T2 range: water trapped in the lipid bilayer membrane of myelin, intra/extracellular water and cerebrospinal fluid. The T2 quantitative map of the intra/extracellular water was compared with FLAIR images. RESULTS: Before PT, in five patients a mismatch was observed between the intra/extracellular water T2 map and FLAIR images, with peri-tumoral areas of high T2 that typically extended outside the area of abnormal FLAIR hyper-intensity. Such mismatch regions evolved into two different types of patterns. The first type, observed in three patients, was a reduced extension of the abnormal regions on T2 map with respect to FLAIR images (T2 decrease pattern). The second type, observed in two patients, was the appearance of new areas of abnormal hyper-intensity on FLAIR images matching the anomalous T2 map extension (FLAIR increase pattern), that was considered as asymptomatic radiation induced damage. CONCLUSION: Our preliminarily results suggest that quantitative T2 mapping of the intra/extracellular water component was more sensitive than conventional FLAIR imaging to subtle cerebral tissue abnormalities, deserving to be further investigated in future clinical studies.

Proton therapy re-irradiation preserves health-related quality of life in large recurrent glioblastoma.

PURPOSE: Proton therapy could minimize the risk of side effects and, therefore, reduce the possible detrimental effect on health-related quality of life (HRQOL) of re-irradiation. The aim of this study was to determine the effect of re-irradiation with active scanning proton therapy on recurrent glioblastoma (GBM) in terms of HRQOL scored by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20). METHODS: Thirty-three patients with recurrent GBM were re-irradiated with active scanning proton therapy. Subscales within the EORTC QLQ-C30 include five functional scales, six single-item scales, and global QoL. The BN20 assessed visual disorders, motor function, communication deficit, various disease symptoms, treatment, toxicity, and future uncertainty. The patients completed the questionnaires before starting proton therapy, the last day of proton therapy, and at every follow-up visit until progression of disease. RESULTS: The treatment was associated with improvement or stability in most of the preselected HRQOL domains. Global health improved over time with a maximum difference of six points between baseline and 3-months follow-up. Social functioning and motor dysfunction improved over time with a maximum difference of eight and two points, respectively. We showed a non-significant decrease in cognitive and emotional functioning. Fatigue remained stable during the analysis such as the other preselected domains. CONCLUSIONS: Re-irradiation with proton therapy is a safe and effective treatment in patients with recurrent glioblastoma. Proton therapy does not negatively effect on HRQOL, but rather it seems to preserve HRQOL until the time of disease progression.

Modelling the risk of radiation induced alopecia in brain tumor patients treated with scanned proton beams.

PURPOSE: To develop normal tissue complication probability (NTCP) models for radiation-induced alopecia (RIA) in brain tumor patients treated with proton therapy (PT). METHODS AND MATERIALS: We analyzed 116 brain tumor adult patients undergoing scanning beam PT (median dose 54 GyRBE; range 36-72) for CTCAE v.4 grade 2 (G2) acute (≤90 days), late (>90 days) and permanent (>12 months) RIA. The relative dose-surface histogram (DSH) of the scalp was extracted and used for Lyman-Kutcher-Burman (LKB) modelling. Moreover, DSH metrics (Sx: the surface receiving ≥ X Gy, D2%: near maximum dose, Dmean: mean dose) and non-dosimetric variables were included in a multivariable logistic regression NTCP model. Model performances were evaluated by the cross-validated area under the receiver operator curve (ROC-AUC). RESULTS: Acute, late and permanent G2-RIA was observed in 52%, 35% and 19% of the patients, respectively. The LKB models showed a weak dose-surface effect (0.09 ≤ n ≤ 0.19) with relative steepness 0.29 ≤ m ≤ 0.56, and increasing tolerance dose values when moving from acute and late (22 and 24 GyRBE) to permanent RIA (44 GyRBE). Multivariable modelling selected S21Gy for acute and S25Gy, for late G2-RIA as the most predictive DSH factors. Younger age was selected as risk factor for acute G2-RIA while surgery as risk factor for late G2-RIA. D2% was the only variable selected for permanent G2-RIA. Both LKB and logistic models exhibited high predictive performances (ROC-AUCs range 0.86-0.90). CONCLUSION: We derived NTCP models to predict G2-RIA after PT, providing a comprehensive modelling framework for acute, late and permanent occurrences that, once externally validated, could be exploited for individualized scalp sparing treatment planning strategies in brain tumor patients.

Clinical implementation in proton therapy of multi-field optimization by a hybrid method combining conventional PTV with robust optimization.

To implement a robust multi-field optimization (MFO) technique compatible with the application of a Monte Carlo (MC) algorithm and to evaluate its robustness. Nine patients (three brain, five head-and-neck, one spine) underwent proton treatment generated by a novel robust MFO technique. A hybrid (hMFO) approach was implemented, planning dose coverage on isotropic PTV compensating for setup errors, whereas range calibration uncertainties are incorporated into PTV robust optimization process. hMFO was compared with single-field optimization (SFO) and full robust multi-field optimization (fMFO), both on the nominal plan and the worst-case scenarios assessed by robustness analysis. The SFO and the fMFO plans were normalized to hMFO on CTV to obtain iso-D95 coverage, and then the organs at risk (OARs) doses were compared. On the same OARs, in the normalized nominal plans the potential impact of variable relative biological effectiveness (RBE) was investigated. hMFO reduces the number of scenarios computed for robust optimization (from twenty-one in fMFO to three), making it practicable with the application of a MC algorithm. After normalizing on D95 CTV coverage, nominal hMFO plans were superior compared to SFO in terms of OARs sparing (p  < 0.01), without significant differences compared to fMFO. The improvement in OAR sparing with hMFO with respect to SFO was preserved in worst-case scenarios (p  < 0.01), confirming that hMFO is as robust as SFO to physical uncertainties, with no significant differences when compared to the worst case scenarios obtained by fMFO. The dose increase on OARs due to variable RBE was comparable to the increase due to physical uncertainties (i.e. 4-5 Gy(RBE)), but without significant differences between these techniques. hMFO allows improving plan quality with respect to SFO, with no significant differences with fMFO and without affecting robustness to setup, range and RBE uncertainties, making clinically feasible the application of MC-based robust optimization.

Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO).

INTRODUCTION: The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy. METHODS: Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1 month after radiation therapy and then every 3 months. RESULTS: Re-irradiation was performed at a median interval time (IT) of 16 months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9 Gy to 52.5 Gy, with a median biological effective dose of 43 Gy. The median, 1, 2 year OS were 9.7 months, 41% and 17.7%. Low grade glioma histology (p  ≪ 0.01), IT > 12 months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival. CONCLUSION: our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.

Practice patterns of image guided particle therapy in Europe: A 2016 survey of the European Particle Therapy Network (EPTN).

BACKGROUND AND PURPOSE: Image guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres. MATERIAL AND METHODS: In 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT. RESULTS: All centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods. CONCLUSIONS: Insight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines.

Policies for reirradiation of recurrent high-grade gliomas: a survey among Italian radiation oncologists.

PURPOSE: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. METHODS: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. RESULTS: A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter <5 cm and an interval from primary radiation ≥6 months, were the prevalent predictive factors considered for reRT. Sixty percent of reirradiated patients had already received a salvage therapy, either chemotherapy (40%) or reoperation (20%). The most common approach for reRT was fractionated stereotactic radiotherapy to a mean (photon) dose of 41.6 Gy. CONCLUSIONS: Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

Water equivalent thickness of immobilization devices in proton therapy planning - Modelling at treatment planning and validation by measurements with a multi-layer ionization chamber.

PURPOSE: To investigate the range errors made in treatment planning due to the presence of the immobilization devices along the proton beam path. METHODS: The measured water equivalent thickness (WET) of selected devices was measured by a high-energy spot and a multi-layer ionization chamber and compared with that predicted by treatment planning system (TPS). Two treatment couches, two thermoplastic masks (both un-stretched and stretched) and one headrest were selected. At TPS, every immobilization device was modelled as being part of the patient. The following parameters were assessed: CT acquisition protocol, dose-calculation grid-sizes (1.5 and 3.0mm) and beam-entrance with respect to the devices (coplanar and non-coplanar). Finally, the potential errors produced by a wrong manual separation between treatment couch and the CT table (not present during treatment) were investigated. RESULTS: In the thermoplastic mask, there was a clear effect due to beam entrance, a moderate effect due to the CT protocols and almost no effect due to TPS grid-size, with 1mm errors observed only when thick un-stretched portions were crossed by non-coplanar beams. In the treatment couches the WET errors were negligible (<0.3mm) regardless of the grid-size and CT protocol. The potential range errors produced in the manual separation between treatment couch and CT table were small with 1.5mm grid-size, but could be >0.5mm with a 3.0mm grid-size. In the headrest, WET errors were negligible (0.2mm). CONCLUSIONS: With only one exception (un-stretched mask, non-coplanar beams), the WET of all the immobilization devices was properly modelled by the TPS.

The role of stereotactic ablative radiotherapy in oncological and non-oncological clinical settings: highlights from the 7th Meeting of AIRO--Young Members Working Group (AIRO Giovani).

Stereotactic ablative radiotherapy is a modern cancer treatment strategy able to deliver highly focused radiation in one or a few fractions with a radical intent in several clinical settings. Young radiation oncologists need a constant and tailored update in this context to improve patient care in daily clinical practice. A recent meeting of AIRO Giovani (AIRO--Young Members Working Group) was specifically addressed to this topic, presenting state-of-the-art knowledge, based on the latest evidence in this field. Highlights of the congress are summarized and presented in this report, including thorough contributions of the speakers dealing with the role of stereotactic ablative radiotherapy in both oncological and non-oncological diseases, divided according to anatomical and clinical scenarios: intra-cranial settings (brain malignant primary tumors, metastases, benign tumors and functional disorders) and extra-cranial indications (lung primary tumors and metastases, thoracic re-irradiation, liver, lymph node and bone metastases, prostate cancer). With literature data discussed during the congress as a background, stereotactic ablative radiotherapy has proved to be a consolidated treatment approach in specific oncological and non-oncological scenarios, as well as a promising option in other clinical settings, requiring a further prospective validation in the near future. We herein present an updated overview of stereotactic ablative radiotherapy use in the clinic.

Analysis of inter- and intrafraction accuracy of a commercial thermoplastic mask system used for image-guided particle radiation therapy.

The present paper reports and discusses the results concerning both the inter- and intrafraction accuracy achievable combining the immobilization system employed in patients with head-and-neck, brain and skull base tumors with image guidance at our particle therapy center. Moreover, we investigated the influence of intrafraction time on positioning displacements. A total of 41 patients treated between January and July 2011 represented the study population. All the patients were immobilized with a tailored commercial thermoplastic head mask with standard head-neck rest (HeadSTEP(®), IT-V). Patient treatment position was verified by two orthogonal kilovoltage images acquired through a ceiling imaging robot (Siemens, Erlangen, Germany). The analysis of the applied daily corrections during the first treatment week before and after treatment delivery allowed the evaluation of the interfraction and intrafraction reproducibility of the thermoplastic mask, respectively. Concerning interfraction reproducibility, translational and rotational systematic errors (Σs) were ≤ 2.2 mm and 0.9º, respectively; translational and rotational random errors (σs) were ≤ 1.6 mm and 0.6º, respectively. Regarding the intrafraction accuracy translational and rotational Σs were ≤ 0.4 mm and 0.4º, respectively; translational and rotational σs were ≤ 0.5 mm and 0.3º, respectively. Concerning the time-intrafraction displacements correlation Pearson coefficient was 0.5 for treatment fractions with time between position checks less than or equal to median value, and 0.2 for those with time between position controls longer than the median figure. These results suggest that intrafractional patient motion is smaller than interfractional patient motion. Moreover, we can state that application of different imaging verification protocols translate into a relevant difference of accuracy for the same immobilization device. The magnitude of intrafraction displacements correlates with the time for short treatment sessions or during the early phase of long treatment delivery.

Early MRI changes in glioblastoma in the period between surgery and adjuvant therapy.

To investigate the increase in MRI contrast enhancement (CE) occurring in glioblastoma during the period between surgery and initiation of chemo-radiotherapy, thirty-seven patients with newly diagnosed glioblastoma were analyzed by early post-operative magnetic resonance (EPMR) imaging within three days of surgery and by pre-adjuvant magnetic resonance (PAMR) examination before adjuvant therapy. Areas of new CE were investigated by use of EPMR diffusion-weighted imaging and PAMR perfusion imaging (by arterial spin-labeling). PAMR was acquired, on average, 29.9 days later than EPMR (range 20-37 days). During this period an increased area of CE was observed for 17/37 patients. For 3/17 patients these regions were confined to areas of reduced EPMR diffusion, suggesting postsurgical infarct. For the other 14/17 patients, these areas suggested progression. For 11/17 patients the co-occurrence of hyperperfusion in PAMR perfusion suggested progression. PAMR perfusion and EPMR diffusion did not give consistent results for 3/17 patients for whom small new areas of CE were observed, presumably because of the poor spatial resolution of perfusion imaging. Before initiation of adjuvant therapy, areas of new CE of resected glioblastomas are frequently observed. Most of these suggest tumor progression, according to EPMR diffusion and PAMR perfusion criteria.

Radiosurgery with photons or protons for benign and malignant tumours of the skull base: a review.

Stereotactic radiosurgery (SRS) is an important treatment option for intracranial lesions. Many studies have shown the effectiveness of photon-SRS for the treatment of skull base (SB) tumours; however, limited data are available for proton-SRS.Several photon-SRS techniques, including Gamma Knife, modified linear accelerators (Linac) and CyberKnife, have been developed and several studies have compared treatment plan characteristics between protons and photons.The principles of classical radiobiology are similar for protons and photons even though they differ in terms of physical properties and interaction with matter resulting in different dose distributions.Protons have special characteristics that allow normal tissues to be spared better than with the use of photons, although their potential clinical superiority remains to be demonstrated.A critical analysis of the fundamental radiobiological principles, dosimetric characteristics, clinical results, and toxicity of proton- and photon-SRS for SB tumours is provided and discussed with an attempt of defining the advantages and limits of each radiosurgical technique.