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Purpose Our aim was to determine the main risk factors related to the occurrence of permanent alopecia in adult survivors of childhood medulloblastoma (MB) to improve their quality of life. Methods We retrospectively analysed the clinical features of all consecutive survivors of MBtreated at our Institute. We divided the patients into 3 groups depending on the craniospinal irradiation (CSI) dose received and defined permanent alopecia first in terms of the skin region affected (whole skin and nape region) then on the basis of the toxicity degree (G). Any relationship between alopecia and other characteristics was investigated by a univariate and multivariate analysis and Odds ratio (OR) with confidence interval (CI) was reported. Results We analysed data from 41 patients with a 10-year follow-up. High dose of CSI was found to be the independent factor leading to permanent hair loss in both groups: alopecia of the whole skin (G1 p-value 0.030, G2 p-value 0.003) and of the nape region (G1 p value 0.038, G2 p value 0.006). The posterior cranial fossa (PCF) boost volume and dose were not significant at multivariate analysis neither in permanent hair loss of the whole skin nor only in the nuchal region. Conclusion In paediatric patients with MB, the development of permanent alopecia seems to depend only on the CSI dose exceeding 36 Gy. Acute damage to the hair follicle is dose dependent, but in terms of late side effects, constant and homogeneous daily irradiation of a large volume may have a stronger effect than a higher but focal dose of radiotherapy.

Background More than 40% of patients with intracranial ependymoma need a salvage treatment within 5 years after diagnosis, and no standard treatment is available as yet. We report the outcome after first relapse of 64 patients treated within the 2nd AIEOP protocol. Methods We considered relapse sites and treatments, that is, various combinations of complete/incomplete surgery, if followed by standard or hypofractionated radiotherapy (RT) ± chemotherapy (CT). Molecular analyses were available for 38/64 samples obtained at first diagnosis. Of the 64 cases, 55 were suitable for subsequent analyses. Results The median follow-up was 147 months after diagnosis, 84 months after first relapse, 5-year EFS/OS were 26.2%/30.8% (median EFS/OS 13/32 months) after relapse. For patients with a local relapse (LR), the 5-year cumulative incidence of second LRs was 51.6%, with a 5-year event-specific probability of being LR-free of 40.0%. Tumor site/grade, need for shunting, age above/below 3 years, molecular subgroup at diagnosis, had no influence on outcomes. Due to variation in the RT dose/fractionation used and the subgroup sizes, it was not possible to assess the impact of the different RT modalities. Multivariable analyses identified completion of surgery, the absence of symptoms at relapse, and female sex as prognostically favorable. Tumors with a 1q gain carried a higher cumulative incidence of dissemination after first relapse. Conclusions Survival after recurrence was significantly influenced by symptoms and completeness of surgery. Only a homogeneous protocol with well-posed, randomized questions could clarify the numerous issues, orient salvage treatment, and ameliorate prognosis for this group of patients.

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13–38.00 vs. 40.93 months, 95% CI: 40.93–40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the “tip of the iceberg”, by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT.

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.

We report two cases of malignant mesothelioma (MM) in childhood brain tumor survivors. A 40-year-old man, who was treated at the age of ten with chemotherapy and craniospinal radiotherapy (up to 54.5 Gy) for a pineal secreting non-germinomatous germ cell tumor, had persistent fever, fatigue, and weight loss. A total body CT scan revealed several pulmonary and abdominal wall nodularities. The histological examination on a biopsy diagnosed a biphasic MM. The karyotype and array-CGH of peripheral blood were normal; a FISH of tumor cells showed a breakage of locus EWSR1 (22q12.2). In this case, environmental exposure was identified (asbestos in public water tanks). His MM followed an aggressive course and resulted in death after three months. A twelve-year-old boy affected by severe neurofibromatosis type 2 (NF2) already treated with several neurosurgical exeresis and chemotherapy lines (hydroxycarbamide, bevacizumab, sirolimus), developed multiple abdominal lesions, associated with pleural effusion and weight loss. The CT scan showed the thickening of the left pleura and multiple peritoneal nodules. The cytological examination on thoracentesis diagnosed an epithelioid MM. The karyotype on paracentesis-obtained cells revealed monosomy of chromosomes 14 and 22, loss of Y, and trisomy of 6, 10, 11, 16, and 20. NGS is currently ongoing to exclude germline or somatic second hits. Importantly, no exposure to asbestos was found. Less than 2% of MMs occur below 45 years of age; it is a rare secondary tumor in cancer survivors and environmental or genetic contributing causes are often detectable on a careful investigation. Variants in NF2 are considered to be the second most common after those in BAP1. To our knowledge, this is the first child with NF2 and concurrent MM reported to date. Compared to the expected prognosis, his MM has followed a mild course, and one year after diagnosis he is still alive.

AIMS: We report a cohort of YCMB cases homogeneously treated with HDCT in two Italian institutions, and the prognostic impact of histology and genetics retrospectively evaluated. METHODS: All YCMB (aged≤3 years) treated with upfront HDCT in the period 1998-2019 were included, reclassified according to the WHO2021 classification of CNS tumours. Mutational status ofPTCH1, SUFU, and TP53 was analysed in selected cases. Histology and genetics were correlated with survival, secondary tumours(STs), and cancer predisposition syndromes(CPSs). RESULTS: Fifty-three patients were enrolled (62.3% male), median age 2.2 years. 21 had classic(CMB), 15 desmoplastic/nodular(DMB), 11 MBEN and 6 large-cell/anaplastic(AMB/LCMB) medulloblastoma. Metastases were present in 18. Genomic pattern showed SHH-TP53wt in 29 cases, non-WNT/non-SHH in 22; 2 were SHH-TP53mut. Induction chemotherapy (VCR/HDMTX, HDVP16, VCR/HDCTX and HDCARBO) was followed by 2-3 HDCT courses; irradiation reserved to cases with metastatic disease and/or residual tumours. 22 patients never received irradiation. SHH-TP53wt cases had significantly less metastasis (p=0.002), while non-WNT/non-SHH received more often irradiation (p

BACKGROUND: Permanent alopecia in adult survivors of childhood cancer is a late effect that has a negative impact on vitality and social function, and it is not clear if it is only associated with radiotherapy or also with high-dose chemotherapy. In this study, we analysed a cohort of medulloblastoma survivors treated with craniospinal irradiation (CSI) with long follow-up looking for radiotherapy parameters associated with permanent hair loss. METHODS: We retrospectively analysed 42 patients with medulloblastoma with median follow up of 10 years. In 27 pts, Eclipse subgroup, the scalp was accurately re-contoured and were estimated specifics dosimetric parameters. Any relationship between presence of alopecia and other characteristics was investigated by univariate and multivariate analysis, in both groups. For each significant predictor variable, a Receiver Operating Characteristic curve was drawn for calculating the Area Under the Curve and identifying the optimal dose discriminatory cut-off value for prediction of alopecia. RESULTS: The best predictor for the occurrence of permanent alopecia was the dose of CSI (OR: 1.002; 95%CI: 1.001-1.003; p=0.003), with a cut-off value of 30.9 Gy. In Eclipse subgroup median Dose hair skin was statistically significant, (OR: 1.216; 95%CI: 1.030-1.435; p=0.021), with a cut-off value of 28.7 Gy. If the median dose of each Gy unit of D median is exceeded, the probability of alopecia increases by 21.6% (3.0% - 43.5%), with a specificity of 90.9%. None of the other variables was statistically significant. CONCLUSIONS: Pediatric Medulloblastoma survivors have a high risk of developing permanent alopecia.Our study supports the finding that permanent hair loss is dose-dependent and identified a threshold dose, the median dose of 28.7 Gy, to prevent the occurrence of permanent alopecia in paediatric patients undergoing radiotherapy. Therefore, we suggest that this dosimetric parameter should be evaluated when planning radiation treatment, especially when planning CSI in low- and standard-risk medulloblastoma.

Enrolling medulloblastoma(MB) patients in the PNET5 protocol is a daily problem in Italy; since June 2015, 59 cases have been enrolled in 13 centres. So far, 44 of the 103 patients claiming for eligibility did not enter the protocol: 13 metastases, 5 for residual, 20 having exclusion criteria, 4 insufficient frozen material, 2 failure to comply with the correct procedures. No case was lost due to delayed centralization, which is respected even with committing weekends; review of the radiation plan was performed on Saturday for 2 cases, and radiotherapy began on the same day. We made some procedural changes to meet expected deadlines; each local centre notifies the national coordinator of a possible case's existence at MRI diagnosis, of the expected surgery date as well as its realization. MRI imaging is reviewed within 2 days after centralization. Paediatricians notify the national coordinator and pathology/biology reference centre of the MB diagnosis; the shipment of frozen tissue, blood and FFPE is booked. A slot is reserved to priority perform the central pathology review, as well as central molecular diagnosis of genetically defined subgroup (WHO classification) upon receipt of the frozen material. Upon receipt of the FFPE and frozen material, the national reference centre undertakes a double-check with the national coordinator and the local treatment centre to validate the eligibility. Within the 7th day from the receipt of the material: IHC, MYC/MYCN, Monosomy 6, beta-catenin mutation and methylation array are performed. Priority execution of somatic (blood control) sequencing of the PTCH, SUFU, and TP53 genes is also triggered for SHH-activated MB, with the deadline on the 15th day. So far we have had 99% agreement between molecular subgrouping and methylation array. CONCLUSIONS: PNET5 requirements are multiple and changing over time; difficulties may and must be overcome by mutual fast collaboration.

BACKGROUND: Central hypothyroidism is a well-known late effect of radiotherapy in children treated for brain tumours. AIM: To determine the risk of central hypothyroidism (CH) and the radiation dose-volume predictors of its onset. METHODS: We retrospectively analyzed 64 patients who received radiotherapy for brain tumours, with at least a 2-year-long serological follow-up, determined CH incidence and radiation predictive factors of its onset. To estimate the risk of CH according to the site of the tumour inside the central nervous system (CNS) we considered the sellar-suprasellar region, anterior cranial region, and others. For the same purpose, a further analysis was conducted comparing craniospinal radiotherapy (CSI) versus involved-field radiotherapy (IF-RT). Dose constraints for CH were determined using the Receiver Operating Characteristic to identify the pituitary mean dose cut-off and the probability of CH over time was assessed with the Cox model. RESULTS: 18 cases were excluded due to the presence of CH before RT; 17 of remaining 46 (37%) patients presented CH during follow-up: 14 of 17 (82%) patients received CSI, 3 (18%) IF-RT sellar-suprasellar region and anterior cranial region. A median dose higher than 30.5 Gy to the pituitary gland results in a 4-fold increased risk of central hypothyroidism (HR=3.9; 95% CI 1.1, 13.4; p=0.03). Almost 90% of events occurred within 5 years after treatment ended. 29 of 46 (63%) patients did not manifest CH and were in the "other regions”. However, 14 of these (48%) underwent CSI. CONCLUSIONS: Our data confirm the relationship between central hypothyroidism and mean pituitary radiation dose, and suggest a minimum of 5 years follow up in children brain tumor survivors. Tumours outside the sellar-suprasellar region, treated with radiotherapy, are not associated with CH onset. A significant association between CSI and risk of CH, highlighted with our analysis, warrants further investigations and a longer follow up

To evaluate the contribution of 18F-dihydroxyphenylalanine (DOPA) PET in association with conventional MRI in predicting treatment response and survival outcome of pediatric patients with diffuse intrinsic pontine gliomas (DIPGs). Methods: We retrospectively analyzed 19 children with newly diagnosed DIPGs who underwent 18F-DOPA PET/CT and conventional MRI within one week of each other at admission and subsequent MRI follow-up. Following co-registration and fusion of PET and MRI, 18F-DOPA uptake avidity and extent (PET tumor volume and uniformity) at admission, along with MRI indices including presence of ring contrast-enhancement, tumor volume at admission and at maximum response following first-line treatment, were evaluated and correlated with overall survival (OS). The association between 18F-DOPA uptake tumor volume at admission and MRI tumor volume following treatment was evaluated. Statistics included Wilcoxon signed-rank and Mann-Whitney U tests, Kaplan-Meier OS curve and Cox analysis. Results: DIPGs with a 18F-DOPA uptake Tumor/Striatum (T/S) ratio >1 presented an OS ≤ 12 months and lower degree of tumor volume reduction following treatment (p = 0.001). On multivariate analysis, T/S (p = 0.001), ring enhancement (p = 0.01) and the degree of MRI tumor volume reduction (p = 0.01) independently correlated with OS. In all patients, areas of increased 18F-DOPA uptake overlapped with regions demonstrating more prominent residual components/lack of response following treatment. Conclusions: 18F-DOPA PET provides useful information for evaluating the metabolism of DIPGs. T/S ratio is an independent predictor of outcome. 18F-DOPA uptake extent delineates tumoral regions with a more aggressive biological behaviour, less sensitive to first line treatment.

Introduction To evaluate stereotactic body radiotherapy (SBRT) in low-risk Prostate Cancer patients as preferred treatment option in emergency health conditions. Materials and methods From April 2013 to September 2015, 28 patients with low-risk prostate cancer were prospectively enrolled. The SBRT prescribed dose was 36.25 Gy in 5 fractions, twice a week. Primary endpoints were acute and late toxicity. Secondary endpoints were biochemical recurrence free survival (bRFS) and overall survival. Results Median follow-up was 65.5 months (range 52–81). No acute G3 or G4 toxicity was recorded. Acute G1 or G2 genitourinary (GU) toxicity occurred in 43% and acute G1–G2 gastrointestinal (GI) toxicity in 14%. Late G1 and G3 GU toxicity in 18% and 3.5%, respectively. The G3 toxicity was not directly attributable to radiotherapy. Late G1 GI toxicity occurred in 18%. 5yy bRFS was 96.5% (95% CI 82.3–99.4%). Conclusions Stereotactic body radiotherapy for early prostate cancer reported safe toxicity profile and a good clinical outcome at the median follow-up of 5 years. It may be an useful option if radiotherapy is required in emergency medical conditions.

To evaluate the contribution of 18F-dihydroxyphenylalanine (DOPA) PET in association with conventional MRI in predicting treatment response and survival outcome of pediatric patients with diffuse intrinsic pontine gliomas (DIPGs). Methods: We retrospectively analyzed 19 children with newly diagnosed DIPGs who underwent 18F-DOPA PET/CT and conventional MRI within one week of each other at admission and subsequent MRI follow-up. Following co-registration and fusion of PET and MRI, 18F-DOPA uptake avidity and extent (PET tumor volume and uniformity) at admission, along with MRI indices including presence of ring contrast-enhancement, tumor volume at admission and at maximum response following first-line treatment, were evaluated and correlated with overall survival (OS). The association between 18F-DOPA uptake tumor volume at admission and MRI tumor volume following treatment was evaluated. Statistics included Wilcoxon signed-rank and Mann-Whitney U tests, Kaplan-Meier OS curve and Cox analysis. Results: DIPGs with a 18F-DOPA uptake Tumor/Striatum (T/S) ratio >1 presented an OS ≤ 12 months and lower degree of tumor volume reduction following treatment (p = 0.001). On multivariate analysis, T/S (p = 0.001), ring enhancement (p = 0.01) and the degree of MRI tumor volume reduction (p = 0.01) independently correlated with OS. In all patients, areas of increased 18F-DOPA uptake overlapped with regions demonstrating more prominent residual components/lack of response following treatment. Conclusions: 18F-DOPA PET provides useful information for evaluating the metabolism of DIPGs. T/S ratio is an independent predictor of outcome. 18F-DOPA uptake extent delineates tumoral regions with a more aggressive biological behaviour, less sensitive to first line treatment.

Salvina Barra,1 Liliana Belgioia,1,2 Michela Marcenaro,1 Serena Callegari,2 Alice Pastorino,2 Luca Trapani,2 Francesca Cavagnetto,3 Stefania Garelli,3 Renzo Corvò1,2 1Radiation Oncology Department, Ospedale Policlinico San Martino, Genoa, Italy; 2Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; 3Medical Physics Department, Ospedale Policlinico San Martino, Genoa, Italy Background: After radical prostatectomy (RP) radiotherapy (RT) plays a role, both as adjuvant or salvage treatment. If negative features are present such as extracapsular extension, seminal vesicle invasion, lymph invasion, and positive surgical margins, RT after RP reduces the risk of recurrence, although it is associated with an increased risk of acute and late toxicities. An intensified RT delivered in a shortened time could improve clinical outcome and be safely combined with hormonal therapy (HT). The aim of this study was to determine the acute and late toxicities associated with hypofractionated RT and to assess the impact of the addition of HT to RT in high-risk prostate cancer (PC) patients on overall response and toxicity.Materials and methods: Sixty-four PC patients undergoing RP were included in this retrospective study. All patients were recommended to receive adjuvant or salvage RT. Prescription doses were 62.5 Gy in 25 fractions to prostate bed, 56.25 Gy in 25 fractions to seminal vesicles bed, and 50 Gy in 25 fractions to pelvis if indicated. HT was administered to patients with additional adverse pathologic features including Gleason score >7, prostate-specific antigen >20 ng/mL before surgery, or prostate-specific antigen with rapid doubling time after relapse or nodal involvement. After completion of RT, patients were observed after 4 weeks, and then followed-up every 3–6 months. Acute and late toxicities were assessed using Common Terminology Criteria for Adverse Events v4 and Radiation Therapy Oncology Group scale, respectively.Results: For acute toxicity, only grade 1 gastrointestinal and genitourinary toxicities were detected in 17% and 11% of patients, respectively. As regards late toxicity, only 5% of the patients developed grade 1 gastrointestinal adverse event; grade 1, grade 2, and grade 3 genitourinary toxicity was recorded in 5%, 3.3%, and 3.3% of patients, respectively. Two and 5 years overall survival were 98% and 96%, respectively. The curves stratified for treatment show a slight difference between patients receiving RT or RT+HT, but the differences did not reach statistical significance (p=0.133).Conclusion: In patients with PC undergoing RP, hypofractionated RT may contribute to achieve a high overall survival with an acceptable toxicity profile. Combination of RT and HT is also well tolerated and efficacious. Keywords: prostate cancer, postoperative radiotherapy, hypofractionation&nbsp

We describe a rare case of intracranial malignant triton tumor (MTT) arising in the middle cranial fossa in a 74-year-old female patient who had previously been exposed to radiation in the Chernobyl disaster. The patient underwent a surgical subtotal removal of the mass and radiation therapy, but the progression-free survival was only 2.5 months and death occurred four months after the onset of symptoms. MTTs are rare aggressive tumors arising from the nerve sheath showing rhabdomyosarcomatous differentiation and associated with a poor prognosis. The intracranial location is very rare, and only 10 cases, including the present report, have been described so far. Among intracranial MTTs, the cerebellopontine angle is the most common location. Neurofibromatosis type 1 (NF-1) and radiation exposure are risk factors as for MTTs located in other sites. The gold standard therapy is surgical excision followed by radiation therapy, but the prognosis is usually very poor.

Background The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

Hidradenocarcinoma (HC) is a very rare disease. This case report illustrates a successful treatment of a 60-year-old woman with vulvo-vaginal localization of hidradenocarcinoma treated with external beam radiotherapy delivered by helical tomotherapy with a simultaneous integrated boost (SIB), followed by brachytherapy. External beam radiotherapy dose prescription was 50.4 Gy in 28 fractions, five fractions per week to whole pelvis (planning target volume 1 – PTV1), 60.2 Gy in 28 fractions to SIB1 (fundus of uterus and right inguinal node), and 58.8 Gy in 28 fractions to SIB2 (lower/middle third of vagina, paraurethral region and right inguinal lymph nodes). Brachytherapy dose prescription was 28 Gy in 4 fractions for cervix, fundus of uterus and upper third of vagina (HR-CTV1), and 22 Gy in 4 fractions to middle third of vagina and paraurethral region (HR-CTV2). D90 for whole treatment was 91.9 Gy and 86.0 Gy for HR-CTV1 and HR-CTV2, respectively. Patient remained 12-months disease-free without treatment related side effects.

Purpose To evaluate neuroendocrine late effects in paediatric patients with low grade glioma (LGG) who underwent radiotherapy. Methods and material We performed a retrospective evaluation of 40 children with LGG treated from July 2002 to January 2015 with external radiotherapy. Tumour locations were cerebral hemisphere ( n = 2); posterior fossa ( n = 15); hypothalamic–pituitary axis (HPA, n = 15); spine ( n = 5). Three patients presented a diffuse disease. We looked for a correlation between endocrine toxicity and tumour and treatment parameters. The impact of some clinical and demographic factors on endocrinal and neuro toxicity was evaluated using the log-rank test. Results The median follow-up was 52 months (range: 2–151). Median age at irradiation was 6. The dose to the HPA was significantly associated with endocrine toxicity ( P value = 0.0190). Patients who received chemotherapy before radiotherapy and younger patients, showed worse performance status and lower IQ. The 5-year overall survival (OS) and progression free survival (PFS) rates were 94% and 73.7%, respectively. Conclusion Radiotherapy showed excellent OS and PFS rates and acceptable late neuroendocrine toxicity profile in this population of LGG patients treated over a period of 13 years. In our experience, the dose to the HPA was predictive of the risk of late endocrine toxicity.

Background Over the last decades, significant advancements have been achieved in the treatment of pediatric brain tumors as a result of radiation therapy (RT). With the increasing diffusion of this treatment, iatrogenic damage to cerebrovascular tissues contouring the radiation target volume has become the subject of debate, especially radiation-induced moyamoya syndrome (RIMS). Methods A systematic literature search was performed on the association between moyamoya vasculopathy and cranial irradiation in children. Large case series of patients with moyamoya were analyzed and clinicoradiologic data were collected reviewing pediatric patients treated with RT for primary brain tumors at our institution. Results The risk of developing RIMS is higher in younger children, in patients with optic pathway glioma, and in those receiving higher radiation doses. Headache is the most common presenting symptom and cerebral infarction is frequent. The preferred surgical techniques were pial synangiosis and encephaloduroarteriosynangiosis. In our case series, surgical revascularization led to neovascularization, with clinical improvement or stability in all patients. Medical therapy did not significantly affect the clinical course. Conclusions Pediatric patients receiving involved field RT for the treatment of brain tumors have an increased risk of developing RIMS. Prompt diagnosis and early surgical revascularization play a pivotal role in decreasing the clinical impact of this complication. The use of new techniques, such as the intensity-modulated RT, and the increasing dose saving for the organs at risk, are essential to prevent iatrogenic vasculopathy. The combination of appropriate medical therapy and surgery will improve patient management and clinical outcome.

Extraosseous Ewing sarcoma of primary cardiac origin is an extremely rare variety among pediatric cardiac neoplasms. We report a case of extraosseous Ewing sarcoma of primary cardiac origin in a 9-year-old girl, treated with debulking surgery, adjuvant chemotherapy, and radiotherapy.

Pediatric radiotherapy (RT) is a highly specialized field, requiring great experience to delineate correctly tumor targets and organs at risk. To reduce treatment failures related to planning inaccuracies and to obtain robust clinical results despite the limited numbers of enrolled pediatric patients, the SIOP PNET5MB clinical trial on medulloblastoma requires a real-time, pre-radiation review of the RT treatment (craniospinal irradiation and boost plan) under the direct responsibility of the national coordinator center. Here we describe the centralized radiotherapy quality assurance (QA) program developed in Italy for this purpose. Using the software package VODCA (MSS, Hagendorn, Switzerland, www.vodca.ch ), we developed a cloud platform able to handle computed tomography (CT) images and RT objects and to support the complete workflow required by the review process in the context of the SIOP PNET5 trial. All Italian centers participating in the PNET5 trial adopted the proposed QA system. 24 patients were successfully enrolled and reviewed. For 15 patients (62.5%), one or more plan revisions were requested for the craniospinal irradiation plan and for 11 patients (45.8%) plan revisions were requested for the boost. RT was delivered after the plan was centrally approved for all enrolled patients. So far, in Italy, no patients have been excluded from PNET5 due to dosimetric incompliance to the protocol or for exceeding the RT starting time limit. The cloud platform successfully supported the trial workflow, producing official review documents. This efficient QA was crucial to guarantee optimized treatments and protocol compliance for all pediatric patients enrolled in the SIOP protocol.

Purpose: The aims of patients’ radiological surveillance are to: ascertain relapse; apply second-line therapy; accrue patients in phase 1/2 protocols if second-line therapy is not standardized/curative; and assess/treat iatrogenic effects. To lessen the emotional and socioeconomic burdens for patients and families, we ideally need to establish whether scheduled radiological surveillance gives patients a better outcome than waiting for symptoms and signs to appear. Methods: We analyzed a prospective series of 160 newly-diagnosed and treated pediatric/adolescent patients with intracranial ependymoma, comparing patients with recurrent disease identified on scheduled MRI (the RECPT group; 34 cases) with those showing signs/symptoms of recurrent disease (the SYMPPT group; 16 cases). The median follow-up was 67 months. Results: No significant differences emerged between the two groups in terms of gender, age, tumor grade/site, shunting, residual disease, or type of relapse (local, distant, or concomitant). The time to relapse (median 19 months; range 5–104) and the MRI follow-up intervals did not differ between the SYMPPT and RECPT groups. The presence of signs/symptoms was an unfavorable factor for overall survival (OS) after recurrence (5-year OS: 8% vs. 37%, p = 0.001). On multivariable analysis, an adjusted model confirmed a significantly worse OS in the SYMPPT than in the RECPT patients. Conclusions: Symptomatic relapses carried a significantly worse survival for ependymoma patients than recurrences detected by MRI alone. It would therefore be desirable to identify recurrences before symptoms develop. Radiological follow-up should be retained in ependymoma patient surveillance because there is a chance of salvage treatment for relapses found on MRI

The aims of radiation therapy of brain metastases include maintaining neurocognitive function and control of disease and, hopefully, improvement of survival. We present a case report with a very long survival in which the role of repeated stereotactic radiosurgery (SRS) was investigated for a patient with a recurrent brain metastasis from non-small cell lung cancer in the same area. Stereotactic re-irradiation was successful and well-tolerated with no neurological toxicity after 16 months.

Aims of patient follow-up are: discovering relapse to apply second-line therapy for possible cure, accruing patients in phase 1/2 protocols if second-line therapy is not standardized/curative, evaluating/treating iatrogenic effects. To lessen the patient/family emotional and social economic burdens, we should ideally understand if scheduled radiological follow-up has a better rationale/outcome than the symptomatic relapse. We analyzed the Italian series of 2016 (doi:10.1093/neuonc/now108) comprehending 160 newly diagnosed pediatric/adolescent patients with intracranial ependymoma (EPD) according to relapse status (recurrence at scheduled exam [RECPT]/sign-symptomatic recurring [SYMPPT]). RECPT and SYMPPT were assessed in Cox model as time-dependent variables for overall survival (OS). Differences in characteristics between RECPT and SYMPPT subgroups were assessed by Wilcoxon-Mann-Whitney or Fisher Exact tests. Kaplan-Meier curves depicted event-free survival (EFS) and OS after recurrence according to signs/symptoms. There were 16 SYMPPT /34 RECPT, at a median follow-up of 55 months. No significant differences were found between SYMPPT/RECPT for gender, age, tumor grade/site, shunt, residual disease, radiation boost, type of relapse (local/distant/combined). Time-to-relapse (median:19 months, range 5–104) and treatment adoption did not differ between SYMPPT/RECPT while signs/symptoms depicted an unfavorable factor for OS after relapse (5-year OS: 8% vs 37%). Adjusted model in multivariate analysis confirmed that presence of signs/symptoms was prognostically unfavorable. In order to improve the OS in symptomatic patients, their early identification-in the first two/three years after diagnosis- would be desirable. Perhaps, this could be obtained paying attention to “heuristically detected” subgroup of patients, not just describing general prognostic variables but discovering possible biology differences according to signs/symptoms.

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT. The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.

The use of imaging to maximize precision and accuracy throughout the entire process of radiation therapy (RT) delivery has been called "Image-guided RT" (IGRT). RT has long been image guided: in fact, historically, the portal films and later electronic megavoltage images represented an early form of IGRT. A broad range of IGRT modalities is now available and adopted. The target location may be defined for each treatment fraction by several methods by localizing surrogates, including implanted fiducial markers, external surface markers or anatomical features (through planar imaging, fluoroscopy, KV or MV computed tomography, magnetic resonance imaging, ultrasound and X-ray imaging, electromagnetic localization, optical surface imaging, etc.). The aim of the present review is to define practical recommendations for IGRT.

EPN-02. FINAL RESULTS OF THE 2ND AIEOP PROTOCOL FOR INTRACRANIAL EPENDYMOMA (EPD) Maura Massimino1, Rosalba Miceli1, Felice Giangaspero2,3, Luna Boschetti1, Paolo Ferroli4, Paola Peretta5, Emilia Pecori1, Laura Valentini4, Veronica Biassoni1, Maria Luisa Garre6, Elisabetta Schiavello1, Iacopo Sardi7, Armando Cama6, Silvia Scoccianti8, Maurizio Mascarin9, Lorenzo Genitori7, Daniele Bertin5, Anna Mussano10, Elisabetta Viscardi11, Piergiorgio Modena12, GiuseppinaCalareso1, Salvina Barra13, Giovanni Scarzello14, LuciaQuaglietta15, Giuseppe Cinalli15, Angela Mastronuzzi16, Carlo Giussani17, Carlo Marras16, Rita Balter18, Patrizia Bertolini19, Ermanno Giombelli19, Francesca Buttarelli2, Manila Antonelli2, and Lorenza Gandola1; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Universita Sapienza Roma, Roma, Italy; Neuromed Pozzilli, Pozzilli, Italy; Fond IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; Ospedale Infantile Regina Margherita, Torino, Italy; Istituto Giannina Gaslini, Genova, Italy; Ospedale Pediatrico Meyer, Firenze, Italy; OspedaleCareggi,Firenze, Italy;CRO,Aviano, Italy;OspedaleS.Anna, Torino, Italy; Clinica di Oncoematologia Pediatrica, Padova, Italy; Genetica, Osp S. Anna, Como, Italy; Istituto dei Tumori, Genova, Italy; Istituto Oncologico del Veneto, Padova, Italy; Ospedale Pausillipon, Napoli, Italy; Ospedale Bambino Gesu, Roma, Italy; Ospedale S. Gerardo, Monza, Italy; Ospedale Borgo Roma, Verona, Italy; Ospedale, Parma, Italy This study stratified patients after surgical resection (complete 1⁄4 NED vs incomplete 1⁄4 ED) and centrally reviewed histology(gr.2 vs gr. 3). Gr2 tumors/NEDpts were focally irradiated with a 3D-conformal technique 1.8Gy/d up to 59.4 Gy, gr3/NED received also 4 VEC(Cyclo,VP16,VCR) after irradiation. EDpts received 1-4 VEC, second-look surgery whenever possible,59.4 Gy followed by 8 Gy boost into 2 fractions on still measurable residue. Children aged 1-3 yrs received the same treatment but for those gr2/NED who could receive only 6 VEC. Between January 2002/December 2014, 160 consecutive children, median age 4.9 years, entered the protocol; follow-up was a median 67 months. M/F was 100/60, infratentorial origin in 110(2 plus metastasis). After surgery, NEDpts were 110,grade 3 was assessed in 84. 100 resections were performed in 46/160 children with another 12 rendered NED after first excision,10 after 1-4 VEC,2 after radiation. Boost was applied to 24/40 still ED patients after surgery/ies and VEC obtaining PFS/OS of 58.1%/68.7% in this severe prognosis subgroup. For the whole series,5-year PFS/OS were 65.4%/81.1% with no toxic deaths. In univariable analysis, female gender, supratentorial origin, NED status before RT, grade 2, shunt absence were favourable for OS, in multivariable NED status and grade 2 were. For PFS, female gender, NED status before RT, grade 2 were significant in univariable, only grade in multivariable. In a multicentric collaboration this trial accrued the highest patient number so far published with comparable results to best monoinstitutional series. Radiation boost was feasible and efficacious in improving local control. Complete surgery, also through multiple excisions, still confirmed its prognostic strength as well as grade. Further biological parameter definition on this series will be the object of next coming studies. Neuro-Oncology 18:iii30–iii39, 2016. doi:10.1093/neuonc/now070.2 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Background This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). Methods WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. Results From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. Conclusions In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports.

Given the limitations in the travel ability of the helical tomotherapy (HT) couch, total marrow irradiation (TMI) has to be split in 2 segments, with the lower limbs treated with feet first orientation. The aim of this work is to present a planning technique useful to reduce the dose inhomogeneity resulting from the matching of the 2 helical dose distributions. Three HT plans were generated for each of the 18 patients enrolled. Upper TMI (UTMI) and lower TMI (LTMI) were planned onto the whole-body computed tomography (CT) and on the lower-limb CT, respectively. A twin lower TMI plan (tLTMI) was designed on the whole-body CT. Agreement between LTMI and tLTMI plans was assessed by computing for each dose-volume histogram (DVH) structure the γ index scored with 1% of dose and volume difference thresholds. UTMI and tLTMI plans were summed together on the whole-body CT, enabling the evaluation of dose inhomogeneity. Moreover, a couple of transition volumes were used to improve the dose uniformity in the abutment region. For every DVH, a number of points >99% passed the γ analysis, validating the method used to generate the twin plan. The planned dose inhomogeneity at the junction level resulted within ±10% of the prescribed dose. Median dose reduction to organs at risk ranged from 30-80% of the prescribed dose. Mean conformity index was 1.41 (range 1.36-1.44) for the whole-body target. The technique provided a "full helical" dose distribution for TMI treatments, which can be considered effective only if the dose agreement between LTMI and tLTMI plans is met. The planning of TMI with HT for the whole body with adequate dose homogeneity and conformity was shown to be feasible.

Somatic mutations of the isocitrate dehydrogenase-1 gene (IDH1), most commonly resulting in replacement of arginine at position 132 by histidine (p.R132H), have been reported for WHO grade II and III diffuse gliomas and secondary glioblastomas. We investigated IDH1/2 mutations in a retrospective series of 165 pediatric brain tumors, including atypical teratoid/rhabdoid tumors (AT/RT) and choroid plexus tumors, which had not previously been investigated. Mutation analysis was performed by use of pyrosequencing and, additionally, data were validated for a cohort of 70 gliomas from among the series by use of the arrayed primer extension technique. We identified one tumor which harbored mutation of IDH1 at codon 132 and no alteration was identified in the matched-germline DNA. No IDH2 mutations were detected. Most noteworthy, the IDH1 mutant tumor was an anaplastic astrocytoma involving the cortex in the left frontal lobe which appeared seven years after radiation treatment for an extensive sellar/suprasellar craniopharyngioma. This anaplastic astrocytoma was regarded as secondary to radiation treatment because it seemed to originate within the irradiation field that received a dose varying from a maximum of 30.6 Gy of 4 MV X-rays down to very few Gy of lower-energy scattered radiation. In this work our observations agree with those in previous reports showing the rarity of IDH1/2 mutations in childhood tumors. The interesting identification of an IDH1 mutation in a radiation-induced secondary malignant glioma raises the likelihood that these types of tumor may develop IDH1/2 mutations. Thus, caution is needed when dealing with these tumors, and further genetic analysis is warranted.

Object Complete ependymoma resection ensures a better prognosis for children with this tumor, but the complete excision of infratentorial ependymomas involves serious risks. Second-look surgery for tumor remnants may be less harmful and enable complete removal. There is a potential, although still unclear, role for neoadjuvant chemotherapy in preparation for further surgery. Methods Since 1994, the authors have adopted two successive protocols for intracranial ependymoma, both including a phase of adjuvant chemotherapy for children with surgical tumor remnants with a plan for potential second-look surgery before radiotherapy. Results In the first protocol, 9 of 63 children underwent further surgery, and 6 became tumor free with no additional sequelae. Their prognosis for progression-free survival and freedom from local relapse was comparable to that of children who were operated on only once. In the second protocol, efforts were made to achieve complete resection and 29 of 110 patients underwent reoperations: 9 after the first surgery, 17 after chemotherapy, and 3 soon after radiotherapy. Fourteen of the 29 patients became tumor free, 1 of them with worsening neurological symptoms. The outcome of the 66 patients who became tumor free after 1 operation was compared with that of the 14 who became tumor free after reoperation. The 3-year progression-free survival of the 66 patients compared with the 14 other patients was 71.4% ± 6.9% and 90% ± 9.5%, respectively; the 3-year freedom from local relapse was 84.7% ± 5.9% and 90% ± 9.5%, respectively; and the 3-year overall survival was 85.9% ± 5.4% and 87.5% ± 11.7%, respectively. Conclusions Second-look surgery proved feasible with no major morbidity, and results improved with time. Local tumor control was comparable in patients undergoing 1 or more resections.

Purpose: We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS). Experimental Design: We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages Results: Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages ≤3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P < 0.001) and had a good prognosis. MBEN was associated with GS in 5 of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5 GS, 1 each NF1, Li-Fraumeni, and Fragile X) and 7 of these patients were ages ≤3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001). Conclusions: Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages ≤3 years, with MB and their families should be investigated for tumor predisposition syndromes such as GS.

Background Primary intradural extramedullary ependymomas are very rare tumors and have never been described in children. Case Description We report on an 11-year-old girl presenting with a 1-month history of neck pain, left arm weakness, paresthesia in the fingers of the left hand and gait disturbances. Magnetic resonance imaging on admission revealed an intradural extramedullary cystic lesion at the cervical level with craniospinal leptomeningeal nodules causing mild hydrocephalus. The multicystic lesion was surgically removed and neuropathologic examination revealed a World Health Organization grade II ependymoma. The patient underwent adjuvant radiotherapy with progressive reduction of the metastatic nodules. At her 2-year follow-up, the patient was symptom free with no evidence of recurrence on magnetic resonance imaging. Conclusions Although a rare entity, intradural extramedullary ependymomas should be included in the differential diagnosis of intradural extramedullary lesions in children. Surgical treatment seems to play a pivotal role in the prognosis of these rare tumors, with a possible role for adjunctive radiotherapy in the case of recurrence, anaplastic transformation, and metastasis.

Purpose The purpose of this study was to evaluate interobserver variability among radiation oncologists with experience in the field of lymphoma radiation therapy in the delineation of clinical target volume (CTV) in a challenging case of primary mediastinal B-cell lymphoma. Methods and materials Ten experienced radiation oncologists were invited to a 1-day contouring session. The case of a 56-year-old man with primary mediastinal B-cell lymphoma with complete metabolic response after chemotherapy was chosen as the sample for the study. A brief presentation of his clinical history was given, together with guidelines for contouring. The 10 CTVs obtained were then compared in terms of variation in total volume and in craniocaudal, laterolateral, and anteroposterior diameters. The CTV with the best Dice similarity coefficient (DSC) between the union of all 10 CTVs and the individual CTV was considered the reference CTV, and the DSC and the Hausdorff distance (HD) for each volume compared with the reference CTV were then calculated. Results A significant variability was found in total volume (mean, 498.3 cm 3 ; range, 181.8-1003 cm 3 ) and craniocaudal (median, 144.7 mm; range, 80.6-159 mm), laterolateral (median, 133.5 mm; range, 83.7-149.5 mm), and anteroposterior diameters (median, 136.2 mm; range, 84-150.5 mm). Analysis of the DSC and the HD showed a mean DSC of 0.53 (range, 0.31-0.74) and a mean HD of 6.4 cm (range, 1.8-14.8 cm). Conclusions Results of this study strongly indicate the need to develop and share appropriate contouring guidelines among experts and suggest the promotion of specific educational activities to improve radiation therapy quality in both clinical trials and routine clinical practice.

To compare late rectal toxicity rates after three-dimensional conformal radiotherapy to the prostate alone (P-3D-CRT) and whole-pelvis intensity-modulated radiotherapy along with a prostate boost (WP-IMRT/PB) to the same nominal total dose to the prostate. 68 patients treated with conformal radiotherapy to the prostate only to 76 Gy at the National Institute for Cancer Research, Genoa, Italy, represented the first group (P-3D-CRT). The second group consisted of 45 patients treated at the University of Texas Medical Branch (UTMB), Galveston, TX, USA, with IMRT covering the pelvic nodes and seminal vesicles to 54 Gy at 1.8 Gy per fraction and the prostate to 60 Gy in the same 30 fractions. A separate phase boosted the prostate to 76 Gy (WP-IMRT/PB). Major aspects of planning were remarkably similar at both institutions leaving the inclusion or not of pelvic nodes as the main treatment-related difference between the two groups. Late rectal toxicity was prospectively scored according to the RTOG scale. All patients have a 12-month minimum follow-up, and mean follow-up, similar in both groups, is 25.9 months (SD [standard deviation]: 8.4 months). At 2 years, the estimated cumulative incidence of grade 2 late rectal toxicity is 6% ± 4% for WP-IMRT/PB and 21.2% ± 6% for P-3D-CRT (p = 0.06). The difference became significant (HR [hazard ratio] = 0.1, 95% CI [confidence interval]: 0.0–0.6; p = 0.01) at multivariate analysis. None of the patients developed grade 3+ toxicity. Despite the larger treated volume, WP-IMRT/PB allows more rectal sparing than P-3D-CRT.

Purpose A postsurgical "stage-based" protocol for ependymoma was designed. Methods and materials Children were given: ( 1 ) focal hyperfractionated radiotherapy (HFRT) if with no evidence of disease (NED), or ( 2 ) 4 courses with VEC followed by HFRT for residual disease (ED). HFRT dose was 70.4 Gy (1.1 Gy/fraction b.i.d.); VEC consisted of VCR 1.5 mg/m 2 1/w, VP16 100 mg/m 2 /day × 3, CTX 3 g/m 2 d 1. When feasible, second-look surgery was recommended. Results Sixty-three consecutive children were enrolled: 46 NED, 17 ED; the tumor was infratentorial in 47 and supratentorial in 16, with spinal metastasis in 1. Of NED patients, 35 of 46 have been treated with HFRT; 8 received conventionally fractionated radiotherapy, and 3 received no treatment. Of the 17 ED patients, 9 received VEC + HFRT; violations due to postsurgical morbidity were as follows: HFRT only (2), conventionally fractionated radiotherapy (3) + VEC (2), and no therapy (1). Objective responses to VEC were seen in 54%; objective responses to RT were seen in 75%. Overall survival and progression-free survival at 5 years for all 63 children were 75% and 56%, respectively; for the NED subgroup, 82% and 65%; and for the ED subgroup, 61% and 35%, respectively. All histologies were centrally reviewed. At multivariate analysis, grading, age, and site proved significant for prognosis. Conclusions HFRT, despite the high total dose adopted, did not change the prognosis of childhood ependymoma as compared to historical series: New radiotherapeutic approaches are needed to improve local control. Future ependymoma strategies should consider grading when stratifying treatment indications.

Aims and background The role of radiotherapy after prostatectomy is controversial. This paper tries to give some guidelines for everyday practice through an analysis of literature data. Methods The potential role of radiotherapy in the adjuvant and salvage setting is discussed. We also report and interpret available literature data for both settings. Results As regards an increase in or detectable prostate-specific antigen (PSA) after radical prostatectomy, about 40–50% of patients are rendered bNED with local salvage radiotherapy, but only 10–50% are long-term (5 years) biochemically controlled. A timely salvage treatment is crucial to optimize control probability. As regards adjuvant radiotherapy for undetectable postoperative PSA in patients at high risk of failure as judged on pathology, results are more encouraging. Recent data report bNED rates ≥70% at 5 years. Conclusions Although results are far from satisfactory, salvage radiotherapy should be considered for every patient with an increased or detectable PSA after surgery. Adjuvant radiotherapy seems preferable to salvage radiotherapy for patients at high (>30%) risk of failure.

Cavernous malformations (CM) are cerebral irradiation-related late complications. Little is known about their natural history and the pathogenetic role of concomitant chemotherapy. We present a retrospective, single-institution study of 108 children affected with medulloblastoma, ependymoma, or germinoma treated with radio- and chemotherapy. The frequency, clinical and radiological presentations, and outcomes were analyzed to investigate the relationship among radiation dose, associated chemotherapy, age, latency and localization of radiation-induced CM. 100 out of 108 children were treated with radiotherapy for primary brain tumor; 34 (27 with medulloblastoma and 7 with other histologies) out of 100 patients developed CM. No significant relationship was found between CM and gender (p = 0.70), age (p = 0.90), use of specific chemotherapy (standard versus high-dose, p = 0.38), methotrexate (p = 0.49), and radiation dose (p = 0.45). However, CM developed more frequently and earlier when radiotherapy was associated with methotrexate (70 % of cases). Radiation-induced CM prevailingly occurred in the cerebral hemispheres (p = 0.0001). Only 3 patients (9 %) were symptomatic with headache. Three patients underwent surgery for intra- or extra-lesional hemorrhage. CM was confirmed by histopathology for all 3 patients. The vast majority of radiation-induced CM is asymptomatic, and macro-hemorrhagic events occur rarely. Concomitant therapy with methotrexate seems to favor their development. We recommend observation for asymptomatic lesions, while surgery should be reserved to symptomatic growth or hemorrhage.