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Abstract Several investigations have recently suggested the existence of a correlation between the dose received by the penile bulb (PB) and the risk of erectile dysfunction (ED) after radical radiotherapy for clinically localized prostate carcinoma. A prospective multi-Institute study (DUE-01) was implemented with the aim to assess the predictive parameters of ED. Previously, an evaluation of inter-observer variations of PB contouring was mandatory in order to quantify its impact on PB dose-volume parameters by means of a dummy run exercise. Fifteen observers, from different Institutes, drew the PB on the planning CT images of ten patients; inter-observer variations were analysed in terms of PB volume variation and cranial/caudal limits. 3DCRT treatment plans were simulated to evaluate the impact of PB contouring inter-variability on dose-volume statistics parameters. For DVH analysis the values of PB mean dose and the volume of PB receiving more than 50 Gy and 70 Gy (V50 and V70, respectively) were considered. Systematic differences from the average values were assessed by the Wilcoxon test. Seven observers systematically overestimated or underestimated the PB volume with deviations from the average volumes ranging between -48% and +34% (p < 0.05). The analysis of the cranial and caudal borders showed a prevalence of random over systematic deviations. Inter-observer contouring variability strongly impacts on DVH parameters, although standard deviations of inter-patient differences were larger than inter-observer variations: 14.5 Gy versus 6.8 Gy for mean PB dose, 23.0% versus 11.0% and 16.8% versus 9.3% for V50 and V70 respectively. In conclusion, despite the large inter-observer variation in contouring PB, a large multi-centric study may have the possibility to detect a possible correlation between PB % dose-volume parameters and ED. The impact of contouring uncertainty could be reduced by "a posteriori" contouring from a single observer or by introducing Magnetic Resonance Imaging (MRI) in the planning procedures and/or in improving the skill of observers through post-dummy run tutoring of those observers showing large systematic deviations from the mean.

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Aims The aim of the present work is to assess the main predictors of the most clinically relevant radio-induced effects after Gamma Knife stereotactic radiosurgery (GKRS) for uveal melanoma (UM). Materials and methods Medical records and three-dimensional dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox's proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for GKRS-related complications. results The fraction of the posterior segment receiving more than 20Gy (V20), Bruch's membrane rupture and tumour thickness were significant prognostic factors for neovascular glaucoma. A clear relationship with the dose received by 1% of the optic nerve (D1%) was found for radiation retinopathy and papillopathy. Multivariables models resulted for visual acuity (VA) reduction >20% of the basal value and for complete VA loss, both including largest tumour diameter and D1% to the optic nerve. The predictive model for complete VA loss includes also Bruch's membrane rupture. An alternative model for complete visual acuity loss, including the optic nerve-prescription isodose minimum distance, was also suggested. Conclusions We found clinical and dosimetric variables to clearly predict the risk of the main side effects after GKRS for UM. These results may provide dose constraints to critical structures, potentially able to reduce side effects. Constraining D1% to the optic nerve below 12-13Gy may result in a dramatic reduction of blindness risk, while reducing V20 of the posterior segment of the bulb could limit the neovascular glaucoma onset. [ABSTRACT FROM AUTHOR]

Objective: To evaluate toxicity and outcomes after salvage robotic stereotactic body radiotherapy-SBRT- (CyberKnife®,Accuray, Sunnyvale, Ca) re-irradiation of patients with intraprostatic/prostatic bed recurrences of pelvic malignancies. Methods: From 11/2018 to 10/2021, 20 patients with intraprostatic/prostatic bed recurrence after radiotherapy, diagnosed on MRI/ PET choline/PSMA and/or biopsyproven, underwent a salvage re-irradiation with SBRT: 9 patients with prostate cancer failure after previous radical radiotherapy, and 11 patients after adjuvant/salvage radiotherapy. Median prior RT dose was 70.7 (38.25- 78) Gy and the median interval to SBRT salvage therapy was 79.3 (11-208) months. Median PSA before robotic SBRT was 2.64 (1.14-26.8) ng/ml. Fiducial markers were implanted into the target in 19 of 20 patients. Median SBRT total dose was 35 (30-35) Gy in 5 fractions (EQD2=85 Gy, for α/β 1.5). Median prescription isodose was 70% (59- 81%). In 12 patients, a “urethral sparing” was used. In 10 cases a precautionary therapy with steroids and alphalytics was prescribed during the salvage treatment. Twelve patients received neoadjuvant or concomitant/adjuvant androgen suppressive therapy during their SBRT course. Toxicity was scored in accordance with CTCAE v 5.0. Results: Median follow-up was 17.4 months (2.35- 38.15) months. Acute genitourinary (GU) toxicity was observed in 40% of patients and was limited to grade (G)1 in 35% of patients and G2 (minimal strangury, urgency and occasional urinary incontinence) in 5%. Ten% of patients reported late GU G3 toxicity (urinary retention requiring catheterization and transurethral resection), and 5% G2 urinary toxicity. No acute and late gastrointestinal toxicity was observed. At the last follow-up 2 patients died due to a non cancer-releated cause. Twenty-four-months Kaplan Meier estimates of biochemical relapse-free survival (bRFS) was 78.2% (see Figure 1), local-relapse-free survival (LRFS) 92.3% and distant-metastases-free survival 85.1%. Conclusions: Prostate SBRT re-irradiation with CK is a feasible treatment option, with good short-term outcomes. Longer follow-up is necessary to assess the long-term benefits and to determine late toxicity. [ABSTRACT FROM AUTHOR]

Objective: We analyzed initial outcomes and toxicities of the 2 schedules of stereotactic body radiotherapy (SBRT) in use in our department for prostate cancer (PCa) patients. Materials and methods: Between 10/2017-05/2021, 102 PCa patients were treated using robotic SBRT with two different schedules. Group I included 73 patients treated at 36.25 Gy/ 5 fractions at the 79% median isodose, group II 29 patients treated at 38 Gy/ 4 fractions at the 63% median isodose (urethral sparing HDR-like technique). Median age was 74.5 vs 75.8 years, median initial PSA 7.20 vs 7.65 ng/ml. Gleason score was 3+3 in 11% vs 17.2%, 3+4 in 58.9% vs 51.7%, 4+3 in 17.8% vs 20.7% and not accorded (due to previous androgen deprivation) in 1.4% vs 3.5% of patients. Androgen deprivation therapy (ADT) was prescribed in 45% vs 31% of patients, with a median duration of 7 vs 6 months. Fiducial markers were implanted into the prostate in all patients. In 52% of patients steroid therapy and/or alpha-lytics were prescribed to prevent side effects. Toxicity was scored in accordance with CTCAE v 5.0. Biochemical failure was assessed using the nadir + 2 definition. Results: Median follow-up was 23.4 (0-47.2) months in group I vs 12 (2.78-36.07) months in group II. For acute and late toxicities see Table 1. No acute grade(G) 3 toxicities were registered. One (1.4%) late G3 genitourinary toxicity (transurethral incision) occurred in a patient treated with 36.25 Gy. Median post-SBRT PSA level was 0.342 (0.001-231.00) ng/ml in group I and 0.603 (0.05-10.210) ng/ml in group II. At the last follow up 3 pts had died due to a non-cancer related cause, 4 pts had a biochemical failure with PSMA/CholinePET positive progression: 3 treated at 36.25 Gy and 1 treated at 38 Gy. Two-year biochemical relapse-free survival(bRFS) was 94.8% for the patients of group I and 88.9% for the patients of group II, respectively (p= 0.6). Overall survival (OS) was 85.7%vs 98.4% at 2 years(p=0.35). Disease-free survival(DFS) was 94.8% and 88.9%, respectively (p=0.6). No correlation was found between target volume and toxicity. Conclusion: The urethral sparing technique allowed dose escalation (from 2 Gy equivalent dose-EQD2-91 Gy to EQD2 ≥ 120 Gy with α/β 1.5) without increasing G3 toxicity and with non-inferior bRFS despite less ADT prescription. Longer follow-up is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Object: Lung metastases from colorectal cancer are more radioresistant, requiring higher dose to obtain a stable local control. Here we evaluate two different techniques of stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer in patients treated in our departmed. Material and methods: From 01/2006 to 07/2020, 69 lung metastases (37 patients) from colorectal cancer were treated with SBRT in our department: 48 lesions (27 patients) with 4DCT simulation and helical/VMAT IGIMRT (4DCT) and 21 lesions (10 patients) with real time-tracking robotic radiosurgery (CK). Median ages were 71.9 years (4DCT) vs 64.1 years (CK). Median GTV were 5.16 (0.31-88.6) cc (4DCT) vs 3.98 (0.16-16) cc (CK), while median PTV were 26.3 (6.3-180) (4DCT) cc vs 16.7 (1.9 vs 45.6) cc (CK), respectively. The tighter margins used with the real-time tracking was the main factor that determined a smaller PTV volume. Central lesions were 17.1% in the 4DCT group vs 23.5% in the CK group. Median BED precribed was 102.6 Gy in the 4DCT group vs 112.5 Gy in the CK group. The tighter margins allowed us not only to prescribe a higher median BED, but also to reduce the number of fractions and the overall treatment time from 2 weeks with 6 fractions every other day to 3 consecutive daily fractions. Results: Median follow-ups were 26.4 (3-85.7) months (4DCT group) vs 16.4 (3.4-37.4) months (CK group). The treatment was well tollerated: one patient presented a grade (G) 3 pneumonitis after a treatment on 6 lesions/4 PTV’s in one month with CK. Fully recovered she died one year later for distant metastases. Five patients presented G1/G2 cough and 1 with G1 dyspnea soon after the 4DCT treatment. Four patients had persistent G1 fibrosis, and 7 G1 dyspnea after the 4DCT treatment. Local control was of 69.3% (4DCT) vs 90.5% (CK) at 12 months, 46.5% vs 81.4% at 24 months (p= 0.08) (see Fig. 1). Overall survival at 12 months was 89.5% in the CK group vs 94.7% in the 4DCT group, at 24 months 64.6 % vs 76.5 %, and at 36 months 64.6% vs 51.7%, respectively. Conclusion: SBRT in lung oligometastases from colorectal cancer have a low toxicity profile. Even a small increase of BED from 102 Gy to 112 Gy, and the higher precision allowed by the real-time tracking shows a tendency towards better local control. [ABSTRACT FROM AUTHOR]

Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)–based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. Methods and Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapse were analyzed on computed tomography–guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. Results: At a median follow-up of 50 months, 21 patients are relapse-free (5-year failure-free survival [FFS], 51%). WBRT doses ≥40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35% and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose ≥40 Gy. Conclusion: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: No longitudinal data on hypothalamic-pituitary (HP) function are available in patients who had received cranial radiation therapy (CRT) for primary extrasellar brain tumors (PBT)., Purpose: To investigate the effects of CRT on HP function in adults with PBT., Patients and Methods: Twenty-six adults irradiated for PBT and six CRT naive controls were studied. CRT was delivered with 6 MV X-ray by a linear accelerator (2 Gy fraction schedule). Gross Tumor Volume (GTV) excluded the HP region that was contoured on the planning CT. Median dose to the HP region was 41.8 Gy (IQR: 30.7-49.8)., Results: All controls maintained normal HP function. Hypopituitarism developed in 38% of CRT patients (GH deficiency 29%, ACTH 22%, TSH 14%, gonadotropin 4%, no abnormal prolactin level or diabetes insipidus). All HP failures occurred within 32 months after CRT., Conclusions: Adults undergoing CRT for PBT are at increased risk for HP dysfunction within 3 years from CRT. Endocrine surveillance is recommended also in adults patients exposed to CRT for primary brain tumors distant from HP region., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)