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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.

BACKGROUND AND OBJECTIVES: Previous studies showed a local tumor control of 80% in patients with relapsed squamous cell vulvar cancer (V-SCC) treated with electrochemotherapy. These results encouraged electrochemotherapy use as neo-adjuvant treatment in V-SCC. The objective of this study was to evaluate the effectiveness of electrochemotherapy in reducing tumor burden in V-SCC. METHODS: Patients with histological diagnosis of primary V-SCC eligible for surgery were enrolled. Following accurate mapping of all the lesions, electrochemotherapy was performed. One month after electrochemotherapy clinical response was evaluated according to RECIST criteria and the type of surgery was confirmed or modified. Adjuvant therapies were prescribed depending on stage and pathological evaluation. RESULTS: We report the results from nine patients treated with electrochemotherapy before surgery. The median age was 64 years (range 51-81 years). Tumor response after electrochemotherapy was observed in seven patients (77.8%) with one CR and six PR, without complications. Tumor downsizing led to more conservative surgery in six patients (66.7%). At a median follow-up of 8 months (range 2-32 months) all patients were alive without disease. CONCLUSIONS: Our preliminary analysis suggests that ECT is a suitable treatment in patients with V-SCC before surgery, reducing the tumor size and the surgical resection.

Purpose Statistical Process Control (SPC) is a tool widely used in industrial engineering for monitoring, controlling and improving a process through statistical analysis. We applied this strategy for patient-specific VMAT pre-treatment verification. Methods From 2009, more than 1700 patients were treated with Elekta VMAT at our institution. Plans were re-grouped according to treatment technique and disease sites Group 1: 736 complex treatments using SIB for head-neck, pelvic, brain and other sites; (2) 441 low-risk prostate treatments and (3) 558 extracranial metastasis treated with SBRT. 4942 planar dose measurements were performed with the PTW Seven29 array/Octavius phantom. Three metrics were simultaneously evaluated: (a) γ %: points-percentage with γ -value less than one, (b) γ mean and (c) γ 1%: the near-maximum gamma. Clinical specifications were: γ % > 90%, γ mean γ 1 % 2 . Shewhart charts were used to calculate the central (CL), upper control (UCL) and lower control limits (LCL). The capability of the processes was evaluated by means of Cpk indexes. Results Using 3%/3 mm γ -analysis, results significantly depend on plan complexity. For γ %, CL and LCL were 93.8%, 99.1%, 99.5% and 87.9%, 96.6%, 97.9%, for group 1,2 and 3 respectively. For γ mean, CL and UCL were 0.42, 0.36, 0.29 and 0.54, 0.49, 0.40, for groups 1, 2 and 3 respectively. For the groups 2 and 3, all processes are in control and within clinical specifications. The Cpl/Cpu indices for γ %, γ mean and γ 1% resulted equal to 2.85, 1.64 and 2.11 in group 2 and 4.20, 2.60 and 2.01 in group 3. For group 1 only the γ mean process is in control; the γ % process is out of control and out of clinical specifications (returning in control with 5%/3 mm specification, with Cpl and Cpu equal to 1.87 and 1.57, respectively). Conclusions SPC is a powerful tool to quantifiably evaluate the QA process performance in advanced radiotherapy.

Purpose Treatment plans for high-risk prostate an gynecological cancer are highly complex due to large irregular-shaped pelvic target volumes, to multiple dose prescription and to several organs at risk (OARs) close to the target. The quality of these plans is highly inter-planner dependent. We assessed the performance of the Auto-Planning module present in the Pinnacle3 TPS (version 16.0), comparing automatically generated VMAT plans (AP) with the historically clinically accepted manually-generated ones (MP). Methods Twenty-four consecutive patients treated with VMAT-SIB for high-risk prostate and endometrial cancer were re-planned with the Auto-Planning engine. For each patient, the AP plan was compared with two MP plans (using Oncentra Masterplan and Pinnacle TPS, respectively) The PTV1 included the primary tumor (prostate or vaginal vault); the PTV2 included the pelvic lymph-nodes. The two target volumes were simultaneously irradiated over 25 daily fractions at 65 Gy/55 Gy and 45 Gy to the PTV1 and PTV2, respectively. All plans were created by means of the “dual arc” feature. For AP plans, a progressive optimization algorithm is used to continually adjust initial targets/OARs objectives. Various dose and dose-volume metrics for target volumes and OARs, as well as conformity (CI) indexes and healthy-tissue integral dose (ID) were evaluated. Results Differences in all dose coverage metrics (V95%, D98%, D50%, D2% and Dmean) for both PTVs were not statistically significant (p Conclusions The Pinnacle3 Auto-Planning module achieved highly consistent treatment plans also in the cases of complex anatomical sites.

Purpose We evaluated an EPID-based IVD method for the dose verification and the treatment reproducibility of SBRT-VMAT treatments in clinical routine. Methods 10 patients with lung metastases treated with Elekta VMAT technique were enrolled. All patients were irradiated in 5 consecutive fractions, with total doses of 50 Gy. Set-up was carried out with the Elekta stereotactic body frame. Eight patients were simulated and treated using the Active Breath Coordinator (ABC) system, a spirometer enabling patients to maintain a breath-hold at a predetermined lung volume. Two patients were simulated and treated in free-breathing using an abdominal compressor. IVD was performed using the SOFTDISO software (Best Medical Italy). IVD tests were evaluated by means of (i) ratio R between daily in vivo isocenter dose and planned dose and (ii) γ -analysis between EPID integral portal images in terms of percentage of points with γ -value smaller than one ( γ %) and mean γ -values ( γ mean). Alert criteria of ±5% for R ratio, γ % γ mean > 0.67 were chosen. Results 50 transit EPID images were acquired. For the patients treated with ABC spirometer, the results reported a high level of accuracy in dose delivery with 100% of tests within ± 5%. The γ -analysis showed a γ mean of 0.21 ± 0.10 and a mean γ % equal to 96.9 ± 3.9%. Relevant discrepancies were observed only for the two patients treated without ABC, all described by the γ % tests which dropped below 90% for all the tests. and mainly due to a blurring dose effect due to residual respiratory motion. Conclusions Our method provided a fast and accurate procedure in clinical routine for verifying delivered dose as well as for detecting errors.

Objective The primary endpoint of this trial was to assess clinical response (cCR) of squamocellular vulvar cancer (V-SCC) in elderly patients treated with electro-chemotherapy (ECT). Secondary endpoints were symptoms relief and local tumor control. Methods A phase II study was designed and elderly patients with V-SCC unfit for other treatments were treated. Response Evaluation Criteria in Solid Tumors (RECIST criteria) were applied to evaluate tumor response. Quality of life (QoL) was evaluated by visual analogue score (VAS) for pain and four items of vulvar cancer subscale (VCS), of functional assessment of vulvar cancer therapy (FACT-V) [16], before, one month after the procedure and during follow-up. Results Median age was 85 years (range 66–96 years). One month after treatment complete response was observed in 13 patients (52%), partial response in 7 (28%), stable disease in 3 (12%), and progressive disease in 2 (8%). Local tumor control at 1 and 6 months was 91% and 53%, respectively. Symptom free survival at 1 and 6 months was 78% and 40%, respectively, with significant reduction of pain (P

The aim of this analysis is to present the methodology used to promote clinical research in a peripheral Italian department of radiotherapy (RT) and the results in terms of scientific output. Internal treatment guidelines were developed, available on the computer network of the department, containing a schematic summary 1–2 pages long of each protocol. Furthermore, a home-made database was designed to be used both as a medical record and for prospective data recording. Data entry was subjected to an “independent check” by a second radiation oncologist. Regular meetings were organized to update all staff on the aim and conduct of the various running trials and to promote the enrollment of patients and the involvement of other specialists in clinical research. In a period of about 11 years: (1) 34 protocols for clinical trials were written and approved; (2) 7463 patients had undergone RT; of these patients, 6321 patients (85 %) were enrolled in clinical trials; (3) 345 papers/book chapters/abstracts were published; of them, 127 papers have been published in journals currently featured on PUBMED; (4) 119 scientific meetings were held. This experience shows that an independent clinical research is possible even in a non-academic and peripheral RT department. In particular, our experience suggests that personnel and resource constraints can be at least partially overcome by a strong personal and group motivation and with the adoption of flexible solutions.

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.

Background/Aim: The Vienna Rectoscopy Score (VRS; from 0, absence of rectal mucosal changes, to 5) assessed 1 year after radiotherapy is a surrogate end-point of late rectal toxicity. The aim of this study was to investigate the association between treatment-related factors and 1-year VRS. Patients and Methods: We performed a retrospective analysis of prospectively collected data. Patients with prostate adenocarcinoma treated with definitive or postoperative radiotherapy (RT) underwent endoscopy 1 year after RT. Relationships between VRS of 2 or more and treatment parameters were investigated by univariate and multivariate logistic analyses. Results: One hundred and ninety-five patients (mean age=69 years; range=43-81 years) were considered eligible for the study. At univariate analysis, patients treated with hypofractionation plus radiosurgery boost (p

Objective To investigate the association between external beam radiotherapy (EBRT) for prostate adenocarcinoma (PA) and malignant peritoneal mesothelioma (MPM) using data from the US Surveillance, Epidemiology and End Results (SEER) program. Methods We identified PA cases diagnosed in 1973–2013 among patients aged ≥45 years. The follow-up started one year after the primary diagnosis (to exclude synchronous cancers and limit surveillance bias) and ended at the diagnosis of MPM, other malignancies, death, or at the study end (12/31/2013). We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) of MPM for EBRT, compared to no radiotherapy, by fitting Cox models incorporating inverse probability weights to account for age at diagnosis, race, year of diagnosis, primary cancer surgery, SEER register, and county’s mesothelioma relative risk (proxy for individual asbestos exposure). Results We observed 34 MPM cases occurring in 4,755,045 person-years (rate of 0.7 per 1 00 000 person-years, 95% CI 0.5–1.0). The risk of MPM was higher among EBRT patients (HR 2.1, 95% CI 0.9–4.8) and increased steadily with increasing latency period (1–4 years, HR 1.3, 95% CI 0.4–4.6; 5–9 years, HR 1.9, 95% CI 0.5–7.7;≥10 years, HR 4.9, 95% CI 0.9–28). However, only 8 MPM were observed for latency periods≥10 years. Conclusions Our study supports the hypothesis that EBRT for PA is associated with MPM. However, the incidence of MPM in our study population was very low; future studies should focus on high-risk populations (e.g. former asbestos workers) to evaluate the clinical significance of the observed association.

We explored the Pareto fronts mathematical strategy to determine the optimal block margin and prescription isodose for stereotactic body radiotherapy (SBRT) treatments of liver metastases using the volumetric-modulated arc therapy (VMAT) technique. Three targets (planning target volumes [PTVs] = 20, 55, and 101 cc) were selected. A single fraction dose of 26 Gy was prescribed (prescription dose [PD]). VMAT plans were generated for 3 different beam energies. Pareto fronts based on (1) different multileaf collimator (MLC) block margin around PTV and (2) different prescription isodose lines (IDL) were produced. For each block margin, the greatest IDL fulfilling the criteria (95% of PTV reached 100%) was considered as providing the optimal clinical plan for PTV coverage. Liver Dmean, V7Gy, and V12Gy were used against the PTV coverage to generate the fronts. Gradient indexes (GI and mGI), homogeneity index (HI), and healthy liver irradiation in terms of Dmean, V7Gy, and V12Gy were calculated to compare different plans. In addition, each target was also optimized with a full-inverse planning engine to obtain a direct comparison with anatomy-based treatment planning system (TPS) results. About 900 plans were calculated to generate the fronts. GI and mGI show a U-shaped behavior as a function of beam margin with minimal values obtained with a +1 mm MLC margin. For these plans, the IDL ranges from 74% to 86%. GI and mGI show also a V-shaped behavior with respect to HI index, with minimum values at 1 mm for all metrics, independent of tumor dimensions and beam energy. Full-inversed optimized plans reported worse results with respect to Pareto plans. In conclusion, Pareto fronts provide a rigorous strategy to choose clinical optimal plans in SBRT treatments. We show that a 1-mm MLC block margin provides the best results with regard to healthy liver tissue irradiation and steepness of dose fallout.

Background Owing to highly conformed dose distribution, intensity modulated radiation therapy (IMRT) has the potential to improve treatment results of radiotherapy (RT). Postoperative RT is a standard adjuvant treatment in conservative treatment of breast cancer (BC). The aim of this review is to analyze available evidence from randomized controlled trials (RCTs) on IMRT in BC, particularly in terms of reduction of side effects. Methods A literature search of the bibliographic database PubMed, from January 1990 through November 2016, was performed. Only RCTs published in English were included. Results Ten articles reporting data from 5 RCTs fulfilled the selection criteria and were included in our review. Three out of 5 studies enrolled only selected patients in terms of increased risk of toxicity. Three studies compared IMRT with standard tangential RT. One study compared the results of IMRT in the supine versus the prone position, and one study compared standard treatment with accelerated partial breast IMRT. Three studies reported reduced acute and/or late toxicity using IMRT compared with standard RT. No study reported improved quality of life. Conclusion IMRT seems able to reduce toxicity in selected patients treated with postoperative RT for BC. Further analyses are needed to better define patients who are candidates for this treatment modality.

Purpose The aim of this study was to investigate the efficacy and toxicity of volumetric modulated arc therapy (VMAT)–simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer. Methods Radiation therapy was performed using the VMAT-SIB technique. The dose to mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered on GTV + 2-cm margin with a total dose of 57.5 Gy (2.3 Gy/fraction). The following concomitant chemotherapy was administered: capecitabine (825 mg/m2 twice daily, 5 days per week) and oxaliplatin (130 mg/m2 on days 1, 17, and 35). Efficacy was evaluated in terms of complete pathological response (pCR). Acute toxicities were evaluated according to Common Terminology Criteria for Adverse Events version 3.0 criteria. Results A total of 18 patients (7 women; median age 62 years; clinical stage: 4 local recurrences, 6 cT4, 5 cT3, 3 cT2, 2 cN0, 7 cN1, 9 cN2) were enrolled. Sixteen patients underwent surgical resection (9 low anterior resection, 6 abdominal perineal amputations; 1 transanal excision) and 2 patients did not undergo surgery for early metastatic progression or death from acute pulmonary edema. R0 resection was achieved in all patients who underwent surgery. Overall, 4 patients had a pCR and 7 patients only a microscopic residual of disease (pT0-Tmic: 11/18 = 61.1%; 95% CI, 36.2-86.1). Acute grade ≥ 3 toxicity was as follows: 1 case of leukopenia, 1 skin toxicity, 1 genitourinary toxicity, and 5 gastrointestinal toxicities, with an overall incidence of 8 (44.4%) of 18 patients. One-, 3-, and 5-year cumulative local control was 100%, 68.6%, and 68.6%, respectively. One-, 3-, and 5-year cumulative disease-free survival was 88.9%, 66.7%, and 66.7%, respectively. One-, 3-, and 5-year cumulative overall survival was 85%, 63.8%, and 63.8%, respectively. Conclusion The regimen used in this study showed excellent results in terms of pathologic responses. However, despite the use of the VMAT technique, more than one-third of patients had severe acute toxicity.

Eye plaque brachytherapy represents a safe and effective therapeutic approach for choroidal melanoma, combining clinical outcomes with an eye and visual preservation. As it represents a complex procedure, a specific quality assurance program is strongly suggested to improve patients and operators safety, and to reduce possible complications linked to surgical procedure and radiation exposure. The aim of this paper is to describe the INTERACTS (Interventional Radiotherapy Active Teaching School) guidelines for quality assurance in choroidal melanoma interventional radiotherapy (brachytherapy) used in our institution.

Introduction. To evaluate the clinical response rate after a postoperative 18F-FDG PET/CT guided external beam radiotherapy (EBRT) in Iodine-refractory differentiated thyroid cancer. Material and Methods. Patients with thyroid cancer locally recurrent after total thyroidectomy plus metabolic radiotherapy and treated with radical EBRT were included. Inclusion criteria were detectable thyroglobulin (Tg), negative postmetabolic radiotherapy whole body scintigraphy, and no surgical indications. The pretreatment 18F-FDG PET/CT resulted positive in all cases (loggia, lymph nodes, and lung). EBRT was delivered with IMRT-SIB technique. A 18F-FDG PET/CT revaluation and Tg dosage were performed 3 months after the treatment. Results. Sixteen consecutive patients were included in this analysis (median follow-up: 6–44 months). Post-EBRT 18F-FDG PET/CT showed CR in 43.7%, PR in 31.2%, SD in 25.0% patients, and PD due to lung metastases in 12.5%. Overall response rate was 75.0% (CI 95%: 41.4–93.3%). Tg levels decreased in 75.0% with a median Δ of 68.0%. Two-year PFS and OS rates were 80.0% and 93.0%, respectively. Acute G3 toxicity occurred in 18.7% and late G2 toxicity in 12.5%. Conclusions. 18F-FDG PET/CT was useful in target definition for radiotherapy planning, identifying positive areas not detected with 131I scintigraphy. IMRT based EBRT was feasible and our results encourage future prospective studies. This clinical trial is registered with ID: NCT03191643.

Highlights • A large population based analysis to evaluate pathologic response according to time of surgery. • LARC patients were treated with modern techniques of radiotherapy and surgery. • The rate of pCR increased according to time interval from 12.6% to 31.1%. • The pCR increasing was 1.5% (about 0.2%/die) per each week of waiting. • Lengthening the interval (>13 weeks) significantly improved the pathological response., Background To retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients. Methods A multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7–12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively. Results Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p 5040 cGy (p = 0.002) and longer interval (p 13 weeks) from CRT to surgery improves the pathological response (pCR and pathologic partial response; pPR) in comparison to historic data. Furthermore, radiotherapy dose >5040 cGy and two drugs chemotherapy correlated with pPR rate.

Patients with metastatic rectal cancer (mRC) have a poor prognosis and suffer from several symptoms like bleeding, pain, and obstruction. Radiation therapy (RT) has been used both for palliation and improvement of overall survival (OS) in potentially curable patients. However, treatment in this setting is debated and a recent literature review included only studies published before 2000. Therefore, an analysis of literature was performed including only studies published in recent years (2010–2016) to better evaluate the effect of modern RT in these patients. The analysis of nine reviewed studies (six retrospective and three phase II) showed that RT is able to achieve pain, bleeding, and obstruction response rate of 79, 87, and 78%, respectively. Moreover, in patients receiving radio-chemo-surgical combined modality treatment, median survivals ranging between 30 and 38 months were recorded, with 5-year survival up to 55% of patients. RT was generally well tolerated with the most common reported side effect being diarrhea/proctitis. Further studies in this field are needed to establish the best therapeutic sequences, to define the optimal RT dose and fractionation, and to evaluate the clinical results in terms of quality of life (QoL).

Background/aim A review of the literature is proposed as a contribution to current knowledge on technical, physical, and clinical issues about PET-guided planning and re-planning radiotherapy (RT) in head and neck cancer. Materials and methods PubMed and Scopus electronic databases were searched for articles including clinical trials. Search terms were "gross tumor volume (GTV) delineation", "head and neck cancer", "radiotherapy", "adaptive radiotherapy" in combination with "PET". Results A 18F-FDG-PET and CT-scan comparison in GTV definition for RT planning of head and neck cancer was shown in twenty-seven clinical trials with a total of 712 patients. Only two clinical trials focused on PET-guided adaptive radiotherapy (ART) with a total of 31 patients. Conclusion 18F-FDG-PET is able to achieve an accurate and precise definition of GTV boundaries during RT planning, especially in combination with CT-scan. ART strategies are proposed to evaluate tumor volume changes, plan boost irradiation on metabolically active residual neoplasm and protect organs at risk (OaRs).

Background This investigation focused on the clinical implications of the use of the Collapsed Cone Convolution algorithm (CCC) in breast radiotherapy and investigated the dosimetric differences as respect to Pencil Beam Convolution algorithm (PBC). Material and methods 15 breast treatment plans produced using the PBC algorithm were re-calculated using the CCC algorithm with the same MUs. In a second step, plans were re-optimized using CCC algorithm with modification of wedges and beam weightings to achieve optimal coverage (CCCr plans). For each patient, dosimetric comparison was performed using the standard tangential technique (SWT) and a forward-planned IMRT technique (f-IMRT). Results The CCC algorithm showed significant increased dose inhomogeneity. Mean and minimum PTV doses decreased by 1.4% and 2.8% (both techniques). Mean V95% decreased to 83.7% and 90.3%, respectively for the SWT and f-IMRT. V95% was correlated to the ratio of PTV and lung volumes into the treatment field. The re-optimized CCCr plans achieved similar target coverage, but high-dose volume was significantly larger (V107%: 7.6% vs 2.3% (SWT), 7.1% vs 2.1% (f-IMRT). There was a significantly increase in the ipsilateral lung volume receiving low doses (V5 Gy: 31.3% vs 26.2% in SWT, 27.0% vs 23.0% in f-IMRT). MUs needed for PTV coverage in CCCr plans were higher by 3%. Conclusions The PBC algorithm overestimated PTV coverage in terms of all important dosimetric metrics. If previous clinical experience are based on the use of PBC model, especially needed is discussion between medical physicists and radiation oncologists to fully understand the dosimetric changes.

MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator roles. As an important class of regulators of many cellular pathways, miRNAs are involved in many signaling pathways and DNA damage repair processes, affecting cellular radiosensitivity. Their role has led to interest in oncological implications to improve treatment results. MiRNAs represent a great opportunity to enhance the efficacy of radiotherapy treatments—they can be used to profile the radioresistance of tumors before radiotherapy, monitor their response throughout the treatment, thus helping to select intensification strategies, and also to define the final response to therapy along with risks of recurrence or metastatization. Even though many interesting studies support such potential, nowadays most studies on patient data are limited to experiments profiling tumor aggressiveness and response to radiotherapy. Moreover many studies report different although not conflicting results on the miRNAs evaluated for each tumor type. Without doubt, the clinical potential of such molecules for radiotherapy is striking and of high interest.

Background: We provided a comprehensive analysis of rate, pattern, and severity of early and late postoperative complications in a very large, single-institution series of locally advanced cervical cancer (LACC) patients administered CT/RT plus radical surgery (RS). Methods: A total of 362 consecutive LACC (FIGO stage IB2-IVA) patients were submitted to RS after CT/RT at the Gynecologic Oncology Unit of the Catholic University (Rome/Campobasso). At 4 weeks after CT/RT, patients were evaluated for objective response and triaged to radical hysterectomy and pelvic ± aortic lymphadenectomy. Surgical morbidity was classified according to the Chassagne's grading system. Results: Most cases underwent type III-IV radical hysterectomy (N = 313, 86.5 %); pelvic lymphadenectomy was performed in all patients, while 116 patients (32.1 %) were also submitted to aortic lymphadenectomy. A total of 93 patients (25.7 %) experienced any grade postoperative complications, and 60 (16.6 %) had ≥grade 2 complications; grade 3-4 complications occurred in 21 patients (5.8 %). Of all early postoperative complications (N = 100), 31 (31.0 %) were urinary, 9 (9.0 %) were gastrointestinal, and 45 (45.0 %) were vascular. Of all late complications (N = 31), 20 (64.5 %) were urinary, 7 (22.6 %) gastrointestinal, and 2 (6.4 %) were vascular. Multivariate analysis showed that not complete clinical response to treatment retained an independent, unfavorable association with risk of development of postoperative morbidity, while advanced stage, and aortic lymphadenectomy showed only a borderline value. Conclusions: Failure to achieve clinical complete response to treatment and, to a lesser extent, more advanced stage, and aortic lymphadenectomy, were associated with a higher risk of developing any grade as well as ≥grade 2 complications. © 2014 Society of Surgical Oncology.

ntensity-modulated radiotherapy (IMRT) allowed the simultaneous delivery of different doses to different target volumes within a single fraction, an approach called simultaneous integrated boost (SIB). As consequence, the fraction dose to the boost volume can be increased while keeping low doses to the elective volumes, and the number of fractions and overall treatment time will be reduced, translating into better radiobiological effectiveness. In recent years, volumetric-modulated arc therapy (VMAT) has been shown to provide similar plan quality with respect to fixed-field IMRT but with large reduction in treatment time and monitor units (MUs) number. However, the feasibility of VMAT when used with SIB strategy has few investigations to date. We explored the potential of VMAT in a SIB strategy for complex cancer sites. A total of 15 patients were selected, including 5 head-and-neck, 5 high-risk prostate, and 5 rectal cancer cases. Both a double-arc VMAT and a 7-field IMRT plan were generated for each case using Oncentra MasterPlan treatment planning system for an Elekta Precise linac. Dosimetric indexes for targets and organs at risk (OARs) were compared based on dose-volume histograms. Conformity index, homogeneity index, and dose-contrast index were used for target analyses. The equivalent uniform doses and the normal tissue complication probabilities were calculated for main OARs. MUs number and treatment time were analyzed to score treatment efficiency. Pretreatment dosimetry was performed using 2-dimensional (2D)-array dosimeter. SIB-VMAT plans showed a high level of fluence modulation needed for SIB treatments, high conformal dose distribution, similar target coverage, and a tendency to improve OARs sparing compared with the benchmark SIB-IMRT plans. The median treatment times reduced from 13 to 20 minutes to approximately 5 minutes for all cases with SIB-VMAT, with a MUs reduction up to 22.5%. The 2D-array ion-chambers' measurements reported an agreement of more than 95% for a criterion of 3% to 3. mm. SIB-VMAT was able to combine the advantages of conventional SIB-IMRT with its highly conformal dose distribution and OARs sparing and the advantages of 3D-conformal radiotherapy with its fast delivery.

Background/Aim: Radiotherapy is a treatment option for both adjuvant and neo-adjuvant settings for biliary tract cancer. Guidelines on the delineation of the target volume of lymph nodes are lacking; only generic indications are available, without specific recommendations for different primary tumour locations (e.g. intrahepatic, extrahepatic biliary tract or gallbladder cancer). The aim of this study was to systematically review available literature to provide recommendations on lymph node target volume delineation in patients with unresectable biliary tumour. Materials and Methods: A systematic search of electronic databases was performed up to July 2016. The primary outcome measure was the rate of lymph node involvement according to the location of primary biliary tumour. Sites with ≥5% of nodal metastases were considered in the clinical target volume for radiotherapy planning. Results: Twelve studies (1075 patients) were included. The most frequent site of lymph node metastasis in intrahepatic biliary tree carcinoma was retroportal (61.1%, 95% confidence interval (CI)=50.7-70-6%). Other frequently involved lymph nodes were along the hepatoduodenal ligament [frequency=38.7%, 95% CI=31.0-47.0%], those along the common hepatic artery (17.0%, 95% CI=8.2-31.9%) and the hilar nodes (16.9%, 95% CI=13.2-21.4%). In extrahepatic biliary tree cancer, the most frequently involved lymph nodes were the pericholedochal (42.7%, 95% CI=33.8-52.1%) and those along the hepatoduodenal ligament (40.3%, 95% CI=32.4-48.8%). Other commonly involved nodal regions included retroportal lymph nodes (30.9%, 95% CI=23.0-40.1%), pancreaticoduodenal anterior and posterior nodes (30.1%, 95% CI=12.2-57.1%), those along the common hepatic artery (19.7%, 95% CI=11.8-31.0%) and para_aortic nodes (15.2%, 95% CI=8.0-27.0%). The most common site of metastases in gallbladder cancer were the pericholedochal nodes (25.2%, 95% CI=18.6-33.2%), those along the cystic duct (23%, 95% CI=16.6-30.8%), and retroportal nodes (17.1%, 95% CI=11.6-24.5%). Conclusion: Biliary tract cancer has a high propensity for regional lymphatic metastases. An evidence-based nodal target definition of biliary tract cancer based on primary tumour location was proposed.