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Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005–2018). Survival curves were calculated using the Kaplan–Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, 95%CI 0.34–0.92, p = 0.022) or SBRT (HR: 0.27, 95%CI 0.13–0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, 95%CI 0.28–0.70, p < 0.001) and SBRT (HR: 0.40, 95%CI 0.22–0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT.

The main treatment of MM metastases are systemic therapies, surgery, limb perfusion, and intralesional talimogene laherparepvec. Electrochemotherapy (ECT) is potentially useful also due to the high response rates recorded in cancers of any histology. No randomized studies comparing ECT with other local therapies have been published on this topic. We analyzed the available evidence on efficacy and toxicity of ECT in this setting. PubMed, Scopus, and Cochrane databases were screened for paper about ECT on MM skin metastases. Data about tumor response, mainly in terms of overall response rate (ORR), toxicity (both for ECT alone and in combination with systemic treatments), local control (LC), and overall survival (OS) were collected. The methodological quality was assessed using a 20-item validated quality appraisal tool for case series. Overall, 18 studies were included in our analysis. In studies reporting “per patient” tumor response the pooled complete response (CR) was 35.7% (95%CI 26.0–46.0%), and the pooled ORR was 80.6% (95%CI 68.7–90.1%). Regarding “per lesion” response, the pooled CR was 53.5% (95%CI 42.1–64.7%) and the pooled ORR was 77.0% (95%CI 56.0–92.6%). One-year LC rate was 80%, and 1-year OS was 67–86.2%. Pain (24.2–92.0%) and erythema (16.6–42.0%) were the most frequent toxicities. Two studies reported 29.2% and 41.6% incidence of necrosis. ECT is effective in terms of tumor response and tolerated in patients with skin metastases from MM, albeit with a wide variability of reported results. Therefore, prospective trials in this setting are warranted.

The aim of this narrative review of the literature was to collect and analyze the results of the published preclinical studies on stereotactic arrhythmia radioablation (STAR) in the treatment of refractory cardiac arrhythmias. A literature search was conducted on PubMed using the following terms: (“stereotactic” OR “SBRT” OR “SABR” OR “radioablation” OR “radiosurgery”) AND (“arrhythmia” OR “tachycardia”). Preclinical and pathological reports published in English without time limit, comprising studies of STAR in animal models and histological analyzes of explanted animal and human hearts were included. The analyzed studies confirm that doses lower than 25 Gy seem to produce sub-optimal therapeutic results whereas doses >35 Gy are less safe in terms of radiation-induced toxicity. However, long-term results (>1 year) are still missing and reporting outcomes based on low dose irradiation (≤15 Gy). Finally, STAR proved to be an effective therapy in the analyzed studies despite the irradiation of rather different cardiac targets. Therefore, additional studies are needed to: 1) compare the outcomes of STAR at doses of 25 Gy versus 30 Gy; 2) evaluate the long-term results (>1 year) in animal models irradiated at doses similar to those used in the clinic; 3) define the optimal target.

Objectives: To assess feasibility and safety of a SHort-course Accelerated RadiatiON therapy (SHARON) regimen, in the treatment of non-melanoma skin cancers (NMSC) in older patients. Methods: Old patients (age ≥ 80 years) with histological confirmed non-melanoma skin cancers were enrolled. The primary endpoint was to determine the maximum tolerated dose (MTD). Radiotherapy regimen was based on the delivery of four radiotherapy fractions (5 Gy per fraction) with a twice daily fractionation in two consecutive days. Three different level of dose were administered: 20 Gy (one cycle), 40 Gy (two cycles) and 60 Gy (three cycles). Results: Thirty patients (median age: 91 years; range: 80-96) were included in this analysis. Among fourteen patients who completed the one cycle, only one (7%) experimented acute G4 skin toxicity. Twelve patients reported an improvement or resolution of baseline symptoms (overall palliative response rate: 85.8%). Nine and seven patients underwent to two and three RT cycles, respectively: of these, no G3 toxicities were recorded. The overall response rate was 100% when three cycles were delivered. The overall six-month symptom-free survival was 78.7% and 77.8% in patients treated with one course and more courses, respectively. Conclusions: Short-course accelerated radiotherapy in older patients with non-melanoma skin cancers is well tolerated. High doses seem to be more effective in terms of response rate. Advances in knowledge: This approach could represent an option for older adults with NMSC, being both palliative (one course) or potentially curative (more courses) in the aim, accordingly to the patient’s condition.

Simple Summary Radiotherapy plays an important role in the management of esophageal cancer. Historically, it has been used in different settings—adjuvant, neoadjuvant, definitive in combination with chemotherapy, and even palliative scenario. The aim of this review is to focus on the role of radiotherapy at different levels, and to describe the new therapeutic opportunities offered by technological advances. Abstract The modern management of esophageal cancer is crucially based on a multidisciplinary and multimodal approach. Radiotherapy is involved in neoadjuvant and adjuvant settings; moreover, it includes radical and palliative treatment intention (with a focus on the use of a stent and its potential integration with radiotherapy). In this review, the above-mentioned settings and approaches will be described. Referring to available international guidelines, the background evidence bases will be reviewed, and the ongoing, more relevant trials will be outlined. Target definitions and radiotherapy doses to administer will be mentioned. Peculiar applications such as brachytherapy (interventional radiation oncology), and data regarding innovative approaches including MRI-guided-RT and radiomic analysis will be reported. A focus on the avoidance of surgery for major clinical responses (particularly for SCC) is detailed.

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.

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.

Purpose or Objective: The emergency situation produced by the COVID-19 pandemic represents a challenge for radiation oncologists (ROs) clinical practice. In our department, we provided guidelines to the ROs regarding omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce patient’s exposure to the hospital environment and to minimize the departmental overcrowding. The aim of this study was to evaluate the ROs compliance to these guidelines. Materials and Methods: ROs were asked to fill out a data collection form during patients first visits in May and June 2020. Collected data included: ROs age and gender, patient age and residence, RT purpose, treated tumor, dose and fractionation that would have been prescribed outside the pandemic, and RT changes (omitted, delayed, or shortened). The chi-square test and binomial logistic regression were used to analyse the correlation between treatment prescription and collected parameters. Results: One hundred twenty-six out of 205 treatments prescribed during the evaluated period were included in this analysis. In fact, 79 treatments were excluded not being considered in the pandemic-adapted guidelines. Treatment was modified in 61.1% of cases. More specifically, treatment was omitted, delayed, or shortened in 7.9%, 15.9%, and 37.3% of patients, respectively. Unmodified treatments were 38.9% (Figure 1). Overall, the reduction of delivered fractions in our department was 27.9%. A statistically significant correlation (p = 0.028) between younger patients age and lower treatment modifications rate was recorded. (Figure Presented) Conclusion: Our analysis showed a reasonably high compliance of ROs to pandemic-adapted guidelines. The adopted strategy was effective in reducing the number of admissions to our department.

Skin metastases occur in 5–30% of breast cancer (BC) patients. Standard treatments include systemic therapies (chemotherapy, endocrine therapy, and immunotherapy) and local treatments (surgery and radiotherapy). Electrochemotherapy (ECT) could be another option in this setting based on preclinical and clinical studies. Aim of this review was to analyze the available evidence on ECT in skin metastases from BC. Studies reporting on ECT in skin metastases from BC were included in this review. Studies not reporting toxicity or tumor response or not reporting results separately from other primary cancers were excluded. The search was based on Medline, Scopus, and The Cochrane Library databases. Eleven studies including 464 patients were analyzed. ECT was performed using intravenous/intratumoral bleomycin (10 studies) or intratumoral cisplatin (one study). Complete and overall pooled response rates were 46.2% (95%CI 33.2–59.4 and 74.6% (95%CI 60.6–86.4) in studies reporting results on a per patient basis and 61.9% (95%CI 53.8–69.6) and 86.9% (95%CI 80.0–92.6) in studies reporting results on a per lesion basis, respectively. Worse response rates in larger lesions were observed in three studies. The incidence of toxicity was heterogeneous but adverse events were mild and manageable in all studies. One- and 3-year local progression-free survival was 86.2% and 81.0% in two studies, respectively. ECT is tolerable and effective in terms of response in BC skin metastases especially in less advanced lesions. Further studies are justified to compare ECT with other treatments in this setting.

INTRODUCTION AND OBJECTIVE:The aim of this study is to evaluate the biochemical recurrence (BCR) free survival (BCR-FS) in man with intermediate-high risk of recurrence after radical prostatectomy ...

Pancreatic cancer represents a modern oncological urgency. Its management is aimed to both distal and local disease control. Resectability is the cornerstone of treatment aim. It influences the clinical presentation’s definitions as up-front resectable, borderline resectable and locally advanced (unresectable). The main treatment categories are neoadjuvant (preoperative), definitive and adjuvant (postoperative). This review will focus on (i) the current indications by the available national and international guidelines; (ii) the current standard indications for target volume delineation in radiotherapy (RT); (iii) the emerging modern technologies (including particle therapy and Magnetic Resonance [MR]-guided-RT); (iv) stereotactic body radiotherapy (SBRT), as the most promising technical delivery application of RT in this framework; (v) a particularly promising dose delivery technique called simultaneous integrated boost (SIB); and (vi) a multimodal integration opportunity: the combination of RT with immunotherapy.

Aim The purpose of the present multicentric study was to review stereotactic body radiotherapy (SBRT) with or without chemotherapy (CHT) experience in locally advanced pancreatic cancer (LAPC). Endpoints were overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). Several parameters' impact on these outcomes was assessed. Materials and methods Fifty-six patients with LAPC undergoing SBRT+/-CHT were included. SBRT median BEDα/β10Gy was 48.0 Gy (range=28.0-78.7). Survival curves were calculated by Kaplan-Meier method. A Cox regression model was fitted. Results At a median follow-up of 15.0 months, 2-year OS, LC, DMFS were: 33.8% 55.4%, and 22.9%, respectively. Patients treated with BEDα/β10Gy≥48 Gy showed improved OS (p=0.020) and LC (p=0.024). At multivariate analysis, BEDα/β10Gy≥48 Gy was significantly associated to both higher OS (p=0.042) and LC (p=0.045), while post-SBRT CHT improved DMFS (p=0.003). Conclusion SBRT proved to be tolerable and effective in LAPC. Moreover, BEDα/β10Gy≥48 Gy was significantly correlated with improved OS and LC.

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: The standard primary treatment for soft tissue sarcoma (STS) is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT) plus postoperative external beam radiation therapy (EBRT) in patients with intermediate-high risk STS. Material and methods : BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT) was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS) and local control (LC) in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS), and OS. Results : From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC) primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015), and in lower limb tumors vs. other sites (p = 0.027). An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034). Conclusions : The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC.

Background Castration-resistant prostate cancer (CRPC) has a dismal prognosis. Despite treatment, median survival of these patients is around 12-22 months. Case Presentation In this report, we present the case of a 71-year-old man, with CRPC and painful bone metastases treated with an association of middle-half-body radiotherapy, androgen deprivation therapy (ADT) and cyclophosphamide-based metronomic chemotherapy. Five years after palliative radiotherapy the patient is still receiving metronomic chemotherapy and ADT. He is totally asymptomatic, with undetectable PSA values and negative 18F-Choline-PET/CT. The only side-effect was the development of non-insulin-dependent diabetes. Conclusion This treatment for its tolerability and feasibility, it could be particularly useful in older patients with CRPC. Furthermore, considering the low costs, it could be an important therapeutic option for patients living in low-resourced countries.

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.

Background: To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). Methods: A multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. Results: Median follow-up was 35 months (range: 3-120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3-4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3-4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. Conclusions: Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.

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

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.

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.

The purpose of the present study was to propose an optimized 2D technique (2D-conformal) for radiotherapy (RT) of pancreatic cancer (CaP). This technique is based on double simulation which resolves the problems of radiographic image distortion. Five patients with locally advanced CaP were identified and enrolled. Treatment planning was simulated in 3 different ways: Two dimensional-standard (2D-SRT), 2D-conformal (2D-CRT), and three dimensional-conformal (3D-CRT) techniques for 10 MV LINAC. Simulation for a cobalt machine was also performed using only the 2D techniques. 2D-SRT technique was planned with fields definition based on anatomical landmarks (bone and duodenum). 3D-CRT was planned with standard virtual simulation technique, and 3D dose evaluation and optimization. 2D-CRT technique was based on manual information transfer from a diagnostic CT-scan to simulation radiograms. To eliminate the X-ray image distortion, a double simulation was employed and the profile of the GTV was delineated on radiographs bearing the simulator isocenter into the target center. Concerning target irradiation of either LINAC (10 MV) or cobalt source, the PTV constraints (ICRU 62) were met in all patients (Dmin >95%, Dmax

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 present a systematic review on efficacy and toxicity of modern concurrent chemoradiation (CCRT) in unresectable biliary tract cancers (BTC). Methods: A systematic review of literature published within the last ten years (1 January 2007-31 December 2017), based on PRISMA methodology and using PubMed electronic database was conducted. Only articles reporting patients’ outcome in terms of toxicity and/or overall survival (OS) or progression-free survival (PFS) after CCRT, with or without other treatments, were analyzed. Only studies of patients with diagnosis of unresectable BTC, including intrahepatic, extrahepatic, and gallbladder neoplasm were considered. Results: Six eligible studies were included reporting data on 195 patients. Median follow-up ranged between 9.4 and 27.7 months (median: 16 months). Four studies were prospective phase II trials and 2 had a retrospective design. Different external beam radiotherapy (EBRT) techniques and chemotherapy (CT) schedules were used while only in one study a brachytherapy boost was delivered. Grade ≥ 3 acute toxicity (hematological or gastrointestinal) ranged between 0.0 and 55.6% (median: 37.0%). One study reported 30.0% gastrointestinal grade ≥ 2 late toxicity. PFS ranged between 6.8 and 10.5 months (median: 7.5 months) in 5 studies. OS ranged between 9.6 and 13.5 months (median: 13 months) in 5 studies. Conclusion: CCRT remains a reasonable treatment option for locally advanced BTC, providing results comparable with the ones of standard CT, particularly in terms of OS. Considering the progressive advance of modern EBRT techniques, further improvement of these results can be expected. Therefore, clinical trials based on advanced radiotherapy techniques and new integrations of CCRT with systemic treatments are warranted.

Milly Buwenge,1 Gabriella Macchia,2 Alessandra Arcelli,1 Rezarta Frakulli,3 Lorenzo Fuccio,4 Sara Guerri,1 Elisa Grassi,1 Silvia Cammelli,1 Francesco Cellini,5 Alessio G Morganti1 1Department of Experimental, Diagnostic and Specialty Medicine – DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; 2Radiation Oncology Unit, Research and Care Foundation “Giovanni Paolo II”, Catholic University of Sacred Heart, Campobasso, Italy; 3Radiation Oncology Unit, Bellaria Hospital, Bologna, Italy; 4Department of Medical and Surgical Sciences – DIMEC, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; 5Department of Radiotherapy, “A. Gemelli” Hospital, Catholic University, Rome, Italy Abstract: Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000–December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%–91.5%), with high heterogeneity (Q2 test: P

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)