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Uterine leiomyosarcoma (U-LMS) is the most common histotype among all primary uterine sarcomas. The lung, peritoneum, pelvic or para-aortic lymph nodes, bone and liver are the most common metastatic sites involved. However, some case series of atypical sites of metastasis such as heart, brain and different endocrine glands have been described. Here we report the clinical presentation and therapeutic management of two patients affected by U-LMS with a very atypical behavior, characterized by soft tissue metastases with an impressive and massive enlargement during chemotherapy despite a good control of the other sites of disease.

Purpose: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. Methods: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. Results: A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter Conclusions: Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection ± adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify independent predictors of OS on 404 patients with complete information was fitted. RESULTS: Median follow-up was 17 months (range: 2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0, diameter 353.1: 10.9%, 50.2%, and 23.4%, respectively. At multivariate analysis, CA19-9 >100 and 30 mm (P50.0 Gy showed improved OS (P

Local management of adult soft tissue sarcoma of the extremities has evolved over the past decades. Until the 1970s, radical surgery (amputations) was the standard therapeutic procedure resulting in significant physical and psychological morbidity for the patients. In the present era, limb sparing surgery combined with radiotherapy represents the current standard of care for high grade and > 5 cm STSs. This approach guarantees high local control rate and function preservation. The aim of this paper is to summarize the current evidence for RT in STSs of the extremities. Outcomes, technical details (techniques, timing, dose, volumes of treatment) and the emerging role of RT in the management of oligometastatic disease will be analysed. Finally, results of the recent clinical trials testing new scenarios in RT of STSs will be described.

BackgroundIt has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients.MethodsA retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and “any site”. The correlation with RT technique was analysed using log-rank test and Cox’s proportional hazard method.ResultsWith a median follow-up of 72 months (range: 9–185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9–152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%;p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07–5.47,p: .034).ConclusionsThe incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results.

AimThe efficacy of low-dose fractionated radiotherapy (LDFRT) and chemotherapy (CHT) combination has large preclinical but little clinical evidence. Therefore, the aim of this review was to collect and analyze the clinical results of LDRT plus concurrent CHT in patients with advanced cancers.MethodsA systematic literature search was conducted on PubMed using the PRISMA methodology. Only studies based on the combination of LDFRT (< 1 Gy/fraction) and CHT were included. Endpoints of the analysis were tumor response, toxicity, and overall survival, with particular focus on any differences between LDFRT-CHT and CHT alone.ResultsTwelve studies (307 patients) fulfilled the selection criteria and were included in this review. Two studies were retrospective, one was a prospective pilot trial, six were phase II studies, two were phase I trials, and one was a phase I/II open label study. No randomized controlled trials were found. Seven out of eight studies comparing clinical response showed higher rates after LDFRT-CHT compared to CHT alone. Three out of four studies comparing survival reported improved results after combined treatment. Three studies compared toxicity of CHT and LDFRT plus CHT, and all of them reported similar adverse events rates. In most cases, toxicity was manageable with only three likely LDFRT-unrelated fatal events (1%), all recorded in the same series on LDFRT plus temozolomide in glioblastoma multiforme patients.ConclusionNone of the analyzed studies provided level I evidence on the clinical impact of LDFRT plus CHT. However, it should be noted that, apart from two small series of breast cancers, all studies reported improved therapeutic outcomes and similar tolerability compared to CHT alone. Systematic Review Registrationwww.crd.york.ac.uk/prospero/, identifier CRD42020206639.

Background: In our department, we provided guidelines to the radiation oncologists (ROs) regarding the omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce the patients’ exposure to the hospital environment and to minimize the departmental overcrowding. The aim was to evaluate the ROs’ compliance to these guidelines. Methods: ROs were asked to fill out a data collection form during patients’ first visits in May and June 2020. The collected data included the ROs’ age and gender, patient age and residence, RT purpose, treated tumor, the dose and fractionation that would have been prescribed, and RT changes. The chi-square test and binomial logistic regression were used to analyze the correlation between the treatment prescription and the collected parameters. Results: One hundred and twenty-six out of 205 prescribed treatments were included in this analysis. Treatment was modified in 61.1% of cases. More specifically, the treatment was omitted, delayed, or shortened in 7.9, 15.9, and 37.3% of patients, respectively. The number of delivered fractions was reduced by 27.9%. A statistically significant correlation (p = 0.028) between younger patients’ age and lower treatment modifications rate was recorded. Conclusion: Our analysis showed a reasonably high compliance of ROs to the pandemic-adapted guidelines. The adopted strategy was effective in reducing the number of admissions to our department.

Pancreatic cancer (PaC) will soon be one of the main causes of cancer mortality. Furthermore, its incidence is higher in the older population and radiotherapy (RT) represents a treatment option. The aim of this review was to evaluate feasibility and outcome of RT in older patients with PaC. A systematic literature review of patients aged ≥65 years with PaC treated with RT was performed using the PRISMA methodology. Eleven papers (1830 patients) fulfilled our inclusion criteria and were analyzed. RT was prescribed either alone or as an adjuvant treatment. Prescribed RT dose ranged from 22.0 to 70.0 Gy with conventional fractionation or hypo-fractionated schedule and delivered by three-dimensional conformal RT, intensity modulated RT or stereotactic body RT. Grade ≥ 3 acute and grade ≥ 2 late toxicity rates ranged between 0.0% and 52.6% (median: 0.5%) and between 0.0% and 15.0% (median: 0%), respectively. Median overall survival and two-year survival rate were 11.3 months (range: 6.4–69.0 months) and 49.0% (range 6.6–75.5%), respectively. RT in older patients seems to be tolerable and safe particularly in terms of late toxicity irrespective of the treatment settings. Therefore, RT can represent a treatment option in PaC even in an older population. Further analyses and prospective trials enrolling older patients are needed to better define the risk/benefit ratio in different treatment settings.

Simple Summary Pancreatic cancer remains a disease with a dismal outlook for patients, with high relapse rates after surgery and adjuvant treatments. Thanks to the high conformality achievable with advanced radiotherapy techniques, a more robust definition of clinical target volume (CTV) margins is mandatory. Moreover, a precise CTV definition may affect local control, minimizing radiation-related toxicity and allowing dose escalation. Contrary to two recent studies, RTOG contouring guidelines are not based on a pattern of failure analysis. We provided a local failure risk map in resected pancreatic cancer, validating the results of previous studies. Moreover, according to a new probabilistic approach, we provided new CTV contouring guidelines for the postoperative radiotherapy of pancreatic cancer, modeling targets’ margins on a combination of our validated local failure map (30% of local failures) and RTOG guidelines (70% of local failures). Abstract The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45–0.53 and 0.58–0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.

Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for &lt, 14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor.

BackgroundGlioblastoma Multiforme (GBM) is the most common primary brain cancer and one of the most lethal tumors. Theoretically, modern radiotherapy (RT) techniques allow dose-escalation due to the reduced irradiation of healthy tissues. This study aimed to define the adjuvant maximum tolerated dose (MTD) using volumetric modulated arc RT with simultaneous integrated boost (VMAT-SIB) plus standard dose temozolomide (TMZ) in GBM.MethodsA Phase I clinical trial was performed in operated GBM patients using VMAT-SIB technique with progressively increased total dose. RT was delivered in 25 fractions (5 weeks) to two planning target volumes (PTVs) defined by adding a 5-mm margin to the clinical target volumes (CTVs). The CTV1 was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV2 was the CTV1 plus 20-mm margin. Only PTV1 dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV2 dose remained unchanged (45 Gy/1.8 Gy). Concurrent and sequential TMZ was prescribed according to the EORTC/NCIC protocol. Dose-limiting toxicities (DLTs) were defined as any G ≥ 3 non-hematological acute toxicity or any G ≥ 4 acute hematological toxicities (RTOG scale) or any G ≥ 2 late toxicities (RTOG-EORTC scale).ResultsThirty-seven patients (M/F: 21/16; median age: 59 years; median follow-up: 12 months) were enrolled and treated as follows: 6 patients (72.5 Gy), 10 patients (75 Gy), 10 patients (77.5 Gy), 9 patients (80 Gy), 2 patients (82.5 Gy), and 0 patients (85 Gy). Eleven patients (29.7%) had G1-2 acute neurological toxicity, while 3 patients (8.1%) showed G ≥ 3 acute neurological toxicities at 77.5 Gy, 80 Gy, and 82.5 Gy levels, respectively. Since two DLTs (G3 neurological: 1 patient and G5 hematological toxicity: 1 patient) were observed at 82.5 Gy level, the trial was closed and the 80 Gy dose-level was defined as the MTD. Two asymptomatic histologically proven radionecrosis were recorded.ConclusionsAccording to the results of this Phase I trial, 80 Gy in 25 fractions accelerated hypofractionated RT is the MTD using VMAT-SIB plus standard dose TMZ in resected GBM.

Kaposi sarcoma (KS) is a rare angioproliferative disorder, which is usually associated with human herpesvirus-8 infection. Electrochemotherapy (ECT) may be an option in the treatment of KS skin lesions due to the high response rate noted in neoplastic lesions of different histological types. The aim of the present systematic review was to analyse the available evidence on using ECT in the treatment of KS skin lesions. Tumor response, local control and toxicity were analyzed. In the three included studies, the complete response rate was 65-100% and the overall response rate in all studies was 100%. The treatment was well tolerated with mild and transient toxicity. However, further studies are required to fully analyze long-term disease control and to compare ECT with other local therapies used for KS.

Introduction: An education strategy was employed in our department to increase the rate of patients with uncomplicated painful bone metastases undergoing single fractionation radiotherapy (SFRT). The purpose of this report is to analyze the results of this strategy over a 5 year period. Materials and Methods: In January 2015, two meetings were organized in our department. In the first, data from an audit on the current SFRT rate were shown. In the second, evidence of SFRT efficacy in the relief of pain from uncomplicated bone metastases was presented. In addition, during the weekly discussion of clinical cases, the opportunity to use the SFRT was systematically recalled. Using our institutional database, all patients treated with radiotherapy for uncomplicated painful bone metastases in the period between 2014 (year considered as a reference) and 2019 were retrieved. Data regarding treatment date (year), radiotherapy fractionation, and tumor, patients, and radiation oncologists characteristics were collected. Results: A total of 627 patients were included in the analysis. The rate of patients undergoing SFRT increased from 4.0% in 2014 to 63.5% in 2019 ( p 80 years), lung cancer as the primary tumor, treatment prescribed by a radiation oncologist dedicated to palliative treatments, and treatment date (2014 vs 2015–2019). Conclusions: This retrospective single-center analysis showed that a simple but intensive and prolonged departmental education strategy can increase the rate of patients treated with SFRT by nearly 16 times.

Purpose This study aimed to assess the feasibility to plan and deliver highly heterogeneous doses to symptomatic large tumors using volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) during a short course palliative accelerated radiotherapy. Methods A patient with a large symptomatic chordoma infiltrating the right gluteal region was selected. A modified SIB treatment was implemented to irradiate the central volume of the tumor (boost target volume, BTV) up to 10 Gy/fraction in a dose escalation trial while maintaining the remaining tumor volume (planning target volume, PTV) and the surrounding healthy tissues within 5 Gy/fraction in twice daily fractions for two consecutive days. Four SIB plans were generated in the dual‐arc modality; a basal dose of 20 Gy was prescribed to the PTV, while the BTV was boosted up to 40 Gy. For comparison purposes, plans obtained with a sequential boost (SEQ plans) were also generated. All plans were optimized to deliver at least 95% of the prescription dose to the targets. Dose contrast index (DCI), conformity index (CI), integral dose (ID), and the irradiated body volumes at 5, 10, and 20 Gy were evaluated. Results At equal targets coverage, SIB plans provided major improvement in DCI, CI, and ID with respect to SEQ plans. When BTV dose escalated up to 200% of PTV prescription, DCI resulted in 66% for SIB plans and 37% for SEQ plans; the ID increase was only 11% for SIB plans (vs 27% for SEQ plans) and the increase in healthy tissues receiving more than 5, 10, and 20 Gy was less than 2%. Pretreatment dose verification reported a γ‐value passing rate greater than 95% with 3%(global)‐2 mm. Conclusion A modified SIB technique is dosimetrically feasible for large tumors, where doses higher than the tolerance dose of healthy tissues are necessary to increase the therapeutic gain.

Metastases with soft tissues invasion, impending fractures or spinal cord compression (complicated bone metastases) represent a common clinical problem in advanced cancers and frequently lead to deterioration of patients' quality of life (QoL). A phase I-II study was planned to define the maximum tolerated dose (MTD) of a short-course radiotherapy (RT) and its efficacy in palliation of complicated bone metastases. A phase I trial was designed with three dose-escalation steps: 16, 18, and 20Gy. Total dose at each level was delivered in 2 days, twice daily. Eligibility criteria were painful complicated bone metastases and ECOG performance status ≤ 3. The presence of acute toxicity ≥ Grade 3 (RTOG scale) was considered the dose limiting toxicity. The MTD was used to plan a phase II trial with pain response as the primary outcome. Pain was recorded using a Visual Analogic Scale (VAS), and QoL using CLAS scales. Forty-five patients were enrolled in this trial. In phase I no Grade ≥ 2 acute toxicities were recorded. Thus 20Gy was established as MTD. In phase II, with a median follow-up of 4 months, rates of complete symptom remission, partial response, no symptomatic change, and symptoms progression were 32.0%, 52.0%, 8.0%, and 8.0%, respectively. This RT protocol tested in our study is effective and tolerable with comparable results to traditional RT treatments delivered in 5-10 daily fractions.

Radio-chemotherapy (RCT) is the primary treatment of anal cancer (AC). However, the role and the optimal total dose of a radiation boost is still unclear. No randomized controlled trials nor systematic reviews have been performed to analyze the efficacy of brachytherapy (BRT) as boost in AC. Therefore, we performed this systematic review based on PRISMA methodology to establish the role of BRT boost in AC. A systematic search of the bibliographic databases: PubMed, Scopus, and Cochrane library from the earliest possible date through January 31, 2018 was performed. At least one of the following outcomes: local control (LC), loco-regional control (LRC), overall survival (OS), disease-free survival (DFS), or colostomy-free survival (CFS) had to be present for inclusion in this systematic review in patients receiving a BRT boost. Data about toxicity and sphincter function were also included. Ten articles fulfilled the inclusion criteria. All the studies had retrospective study design. All studies were classified to provide a level of evidence graded as 3 according to SIGN classification. Median 5-year LC/LRC, CFS, DFS, and OS were: 78.6% (range, 70.7-92.0%), 76.1% (range, 61.4-86.4%), 75.8% (range, 65.9-85.7%), and 69.4% (63.4-82.0%), respectively. The reported toxicities were acceptable. RCT is the treatment cornerstone in AC. High-level evidences from studies on BRT boost in AC are lacking. Further studies should investigate: efficacy of BRT boost in comparison to no boost and to external beam boost, patients who can benefit from this treatment intensification, and optimal radiation dose.

Purpose: To assess the feasibility of automated stereotactic volumetric modulated arc therapy (SBRT-VMAT) planning using a simultaneous integrated boost (SIB) approach as a dose escalation strategy for SBRT in pancreatic cancer. Methods: Twelve patients with pancreatic cancer were retrospectively replanned. Dose prescription was 30Gy to the planning target volume (PTV) and was escalated up to 50Gy to the boost target volume (BTV) using a SIB technique in 5 fractions. All plans were generated by Pinnacle3 Autoplanning using 6MV dual-arc VMAT technique for flattened (FF) and flattening filter-free beams (FFF). An overlap volume (OLV) between the PRV duodenum and the PTV was defined to correlate with the ability to boost the BTV. Dosimetric metrics for BTV and PTV coverage, maximal doses for serial OARs, integral dose, conformation numbers, and dose contrast indexes were used to analyze the dosimetric results. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Differences between FF and FFF plans were quantified using the Wilcoxon matched-pair signed rank. Results: Full prescription doses to the 95% of PTV and BTV can be delivered to patients with no OLV. BTV mean dose was >90% of the prescribed doses for all patients at all dose levels. Compared to FF plans, FFF plans showed significant reduced integral doses, larger number of MUs, and reduced beam-on-times up to 51% for the highest dose level. Despite plan complexity, pre-treatment verification reported a gamma pass-rate greater than the acceptance threshold of 95% for all FF and FFF plans for 3%-2mm criteria. Conclusions: The SIB-SBRT strategy with Autoplanning was dosimetrically feasible. Ablative doses up to 50Gy in 5 fractions can be delivered to the BTV for almost all patients respecting all the normal tissue constraints. A prospective clinical trial based on SBRT strategy using SIB-VMAT technique with FFF beams seems to be justified.

Background/aim The primary endpoint of this phase I study was the maximum tolerated dose (MTD) of middle half body (MHB) accelerated radiotherapy (RT) in multiple bone metastatic (BM) prostate cancer (PCa) patients. Patients and methods Three step dose escalation [13 Gy (3.25 Gy/fraction), 14 Gy (3.5 Gy/fraction), and 15 Gy (3.75 Gy/fraction)] in three consecutive patient cohorts were planned. RT was delivered in two consecutive days and two daily fractions. Six patients were enrolled in the first two cohorts and 12 in the third cohort. Grade ≥3 toxicity was considered as a dose-limiting toxicity (DLT). Results Twenty-five patients (median age=71 years, median follow-up=7.4 months) were enrolled. Defined MTD dose was 15 Gy. Overall pain response rate was 76%: 9 patients (36%) showed complete and 10 patients (40%) reported partial response of pain. Conclusion MHB accelerated RT (total dose: 15 Gy) delivered in two consecutive days and two daily fractions is well tolerated.

Aim To define safety and efficacy of a palliative, short-course accelerated radiation therapy for symptomatic locally advanced primary pelvic cancer. Materials and methods A phase II trial was planned based on the minimax Simon's two-stage design. A total of 18 Gy in 4.5 Gy/fraction administered twice a day was delivered (SHARON). Pain and quality of life were recorded according to the Visual Analogue self-assessment and the cancer linear analog scales (CLAS), respectively. Results Twenty-five patients were enrolled in the study. The most frequent baseline symptoms were pain (48%), bleeding (40%), bleeding/pain (8%), and intestinal sub-occlusion (4%). The overall palliative response rate was 96.0%, with a median palliative duration of 6 months. An improvement of quality-of-life indices (well-being, fatigue, and ability to perform daily activities) was noted in 64.0%, 36.0%, and 48.0% of patients, respectively. Conclusion The SHARON regimen was well tolerated and effective in the palliative treatment of patients with locally advanced pelvic cancer. Based on these results, a multicentric prospective phase III trial is ongoing to compare this regimen with traditional 2-week radiotherapy treatment.

e22507 Background: We compared toxicity and outcomes of BuMel and TreoMel HDCT consolidation with stem cell rescue in high-risk ES pts prospectively treated in 5 consecutive trials at the Istituto Ortopedico Rizzoli, Bologna, Italy. Methods: Eligible pts had histologically proven diagnosis of ES, high-risk disease defined as localized disease with poor histological/radiological response to standard chemotherapy or lung/pleural metastases or extra-pulmonary metastases or relapsed disease, were aged < 40. All pts received previous standard chemotherapy (vincristine, ifosfamide, doxorubicin, etoposide, cyclophosphamide actinomycin-D) and surgery and/or radiation therapy (RT) as local treatment. From June 1, 2011, TreoMel was used instead of BuMel to avoid potential severe complications related to busulfan, as in case of previous RT on axial skeleton/pelvis. Pts with lung metastases received lung irradiation 12-15 Gy at least 2 months after HDCT. Results: Between January 1, 2007, and September 30, 2018, 98 pts received BuMel or TreoMel: 52 pts with localized disease (7 TreoMel), 26 pts with lung/pleural metastases (5 TreoMel), 10 pts with extra-pulmonary metastases (4 TreoMel) and 10 pts with relapsed disease (1 TreoMel). Median age was 18 yrs (range 3-39 yrs). 14 out of 17 TreoMel pts received previous RT on axial skeleton/pelvis. Median follow up is 4.2 yrs (range 10 mo. - 12 yrs). Pts treated with TreoMel showed a significant lower incidence of grade 3-4 stomatitis (p = < 0.001) and of all grade ≥ 3 non-hematological toxicities (p = < 0.001). One pt died of BuMel-related toxicity (sinusoidal obstruction syndrome/veno-occlusive disease) and none after TreoMel. For localized ES, the 5yr-EFS was 66.7% (95%CI, 47.9-78) for BuMel pts and 66.7% (95CI%, 19.5-90.4) for TreoMel pts. Conclusions: In high-risk ES, TreoMel is significantly less toxic then BuMel. Combining RT on central/axial sites and TreoMel is feasible. In localized ES, results show similar 5yr-EFS between BuMel and TreoMel. TreoMel could be used instead of BuMel when busulfan is contraindicated.

Aim Radical radiotherapy of prostate cancer requires a relatively high dose to achieve an optimal tumor control probability and a reduced dose to the critical structures related to the sexual function (S_OARs) in order to avoid erectile dysfunction. The aim of this study was to perform a planning feasibility analysis of a 3-level dose prescription with Simultaneous Integrated Boost (SIB) on the dominant intraprostatic lesion (DIL) and with S_OARs sparing. Material and methods Twelve patients with clinically localized intermediate risk prostate cancer were included. The prostate, seminal vescicles, and DIL Clinical Target Volumes were delineated on rigid fused MRI-CT simulation images using mp-MRI as a separate guide. A 5 mm margin was added to define the PTVs. Penile bulb (PB), corpora cavernosa (CC), internal pudendal arteries (IPAs) and neurovascular bundles were contoured as S_OARs. The following doses were prescribed in 25 fractions: 56.25 Gy to PTVsv, 67.50 Gy to PTVp, and 75 Gy to PTVdil. Standard plans (SD-VMAT) were created to fulfil targets coverage and Quantec constraints for conventional OARs (SD_OARs: rectum, bladder, and femoral heads). For each patient, a new “sexual-sparing” plan (SS-VMAT) was created adding new objectives for S_OARs with priority to minimize mean doses to IPAs, CC, and PB. Dose-volume histogram end points were compared between the 2 plans using Wilcoxon test. Results D98% were >95% of prescribed doses for all targets and techniques. No significant differences were found in sparing SD_OARs for considered metrics. Regarding S_OARs, SS_VMAT plans provided a significant reduction of the dose. Mean dose reduction for IPAs, CC, PB, and neurovascular bundles was 32.4% (11.2 Gy, p = 0.002), 22.5% (4.1 Gy, p = 0.006), 10.0% (4.6 Gy, p = 0.010), and 2.6% (1.8 Gy, p = 0.020), respectively. Conclusions We showed that a significant dose sparing for S_OARs using VMAT-SIB strategy is feasible allowing “sexual-sparing” and highly conformal plans with dose escalation to the DIL.

Background: Surgery is the first-line therapy for treatment of cutaneous squamous cell carcinoma (cSCC), and interventional radiotherapy is recommended when surgery is not feasible, contraindicated, or refused by the patient. Objectives: To provide a multidisciplinary systematic review of the role of interventional radiotherapy for the treatment of cSCC of the nasal vestibule. Materials and Methods: A systematic search was performed; primary outcomes were tumour local control and overall survival. Acute toxicity, late toxicity, and functional cosmetic results, regardless of the scoring systems used, were secondary outcomes. Results: After full-text reviewof the 92 papers initially identified, we included only 10 papers in the review; no randomized controlled trials or prospective studies were identified. Five studies reported five-year local control, with rates ranging between 69% and 97%. A high level of heterogeneity was observed regarding the methods used to assess treatment-related toxicity. Conclusion: Interventional radiotherapy may be considered for lesions specifically arising from the area of the nasal vestibule. A multidisciplinary approach might help to select cases that are potential candidates for conservative treatment according to the tumour and the patient’s features.

Purpose: Concurrent chemoradiation (CCRT) is the standard curative treatment of anal canal cancer (ACC). The role of a brachytherapy (BRT) boost in this setting is still debated. Therefore, the aim of this analysis was to retrospectively evaluate the clinical outcomes in a large cohort of ACC patients treated with CCRT plus BRT boost or external beam radiotherapy (EBRT) boost.Material and methods: Patients with non-metastatic ACC, treated in our department between January 2003 and December 2014 were included in this analysis. The initial treatment was based on EBRT to the pelvis (prescribed dose, 45 Gy/1.8 Gy) plus concurrent chemotherapy (5-fluorouracil and mitomycin-C). Patients received a pulsed-dose-rate BRT boost on the primary tumor (median dose, 20 Gy; range, 13-25 Gy) 2-3 weeks after the end of CCRT. In patients with contraindications to BRT, an EBRT boost (prescribed dose, 16 Gy, 2 Gy/fraction) was delivered immediately after CCRT.Results: One-hundred-twenty-three patients were included in this analysis (median age, 61 years; range, 36-93 years; squamous-cell carcinoma, 78%; HIV+, 6%; median follow-up, 71 months; range, 2-158 months). The actuarial 5-year local control (LC), distant metastasis-free survival, colostomy-free survival, and overall survival (OS) rates were 81.7%, 92.3%, 62.3%, and 74.0%, respectively. At univariate analysis, patients aged 65 years (HR, 3.03; 95% CI: 1.54-5.95; p = 0.001) significantly predicted increased risk of mortality. The crude rate of toxicity-related colostomies was 4.9%.Conclusions: The role of BRT boost in ACC remains unclear since the outcomes were not clearly different compared to CCRT alone. However, further improvement of clinical results in ACC treatment is needed, and therefore prospective trials based on advanced (image-guided/adapted) BRT techniques are warranted.

Aim This study systematically reviews the recent literature on the role of definitive radiotherapy (RT) in the management of vaginal cancer (VC) and presents comprehensive data on clinical outcomes and toxicity. Methods The authors performed a literature search using PubMed (2007–2016) to identify all prospective and retrospective studies that have been published on RT in invasive VC. Results Of the 199 identified studies, 13 met the inclusion criteria. All studies had a retrospective design. Overall, 793 patients (median, 45; range, 26–138) were included. A high heterogeneity was found across studies in terms of RT techniques, assessment criteria, and reported outcomes. The majority of the patients were treated with a combination of external beam RT and brachytherapy (74.2%). Acute and late grade ≥3 toxicity rates ranged from 0.0% to 24.4% (median, 8.7%) and from 0.0% to 22.5% (median, 12.8%), respectively. The 5-year local control rates ranged between 39% and 79%. The 5-year overall survival ranged between 34% and 71.0% (median, 63.5%). Early stage of the disease (International Federation of Gynecology and Obstetrics stages I–II vs. III–IV), small tumor size ( Conclusion Only retrospective studies, in a limited number, have been published on RT in VC in the past decade, with significant heterogeneity in terms of treatment characteristic and evaluation criteria. Clinical results were strongly influenced by tumor stage. Prospective randomized studies are needed to improve patients’ outcomes, especially in advanced-stage disease. Implications for Practice This study systematically reviews the recent literature on the role of definitive radiotherapy in the management of vaginal cancer and presents comprehensive data on clinical outcome and toxicity. The prognosis of patients is dismal, with a 5-year overall survival of approximately 50%. Early stage of the disease, small tumor size, previous hysterectomy, high pretreatment/treatment hemoglobin levels, and patients’ age were correlated with a better clinical outcome. A brachytherapy boost should be delivered, especially in patients with higher-stage disease. The addition of concurrent weekly cisplatin should be considered in most patients, and transfusion should be used to maintain high hemoglobin levels.

BACKGROUND/AIM Whole lung irradiation (WLI) represents standard therapy for patients with pulmonary metastases from Ewing sarcoma although the impact on clinical outcomes and toxicity is still unclear. The aim of this study was to evaluate toxicity after WLI in patients with Ewing sarcoma and osteosarcoma as well as overall survival (OS) and event-free survival (EFS). MATERIALS AND METHODS A systematic review of studies on bilateral pulmonary irradiation treatments for prophylactic or curative therapy was performed based on PRISMA methodology. Data base searches on PubMed and Cochrane Library from the earliest time possible through 31st March 2018 were carried out. Combination with other treatments, such as chemotherapy and surgery were allowed. Only articles published in English were considered. RESULTS Toxicity was evaluated in 13 of the 14 analyzed studies (640 patients). Reported lung acute toxicity grade ≥3 ranged between 0.0 and 12.2%. Three studies reported 12 cases (1.8%) of severe pneumonitis. Grade ≥2 late toxicity was mainly recorded in patients who received boost irradiation, previous thoracic surgery, chemotherapy or who were smokers. Lack of a significant impact of WLI on OS was reported in comparative studies although patients treated with WLI showed higher survival in most individual studies. CONCLUSION Although the rate of severe toxicity was very low, the real impact of WLI on patients' outcomes remains unproven, probably due to the narrow dose limits that can be delivered to the whole lung parenchyma. New strategies to prevent or treat lung metastases in these patients should be tested. Ultra-fractionated radiotherapy concurrent with modern chemotherapy protocols could be tested in this setting due to the chemo-sensitizing effect and negligible radio-induced toxicity of fraction doses

Aim To determine the maximum tolerated dose (MTD) of a short-course accelerated radiotherapy and its feasibility for symptomatic palliation of advanced head and neck cancer or head and neck metastases from any primary site. Patients and methods A phase I trial in four dose-escalation steps was planned: total dose ranged between 14 and 20 Gy in a total of four fractions administered twice a day. The dose-limiting toxicity (DLT) was determined as grade 3 or more toxicity occurring during treatment. The MTD obtained was used to plan a phase II trial. Results A total of 48 patients were treated. In the phase I trial, the 20 Gy dose level was determined to be the MTD. In the phase II trial, the palliative response rate was 82.7%, with a median duration of palliation of 3 months. Conclusion Short-course accelerated radiotherapy was well tolerated and effective for palliation. These findings may help design future prospective randomized studies.

Objective/PurposeExtramammary Paget disease (EMPD) is a rare neoplasm of the skin generally affecting the anogenital area. Because of the low-frequency of the disease, no specific guidelines about the treatment strategy are available. Surgery is the recommended therapy for resectable and localized disease, but several other local treatments have been reported such as radiotherapy (RT). Most articles report small retrospective studies, referring to patients treated decades ago with large heterogeneity in terms of RT dose and technique. The aim of this study was to systematically review the main experiences in RT for the treatment of EMPD in the past 30 years.Materials and MethodsA systematic search of the bibliographic databases PubMed and Scopus from January 1986 to January 2017 was performed including studies published in English, Italian, Spanish, French, and German language.ResultsAccording to the search strategy, 19 full-text articles, published from 1991 to 2015, fulfilled inclusion criteria and were included in the final review. All articles were retrospective analyses with no randomized controlled trials. These studies evaluated 195 EMPD patients treated with RT, delivered in several settings. A large variability in terms of RT doses, fractionation, clinical setting, and techniques was found.Radiotherapy was administered as definitive treatment for primary or recurrent disease after surgery in 18 studies with doses ranging from 30 to 80.2 Gy delivered in 3 to 43 fractions. Radiotherapy was administered as postoperative adjuvant treatment in 9 articles with doses ranging between 32 and 64.8 Gy in 20 to 30 fractions. Two studies reported the RT use in preoperative neoadjuvant setting with doses ranging between 40 and 43.30 Gy, and 2 experiences reported the RT treatment for in situ EMPD, using 39.6 to 40 Gy. Adverse events were reported in almost all but 2 articles and were grade 2 or lower.The 18 studies evaluating RT as definitive treatment for primary or recurrent disease after surgery reported a complete response rate ranging from 50% to 100%, with a variable rate of local relapse or persistent disease ranging from 0% to 80% of cases. The 9 studies evaluating RT as postoperative adjuvant treatment reported a local relapse or persistent disease rate of 0% to 62.5%. A dose-response relationship was reported suggesting doses greater than or equal to 60 Gy for gross tumor volume treatment. Local control, disease-free survival, and overall survival at 12, 20, and 60 months have been retrieved for available data, respectively.In patients with EMPD and concurrent underlying internal malignancy, the prognosis was often worsened by the latter. In this setting, literature analysis showed a potential RT palliative role for symptoms control or local control maintenance.Derma tumor invasion greater than 1 mm and lymph node metastases were reported to be important prognostic factors for distant metastases or death.ConclusionsTo date, literature highlights the role of RT in the management of EMPD, but with low level of evidences.

Half-body irradiation (HBI) represented a standard treatment for multiple painful bone metastases (BMs). However, its use has progressively reduced due to the associated toxicity rates. The aim of this paper was to evaluate HBI delivered by conformal radiotherapy (RT) technique in a large patients population with widespread BMs. HBI was delivered in 3Gy fractions, bid, ≥ 6h apart, on 2 consecutive days (total dose: 12Gy) using 3-dimensional conformal RT (3D-CRT) box technique. The target included pelvic bones, lumbar-sacral vertebrae and upper third of femurs. Acute and late toxicity was scored based on RTOG and EORTC-RTOG scales, respectively. Pain was evaluated using the Pain-Drug scores and the Visual Analog Scale (VAS). One hundred and eighty patients were eligible for inclusion in this retrospective analysis. Grade 3 and 4 acute toxicity rates were 1.1% and 0.0%, respectively. Mean VAS before and after HBI was 5.3 versus 2.7, respectively (p: 0.0001). Based on VAS, 37.5% of patients showed complete pain relief (VAS: 0) while 38.1% had partial response (≥ 2-point VAS reduction). Overall, Pain and Drug Score reduction was observed in 76.3% and 50.4% of patients, respectively. 1-, 2-, and 3-year pain progression free survival was 77.0%, 63.4%, and 52.7%, respectively. Thirty patients (16.7%) underwent RT retreatment on the same site with median 15.9months interval (range 2-126months). HBI delivered with 3D-CRT technique is safe and effective. It provides long lasting pain control in patients with multiple BMs with negligible rates of relevant toxicity.

Objectives To evaluate the efficacy and safety of a conformal Short Course Accelerated Radiation therapy (SHARON) for symptomatic palliation of locally advanced or metastatic cancers in older patients. Materials and Methods This is a pooled analysis on patients aged ≥ 80 years selected between subjects enrolled in 3 phase I-II studies on a short course palliative treatment of advanced or metastatic cancer. The primary endpoint was to evaluate the symptoms response rate produced by accelerated radiotherapy delivered in 4 total fractions in twice a day. Total dose ranged between 14 Gy and 20 Gy while dose/fraction between 3.5 and 5 Gy. Results A total of 48 patients were included in this analysis. Twenty-six patients (54.2%) had advanced primary or metastatic head and neck tumors, 11 (22.9%) locally advanced or metastatic thoracic cancers, 11 (22.9%) complicated bone metastases. The majority of patients presented pain (60.4%). With a median follow-up time of 5.5 months, no G4 acute and late toxicities were recorded. The overall palliative response rate was 91.7% with a median duration of palliation of 4 months. Conclusion Short course accelerated radiotherapy in locally advanced or metastatic cancers is effective in terms of symptom relief and well tolerated even in older patients.

Backgroud The European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP. Materials and methods This phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age 0.2 ng/ml. Results A total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37–120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively. Conclusion A higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933)

Background/aim A systematic review on toxicity, local control (LC), overall survival (OS), and biochemical relapse-free survival (bRFS) after postoperative hypofractionated radiotherapy (HFRT) on prostate cancer (PCa) was performed. Materials and methods Based on the PRISMA methodology, studies reporting clinical results after adjuvant or salvage HFRT were included. Results A total of 1,208 patients from 17 eligible studies were included. Median follow-up was 30 months. No case of severe acute gastrointestinal (GI) toxicity was recorded. Grade ≥3 acute genitourinary (GU) toxicity ranged between 0% and 3%. Different rates of grade ≥2 late GI (range=0-8.7%) and GU (range=0-66%) toxicity were recorded. Encouraging results on LC, OS, and bRFS were reported. Conclusion Acute toxicity does not seem to be increased in patients receiving postoperative HFRT, but the results of late-GU toxicity are conflicting. Further prospective studies are needed before including postoperative HFRT in clinical practice.

The present study aimed to provide practical guidelines for palliative treatment of advanced carcinoma of the pancreas (CAP) with the 2D technique. Fifteen patients with locally advanced CAP consecutively treated with radiation therapy at the Radiation Oncology Center, Research and Care Foundation 'Giovanni Paolo II' (Campobasso, Italy) underwent computed tomography simulation in supine position. Definition of the clinical target volume (CTV) included the head and body of the pancreas, and the retropancreatic space. The planning target volume was defined by adding a margin of 14 mm to the CTV in the cranio-caudal direction and of 11 mm in radial direction. For each patient, 3 treatment plans were calculated using a cobalt source, 6 MV photons and 15 MV photons (box technique). Beams were drawn using the primary collimators without using multileaf collimators, and progressively optimized in order to respect the minimum dose (Dmin>90%) constraint. Once the final plan was achieved, distances of the fields edges from a set of reference points (bony or duodenal landmarks) were measured. Using this technique, 15 anterior-posterior and postero-anterior (AP-PA) beams and 15 pairs of lateral-lateral (LL) beams were defined for the different patients. Finally, the single minimal AP-PA and LL beams able to include the 15 sets of AP-PA and LL beams were defined. The results of this analysis are reported in tabular form. Guidelines are provided for treatment based on cobalt unit or Linear accelerator (both 6 and 15 MV photons). This study provides information regarding field size and position. A dosimetric study has been planned to identify the dose to be administered with this technique taking into account current dose-volume constraints.

Purpose A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) in a large series of patients with high-risk and intermediate-risk endometrial cancer (HIR-EC) is presented. The study also evaluated the association between rate and severity of toxicity and comorbidities and the clinical outcomes. Methods and Materials Two SIB-VMAT dose levels were investigated for boost to the vaginal vault, whereas the pelvic lymph nodes were always treated with 45 Gy. The first cohort received a SIB-VMAT dose of 55 Gy in 25 consecutive 2.2-Gy fractions, and the subsequent cohort received higher doses (60 Gy in 2.4-Gy fractions). Results Seventy consecutive HIR-EC patients, roughly half of whom were obese (47.1%) or overweight (37.1%), with Charlson Age-Comorbidity Index >2 (48.5%), were enrolled. Thirty-one patients (44.3%) were administered adjuvant chemotherapy before starting radiation therapy. All patients (n=35 per dose level) completed irradiation without any dose-limiting toxicity. Proctitis (any grade) was associated with radiation therapy dose ( P =.001); not so enterocolitis. Grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity were recorded in 17 (24.3%) and 14 patients (20.0%), respectively, and were not associated with radiation dose. As for late toxicity, none of patients experienced late grade ≥3 GI or grade ≥2 GU toxicity. The 3-year late grade ≥2 GI and GU toxicity–free survival were 92.8% and 100%, respectively, with no difference between the 2 dose levels. With a median follow-up period of 25 months (range, 4-60 months), relapse/progression of disease was observed in 10 of 70 patients (14.2%). The 3-year cumulative incidence of recurrence was 1.5% (95% confidence interval (CI): 0.2-10.7), whereas the 3-year disease-free survival was 81.3% (95% CI: 65.0-90.0). Conclusions This clinical study showed the feasibility of this technique and its good profile in terms of acute and late toxicity at the recommended doses even in aged and frail patients.