Search

The risk of survivors developing a secondary bone sarcoma after being treated for pediatric cancers is well established. The aim of this study was to examine the clinical characteristics and outcomes of patients with secondary osteosarcoma (SOS).The study concerns survivors of childhood and adolescence primary neoplasms (PN) treated with chemotherapy, with or without radiotherapy and surgery, subsequently diagnosed with SOS.We identified 26 patients (13 females, 13 males) who developed SOS a median 7.3 years after being diagnosed with a PN (5/7 of these patients tested for Li-Fraumeni and found positive for the syndrome). The sample's median age was 8.0 and 15.0 years when their PN and SOS were diagnosed, respectively. To treat their PN, 24 out of 26 patients had been given radiotherapy, and 19 had received chemotherapy including doxorubicin. A considerable number of SOS occurred at unfavorable sites (nine hip bone, six skull). All but one patient received chemotherapy with tailored schedules, omitting doxorubicin in 19 cases. Eighteen of the 26 patients underwent surgery. The 5- and 10-year overall survival and probabilities after the diagnosis of SOS (95% confidence interval) were 50% (32.7-76.5%) and 38.9% (22.4-67.4%); 5- and 10-year progression-free survival was 47% (29.9-73.7%) and 35.2% (19.3-64.4%), respectively.The survival rates after SOS are lower than in patients with primary osteosarcoma, but not negligible. It is therefore mandatory to discuss the best choice of treatment for such patients at a referral center, in terms of their chances of cure and quality of life.

The chances of patients with relapsing pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) being cured are limited. This retrospective single-institutional study examines the potential role of routine surveillance imaging for detecting recurrent tumor, and its impact on post-relapse survival.The analysis concerned 86 patientslt; 21 years old with relapsing NRSTS treated from 1985 to 2020. Clinical findings, treatment modalities and survival were analyzed, comparing patients whose relapse was first suspected from symptoms (symptomatic group) with those whose relapse was detected by radiological surveillance (imaging group).Tumor relapses were identified from clinical symptoms in 49 cases and on routine imaging in 37. Time to relapse was similar in the two groups. Routine imaging detected 6/32 local relapses and 31/48 distant relapses (and 79% of the cases of lung metastases). Overall survival (OS) at 5 years was 34.3% for the symptomatic group, and 24.0% for the imaging group (p-value 0.270). In patients with lung metastases at relapse, the 5-year OS was statistically better for the imaging group, that is, 25.8% versus 0% for the symptomatic group (p-value 0.044).This is the first study to explore the role of surveillance imaging in pediatric NRSTS. Judging from our findings, the value of routine scanning of primary sites seems limited, while radiological surveillance may help to detect lung metastases, improving survival for this patient category. The potentially negative effects of periodic radiological exams should be considered in deciding the optimal follow-up for patients off therapy.

The Rail and Road transportation systems are evolving to progressively introduce automation with the ultimate goal of autonomous driving. The expectations are to improve efficiency and to guarantee higher level of safety. As transport networks will evolve towards high mobility, vehicles will become connected and self-positioned opening new challenges to comply with stringent safety requirements. Although vehicles are increasingly equipped with multiple advanced onboard positioning sensors, GNSS corrections allow to minimize the confidence error and to standardize the on board units. In the ERTMS (European Railways Train Management System) GNSS positioning must comply with the Tolerable Hazard Rate of 10E-9/hour at system level. Similar requirements are targeted by the connected cars when the management of vehicles is performed by a centralized authority as in the ERTMS system. Both ERTMS and Connected Car applications rely on the knowledge of the vehicle’s position with similar integrity levels. Considering also that rail and roads are frequently close to each other’s sharing the same operational environment, a multimodal augmentation network has been designed in the HELMET project to satisfy the new market needs. The aim of this paper is to assess the technical feasibility and the economic sustainability of this multi-modal augmentation network designed for the rail and road applications. The prerequisites are to reuse existing and future EGNSS infrastructures - without creating a direct dependence on themselves - to guarantee the interoperability and to allow a stepped deployment in line with the plans of the rail and road infrastructure managers. The paper includes the results of a recently concluded field test and the requirements of RFI – the Italian railways infrastructure manager who is managing a working group with rail industries to contributing to a standardizable and interoperable GNSS-based ERTMS system. Follow up activities to consolidate results for an operational system are on-going.

Background. First-line therapies for medulloblastoma(MBL) are obtaining higher survival-rates while decreasing late-effects, but treatment at relapse is not standardized. We report the experience with MBL re-irradiation(re-RT), its timing and outcome in different clinical settings and tumor groups. Methods. Patient’s staging/treatment at diagnosis, histotypes/molecular subgroups, relapse site/s, re-treatments outcome are reported. Results. Patients were 25, median age 11.4 years, 8 had metastases, three LCA histotype. According to 2016-2021 WHO-classification, 14 had SHH subgroup tumors(6 TP53 mutated,1 + MYC and 1 + NMYC amplification), 11 non-WNT/non-SHH (2 with MYC/MYCN amplification).Thirteen had received HART-CSI, 11 standard-CSI, one HFRT; all post-radiation chemotherapy(CT), 16 also pre-RT. Median time to relapse (local-LR in 9, distant-DR in 14, LR+DR in two) was 26 months. Fourteen patients were re-operated, in 5 excising single DR-sites, thereafter 3 received CT, two after re-RT; out of 11 not re-operated patients, 4 had re-RT as first treatment and 7 after CT. Re-RT was administered at median 32 months after first RT: focally in 20 cases, CSI in 5, never resulting in radionecrosis. Median post-relapse-PFS/after re-RT were 16.7/8.2 months, while overall survival-OS were 35.1/23.9 months, respectively. Metastatic status both at diagnosis/relapse negatively affected outcome and re-surgery was prognostically favorable.MYC,MYCN,P53 status and molecular subgroups, RT extension/fractionation, gender and age were not statistically prognostic; in the multivariable model, OSs were positively influenced by longer intervals before re-RT, re-surgery and not-SHH subgroups (P=0.019 from recurrence and 0.004 from second RT). Conclusions. Re-surgery+reRT can prolong survival; a substantial fraction of patients with worse outcome belongs to SHH-subgroup.

Purpose To evaluate the clinical outcomes, toxicity and prognostic factors conditioning survival of reirradiation with Proton therapy for recurrent meningiomas. Methods Recurrent meningioma who failed after radiotherapy were re-irradiated with active scanning proton therapy with a median dose of 54 GyRBE (range 50.4-60 GyRBE). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The log rank test was performed to compare the entire survival experience between groups (significant p-value ≤ 0.05). Associations between qualitative variables were analyzed with the Fisher exact test (significant p-value ≤ 0.05). Results Thirty-two patients were re-irradiated with Proton therapy (10 grade I, 22 grade II-III). Median tumor volume at the time of re-irradiation was 43 cc (range 1.2-225.5) and median time from prior RT to reirradiation was 66 months (range 4-288). At a median follow-up of 27 months, 1-yr and 2-yr PFS were 89.4% and 74.5% (1-yr and 2-yr PFS were 100% for grade I, 100% and 76% for grade II, 66% and 50% for grade III). 1-yr and 2-yr OS were 86.6% and 83.0% (2-yr OS were 87% for grade I, 86% for grade II, 66% for grade III). Local recurrence rate was 34% with a median time of recurrence of 13.4 months. Five patients (14%) developed radionecrosis with a median time of 3.4 months from the end of PT (range 3-8.8). Conclusions Re-irradiation with proton therapy seems to be a safe and effective treatment in patients with recurrent meningioma, also for large volume and aggressive lesions (grade II-III).

Neuroblastic tumors (NTs) represent the most common extracranial neoplasm occurring in childhood. Although ganglioneuroblastoma intermixed (GNBI) and ganglioneuroma (GN) are classified as very low-risk tumors, neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) may represent a serious risk to survival. Unfortunately, areas of GNBI and GNBN can coexist in the same mass, leading to incorrect risk staging when only biopsy is performed. Herein, we describe a case of multifocal NT (thoracic and abdominal localization) occurring in a 4-year-old male. Different histological subtypes, namely GNBI and GNBN, were revealed in the two lesions. We focus on the difficulties of proper diagnosis and risk stratification, underlining the usefulness of several diagnostic tools for appropriate management and therapeutic choices.

Central nervous system (CNS) metastatic spread in neuroblastoma (NB) is rare and occurs more often at relapse/progression. We report on CNS involvement in high risk (HR) NB over 25 years. For this retrospective study, we reviewed the CNS imaging of all the patients treated at Bambino Gesù Children Hospital from 1 July 1996 to 30 June 2022. A total of 128 patients with HR NB were diagnosed over 26 years. Out of 128 patients, CNS metastatic spread occurred in 6 patients: 3 patients presented a metastatic spread at diagnosis, while in 3 patients, CNS was involved at relapse. Overall, the rate of occurrence of CNS spread is 4.7% with the same distribution at diagnosis and at relapse, namely 2.3%. Interestingly, CNS spread at diagnosis was observed only before 2012, whereas CNS was observed at relapse only after 2012, in the immunotherapy era. CNS metastases presented similar imaging features at diagnosis and at relapse, with a peculiar hemorrhagic aspect and mainly hemispheric localization in patients with bone skull involvement at the time of diagnosis. The outcome is dismal, and 3 out of 6 patients died for progressive disease.

Patients with rhabdomyosarcoma (RMS) whose disease relapses have little chance of being cured, so front-line treatments are usually followed up with surveillance imaging in an effort to detect any recurrences as early as possible, and thereby improve post-relapse outcomes. The real benefit of such routine surveillance imaging in RMS remains to be demonstrated, however. This retrospective, single-center study examines how well surveillance imaging identifies recurrent tumors and its impact on post-relapse survival.The analysis concerned 79 patients21 years old treated between 1985 and 2020 whose initially localized RMS relapsed. Clinical findings, treatment modalities, and survival were analyzed, comparing patients whose relapse was first suspected from symptoms they developed (clinical symptoms group) with those whose relapse was identified by radiological surveillance (routine imaging group).Tumor relapses came to light because of clinical symptoms in 42 cases, and on routine imaging in 37. The time to relapse was much the same in the two groups. The median overall survival (OS) and 5-year OS rate were, respectively, 10 months and 12.6% in the clinical symptoms group, and 11 months and 27.5% in the routine imaging group (p-value .327). Among patients with favorable prognostic scores, survival was better for those in the routine imaging group (5-year OS 75.0% vs. 33.0%, p-value .047).It remains doubtful whether surveillance imaging has any real impact on RMS relapse detection and patients' post-relapse survival. Further studies are needed to establish the most appropriate follow-up recommendations, taking the potentially negative effects of regular radiological exams into account.

Patients with relapsing rhabdomyosarcoma (RMS) pose a therapeutic challenge, and the survival rate is reportedly poor. We describe a retrospective series of relapsing RMS patients treated at a referral center for pediatric sarcoma, investigating the pattern of relapse, salvage rates, and factors correlating with final outcomes.The analysis concerned 105 patients21 years old treated from 1985 to 2020 with initially localized RMS at first relapse. For risk-adapted stratification purposes, patient outcomes were examined using univariable and multivariable analyses based on patients' clinical features at first diagnosis, first-line treatments, clinical findings at first relapse, and second-line treatments.First relapses occurred 0.08-4.8 years (median 1 year) following initial diagnosis and were local/locoregional in 59% of cases. Treatment at first relapse included chemotherapy in all but two cases, radiotherapy in 38, and surgery in 21. Median event-free survival (EFS) after first relapse was 4 months, while 5-year EFS was 16.3%; median overall survival (OS) was 9 months, while 5-year OS was 16.7%. Several variables influenced survival rates. Considering only clinical findings and treatment at relapse, Cox's multivariable analysis showed that OS correlated significantly with time to relapse, radiotherapy administered at relapse, response to chemotherapy, and whether a second remission was achieved.Survival following first relapse of patients with localized RMS at initial diagnosis is poor. The variables found to influence survival can be utilized in a risk-adapted model to estimate the chances of salvage to guide decisions for second-line treatments.

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.

Recurrence incidence for paediatric/adolescent high-grade glioma (HGG) exceeds 80%. Reirradiation (reRT) palliates symptoms and delays further progression. Strategies for reRT are scarce: we retrospectively analysed our series to develop rational future approaches.We re-evaluated MRI + RT plans of 21 relapsed HGG-patients, accrued 2010-2021, aged under 18 years. All underwent surgery and RT + chemotherapy at diagnosis. Pathologic/molecular re-evaluation allowed classification based on WHO 2021 criteria in 20/21 patients. Survival analyses and association with clinical parameters were performed.Relapse after 1st RT was local in 12 (7 marginal), 4 disseminated, 5 local + disseminated. Re-RT obtained 8 SD, 1 PR, 1PsPD, 1 mixed response, 10 PD; neurological signs/symptoms improved in 8. Local reRT was given to 12, followed again by 6 local (2 marginal) and 4 local + disseminated second relapses in 10/12 re-evaluated. The 4 with dissemination had 1 whole brain, 2 craniospinal irradiation (CSI), 1 spine reRT and further relapsed with dissemination and local + dissemination in 3/four assessed. Five local + disseminated tumours had 3 CSI, 1 spine reRT, further progressing locally (2), disseminated (1), n.a. (1). Three had a third RT; three were alive at 19.4, 29, 50.3 months after diagnosis. Median times to progression/survival after re-RT were 3.7 months (0.6-16.2 months)/6.9 months (0.6-17.9 months), improved for longer interval between 1st RT and re-RT (P = 0.017) and for non-PD after reRT (P 0.001). First marginal relapse showed potential association with dissemination after re-RT (P = 0.081).This is the biggest series of re-RT in paediatric HGG. Considering the dissemination observed at relapse, our results could prompt the investigation of different first RT fields in a randomized trial.

The prognosis for patients with metastatic rhabdomyosarcoma (RMS) remains largely unsatisfactory despite the adoption of intensive multimodal therapy. To assess the role of different treatments adopted over the years, we retrospectively analyzed a cohort of patientslt;21 years old with metastatic RMS, treated from 1990 to 2020 at a referral center for pediatric sarcomas.Patients were treated using a multimodal approach that included surgery, radiotherapy, and chemotherapy (both high-dose chemotherapy and maintenance therapy in some cases). The type of radiotherapy administered was categorized as radical (to all sites of disease); partial (to at least one, but not all sites of disease); or none. A landmark analysis was used to examine the impact of radiotherapy on survival, that is, patients who had an event before day 221 were excluded from the analysis.The series included 80 patients. Event-free survival (EFS) and overall survival (OS) rates at 5 years were 17.3% and 21.3%, respectively. Survival was significantly associated with radiotherapy to metastatic sites, and with the radiotherapy category. In particular, 5-year EFS and OS rates were 70.6% and 76.0% for patients given radical radiotherapy, and 4.8% and 10.7%, respectively, for those given partial radiotherapy or none. Using the Cox multivariable analysis, OS correlated significantly with radiotherapy category.While confirming the poor overall outcome of patients with metastatic RMS, this study identified radiotherapy-when given to all sites of disease (including metastases)-as the main variable influencing survival.

Each year approximately 35,000 children and adolescents are diagnosed with cancer in Europe. Five-year survival rates have improved and now reach 80% in most European countries, thanks to a combination of chemotherapy, radiotherapy, and surgery. To date, there are more than 44,000 Italians still living several years after being diagnosed with cancer in developmental age. The risk of premature morbidity and mortality for cancer survivors is well known and documented. Approximately 60% of survivors of cancer in childhood and adolescence have at least one chronic health condition in later life, and more than one in four develop severe or life-threatening disorders. Among the various long-term iatrogenic sequelae of cancer treatments, the most worrisome are second malignant neoplasms. We reported on our mono-institutional experiences of screening and treating secondary breast cancer, secondary thyroid cancer and secondary osteosarcoma. Recommendations on the surveillance needed for cancer survivors because of the risk of late effects of their disease or its treatment suggest that discussing the potential problems early on can be crucial to a patient’s future health. These considerations and our consolidated experience strengthen our conviction that survivors of cancer in childhood and adolescence who develop second malignant neoplasms should be treated at highly-specialized centers. Multidisciplinary care requires close communications and high levels of up-to-date professional expertise. This challenging area of health care is also changing rapidly because cancer survivorship is a work in progress, but we cannot wait for definitive conclusions on many aspects because this will take decades, especially for pediatric patients.

OBJECTIVES: To provide an overview of the impact of the pandemic on the clinical activity and take a snapshot of the contingent challenges that European particle therapy centers are called to face, we surveyed the members of the European Particle Therapy Network (EPTN). MATERIAL AND METHODS: A 52-question survey was conducted from 4th April 2021 to 30th July 2021 using the Google Forms platform. Three dedicated sections analysed the clinical context of each participating institution, the staff management, and the clinical changes in the oncological workflow. RESULTS: Out of the 23 contacted European hubs of particle radiotherapy, a total of 9 (39%) responded to the survey. The number of in-person first evaluations and follow-up visits decreased, but telemedicine was implemented. Multidisciplinary tumour board discussions continued during the outbreak using web-based solutions. A delay in cancer diagnosis and oncological staging leading to an increment in more advanced diseases at first presentation was generally observed. Even if the total number of treatments (photons and particles) in the responding institutions showed a trend of decrease, there was or a stable situation or slight increase in particle treatments. The clinical treatment choices followed the national and international scientific recommendations and were patient/disease-oriented. Hypofractionation and short-schedule of chemotherapy, when applicable, were preferred. CONCLUSIONS: Our findings show a rapid and effective reaction of European particle RT hubs to manage the healthcare crisis. Considering the new waves and virus variants, the vaccination campaign will hopefully reduce the oncological impacts and consequences of the prolonged outbreak. ispartof: CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY vol:34 pages:1-6 ispartof: location:Ireland status: published

BACKGROUND: The purposes of this trial were to evaluate the feasibility, response, PFS/OS of a randomized study comparing two different RT schedules for DIPG while administering the same systemic treatment. METHODS: Patients: 2-21 years-old with a not-pretreated radiologically verified DIPG (MRI blindly reviewed at diagnosis and every 12 weeks thereafter) and symptoms duration below 6 months. Biopsy was required if suggested by atypical imaging. Vinorelbine 20 mg/m2+nimotuzumab 150 mg/m2 were administered weekly for 12 weeks; thereafter every other week until tumor progression or for up to 2 years. Standard(ST) arm included focal RT at total dose of 54Gy (1.8Gy/day); for local progression re-irradiation was proposed at 19.8Gy, in case of dissemination craniospinal irradiation(CSI) at 36Gy was adopted. Experimental(SP) arm included three elective courses of RT at defined timepoints at 36Gy, 19.8Gy and 19.8Gy with possible reirradiation for relapse at 9 Gy. Incidences of local(L) and distant(D) progression were assessed in a competing risk setting. RESULTS: Aggregated preliminary results are given for 4 Italian centers. 54 pts were screened and 51 included, 27 in ST, 28 males, median age 7 years (range 3-17). Median time of observation was 17.9 months. Twelve patients needed a shunt, 10 during treatment; 20 were biopsied, in 18 cases according local protocols. 19/20 tumors had H3.3 K27 mutation. 41 relapsed, 28 locally, 13 with a component of dissemination. 36 died, one for tracheotomy bleeding. SP irradiation was feasible and never produced significant radionecrosis. Median EFS/OS were 7.3/12.9 months, respectively; EFS/OS at 1 year were 19.0%/57.3%, not differing between patients with local vs. disseminated relapses. Patients submitted to biopsies had more dissemination (P=0.04) and less local progression (P=0.077). CONCLUSIONS: Treatment was feasible and OS confirmed previous results obtained in a single center. Randomization results will be later reported.

Proton therapy (PT) represents an advanced form of radiotherapy with unique physical properties which could be of great advantage in reducing long-term radiation morbidity for cancer survivors. Here, we aim to describe the whole process leading to the clinical implementation of consolidative active scanning proton therapy treatment (PT) for mediastinal lymphoma.The process included administrative, technical and clinical issues. Authorization of PT is required in all cases as mediastinal lymphoma is currently not on the list of diseases reimbursable by the Italian National Health Service. Technically, active scanning PT treatment for mediastinal lymphoma is complex, due to the interaction between actively scanned protons and the usually irregular and large volumes to be irradiated, the nearby healthy tissues and the target motion caused by breathing. A road map to implement the technical procedures was prepared. The clinical selection of patients was of utmost importance and took into account both patient and tumor characteristics.The first mediastinal lymphoma was treated at our PT center in 2018, four years after the start of the clinical activities. The treatment technique implementation included mechanical deep inspiration breath-hold simulation computed tomography (CT), clinical target volume (CTV)-based multifield optimization planning and plan robustness analysis. The ultimate authorization rate was 93%. In 4 cases a proton-photon plan comparison was required. Between May 2018 and February, 2021, 14 patients were treated with consolidative PT. The main clinical reasons for choosing PT over photons was a bulky disease in 8 patients (57%), patient's age in 11 patients (78%) and the proximity of the lymphoma to cardiac structures in 10 patients (71%). With a median follow-up of 15 months (range, 1-33 months) all patients but one (out-of-field relapse) are without evidence of disease, all are alive and no late toxicities were observed during the follow-up period.The clinical implementation of consolidative active scanning PT for mediastinal lymphoma required specific technical procedures and a prolonged experience with PT treatments. An accurate selection of patients for which PT could be of advantage in comparison with photons is mandatory.

To comprehensively describe the treatment of mediastinal lymphoma by pencil beam scanning (PBS) proton therapy.Fourteen patients underwent PBS proton treatment in a supine position in deep inspiration breath-hold (DIBH). Three DIBH computed tomography (CT) scans were acquired for each patient to delineate the Internal Target Volume (ITV). Intensity-modulated proton therapy (IMPT) was planned by min-max robust optimization on the ITV, with a 6 mm setup and 3.5% range uncertainties. Robustness analysis was performed and dose coverage was visually inspected on the corresponding voxel-wise minimum map. Layer repainting was set equal to 5 to compensate for cardiac motion. Intra-fraction reproducibility during treatment was assessed by repeated daily DIBH X-ray imaging. Finally, an additional CT was acquired at half treatment to estimate the impact of inter-fraction dosimetric reproducibility.IMPT guaranteed robust mediastinal target coverage and organs-at-risk sparing. However, visual voxel-wise robustness evaluation showed that in five patients a second optimization with focused objectives in the cost-function was necessary to achieve a robust coverage of the target regions at the interface between lungs and soft tissue. In six patients, repainting was not used due to excessive treatment time length and poor patient compliance. Intra-fraction average reproducibility was within 1 mm/1degree. On repeated CT scans, inter-fraction setup errors and/or anatomical changes showed minimal dosimetric differences in CTV coverage.IMPT in DIBH is effective and reproducible to treat mediastinal lymphomas. Caution is recommended to guarantee robust dose delivery to high-risk regions at the interface between lungs and soft tissue.

A PENTEC review of childhood cancer survivors who received brain radiation therapy (RT) was performed to develop models that aid in developing dose constraints for RT-associated central nervous system (CNS) morbidities.A comprehensive literature search, through the PENTEC initiative, was performed to identify published data pertaining to 6 specific CNS toxicities in children treated with brain RT. Treatment and outcome data on survivors were extracted and used to generate normal tissue complication probability (NTCP) models.The search identified investigations pertaining to 2 of the 6 predefined CNS outcomes: neurocognition and brain necrosis. For neurocognition, models for 2 post-RT outcomes were developed to (1) calculate the risk for a below-average intelligence quotient (IQ) (IQ85) and (2) estimate the expected IQ value. The models suggest that there is a 5% risk of a subsequent IQ85 when 10%, 20%, 50%, or 100% of the brain is irradiated to 35.7, 29.1, 22.2, or 18.1 Gy, respectively (all at 2 Gy/fraction and without methotrexate). Methotrexate (MTX) increased the risk for an IQ85 similar to a generalized uniform brain dose of 5.9 Gy. The model for predicting expected IQ also includes the effect of dose, age, and MTX. Each of these factors has an independent, but probably cumulative effect on IQ. The necrosis model estimates a 5% risk of necrosis for children after 58.9 Gy or 59.9 Gy (2 Gy/fraction) to any part of the brain if delivered as primary RT or reirradiation, respectively.This PENTEC comprehensive review establishes objective relationships between patient age, RT dose, RT volume, and MTX to subsequent risks of neurocognitive injury and necrosis. A lack of consistent RT data and outcome reporting in the published literature hindered investigation of the other predefined CNS morbidity endpoints.

Background and purpose Proton therapy is the emerging treatment modality for craniospinal irradiation (CSI) in pediatric patients. Herein, special methods adopted for CSI at proton Therapy Center of Trento by pencil beam scanning (PBS) are comprehensively described. Materials and methods Twelve pediatric patients were treated by proton PBS using two/three isocenters. Special methods refer to: (i) patient positioning in supine position on immobilization devices crossed by the beams; (ii) planning field-junctions via the ancillary-beam technique; (iii) achieving lens-sparing by three-beams whole-brain-irradiation; (iv) applying a movable-snout and beam-splitting technique to reduce the lateral penumbra. Patient-specific quality assurance (QA) program was performed using two-dimensional ion chamber array and γ-analysis. Daily kilovoltage alignment was performed. Results PBS allowed to obtain optimal target coverage (mean D98%>98%) with reduced dose to organs-at-risk. Lens sparing was obtained (mean D1∼730cGyE). Reducing lateral penumbra decreased the dose to the kidneys (mean Dmean4cm (mean γ>95%) than at depths&nbsp

BackgroundProton beam therapy (PBT) is an effective pediatric brain tumor treatment. However, resulting microstructural changes within and around irradiated tumors are unknown. We retrospectively applied Diffusion-Tensor-Imaging (DTI) and Free-Water-Imaging (FWI) on diffusion-weighted Magnetic Resonance Imaging (dMRI) data to monitor microstructural changes during-PBT and after 8 months, in a pilocytic astrocytoma (PA) and normal-appearing white matter (NAWM).MethodsWe evaluated conventional MRI and dMRI-derived indices from six MRI sessions in a child with a hypothalamic PA: at baseline (t0), during-PBT (t1-t4), and after 8 months (t5). Tumor voxels were classified as “solid” or “fluid” based on FWI.ResultsWhile during PBT tumor volume remained stable, dMRI analyses identified two different response patterns: i) an increase in fluid content and diffusivity with anisotropy reductions in solid voxels at t1, followed by ii) smaller variations in fluid content but higher anisotropy in solid voxels at t2-t4. At follow-up (t5), tumor volume, its fluid content, and diffusivity in solid voxels increased. NAWM showed dose-dependent microstructural changes.ConclusionsThe use of dMRI and FWI showed complex dynamic microstructural changes in the irradiated mass during PBT and at follow-up, opening new avenues in our understanding of radiation-induced pathophysiologic mechanisms in tumor and surrounding tissues.

In this paper we present a modular framework to classify railway track areas regarding the expected presence of local GNSS threats. This information might be critical for a safe signalling operation, for example to determine where virtual balises could be placed safely. We show first how different GNSS threats can be detected using dedicated detection algorithms and how these individual detection results can be then transformed from time to the track domain. An overall decision logic is subsequently used to identify an area as suitable or unsuitable for GNSS usage by combining all available GNSS data collected over the same track area. Finally, the framework implementation is evaluated with railway data obtained during a measurement campaign in Sardinia, Italy in 2019. Even though developed in the railway context, the presented framework architecture and methodology may be also considered to perform similar classification tasks for other means of transport.

Background: Embryonal tumors represent a heterogeneous entity of brain tumors that need a multidisciplinary treatment including cranio-spinal irradiation (CSI), with a known impact on the acute toxicity. Proton therapy (PT) boasts a reduction in acute hematological toxicity. Methods: We retrospectively examined 20 pediatric patients affected by high-risk medulloblastoma and other rare embryonal brain tumors subjected to CSI with PT from September 2016 to April 2020. Before CSI, all patients received induction chemotherapy, and three patients additionally received two high-dose courses with thiotepa, followed by an autologous haemopoietic stem cell transplantation. We recorded the total white blood cell count, absolute neutrophil count, platelets, and hemoglobin levels for all patients during PT. Results: Leucocytes and neutrophils decreased directly after the beginning of treatment, reaching a complete recovery at the end of treatment. Hemoglobin values remained constant over the treatment course. The median platelet value decreased until reaching a plateau around halfway through therapy, followed by a slow increase. No cases of febrile neutropenia or severe infections were reported. No treatment discontinuation due to hematological toxicity was necessary. Conclusions: CSI with PT was proven to be safe in this setting of pediatric patients. Our study showed that despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with PT, and, therefore, no treatment was discontinued or delayed.

Purpose To present an advanced junction concept in craniospinal irradiation (CSI) by proton pencil beam scanning (PBS). Materials and methods In PBS CSI, whole brain irradiation (WBI) is commonly delivered by opposed lateral-beams, whereas spine irradiation is delivered by posterior entrances. Since lateral-beams would cross a large portion of the patient at the shoulder level, the junction between WBI and spine irradiation cannot extend below that level, thus the size of the lateral-beams needs to be limited and the number of required isocenters can increase. To overcome such limitation, a pseudo-junction was introduced below the posterior fossa, to turn in this region the WBI beam arrangement to a single posterior beam pointed at the same isocenter, that was matched to the posterior spinal beam more caudally, below shoulder level, in the true-junction. After assessing robustness of the technique to range and setup uncertainties, twenty-three treated patients were reviewed to estimate the percentage that might benefit of being treated by two instead of three isocenters. Results Target coverage at the junction levels resulted robust, with D95% > 95% on pseudo-junction and D95% > 90% on the true-junction. By the advanced junction concept, 91% of patients might by treated with only two isocenters, whereas, by the conventional method, 83% of patients required three isocenters. Conclusion With the presented junction concept the number of isocenters can be reduced, with a consequent relevant reduction of treatment time, which is particularly valuable in the management of pediatric patients under anesthesia.

Rosette-forming glioneuronal tumors (RGNTs) are rare, grade I, central nervous system (CNS) tumors typically localized to the fourth ventricle. We describe a 9-year-old girl with dizziness and occipital headache. A magnetic resonance imaging (MRI) revealed a large hypodense posterior fossa mass lesion in relation to the vermis, with cystic component. Surgical resection of the tumor was performed. A RGNT diagnosis was made at the histopathological examination. During follow-up, the patient experienced a first relapse, which was again surgically removed. Eight months after, MRI documented a second recurrence at the local level. She was a candidate for the proton beam therapy (PBT) program. Three years after the end of PBT, the patient had no evidence of disease recurrence. This report underlines that, although RGNTs are commonly associated with an indolent course, they may have the potential for aggressive behavior, suggesting the need for treatment in addition to surgery. Controversy exists in the literature regarding effective management of RGNTs. Chemotherapy and radiation are used as adjuvant therapy, but their efficacy management has not been adequately described in the literature. This is the first case report published in which PBT was proposed for adjuvant therapy in place of chemotherapy in RGNT relapse.

Brain tumors are the most common solid neoplasms of childhood. They are frequently reported in children with Neurofibromatosis type 1 (NF1). The most frequent central nervous system malignancies described in NF1 are optic pathway gliomas and brainstem gliomas. Medulloblastoma (MB) in NF1 patients is extremely rare, and to our knowledge, only 10 cases without molecular characterization are described in the literature to date. We report the case of a 14-year-old girl with NF1 that came to our attention for an incidental finding of a lesion arising from cerebellar vermis. The mass was completely resected, revealing a localized classic medulloblastoma (MB), subgroup 4. She was treated as a standard-risk MB with a dose-adapted personalized protocol. The treatment proved to be effective, with minor toxicity. Brain and spine MRI one year after diagnosis confirmed the complete remission of the disease. To our knowledge, this is the only case of MB reported in a patient with NF1 with molecular characterization by the methylation profile. The association between NF1 and MB, although uncommon, may not be an accidental occurrence.

PURPOSE Diffusion kurtosis imaging (DKI) has not yet been tested for pediatric brain tumors. Estimating diffusion values from whole-tumor based (VOI) segmentations may improve diffusion measurement repeatability compared to conventional region-of-interest (ROI) approaches. Our purpose was to compare repeatability between ROI and VOI DKI-derived diffusion measurements and to assess VOI-based DKI accuracy in discriminating among pediatric posterior fossa tumors. MATERIALS AND METHODS We retrospectively analyzed 34 children (19 M, 15F, mean age 7.48 years) with posterior fossa tumors who underwent preoperative 3T MRI including DKI. For each patient, two neuroradiologists independently segmented the whole solid tumor (VOI), the area of maximum tumor diameter and a smallROI.Inter-observer variability was assessed with coefficient of variation (COV) and Bland-Altman plots. VOI-based DKI metrics accuracy in discriminating among tumor histology and for tumor grading were assessed with MANOVA and ROC analyses respectively. Correlation between grading accuracy and inter-observer variability was assessed with Spearman’s rho. RESULTS Tumor histology included medulloblastoma (15), pilocytic astrocytoma (14) and ependymoma (5). VOI-based measurements presented lower variability than ROI-based measurements across all DKI metrics. DKI-derived metrics could accurately discriminate between tumor subtypes (Pillai’s trace: p CONCLUSIONS DKI-derived metrics are useful for pediatric posterior fossa tumor discrimination and grading. VOI-based diffusion measurements present improved repeatability compared to ROI-based measurements and are significantly correlated to diagnostic accuracy.

Background Proton therapy has proven to be effective and safe in the treatment of radioresistant skull base tumors such as chordomas. Thanks to the peculiar physical properties of the proton beam, radiation energy is delivered in a narrow space called the Bragg peak and the surrounding normal tissues receive a minimal amount of the radiation dose. This is important to lower the risk of radiation-induced damage, especially in children. However, local adverse effects in proximity to the target volume may occur. In particular, the development of moyamoya syndrome (MMS) has been rarely reported in children receiving proton beam therapy for brain tumors. Case Description We report on a child who developed rapidly progressive MMS after proton beam therapy for a clivus chordoma. A combined indirect revascularization procedure by encephalo-duro-arterio-synangiosis and encephalo-myo-synangiosis was performed with good neuroradiologic and clinical outcome. Conclusions Regardless of the presence of known risk factors for MMS, strict neuroimaging surveillance is indicated in all patients treated with radiotherapy including those receiving proton beam therapy. We suggest that an early revascularization procedure should be considered in patients with worsening symptoms and/or sign of neuroradiologic progression of cerebral vasculopathy. This management of MMS could lower the risk of permanent neurologic deficits and improve patients' quality of life.

The purpose of this study was to compare the dose to heart, left anterior descending (LAD) artery and lung between proton and photon beam irradiation for left-sided early stage breast cancer.Ten women with early stage left-sided breast cancer were treated with breast conserving surgery and radiation. Whole breast radiation was delivered for actual treatment via a tangential technique with deep inspiration breath hold (DIBH) utilizing inverse planned intensity-modulated radiation therapy (IMRT). Each patient was replanned on an Institutional Review Board (IRB)-approved prospective study using en face proton beam radiation with both uniform scanning (US) and pencil beam scanning (PBS) techniques.Both PBS (0.011 Gy) and US (0.009 Gy) proton plans resulted in a significantly lower mean heart dose compared to IMRT (1.612 Gy) (p0.05 for PBS vs. IMRT and US vs. IMRT). The Dmean, Dmin, Dmax, and D0.2cm(3) of the LAD with either proton technique were significantly lower (p = 0.005) compared to IMRT. Both US and PBS reduced the mean dose to the lungs compared to IMRT. The coverage of the breast planning target volume was comparable between photon and proton plans.The dose to whole heart was relatively low in this study of patients treated under conditions of DIBH. However, proton beam radiation was associated with lower minimum, maximum, and dose to 0.2 cm(3) of the LAD, which is the critical structure for late radiation therapy effects, compared to even the most optimized photon beam plan with DIBH and IMRT.

Purpose To assess the feasibility of radiation therapy treatment planning 4-dimensional computed tomography (4DCT) and deep-inspiration breath-hold (DIBH) CT to accurately contour the left anterior descending artery (LAD), a primary indicator of radiation-induced cardiac toxicity for patients undergoing radiation therapy. Methods and Materials Ten subjects were prospectively imaged with a cardiac-gated MRI protocol to determine cardiac motion effects, including the displacement of a region of interest comprising the LAD. A series of planar views were obtained and resampled to create a 3-dimensional (3D) volume. A 3D optical flow deformable image registration algorithm determined tissue displacement during the cardiac cycle. The measured motion was then used as a spatial boundary to characterize motion blurring of the radiologist-delineated LAD structure for a cohort of 10 consecutive patients enrolled prospectively on a breast study including 4DCT and DIBH scans. Coronary motion–induced blurring artifacts were quantified by applying an unsharp filter to accentuate the LAD structure despite the presence of motion blurring. The 4DCT maximum inhalation and exhalation respiratory phases were coregistered to determine the LAD displacement during tidal respiration, as visualized in 4DCT. Results The average 90th percentile heart motion for the region of interest was 0.7 ± 0.1 mm (left–right [LR]), 1.3 ± 0.6 mm (superior–inferior [SI]), and 0.6 ± 0.2 mm (anterior–posterior [AP]) in the cardiac-gated MRI cohort. The average relative increase in the number of voxels comprising the LAD contour was 69.4% ± 4.5% for the DIBH. The LAD volume overestimation had the dosimetric impact of decreasing the reported mean LAD dose by 23% ± 9% on average in the DIBH. During tidal respiration the average relative LAD contour increase was 69.3% ± 5.9% and 67.9% ± 4.6% for inhalation and exhalation respiratory phases, respectively. The average 90th percentile LAD motion was 4.8 ± 1.1 mm (LR), 0.9 ± 0.4 mm (SI), and 1.9 ± 0.6 mm (AP) for the 4DCT cohort, in the absence of cardiac gating. Conclusions An anisotropic margin of 2.7 mm (LR), 4.1 mm (SI), and 2.4 mm (AP) was quantitatively determined to account for motion blurring and patient setup error while placing minimum constraint on the plan optimization.

The evolution plan of the European Railways Train Management System (ERTMS) includes the GNSS localization as one of the Game Changer technologies to improve the competitiveness of the ERTMS. GNSS will allow the implementation of cost-effective solutions to reduce the maintenance and operational cost without reducing the safety levels required by railway operations. The inherent low power of satellite navigation signals exposes GNSS-based solution to Radio Frequency threats, namely intentional or unintentional interference, that can lead to performance degradation or denial of service, and to spoofing/meaconing attacks, that can lead to receiver deception and hence to misleading PVT (Position, Velocity and Time) estimation. The aim of this paper is to present an architecture for detection and mitigation of radio-frequency hazards in a rail operational environment. The investigated solution is based on a Digital Beamforming Platform (DBP) coupled with advanced GNSS signal processing techniques for high rejection of GNSS interfering and counterfeit signals. This approach fully exploits the characteristics of the railway context, to support the evolution of the Location Determination System (LDS) based on GNSS in ERTMS Train Control System (TCS). This paper presents the DBP architectural design, focusing on the most meaningful and innovative solution foreseen for the prototype implementation. Each subsystem of the DBP is described in details, and a preliminary assessment of the performances is provided, by means of simulative and analytic tools.

The adoption of the GNSS for the European Rail Train Management System – ERTMS is one of the objectives included into the ERTMS evolution plan to improve its competitiveness on the market. To this aim, in 2015 the European Global Navigation Satellite System Agency (GSA) approved the “ERTMS on SATELLITE –Enabling Application Validation (ERSAT–EAV)”, project with the object to verify the suitability of GNSS to generate Virtual Balises as an alternative/complement means to the physical balises prescribed by the ERTMS. The architecture of ERSAT EAV – based on joint use of multiple constellations and public augmentation networks - would be a contribution to foster cost-effective ERTMS solutions, primarily for the local and regional lines in Europe for which the economical sustainability is a priority. The paper describes the hazard’s mitigation techniques affecting the on board GNSS receiver when operating in harsh environments, and the scenarios for a smooth introduction of GNSS into the ERTMS system. Field test results carried out on a Test Bed implemented on a 50km line in Sardinia are presented and discussed.

INTRODUCTION: Proton therapy (PT) is a radiation therapy in increasing use for paediatric cerebral tumours, as in medulloblastoma. Although publications to date are relatively limited, they however include cases of potential development of radionecrosis. The aim of this study has been to compare our experience with data found in literature relating to the insurgence of premature radionecrosis, evaluating incidence, timing, appearance of clinical symptoms, risk factors and radiological characteristics. MATERIALS AND METHODS: We have retrospectively analysed 10 children with high risk medulloblastoma using protons on the cranio-spinal axis with a dose equal to 36 Gy RBE and with a successive higher dose in the posterior cranial fossa of 18 Gy RBE, at the PT Centre in Trento. All patients underwent PT, post-surgery on the primary tumour and intensive myeloablative chemotherapy: both are two potential risk factors in the appearance of premature radionecrosis. All the patients also underwent MRI on the brain and bone marrow, before and after proton therapy treatment, at an interval of 1 month at the end of PT and then every 3 months. RESULTS: In our clinical records in a median follow up of 4.9 months we did not encounter cases of radionecrosis according to the definition criteria as discussed or published in the consulted publications. CONCLUSIONS: The paediatric patients with high risk medulloblastoma undergoing treatment with proton therapy, the subjects of our study, presented a lower risk to premature radionecrosis in respect to the data present in current publications.

Purpose. The purpose of this study was to compare the dose to heart, left anterior descending (LAD) artery and lung between proton and photon beam irradiation for left-sided early stage breast cancer. Material and methods. Ten women with early stage left-sided breast cancer were treated with breast conserving surgery and radiation. Whole breast radiation was delivered for actual treatment via a tangential technique with deep inspiration breath hold (DIBH) utilizing inverse planned intensity-modulated radiation therapy (IMRT). Each patient was replanned on an Institutional Review Board (IRB)-approved prospective study using en face proton beam radiation with both uniform scanning (US) and pencil beam scanning (PBS) techniques. Results. Both PBS (0.011 Gy) and US (0.009 Gy) proton plans resulted in a significantly lower mean heart dose compared to IMRT (1.612 Gy) (p < 0.05 for PBS vs. IMRT and US vs. IMRT). The Dmean, Dmin, Dmax, and D0.2cm3 of the LAD with either proton technique were significantly lower (p = 0.005) compared to IMRT. Both US and PBS reduced the mean dose to the lungs compared to IMRT. The coverage of the breast planning target volume was comparable between photon and proton plans. Conclusions. The dose to whole heart was relatively low in this study of patients treated under conditions of DIBH. However, proton beam radiation was associated with lower minimum, maximum, and dose to 0.2 cm3 of the LAD, which is the critical structure for late radiation therapy effects, compared to even the most optimized photon beam plan with DIBH and IMRT.

Chordoma is a slow-growing neoplasm arising from remnants of the embryonic notochord. Surgery is recognized as the gold standard approach, however gross total resection is rarely possible for this reason most patients undergo subtotal resection or biopsy followed by radiotherapy. Myasthenia gravis (MG) is neuromuscular autoimmune disorder .The feasibility and safety of radiotherapy and especially of proton therapy (PT) in patients affected by MG has never been adequately documented. We report the case of a patient with lumbar chordoma who was diagnosed of MG just at the beginning of PT.

Radiation therapy is a part of multidisciplinary management of several childhood cancers. Proton therapy is a new method of irradiation, which uses protons instead of photons. Proton radiation has been used safely and effectively for medulloblastoma, primitive neuro-ectodermal tumors, craniopharyngioma, ependymoma, germ cell intracranial tumors, low-grade glioma, retinoblastoma, rhabdomyosarcoma and other soft tissue sarcomas, Ewing’s sarcoma and other bone sarcomas. Moreover, other possible applications are emerging, in particular for lymphoma and neuroblastoma. Although both photon and proton techniques allow similar target volume coverage, the main advantage of proton radiation therapy is to sparing of intermediate-to-low-dose to healthy tissues. This characteristic could translate into clinical reduction of side effects, including a lower risk for secondary cancers. The following review presents the state of the art of proton therapy in the treatment of pediatric malignancies.

Radiation therapy (RT) is the mainstay of treatment of solitary plasmacytoma. In most cases, doses ranging from 40 to 50 Gy yield in a local control more than 80%. However, the prognosis of patients with SP is marked by a high rate of transformation to multiple myeloma (MM), and there is no demonstrated benefit of adjuvant chemotherapy for decreasing this probability. However, clinical benefits could be reached from improving screening for other primary sites of plasmacytoma and earlier discovering signs suggestive of MM. Since such strategy could provide significant information regarding both prognosis and therapy, it has become first importance to improve initial staging of tumor widespread. Although conventional skeletal X-ray survey remains standard, usual sensitivity of radiographies does not permit diagnosing early myeloma lesions and a significant number of patients with supposed SP might be understaged and do not receive the appropriate treatment. The development of more sensitive and specific imaging modalities will make it feasible to earlier detect subclinical lesions, thus leading lead to new approaches in the treatment strategies. Here, we discuss the benefits and limitations of magnetic resonance imaging and positron emission tomography for primary staging of patients with solitary plasmacytoma. Both imaging modalities could also improve target volume delineation and assessment of tumor response after RT.

Purpose Proton therapy reduces lung dose and mean heart dose in breast cancer irradiation in adjuvant breast cancer, in particular with nodal involvement [1] . In this work we compare 10 selected intensity modulated photon therapy (IMXT) treatment cases selected from the sending institution with PBS proton therapy. Methods and materials The eligibly criteria of the sending institution were: poor coverage of the target volumes, unfavourable dose volume histograms (DVH) to the organs at risk (OAR) lung and heart or wide irradiated volume (IV) with static IMXT. The type of case were heterogeneous as shown in Table 1. All plans were performed on the CT and volumes send applying a class solution of 3 proton field with range shifter with treatment planning system (TPS) Raystation. All plans were performed in robust Single Field Optimization technique (rSFO) optimizing the target and the OAR heart and the ipsilateral lung. The optimization was done with clinical pencil beam algorithm and 5 mm geometrical robust optimization tool provided by the TPS. No robust optimization of the range was applied. Results Comparing the proton and photon plans there was a significant improvement in at least one of the following parameter: IV, DVH of lung, DVH of heart for each case (e.g. Fig. 1). Conclusion The results of this study are promising. The heuristic eligibility method provide positive answer in 100% of the cases. Further work are necessary to assess role of range errors of proton peak.

BACKGROUND: To report preliminary results of re-irradiation with proton therapy (PT) with or without chemotherapy (CHT) in difficult-to-treat recurrent glioblastoma (rGBM): patients (pts) were selected for PT because of the large tumor size or proximity to dose-limiting organs at risk that previously had received near-maximum dose tolerance during the first radiation course MATERIAL AND METHODS: Between January 2015 and January 2018, 34 pts with rGBM were re-irradiated with PT. All pts had been previously treated with Stupp regimen. Twenty-nine (85%) were re-irradiated at first relapse/progression, 5 at the second/third one. Nine pts (26%) were re-irradiated after partial tumor resection. Median (med) age and KPS at re-irradiation were 56 years and 90%, respectively. Med time between prior radiotherapy and PT was 13 months. Target definition was based on CT, MR, and 18F-DOPA PET imaging. Gross Tumor Volume (GTV) included any area of contrast enhancement after contrast medium administration plus any pathological PET uptake regions. Clinical Target Volume (CTV) was generated by adding to GTV a 3-mm margin. Med CTV volume was 47 cc (range, 13–153 cc). All pts received 36 GyRBE in 18 fractions. PT was delivered with or without chemotherapy as follows: eight (23.5%) pts (Group 1) also received concomitant TMZ (75 mg/m2/die, 7 days/week); 4 (12%) pts (Group 2) also received concomitant (as above) and adjuvant TMZ (150–200 mg/m2/die, 5 days/month); 9 (26.5%) pts (Group 3) received PT only; 13 (38%) pts (Group 4) received PT followed by CHT (different regimens/drugs). All pts were treated with active pencil beam scanning PT. Registered side effects were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment response was assessed according to Response Assessment in Neuro-Oncology criteria. Survival and progression-free survival after re-irradiation were calculated from initiation of PT until tumor progression or death (by any cause), using the Kaplan Meier method RESULTS: All pts completed the treatment without breaks. There were no grade 3 or higher acute toxicities. One pts developed TMZ-related grade 1 neutropenia. There were no grade 3 or higher late toxicities. During follow-up five pts (15%) developed radionecrosis (diagnosed at imaging) with mild symptoms controlled with steroids. The med progression-free survival (PFS) was 6.3 months, while 6-month PFS rate was 60%. The med PFS was 6.8, 4.3, 5.4, and 5.5 for Group 1-2-3-4, respectively. Med overall survival (OS) after PT was 10.7 months CONCLUSION: PT re-irradiation of difficult-to-treat rGBM showed to be feasible and safe even with concomitant and adjuvant chemotherapy administration. Despite the small number of patients of this series and the retrospective nature of the study PFS and OS rates are promising and deserve further evaluation in a larger pts sample to assess the most effective strategy