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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.

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.

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.

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.

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.

To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT).32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnife(TM) (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml(-1)).Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes.re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment.Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients.