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Perineal seeding of tumor cells from prostate cancer (PCa) is very rare, and no standard treatment exists for this atypical presentation with no evidence of distant metastases. Local excision or external beam radiotherapy are used as local salvage treatments for such perineal masses, including those occurring after biopsy, surgery, or interstitial brachytherapy. We report on a patient who presented no evidence of disease and no late urinary or gastrointestinal toxicities at 58 months after receiving high-dose-rate brachytherapy (HDR-BT) for perineal recurrence of PCa after radical prostatectomy and salvage external beam radiotherapy. To the best of our knowledge, this is the first case treated with HDR-BT in this scenario.

Background and purpose The aim was to evaluate dosimetric uncertainties of a mixed beam approach for patients with high-risk prostate cancer (PCa). The treatment consists of a carbon ion radiotherapy (CIRT) boost followed by whole-pelvis intensity-modulated RT (IMRT). Materials and methods Patients were treated with a CIRT boost of 16.6 Gy/4 fractions followed by whole-pelvis IMRT of 50 Gy/25 fractions, with consequent long term androgen deprivation therapy. Deformable computed tomography image registration (DIR) was performed and corresponding doses were used for plan sum. A comparative IMRT photon plan was obtained as whole-pelvis IMRT of 50 Gy/25 fractions followed by a boost of 28 Gy/14 fractions. DIR performances were evaluated through structure-related and image characteristics parameters. Results Until now, five patients out of ten total enrolled ended the treatment. Dosimetric parameters were lower in CIRT + IMRT than IMRT-only plans for all organs at risk (OARs) except femoral heads. Regarding DIR evaluation, femoral heads were the less deformed OAR. Penile bulb, bladder and anal canal showed intermediate deformation. Rectum was the most deformed. DIR algorithms were patient (P)-dependent, as performances were the highest for P3 and P4, intermediate for P2 and P5, and the lowest for P1. Conclusions CIRT allows better OARs sparing while increasing the efficacy due to the higher radio-biological effect of carbon ions. However, a mixed beam approach could introduce DIR problems in multi-centric treatments with different operative protocols. The development of this prospective trial will lead to more mature data concerning the clinical impact of implementing DIR procedures in dose accumulation applications for high-risk PCa treatments.

Purpose Evaluation of Raystation ANAtomically CONstrained Deformation Algorithm (ANACONDA) performance to different urinary bladder filling levels in male pelvis anatomic site varying the controlling Regions Of Interest (ROIs). Methods Different image datasets were obtained with ImSimQA (Oncology System Limited, Shrewsbury, UK) to evaluate ANACONDA performances (RaySearch Laboratories, Stockholm, Sweden). Deformation vector fields were applied to a synthetic man pelvis and a real patient computed tomography (CT) dataset (reference CTs) resulting in deformed CTs (target CTs) with various bladder filling levels. Different deformable image registrations (DIRs) were generated between each target CTs and reference CTs varying the controlling ROIs subset. Deformed ROIs were mapped from target CT to reference CT and then compared to reference ROIs. Evaluation was performed by Dice Similarity Coefficient (DSC), Correlation Coefficient (CC), Mean Distance to Agreement (MDA), maximum Distance to Agreement (maxDA) and with the introduction of global DSC (global_DSC) and global CC (global_CC) parameters. Results In both synthetic and real patient CT cases, DSC scored less than 0.75 and MDA greater than 3 mm when no ROIs or only bladder were exploited as controlling ROI. DSC and CC increased by increasing the number of controlling ROIs selected whereas, an opposite behavior was observed for MDA and maxDA. Conclusions ANACONDA performances can be influenced by bladder filling fluctuation if no controlling ROIs are selected. Global_DSC and global_CC are useful parameters to quantitatively compare DIR algorithms. DIR performances improve by increasing the number of controlling ROIs selected, reaching a saturation level after a defined ROIs subset selection.

To compare clinical outcomes and toxicities of 2 radiation therapy (RT) schemes for localized prostate cancer (PCa): extreme hypofractionation (EH; fractions of 6.5-7 Gy to a total dose of 32.5-35 Gy) and the moderate hypofractionation (MH; 26 fractions of 2.7 Gy to a total dose of 70.2 Gy). A propensity score method was used to compare the EH-RT and MH-RT groups.Our analysis included a total of 421 patients divided in 2 groups: 227 treated with MH-RT and 194 treated with EH-RT (43 and 30 months median follow-up, respectively). Propensity matching created comparable cohorts. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. Multivariate proportional hazard Cox models were used to compare the 2 groups, mainly for gastrointestinal and genitourinary toxicity and secondarily for clinical progression-free survival, biochemical progression-free survival, and overall survival.Considering the whole population, acute genitourinary and gastrointestinal greater than grade 1 was significantly more frequent in the whole MH-RT group (P.001 and P.002, respectively). A borderline significantly greater late genitourinary was confirmed with the multivariate analysis (P = .07). Concerning tumor outcome, no statistically significant differences were observed. After propensity score matching, 226 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups.EH-RT yields a decreased risk of acute or late toxicities compared with MH-RT, and oncologic outcomes were comparable. Our data indicate that EH-RT might be considered as a treatment modality of choice for select patients with PCa.

This paper presents a retrospective report on radiotherapy (RT) in the oligometastastic recurrence of bladder cancer. Thirteen patients treated for low-volume metastatic transitional cell urinary bladder carcinoma (TCC) were reviewed, with the primary endpoint to evaluate the safety and efficacy of RT, proposed as an alternative to systemic treatment and/or to defer commencement of systemic therapy. The inclusion criteria were: patients who received RT without other local/systemic therapy for oligometastatic TCC with lymph node, bone and lung lesions or local recurrence. Previous systemic therapy and surgery on the primary tumor were allowed in this tumor response, and toxicity evaluation and progression free-survival was also assessed. Thirteen patients with 21 lesions were treated with stereotactic body radiotherapy (SBRT) or conformal 3D radiotherapy (3D-CRT) between 2012 and 2017. All participants were discussed by a multidisciplinary urological board. The median age at RT was 68 years (range 50-80), the median Karnofsky performance status (KPS) was 90 (range 80-90) and the median interval between TCC diagnosis and commencement of RT on oligometastasis was 23 months (range 8-105). The median treatment dose was 25 Gy (range 20-36 Gy) given over a median of 5 fractions (range 3-10 fractions) with a median follow-up of 25 months (range 3-43 months). Imaging assessment was available for 20 lesions. The radiological progression of disease was registered in 9 patients at the median of 4.2 months from radiotherapy (range 1.9-18.8 months). This identified in-field and out-field progression in 6 patients and only out-field progression in the remaining 3. At last contact, 3 patients were alive with no evidence of disease, 3 had evidence of disease, 6 died of cancer-related disease and one died from another cause. No severe acute and late toxicity was observed. The literature contains no consistent data on TCC oligometastatic setting, but radiotherapy on lymph node, bone and/or lung oligo-recurrence from TCC offers durable disease control in a small number of patients with a very low toxicity profile. Further studies are required to establish the radiotherapy role in oligometastatic recurrent bladder cancer.

Purpose To analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution. Material and methods Between March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) - European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria. Results Two patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy. Conclusions Our study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

The aim is to present the technical feasibility and efficacy of multiple re-irradiation (re-EBRT) for local recurrence of prostate cancer (PCa) using retrospective analysis of an updated series of patients who received ablative re-EBRT with stereotactic image-guided technique for isolated local recurrence of PCa. Eight patients received three RT courses (2 re-RTs); of those 2 received 4 RT courses (3 re-RTs). Local relapse in the prostate was assessed by multiparametric magnetic resonance and/ or choline positron emission tomography. Before treatment planning, all patients had been evaluated for late toxicity from previous RT according to RTOG/EORTC. Biochemical control was assessed according to Phoenix definition. Mean age at the third RT course was 68 (standard deviation, SD: 7.2); all patients had a good performance status. At diagnosis, four cases were classified as high risk PCa, three as intermediate and one as low per NCCN 2017. Biochemical progression free interval after first and second RT-course were 74 (IQR: 59.3-133.6) months and 33 (IQR: 20.8-53.1) months, respectively. Biochemical and radiological response was registered in all patients. At present, seven out of eight patients are disease free. Overall toxicity profile was good; no severe acute or late genitourinary or gastrointestinal events were recorded. Multiple RT courses with high precision technology and image guidance can be proposed as a possible salvage therapy for locally recurrent, low-burden PCa recurrence in adequately selected patients. Deeper understanding of radiobiological effects of hypofractionation and larger series of patients are warranted to fully evaluate the applicability of multiple RT courses in the setting of locally recurrent PCa.

Soft tissue sarcomas (STS) are uncommon, heterogeneous malignant tumors of mesodermal origin. Other than conservative surgery (CS), neoadjuvant or adjuvant radiotherapy (RT) is recommended when the risk of local recurrence is high. The aim of this study is to present our Institutional experience in adjuvant RT for treatment of STS of extremities and trunk (with either brachytherapy (BRT), external beam RT (EBRT), or both) and to provide an insight of toxicity and oncological outcomes for each RT modality. According to the RT treatment approach, patients were divided into three categories: 1) BRT alone; 2) EBRT alone; 3) combined BRT+EBRT. Differences among the three groups were assessed by the Chi-squared test. Patients' follow-up was performed every 6 months for the first two years after the end of RT and then once a year. Data from 90 patients were analyzed. The overall 3-year distant relapse-free survival (DRFS), progression-free survival (PFS), and overall survival (OS) were 84%, 80%, and 97%, respectively. Acute erythema was the most frequent side effect, although severe grade 3 toxicity was present in 5 patients. Chronic toxicity of any grade was reported in 14 patients. The incidence of chronic toxicity did not show any association with treatment modality. Multivariate analysis suggested a significant correlation between acute toxicity and tumor size, RT modality, and RT dose. In conclusion, good local control and toxicity profile were observed, despite negative patients' selection at baseline. Further investigation on wider series is warranted in order to define the optimal combination with systemic therapy.

Purpose To evaluate clinical results of catheter-based interstitial high-dose-rate (HDR) brachytherapy (BT) as adjuvant treatment in previously irradiated recurrent breast cancer. Material and methods Between January 2011 and September 2015, 31 consecutive patients with histologically confirmed recurrent breast cancer after conservative surgery and conventional whole breast radiotherapy, were retreated with a second conservative surgical resection and reirradiated with adjuvant interstitial HDR-BT. None of the brachytherapy implant was performed during the quadrantectomy procedure. A dose of 34 Gy in 10 fractions, 2 fractions per day, with a minimal interval of 6 hours was delivered. Results At the time of the implant, the median age of patients was 59.7 years (range, 39.3-74.9 years). The median time from first treatment until BT for local recurrence was 11.9 years (range, 2.5-27.8 years). The median interval between salvage surgery and BT was 3.6 months (range, 1-8.2 months). No acute epidermitis or soft tissue side effects higher than grade 2 were recorded, with good cosmetic results in all patients. Most of the patients presented grade 1-2 late side effects. Only one patient developed grade 3 liponecrosis. After a median follow-up of 73.7 months (range, 28.8-102.4 months), the overall survival and cancer specific survival were 87.1% and 90.3%, respectively; 5-year local control and 5-year progression-free survival rate were 90.3% and 83.9%, respectively. Conclusions Our preliminary analysis showed that HDR-BT is a feasible treatment for partial breast reirradiation offering very low complications rate and fast procedure. Higher patients' cohort is warranted in order to define the role of this treatment modality in the breast conservative management of local recurrence.

ObjectiveStandard treatment in locally-advanced cervical cancer is external beam radiotherapy concomitant with platinum-based chemotherapy, followed by brachytherapy. The goal of our study was to determine whether an intensity modulated radiation therapy (IMRT) boost is feasible in patients unfit for brachytherapy.MethodsWe retrospectively analyzed data of 25 patients unfit for brachytherapy with median age 55 years (range, 30–82) with locally-advanced/metastatic cervical cancer who underwent external beam radiotherapy to pelvis ±para-aortic lymph nodes and sequential IMRT boost between July 2014 and December 2017. Total dose of 45–50.4 Gy in 25–28 fractions (1.8 Gy/fraction) was administered to the cervix, uterus, parametria, ovaries, vaginal tissues (based on vaginal extension), involved lymph nodes, or relevant draining lymph-nodal groups. Para-aortic nodes were included if involved at radiological staging or if common iliac nodes were positive. The IMRT boost included all residual tumor after external beam radiotherapy identified on MRI. The Kaplan–Meier method was used to calculate 2 years' overall survival, 2 years' progression-free survival, and 2 years' local control. Overall survival- and progression-free survival were calculated considering the starting of radiotherapy or neo-adjuvant chemotherapy if prescribed, while local control was calculated from the end of radiotherapy.ResultsMedian radiation dose to pelvis ±para-aortic lymph nodes was 50.4 Gy (45–50.4), boost treatment was homogeneously performed to a total dose of 25 Gy in five fractions every other day.After a median follow-up of 26 months (range, 4–77), tumor persistence at cervix at 6 months from the end of radiotherapy or local recurrence occurred in five women (20%), eight (32%) experienced a further distant progression (two of them had also tumor persistence). Two-year local control and overall survival rates for all stages were 78% and 67%, respectively. According to Common Terminology Criteria for Adverse Events v.4 scoring criteria, 10 patients experienced gastrointestinal and/or genitourinary grade G1-2 acute toxicity. G2 rectal late toxicity requiring laser-coagulation was registered in two patients, there were no gastrointestinal and/or genitourinary acute or late toxicities≥G3.ConclusionThe combination of external beam radiotherapy and brachytherapy remains the standard of care, however our preliminary data show the feasibility of IMRT boost in terms of toxicity with promising results in terms of local control and overall survival.

Purpose The first clinical genetic autoplanning algorithm (Genetic Planning Solution, GPS) was validated in ten radiotherapy centres for prostate cancer VMAT by comparison with manual planning (Manual). Methods Although there were large differences among centres in planning protocol, GPS was tuned with the data of a single centre and then applied everywhere without any centre-specific fine-tuning. For each centre, ten Manual plans were compared with autoGPS plans, considering dosimetric plan parameters and the Clinical Blind Score (CBS) resulting from blind clinician plan comparisons. AutoGPS plans were used as is, i.e. there was no patient-specific fine-tuning. Results For nine centres, all ten plans were clinically acceptable. In the remaining centre, only one plan was acceptable. For the 91% acceptable plans, differences between Manual and AutoGPS in target coverage were negligible. OAR doses were significantly lower in AutoGPS plans (p Conclusion A novel, clinically applied genetic autoplanning algorithm was validated in 10 centres for in total 100 prostate cancer patients. High quality plans could be generated at different centres without centre-specific algorithm tuning.

Purpose To evaluate stereotactic body radiation therapy (SBRT) for metachronous oligometastatic ovarian cancer patients in terms of local control, delay of systemic treatment, survival outcomes, and toxicity. Methods and Materials Retrospective data collection from a single institution was performed. The inclusion criteria were as follows: (1) oligorecurrent or oligoprogressive disease in ovarian cancer patients during or after systemic therapy; (2) surgery or other local therapies not feasible; and (3) relative contraindication to systemic therapy for reasons such as unavailability of additional chemotherapy lines or refusal of the patient. Tumor response and toxicity were evaluated using the Response Evaluation Criteria in Solid Tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. A new systemic therapy regimen was started after an SBRT treatment course in 57 of 109 cases (52.3%). Local progression–free survival, progression-free survival, and overall survival were calculated via the Kaplan-Meier method. The systemic treatment–free interval was calculated in cases without concomitant systemic therapy. Results Between May 2012 and December 2016, 82 patients (156 lesions) underwent SBRT with a median dose of 24 Gy in 3 fractions. The median follow-up period was 17.4 months. Patients received a median of 3 systemic therapy regimens prior to SBRT. Concomitant systemic therapy was performed for 29 lesions (18.6%). Among 152 evaluable lesions, a complete radiologic response, partial response, stabilization, and progressive disease were observed in 91 (60%), 26 (17%), 24 (16%), and 11 (7%), respectively. No grade 3 or 4 acute or late toxicities were observed. The median systemic treatment–free interval after SBRT was 7.4 months, and 1 of 3 patients was disease free at 1 year after SBRT. The actuarial 2-year local progression–free survival, progression-free survival, and overall survival rates were 68%, 18%, and 71%, respectively. The pattern of failure was predominantly out of field. Conclusions SBRT for oligometastatic ovarian cancer showed good local control and a good toxicity profile. It might be an appealing alternative to other invasive local therapies to delay systemic therapy in the case of chemorefractory disease or intolerance to systemic agents.

Dosiomics is a texture analysis method to produce dose features that encode the spatial 3D distribution of radiotherapy dose. Dosiomic studies, in a multicentre setting, require assessing the features’ stability to dose calculation settings and the features’ capability in distinguishing different dose distributions. Dose distributions were generated by eight Italian centres on a shared image dataset acquired on a dedicated phantom. Treatment planning protocols, in terms of planning target volume coverage and dose–volume constraints to the organs at risk, were shared among the centres to produce comparable dose distributions for measuring reproducibility/stability and sensitivity of dosiomic features. In addition, coefficient of variation (CV) was employed to evaluate the dosiomic features’ variation. We extracted 38,160 features from 30 different dose distributions from six regions of interest, grouped by four features’ families. A selected group of features (CV &lt, 3 for the reproducibility/stability studies, CV &gt, 1 for the sensitivity studies) were identified to support future multicentre studies, assuring both stable features when dose distributions variation is minimal and sensitive features when dose distribution variations need to be clearly identified. Dosiomic is a promising tool that could support multicentre studies, especially for predictive models, and encode the spatial and statistical characteristics of the 3D dose distribution.

Purpose Post-implant CT-scanning is an essential part of permanent prostate brachytherapy. However, the evaluation of post-implant CT dosimetry is not straightforward due to the edema that can modify the dose to the prostate and to the organs at risk. The aim of this study is to evaluate the impact of the timing of the post-implant CT-scan on the dosimetric results and to verify if the Day 0 scan findings can predict Day 50 scanning. Methods 136 consecutive patients who received monotherapy with I-125 implants were selected for this study. Two sets of 8 dosimetric quality parameters corresponding to 2 different CT-scans (Day 0 and Day 50) were calculated and compared. The dosimetric parameters included are the percentage volume of the post-implant prostate receiving 80%, 100% and 150% of the prescribed dose, the doses covering 80% and 90% of the prostate volume and the Dose Homogeneity Index. The values of the dose covering 1 cm3 of the rectum and urethra were assessed. Results All the dosimetric parameters of the Day 50 were higher than those of the Day 0 scan. Linear functions were obtained that calculate D90 and V100 values at Day 50 based on the Day 0 findings. Rectal and urethral parameters tended to be underestimated on Day 0 CT-scan relative to Day 50 based dosimetry. Conclusions Predicting the Day 50 dosimetry from the Day 0 scan could be a possible alternative to a Day 50 scan only in specific situations, but with a degree of uncertainty in the predicted values.

Background and purpose 3D printing is rapidly evolving and further assessment of materials and technique is required for clinical applications. We evaluated 3D printed boluses with acrylonitrile butadiene styrene (ABS) and polylactide (PLA) at different infill percentage. Material and methods A low-cost 3D printer was used. The influence of the air inclusion within the 3D printed boluses was assessed thoroughly both with treatment planning system (TPS) and with physical measurements. For each bolus, two treatment plans were calculated with Monte Carlo algorithm, considering the computed tomography (CT) scan of the 3D printed bolus or modelling the 3D printed bolus as a virtual bolus structure with a homogeneous density. Depth dose measurements were performed with Gafchromic films. Results High infill percentage corresponds to high density and high homogeneity within bolus material. The approximation of the bolus in the TPS as a homogeneous material is satisfying for infill percentages greater than 20%. Measurements performed with PLA boluses are more comparable to the TPS calculated profiles. For boluses printed at 40% and 60% infill, the discrepancies between calculated and measured dose distribution are within 5%. Conclusions 3D printing technology allows modulating the shift of the build-up region by tuning the infill percentage of the 3D printed bolus in order to improve superficial target coverage.

Aims To compare the contouring of organs at risk (OAR) between a clinical specialist radiation therapist (CSRT) and radiation oncologists (ROs) with different levels of expertise (senior–SRO, junior–JRO, fellow–FRO). Methods On ten planning computed tomography (CT) image sets of patients undergoing breast radiotherapy (RT), the observers independently contoured the contralateral breast, heart, left anterior descending artery (LAD), oesophagus, kidney, liver, spinal cord, stomach and trachea. The CSRT was instructed by the JRO e SRO. The inter-observer variability of contoured volumes was measured using the Dice similarity coefficient (DSC) (threshold of ≥ 0.7 for good concordance) and the centre of mass distance (CMD). The analysis of variance (ANOVA) was performed and a p-value < 0.01 was considered statistically significant. Results Good overlaps (DSC > 0.7) were obtained for all OARs, except for LAD (DSC = 0.34 ± 0.17, mean ± standard deviation) and oesophagus (DSC = 0.66 ± 0.06, mean ± SD). The mean CMD < 1 cm was achieved for all the OARs, but spinal cord (CMD = 1.22 cm). By pairing the observers, mean DSC > 0.7 and mean CMD < 1 cm were achieved in all cases. The best overlaps were seen for the pairs JRO-CSRT(DSC = 0.82; CMD = 0.49 cm) and SRO-JRO (DSC = 0.80; CMD = 0.51 cm). Conclusions Overall, good concordance was found for all the observers. Despite the short training in contouring, CSRT obtained good concordance with his tutor (JRO). Great variability was seen in contouring the LAD, due to its difficult visualization and identification of CT scans without contrast.

Purpose To evaluate toxicity and clinical outcomes in patients with eyelid tumour treated with contact high-dose-rate brachytherapy (HDR-BT). Material and methods Between April 2010 and August 2017, 10 consecutive patients with tumour of the eyelid underwent contact HDR-BT and custom-made surface mould. Every applicator was manually built using conventional thermoplastic material and standard plastic catheters. The median dose prescribed was 42 Gy (range, 30-48) with a median dose per fraction of 3.5 Gy (range, 2-4.5). The dose was delivered in a median of 12 fractions (range, 10-17) over a median of 16 days. In all cases, an ocular shield was placed to reduce the dose to the eye. Acute and late toxicity was evaluated according to RTOG toxicity criteria. Results We analyzed data of 9 of 10 patients (one patient was excluded because he did not give consent for investigation). The median age was 68 years (range, 31-88). According to the TNM-UICC staging system, 4, 1 and 4 patients were stage IA, IB and IC, respectively. Basal cell and sebaceous gland carcinomas were reported in 5 and 2 patients, respectively; other histological types were non-Hodgkin lymphoma and plasmacytoma. After a median follow-up of 51 months (range, 16-90), there was no evidence of local or distant recurrence. The treatment was very well tolerated. Most commonly acute reactions consisted of low grade (G1-G2) conjunctivitis and skin erythema. Only one patient required a temporary interruption of the treatment due to acute G2 conjunctivitis and G3 lid erythema. Only one G2 late toxicity was reported (corneal ulceration), without resulting in functional impairment or blindness. Conclusions Our results suggest that contact HDR-BT with a customized applicator is safe, effective and offers very good local control and can be considered for the treatment of eyelid tumours.

Purpose: To evaluate the treatment-induced toxicity (as primary endpoint) and the efficacy (as secondary endpoint) of stereotactic body radiation therapy (SBRT) in the treatment of mediastinal lymph nodes (LNs) in the so-called no-fly zone (NFZ) in cancers with various histology. Material and methods: Forty-two patients were retrospectively analyzed. Institutional dose/volume constraints for organs at risk (OARs) derived by published data were strictly respected. The correlation between treatment-related variables and toxicity was investigated by logistic regression, Chi-squared test or Fisher’s exact test. Overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS) and local control (LC) were collected from the follow-up reports. The impact of potential predictive factors on LC, PFS and OS were estimated by Cox proportional-hazard regression. Results: Median follow-up time was 16 months (range 1–41). Four patients had esophageal G1 toxicity. Ten and six patients had G1 and G2 pulmonary toxicity, respectively. Treatment site and irradiation technique were significantly correlated with G ≥ 2 and G ≥ 1 toxicity, respectively. OS probability at 19 months was 88.3% and corresponded to CSS. LC probability at 16 months was 66.3% (median LC duration: 22 months, range 1–41). Fifteen patients (35.7%) were disease-free at 25 months (median time, range 1–41). The biologically effective dose (BED) and the target dose coverage indexes were significantly correlated with LC. Conclusions: SBRT can be considered as a safe treatment option for selected patients with oligo-metastases/recurrences in the NFZ, if strict dose/volume constraints are applied.

To evaluate outcome in patients treated with stereotactic body radiotherapy (SBRT) on bone oligometastases from castration-sensitive prostate cancer after primary treatment. We retrospectively collected data of patients with less than five lesions at time of SBRT and hormone-naive disease at the first extra-regional localization, treated between 03/2012 and 11/2016. Prostate-specific antigen (PSA) was measured every 3 months after SBRT. Imaging was performed in case of progression. Survival analysis was performed with Kaplan–Meier (log-rank test) approach. Fifty-five patients were treated on 77 bone oligometastases. Median age, initial PSA and pre-SBRT PSA were 72 years, 9.12 and 3.5 ng/mL, respectively. Twenty-five patients (45%) received SBRT alone while the remaining 30 patients (55%) received concomitant ADT. Median follow-up was 24.6 months (range 3.0–67.2 months). No acute or late toxicity of grade > 1 was reported. Clinical progression was observed in 38 (69%) patients. 1-year biochemical progression-free survival (b-PFS), clinical progression-free survival (c-PFS), prostate-specific survival (PCSS) and local control (LC) rates were 51, 56, 100 and 83%, respectively. Comparing patients treated with SBRT alone and with concomitant ADT, no significant differences were found for those outcomes. SBRT is safe and allows high 1-year LC rate (83%) with low toxicity profile. No significant improvement in outcomes was registered with the addition of ADT to SBRT.

Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses with respect to conventional fractionation in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low α/β-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study is to review our data regarding oncological outcomes, namely biochemical progression-free survival (b-PFS) and clinical progression-free survival (c-PFS), acute and long-term toxicities in patients treated with a ultra-hypofractionated RT. A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensity modulated RT (IG-IMRT) at our Institute from 2012 to 2015 was included in this analysis. According to NCCN risk group classification, 65 (33.5%) patients were low risk, 101 (52.1%) intermediate risk, and 28 (14.4%) high risk. Androgen deprivation therapy (ADT) was given to 61 patients (31.4%). A 169 patients (87.1%) received 35 Gy in 5 fractions, while 25 patients (13%) received 32.5 Gy in 5 fractions (usually given in patients with comorbidity). The median duration of the treatment was 10 days (IQR 9–12). Biochemical relapse was defined as a rise of prostate specific antigen (PSA) > 2 ng/ml above nadir. b-PFS, c-PFS, and freedom from gastro-intestinal (GI) and genito-urinary (GU) toxicity curves were calculated by the Kaplan–Meier method. Log-rank test and multivariate Cox models were used to investigate the role RT dose and heterogeneity by NCCN risk groups adjusting for prognostic factors. Data on acute and late term toxicities were collected according to RTOG/EORTC grading system. With a median follow-up of 30 months, 17 patients experienced PSA failure (9%). The 3-year b-PFS was 87% for all patients and rates stratified for the NCCN risk were 94, 82, and 66% for low-, intermediate-, and high-risk groups, respectively. Log-rank tests indicate that biochemical progression was significantly greater for patients with initial PSA (iPSA) greater than 7 ng/ml (P = 0.04), high- and intermediate-risk groups (P = 0.002), low total dose (P = 0.02) and Gleason score (GS) equal or greater than 7 (P = 0.04). No statistically significant association was found with T stage nor ADT. In multivariate analyses, total dose (P = 0.03) and risk groups (P = 0.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients was tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients’ quality of life and potential overall health system and social benefits.

Purpose Formulation of a global Unified Dosimetry Index (gUDI) for the evaluation of prostate simultaneous integrated boost Volumetric Modulated Arc Therapy (VMAT by RapidArc) radiotherapy plans. Methods and materials Dose coverage, conformity, homogeneity and dose gradient index could be included in the Unified Dosimetry Index (UDI). We developed a global UDI to evaluate treatment plans containing volumes irradiated with different dose prescriptions: Intensity Modulated Radiation Therapy with simultaneous integrated boost (IMRT-SIB) with 2 dose levels (36.25 Gy/5 fz for the whole prostate gland and 37.5 Gy/5 fz for Dominant Intraprostatic Lesion (DIL)). To validate gUDI scoring system, 65 prostate cancer patients were evaluated. Mean (µ) and standard deviations (σ) were calculated for all dosimetry indices and gUDI. Furthermore, gUDI µ and σ were analyzed to compare and classify treatment plans: plans can be ranked as “excellent”, “good”, “average” or “poor”. Results Prostate Dose Gradient, Prostate Conformity and DIL Conformity indices had highlighted a major deviation from ideal scores. gUDI index classification showed most of the plans scored as “average” and “good”. Conclusion gUDI score can be a useful tool to quantify treatment plans quality also when volumes with different dose-prescription are treated.

We report the experience of the Radiation Oncology Department of the European Institute of Oncology in Milan, Italy, on the adjuvant low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy. Brachytherapy might be useful to improve keloids recurrence rate or reduce keloids treatment side effects instead of external beam radiotherapy.Data on 70 consecutive patients treated after complete keloid surgical excision were retrospectively analyzed. First 38 patients and 46 keloids were treated with adjuvant LDR brachytherapy and the following 39 patients and 50 keloids underwent HDR treatment. Median delivered dose of LDR therapy was 16 Gy; HDR median dose was 12 Gy. Sixty-four keloids (66.7%) were symptomatic at diagnosis with pain, itching, or stress.Fourteen relapses over 46 treated keloids (30.4%) were observed in the LDR group and 19 of 50 keloids (38%) in the HDR group (p = 0.521). Recurrence rate was significantly higher in males (p = 0.009), in patients younger than 44 years (p0.0001), for arms, neck, and chest wall anatomic sites (p = 0.0001) and for symptomatic keloids (p = 0.017). Aesthetic outcome was better in case of larger keloids (8 cm) (p = 0.064). Symptomatic relief was achieved in 92% of HDR patients and only 68% of LDR patients (p = 0.032).Postoperative brachytherapy is an effective treatment for keloids. In our study, LDR and HDR treatments resulted in similar recurrence rate. Better symptomatic relief was reported in case of HDR treatment compared with the LDR regimen.

Purpose Formulation of a global Unified Dosimetry Index (gUDI) for the evaluation of ultra-hypofractionated prostate Volumetric Modulated Arc Therapy (VMAT by RapidArc) treatment plans. Methods Radiotherapy treatment plan quality can be assessed in terms of dose coverage, conformity, homogeneity and dose gradient index. All these parameters could be included in the Unified Dosimetry Index (UDI). We developed a global UDI (gUDI) to evaluate treatment plans containing volumes irradiated with different dose prescriptions: Intensity Modulated Radiation Therapy with simultaneous integrated boost IMRT-SIB with 2 dose levels (36.25 Gy/5 fz for the whole prostate gland and 37.5 Gy/5 fz for Dominant Intraprostatic Lesion (DIL)). gUDI score equals to one for an ideal plan. To validate gUDI scoring system, 65 prostate cancer patients treated with ultra-hypofractionated IMRT-SIB using VMAT technique were evaluated. The computation of gUDI index was performed separately for plans with single or double DIL. Mean ( μ ) and standard deviations ( σ ) were calculated for all dosimetry indices and gUDI. Furthermore, gUDI μ and σ were analyzed to compare and classify treatment plans: under this ranking system, plans can be ranked as “excellent”, “good”, “average” or “poor”. Results Dose Coverage and Homogeneity index scores did not get away from the ideal values, both for the prostate and DIL. No statistical differences were founded for plans with single or double DIL. The gUDI index classification showed only 6 cases in the “poor” region and most of the plans scored as “average” and “good”. Conclusions gUDI score can be a useful tool to quantify treatment plans quality also when different dose prescriptions volumes are treated. Furthermore, gUDI allows to establish a standard on which dosimetry plans can be ranked.

Background The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression-free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer. Patients and Methods Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3-month PSA decrease from pre-SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT. Results Median follow-up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). Two-year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS. Conclusion SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD.

Purpose The aim of this retrospective study is to evaluate patient profile, feasibility, and acute toxicity of RadioTherapy (RT) delivered by VERO® in the first 20 months of clinical activity. Methods Inclusion criteria: 1) adult patients; 2) limited volume cancer (M0 or oligometastatic); 3) small extracranial lesions; 4) treatment between April 2012 and December 2013 and 5) written informed consent. Two techniques were employed: intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). Toxicity was evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria. Results Between April 2012 and December 2013, 789 consecutive patients (957 lesions) were treated. In 84% of them one lesion was treated and in 16% more than one lesion were treated synchronously/metachronously; first radiotherapy course in 85%, re-irradiation in 13%, and boost in 2% of cases. The treated region included pelvis 46%, thorax 38%, upper abdomen 15%, and neck 1%. Radiotherapy schedules included 5 fractions in 75% and 25% respectively. All patients completed the planned treatment and an acceptable acute toxicity was observed. Conclusions RT delivered by VERO® was administrated predominantly to thoracic and pelvic lesions (lung and urologic tumours) using hypofractionation. It is a feasible approach for limited burden cancer offering short and well accepted treatment with favourable acute toxicity profile. Further investigation including dose escalation and other available VERO® functionalities such as real-time dynamic tumour tracking is warranted in order to fully evaluate this innovative radiotherapy system.

Purpose: To improve the contouring of clinical target volume for the radiotherapy of neck Hodgkin/non-Hodgkin lymphoma by localizing the prechemotherapy gross target volume onto the simulation computed tomography using [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. Material and Methods: The gross target volume delineated on prechemotherapy [18F]-fluorodeoxyglucose positron emission tomography/computed tomography images was warped onto simulation computed tomography using deformable image registration. Fifteen patients with neck Hodgkin/non-Hodgkin lymphoma were analyzed. Quality of image registration was measured by computing the Dice similarity coefficient on warped organs at risk. Five radiation oncologists visually scored the localization of automatic gross target volume, ranking it from 1 (wrong) to 5 (excellent). Deformable registration was compared to rigid registration by computing the overlap index between the automatic gross target volume and the planned clinical target volume and quantifying the V95 coverage. Results: The Dice similarity coefficient was 0.80 ± 0.07 (median ± quartiles). The physicians’ survey had a median score equal to 4 (good). By comparing the rigid versus deformable registration, the overlap index increased from a factor of about 4 and the V95 (percentage of volume receiving the 95% of the prescribed dose) went from 0.84 ± 0.38 to 0.99 ± 0.10 (median ± quartiles). Conclusion: This study demonstrates the impact of using deformable registration between prechemotherapy [18F]-fluorodeoxyglucose positron emission tomography/computed tomography and simulation computed tomography, in order to automatically localize the gross target volume for radiotherapy treatment of patients with Hodgkin/non-Hodgkin lymphoma.