Cholangiocarcinoma (CC) is an uncommon neoplasm representing 3% of gastrointestinal (GI) cancers and the second most common primary liver malignancy. 1 They represent a very heterogeneous group of neoplasm arising from the epithelial cells of the bile duct. CC are classified according to their anatomical location as intra hepatic or extra hepatic. Radical surgery with negative histological margins is the only treatment allowing long-term survival but even after tumor resection, the prognosis is dismal with 5 year overall survival (OS) <20%. 1 Moreover, most of these patients have advanced disease at the time of diagnosis and are candidates for non-surgical treatments. Furthermore, in patients undergoing surgery, 15 to 25% microscopic (R1) or macroscopic (R2) residual disease was reported. 2 Some studies have demonstrated that external beam radiotherapy (EBRT) with or without systemic chemotherapy (CHT) is a treatment option in unresectable or R1-R2 residual CC with median OS ranging between 10 and 15 months. [3][4][5] Furthermore, a significant correlation between radiotherapy (RT) dose and OS has been reported. [6][7][8] However, the possibility to deliver very high RT dose on this site is limited by the low radiation tolerance of both liver and GI tract.In the last decade, technological improvements in EBRT delivery accuracy and in respiratory motion compensation has enabled the widespread implementation of stereotactic body radiation therapy (SBRT). Particularly, due to its ability to deliver a high and focused dose in few

Radiotherapy (RT) is a treatment option for advanced biliary tract cancer (BTC), often combined with sequential and/or concurrent chemotherapy. The use of modern RT techniques requires accurate clinical target volume (CTV) definition and delineation. However, guidelines for CTV delineation in BTC are lacking. Therefore, the aim of this study was to propose a computer tomography (CT) atlas for CTV definition of BTC. We previously proposed guidelines to define the nodal CTV (CTV-N) in BTC. In this study, based on a literature analysis, we defined the margins to be added to the gross tumor volume (GTV; subclinical and microscopic disease) to define the primary tumor CTV (CTV-T). An abdominal contrast enhanced planning CT scan was performed on three different patients with unresectable intrahepatic cholangiocarcinoma (CC), extrahepatic CC and gallbladder cancer. The GTV and anatomical reference structures were outlined on CT images. Then, based on our guidelines, the CTV-T and CTV-N were delineated and merged to define the final CTV in the three patients. An atlas, showing the defined CTV, was generated from the reference CT images to illustrate the CTV for intra-hepatic CC, extra-hepatic CC and gallbladder cancer. This atlas can be used as an aid for CTV definition in patients with BTC treated with modern RT techniques.

Background/Aim: To retrospectively evaluate the outcome of patients with unresectable biliary cholangiocarcinoma (CC) treated with radiotherapy (RT) plus/minus chemotherapy (CHT). Materials and Methods: Data of patients with intrahepatic CC (ICC), Klatskin's tumor (KT), distal extrahepatic CC (ECC), and gallbladder cancer (GBC) diagnosed from 1991 to 2017 were retrospectively analyzed. The treatment was mainly based on RT plus concurrent CHT +/-brachytherapy (BRT) boost. The Kaplan-Meier method was used to calculate survival curves that were compared using the log-rank test. Results: Seventy-six patients were included in this analysis (males: 59%; females: 41%; median age: 66.5 years). A minority of patients (7.9%) were treated for disease recurrence after surgery. According to TNM, 78.5% of patients had T stage >3 and 77.6% of patients were treated with concurrent CHT-RT while 22.3% received RT followed by sequential CHT. Median RT dose was 50 Gy (range: 16-75 Gy) delivered with conventional fractionation. CHT was based on Gemcitabine or 5-fluorouracil. BRT was prescribed to 51.3% of patient with a median dose of 14 Gy. Reported Grade ≥3 acute GI and hematological toxicity were 13.2% and 8.1%, respectively. No other severe acute toxicities were reported. One-and 2-year overall survival (OS) were 58.1% and 25.8%, respectively (median: 13.5 months), while 1-and 2year progression-free survival (PFS) were 43.4% and 9.4%, respectively. None of the following variables had a significant impact on OS and PFS: BRT boost, tumor site, concurrent CHT, and the drugs used in concurrent CHT. In contrast, patients receiving RT with 2D technique showed a PFS significantly higher compared to patients treated with the 3D technique (median: 15.5 vs. 8.5 months; p=0.02). Conclusion: Combined modality treatment (RT+CHT±BRT) in unresectable biliary cancer was associated with acceptable toxicity and OS comparable to the actual standard treatment (CHT). The significantly improved PFS in patients undergoing 2D-RT raises doubts regarding the adequacy of target delineation in these neoplasms.Biliary tract cancers (BTC) are aggressive malignancies that are rare in the western world, but largely diffused in many Asian countries. BTC are commonly classified into intrahepatic cholangiocarcinoma (ICC), Klatskin's tumor (KT), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC) (1). Surgery, when feasible, represents the standard of care and in some cases is followed by adjuvant chemotherapy (CHT) or chemoradiation (CHTRT). However, the most common presentation of these tumors is locally advanced stage with a life expectancy of few months (2, 3).The treatment of unresectable disease is challenging due to patients' old age and the aggressive nature of BTC. The standard treatment is CHT, with radiotherapy (RT) or 3095

Background: It 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. Methods: A 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. Results: With 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). Conclusions: The 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.

Background: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. Material and Methods: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin’s lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrythmia). The information provided in terms of DVCs was graded based on levels of evidence. Results: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. Conclusions: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations.

Among biliary tract cancers, intrahepatic cholangiocarcinoma (ICC) has different characteristics compared with those in other sites. Current guidelines suggest several treatment options for ICC, including stereotactic body radiation therapy (SBRT). However, the role of SBRT in locally advanced ICC is unclear. The aim of the present study was to present a systematic review on the efficacy and safety of SBRT in ICC. A systematic review based on the PRISMA methodology was performed. Only papers reporting outcomes in terms of overall survival (OS) after SBRT in inoperable patients with ICC were included. Secondary aims were local control (LC), progression-free survival (PFS) and treatment-related toxicity. Six papers (145 patients) were included in the present analysis. SBRT was frequently used as a salvage treatment, since 28.6-66.7% of patients received previous systemic or local treatments. The median SBRT dose was 45 Gy delivered in 3-5 fractions. The median follow-up was 16 months, and median OS time was 14 months (range, 10-48 months). In one of the included studies, SBRT was significantly superior in terms of OS compared with both chemoradiation and trans-arterial-radio-embolization. The 1-year LC rate was 85% in one study, and 1-year PFS rates were 50 and 68% in two studies, respectively. Toxicity was generally not reported in detail or was reported including other sites of biliary cancers. Overall, limited evidence was available on the efficacy of SBRT in ICC, which should be further investigated in prospective studies with a larger number of patients. However, based on the available data, SBRT seems to produce similar results compared with other ICC treatments, with the advantage of being a very short and non-invasive therapy. Therefore, SBRT should be considered in selected patients with ICC.

Background/Aim: Radiotherapy (RT) with adjuvant hormone therapy (HT) improves prognosis in prostate cancer (PC) patients. Gonadotrophin-releasing hormone agonist (GnRHa) with luteinizing hormonereleasing hormone (LH-RH) analogues is the standard HT. High-dose antiandrogen therapy also improves survival in patients with locally advanced PC. The aim of this study was to compare the results of patients treated with RT plus GnRHa and patients treated with RT plus bicalutamide. Patients and Methods: Our institutional PC database was used to identify patients treated with definitive or postoperative RT +/-HT which were included in this study. Results: Three hundred and eighteen patients were retrospectively reviewed (median follow-up=56 months). Five-year biochemical relapse-free survival was 85.5% and 88.3% in patients treated with GnRHa and bicalutamide, respectively (p=0.712). Conclusion: Bicalutamide may be offered as an adjuvant treatment to RT in patients who refuse GnRHa because of related side effects. Furthermore, our study justifies randomized trials comparing RT plus GnRHa and RT plus bicalutamide.Almost 1.3 million new cases of prostate cancer (PC) and 359,000 associated deaths were estimated worldwide in 2018, ranking PC as the second most frequent cancer and the fifth leading cause of cancer death in men. Moreover, PC is the most diagnosed cancer in 105 of 185 countries in the world (1). Radiotherapy (RT) as either curative, adjuvant, or salvage therapy is a treatment option in several PC risk categories (2).RT particularly in intermediate-and high-risk PC is commonly prescribed in combination with Gonadotrophinreleasing hormone agonist (GnRHa) therapy based on the results of several trials showing improved overall survival (OS) (3). However, GnRHa therapy is associated with significant complications like loss of libido, erectile dysfunction, vasomotor flushing, anemia, fatigue, gynecomastia, osteoporosis potentially complicated by skeletal fractures, musculoskeletal deficits, and significant cardiovascular and metabolic complications (4).Bicalutamide is a competitive androgen receptor antagonist leading to cell apoptosis and inhibition of PC growth. It does not suppress gonadotropin secretion or sex hormones production (5). A large randomized trial has shown that high dose (150 mg, daily) bicalutamide is able to prolong OS in locally advanced PC treated with RT (6). Furthermore, the toxicity profile of bicalutamide is different from that of GnRHa therapy with breast pain being the main side effect (7). Some studies have demonstrated better tolerability and quality of life (QoL) in patients receiving 6373

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