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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.

Despite the recent advanced developments in radiation therapy planning, treatment planning for head-neck and pelvic cancers remains challenging due to large concave target volumes, multiple dose prescriptions and numerous organs at risk close to targets. Inter-institutional studies highlighted that plan quality strongly depends on planner experience and skills. Automated optimization of planning procedure may improve plan quality and best practice. We performed a comprehensive dosimetric and clinical evaluation of the Pinnacle3 AutoPlanning engine, comparing automatically generated plans (AP) with the historically clinically accepted manually-generated ones (MP). Thirty-six patients (12 for each of the following anatomical sites: head-neck, high-risk prostate and endometrial cancer) were re-planned with the AutoPlanning engine. Planning and optimization workflow was developed to automatically generate “dual-arc” VMAT plans with simultaneously integrated boost. Various dose and dose-volume parameters were used to build three metrics able to supply a global Plan Quality Index evaluation in terms of dose conformity indexes, targets coverage and sparing of critical organs. All plans were scored in a blinded clinical evaluation by two senior radiation oncologists. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Autoplanning was able to produce high-quality clinically acceptable plans in all cases. The main benefit of Autoplanning strategy was the improvement of overall treatment quality due to significant increased dose conformity and reduction of integral dose by 6–10%, keeping similar targets coverage. Overall planning time was reduced to 60–80 minutes, about a third of time needed for manual planning. In 94% of clinical evaluations, the AP plans scored equal or better to MP plans. Despite the increased fluence modulation, dose measurements reported an optimal agreement with dose calculations with a γ-pass-rate greater than 95% for 3%(global)-2 mm criteria. Autoplanning engine is an effective device enabling the generation of VMAT high quality treatment plans according to institutional specific planning protocols.

Introduction Non-small cell lung cancer presents at an advanced stage at diagnosis in two-thirds of cases. The most frequent metastatic sites are the central nervous system, adrenal glands and bones. By contrast, the thyroid gland is an extremely rare site of dissemination. Case description A 64-year-old Caucasian man previously treated with radiosurgery and brain metastasectomy followed by right middle lobectomy for a squamous cell lung carcinoma had a metachronous solitary metastasis to the thyroid gland, as confirmed by fine-needle aspiration cytology and open biopsy. He underwent curative radiotherapy, with an initial response. At 9 months’ follow-up the tumor relapsed both in the thyroid and the lung. Discussion and conclusions Review of the literature confirmed that thyroid metastasis from lung cancer is very uncommon in clinical practice. No data on the role of surgery or curative radiotherapy in thyroid metastasis are available because of the lack of prospective studies addressing the impact on survival of these treatment strategies either alone or in combination. In the case described here, radical treatment with radiotherapy allowed to obtain a modest benefit in terms of relapse-free survival. A diagnosis of metastasis to the thyroid gland should be suspected in patients who present a thyroid nodule or suggestive imaging findings when there is a history of malignancy, including lung cancer. Indeed, an early diagnosis allows to pursue radical treatment that, in selected patients, could lead to long-term survival.

Purpose of Review: Preoperative radiotherapy (RT) or chemoradiation represents a standard option in neoadjuvant treatment of rectal cancer (RC). The aim of this analysis is to present a systematic review of clinical target volume (CTV) definition in preoperative RT of RC. A systematic review of published literature was performed. Studies providing clear indications for CTV definition in preoperative RT of RC were eligible. Only studies published as full text were considered. The search was restricted to English, German, and French languages. The CTV delineation, based on the different guidelines, was drawn on selected slices of a CT scan and the CTV definition based on different guidelines was reported in a table to facilitate the comparison. Recent Findings: A total of six publications containing indications for CTV delineation fulfilled the selection criteria and were included in our review. The studies showed a large variability in available indications between CTV contouring guidelines of RC, partly arising from differences in methods used to propose the single guidelines: expert opinion, systematic review, computer-generated consensus, and 3D modeling of recurrence sites. Summary: In our systematic analysis, the available indications for CTV definition in preoperative RT of RC were reviewed. A large variation in target volume delineation was observed.

Purpose To investigate the maximum tolerated dose of intensity modulated radiation therapy simultaneous integrated boost whole-brain radiation therapy for palliative treatment of patients with

Anal canal adenocarcinoma is generally treated like rectal cancer. Surgery is the standard treatment in early stages and neoadjuvant chemoradiation in locally advanced tumors. Local recurrences treatment paradigm often depends on the previous therapies of either surgery or radiotherapy or systemic therapy. We present the case of a patient with tubulovillous adenocarcinoma of the anal canal which relapsed after chemoradiation. The patient refused salvage surgery and was treated with definitive electrochemotherapy under general anesthesia. Tumor electroporation performed with the insertion of three needles in the recurred site was preceded by an intravenous bolus of bleomycin. After the administered treatment, the patient showed a complete clinical response. A year after electrochemotherapy, the patient is free from local disease with excellent preservation of the sphincter function. Electrochemotherapy may be considered as an alternative to surgery in small lesion in the anorectal region when other approaches are excluded.

OBJECTIVE: Stereotactic body radiation therapy (SBRT) has been used in the treatment of cholangiocarcinoma (CC) but toxicity and clinical results of SBRT in CC are still limited and sparse. Therefore, the aim of this systematic review was to analyze the results of SBRT in the setting of advanced CC. METHODS: A systematic literature search was conducted on PubMed, Scopus, and Cochrane library using the PRISMA methodology. Studies including at least 10 patients with diagnosis of advanced CC regardless of tumor site and other treatments were included. The primary outcome was overall survival (OS) and secondary endpoints were local control (LC) and toxicity rates. The ROBINS-I risk of bias tool was used. RESULTS: 10 studies (231 patients) fulfilled the selection criteria and were included in this review. All but one study showed moderate to serious risk of bias. Median follow up was 15 months (range: 7.8–64.0 months). Pooled 1 year OS was 58.3% ((95%) CI: 50.2–66.1%) and pooled 2 year OS was 35.5% ((95%) CI: 22.1–50.1%). Pooled 1 year LC was 83.4%, ((95%) CI: 76.5–89.4%). The reported toxicities were acceptable and manageable with only one treatment-related death. CONCLUSION: The role of SBRT in CC is not yet supported by robust evidence in literature. However, within this limit, preliminary results seem almost comparable to the ones of standard chemotherapy or chemoradiation. ADVANCES IN KNOWLEDGE: SBRT seems effective in terms of LC with acceptable treatment-related toxicities. Therefore, SBRT can be considered a therapeutic option at least in selected patients with CC, possibly combined with adjuvant chemotherapy (CHT).

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.

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

patients Abstract Fulltext Metrics Get Permission Cite this article Authors Digesù C, Deodato F, Macchia G, Cilla S, Pieri M, Zamagni A, Farioli A, Buwenge M, Ferrandina G, Morganti AG Received 12 March 2018 Accepted for publication 23 May 2018 Published 3 October 2018 Volume 2018:10 Pages 143—151 DOI https://doi.org/10.2147/BCTT.S167914 Checked for plagiarism Yes Review by Single-blind Peer reviewer comments 3 Editor who approved publication: Professor Pranela Rameshwar Article has an altmetric score of 2 Cinzia Digesù,1 Francesco Deodato,1 Gabriella Macchia,1 Savino Cilla,2 Martina Pieri,3 Alice Zamagni,4 Andrea Farioli,5 Milly Buwenge,4 Gabriella Ferrandina,6,* Alessio G Morganti4,* 1Radiotherapy Unit, General Oncology Unit, Fondazione Giovanni Paolo II, Campobasso, Italy; 2Medical Physics Unit, Fondazione Giovanni Paolo II, Campobasso, Italy; 3Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; 4Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 5Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 6Department of Woman and Child Health, Gynecologic Oncology Unit, Fondazione “Policlinico Universitario A. Gemelli”, IRCSS, Universita’ Cattolica Sacro Cuore, Rome, Italy *These authors contributed equally to this work Aim: To compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma. Methods: This retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224. Results: Median follow-up was 52 months (range: 3–115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38–3.34 and HR: 1.12, 95% CI: 1.07–1.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08–1.20 and HR: 1.14, 95% CI: 1.01–1.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61–3.41 and HR: 3.07, 95% CI: 1.11–8.53, respectively) compared to CG. Conclusion: In this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1–G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity.

The main clinical goal for patients with advanced or metastatic thoracic cancer is palliation of tumor-related symptoms and improvement of quality of life. The aim of this phase I–II trial was to define the maximum tolerated dose (MTD) of a short-course of palliative radiotherapy (RT) and to evaluate its efficacy in terms of palliative response. A phase I trial was planned with escalating dose increments. Total doses ranged from 16 to 20 Gy delivered (BID) in two consecutive days. Dose limiting toxicity was defined as any acute grade ≥ 3 toxicity based on the RTOG scale. MTD was used in the phase II trial to evaluate the efficacy of this regimen using a two stage Simon’s design. Fifty-four patients were enrolled. The upper dose level of 20 Gy was defined as the MTD. In patients treated with this dose, the overall palliative response rate was 96.5% (CI 0.95: 81.3–99.9%). Complete pain relief rate was 50.0%. Median survival without symptomatic progression was 3 months. The tested short course accelerated regimen was well tolerated and effective in the palliative setting of metastatic or locally advanced chest cancer. A phase III trial is ongoing to validate this RT schedule. Trial registration: NCT03465553.

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

Aim: To evaluate outcome of an accelerated radiotherapy (RT) regimen in elderly patients with an early stage non-melanoma skin cancer (NMSC). Methods: Total RT dose was 30 Gy in 5 Gy fractions in six consecutive days. Results: Thirty-one patients were enrolled. Fourteen were aged ≥80 years. Acute skin and observed late toxicity were exclusively of grade 1. Thirty patients showed a complete response (median follow-up 30 months). Two-year actuarial local control was 93.2%. The cosmetic result was mostly judged as good or excellent. Conclusions: Short-course RT in elderly NMSC patients produces >90% local control of disease.

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

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.

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.

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).

Objective: A multiarm Phase I clinical trial was performed to define the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) delivered by non-coplanar conformal beams or volumetric modulated arc therapy technique in seven predefined clinical settings. Methods: The (a) and (b) arms investigated primary and metastatic lung cancer differentiated by site of onset, arm (c) included primary or metastatic lesions outside the thorax, the (d) and (e) arms were for in-field reirradiation of recurrence, and finally, the (f) and (g) arms were for boost irradiation to the lesions after an adjuvant RT prescribed dose. A 4 months cut-off after previous irradiation course was fixed to distinguish the boost from the retreatment (4 months, respectively). Patients were prospectively enrolled in study arms according to tumor site, clinical stage and previous treatment. The total dose prescribed to the isocenter, ranged from 20 to 50 Gy according to the protocol design and the doses per fraction ranged from 4 to 10 Gy in 5 days. results: A total of 281 patients (M/F: 167/114; median age: 69 years) with 376 lesions underwent SBRT. No acute toxicity was reported in 175 patients (62.3%) while 106 (37.7%) experienced only low-grade (G < 2) acute toxicity. Four patients (all previously irradiated in the same site) showed >Grade 2 toxicity within 6 months from SBRT. With a median follow-up of 19 months, 204 patients (72.6%) did not experience late toxicity, and 77 (27.4%) experienced low grade late toxicity. On per-lesion basis, the 12-and 24 months actuarial local control inside the SBRT field were 84.3 and 73.7 %, respectively. conclusions: SBRT delivered in five consecutive fractions up to the doses evaluated is well tolerated. The MTD was reached in four (a, b, c and f) of the seven study arms. Recruitment for (d), (e) and (g) arms is still ongoing. advances in knowledge: In a prospective dose-escalation trial, the MTD of 50 Gy/10 Gy fraction and 35 Gy/7 Gy fraction were defined for primary and metastatic lesions and as boost after prior RT dose ≤50 Gy, respectively.

Purpose The management of patients with symptomatic rectal cancer not amenable to curative treatment may be challenging. The aim of this phase 2 study was to evaluate the efficacy of short-course radiation therapy in patients with obstructing rectal cancer. Methods and Materials Patients who were not candidates for surgical resection because of synchronous metastases, age, and/or comorbidities were considered eligible. The sample size was calculated based on the 2-stage design of Simon. Short-course radiation therapy was delivered with an isocentric 4-field box technique (total, 25 Gy; 5 fractions in 5 days). Chemotherapy was suspended during radiation treatment. Clinical outcome measures were symptomatic response rate, toxicity, colostomy-free survival, and overall survival. Results From October 2003 to November 2012, 18 patients (median age, 77.5 years) were enrolled. The median follow-up was 11.5 months (range, 3-36 months). Four weeks after treatment, a complete response (ie, complete symptom resolution) was observed in 38.9% of patients and a partial response in 50.0% cases, whereas 11.1% had no response. The rates of reduction or resolution of pain and bleeding were 87.5% and 100%, respectively. The 1-, 2-, and 3-year colostomy-free survival rates were 100%, 71.4%, and 47.6%, respectively (median, 30 months). The 1-, 2-, and 3-year cumulative overall survival rates were 85.2%, 53%, and 39.8%, respectively (median, 25 months). No patients stopped treatment because of gastrointestinal or genitourinary toxicities: 38.9% of patients had grade 1 to 2 toxicity, and 16.7% had grade 3 toxicity. Only 1 patient had hematologic grade 2 toxicity, and 2 patients had grade 2 skin toxicity. Conclusions Short-course radiation therapy may represent a safe and effective alternative treatment option in patients with obstructing rectal cancer not eligible for curative treatment, allowing colostomy to be avoided in a substantial proportion of patients.

Aim Aim of this study was to perform a planning feasibility analysis of a 3-level dose prescription using an IMRT-SIB technique. Background Radiation therapy of locally advanced pancreatic cancer should administer a minimum dose to the duodenum and a very high dose to the vascular infiltration areas to improve the possibility of a radical resection. Materials and methods Fifteen patients with pancreatic head adenocarcinoma and vascular involvement were included. The duodenal PTV (PTVd) was defined as the GTV overlapping the duodenal PRV. Vascular CTV (CTVv) was defined as the surface of contact or infiltration between the tumor and vessel plus a 5mm margin. Vascular PTV (PTVv) was considered as the CTVv plus an anisotropic margin. The tumor PTV (PTVt) was defined as the GTV plus a margin including the PTVv and excluding the PTVd. The following doses were prescribed: 30Gy (6Gy/fraction) to PTVd, 37.5Gy (7.5Gy/fraction) to PTVt, and 45Gy (9Gy/fraction) to PTVv, respectively. Treatment was planned with an IMRT technique. Results The primary end-point (PTVv Dmean>90%) was achieved in all patients. PTVv D98%>90% was achieved in 6 patients (40%). OARs constraints were achieved in all patients. Conclusions Although the PTVv D95%>95% objective was achieved only in 40% of patients, the study showed that in 100% of patients it was possible to administer a strongly differentiated mean/median dose. Prospective trials based on clinical application of this strategy seem to be justified in selected patients without overlap between PTVd and PTVv.

We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. For a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36. min/Gy. The mean number of monitor units was 3162, i.e., 121.6. MU/Gy. Pretreatment verification (3%-3. mm) showed an optimal agreement with calculated values; mean γ value was 0.27 and 98.2% of measured points resulted with γ < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation-induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity.

We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long-term (>5years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973-2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose-response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04-1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01-1.77), but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99-4.88), particularly for latencies ≥10years (HR 3.28, 95% CI 1.14-9.43). A competing risks analysis revealed that the clinical impact of radiation-induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose-response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited.

The most common sites of metastatic differentiated thyroid cancer are the neck lymph nodes, while distant metastases typically involve the lungs, the bones, and less frequently the brain. Uncommon metastatic sites include the liver, adrenal gland, kidney, pancreas, and skin. The epidemiological aspects of thyroid metastases in rare sites are largely unknown and their identification could have a significant impact on patients management. A mini-series of unusual metastatic sites of thyroid carcinoma is proposed as a contribution to current knowledge on anatomopathological characteristics and clinical outcome. Of the six cases that were assessed, the metastases were the following: skin metastases (2), skin and pancreas metastases (1), renal metastasis (1), adrenal metastasis (1), and liver metastasis (1). In our experience, metastases in rare sites do not always represent a negative prognostic factor for disease outcome. In fact they can occur as single distant lesion and if surgically resectable, their treatment can also lead to local disease remission.

Objective. To determine the recommended preoperative dose of large-field chemoradiation along with concomitant boost dose escalation on the tumor in locally advanced cervical carcinoma (LACC). Patients and methods. A radiation dose of 40 Gy over four weeks, 2 Gy per fraction, was delivered to the tumor and the lymphatic drainage (planning target volume, PTV2), which encompassed a volume larger than standard (upper field border: L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the macroscopic tumor only (PTV1) with a concomitant boost strategy. Three dose levels were planned: levels 1 (no PTV1 boost), 2 (45/2.25 Gy) and 3 (50/2.5 Gy). Patients were treated in cohorts of six to twelve per group using a standard phase I study design. The recommended dose was exceeded if N2 of 6 patients in a cohort experienced dose-limiting toxicity (DLT). Results. 32 patients (median age: 50 years; FIGO stage IB2: 4, IIA: 3, IIB: 21, III-IVA: 4) were enrolled. Median follow-up was 18 months (3-49 months). The most common grade 3/4 toxicity was gastrointestinal (diarrhea). Since three DLTs (grade 3 diarrhea, n=2; grade 3 proctitis, n=1), were observed in 4 patients at level 3, the trial was closed and level 2 was judged as the recommended dose. Conclusion. Based on the data from this phase I study, 45 Gy/2.25 Gy to macroscopic tumor and 40 Gy/2 Gy to lymphatic drainage may be considered the recommended doses. © 2010 Elsevier Inc. All rights reserved.

Benign skin diseases have seldom been treated with radiotherapy, unless resistant to other treatments. Eccrine syringofibroadenoma (ESFA) is a rare benign eccrine tumor. ESFA very rarely presents bilateral lesions, and seldom a nonsurgical treatment has been proposed. An exceptional case of bilateral ESFA of the foot is presented; radiotherapy was effective in treating both lesions with good cosmetic results. © 2010 Wiley Periodicals, Inc.

Background and Purpose: Quality assurance procedures (QA) may reduce the risk of errors in radiotherapy. The aim of this study was to assess a QA program based on independent check (IC) procedures in patients undergoing 3D, intensity modulated (IMRT) and extracranial stereotactic (ESRT) radiotherapy. Materials and methods: IC for set-up (IC1) and for radiotherapy treatments (IC2) was tested on 622 patients over a year. Fifteen events/parameters and 17 parameters were verified by IC1 and IC2, respectively. A third evaluation check (IC3) was performed before treatment. Potential errors were classified based on their magnitude. Incidents involving only incorrect or incomplete documentation were segregated. Treatments were classified based on a complexity index (COMIX). Results: With IC1, 75 documentation incidents and 31 potential errors were checked, and with IC2 111 documentation incidents and 6 potential errors were checked. During the study period 10 errors undetected by standard procedures (IC1, IC2) were detected by chance or by IC3. The incidence of errors and serious errors undetected by standard procedures was 1.6% and 0.6%, respectively. There was no higher incidence of errors undetected in patients undergoing IMRT or ESRT, while there was a higher incidence of errors undetected in more complex treatments (p < 0.001). Conclusions: Systematic QA procedures can reduce the risk of errors. The risk of errors undetected by standard procedures is not correlated with the treatment technological level (3D versus IMRT/ESRT). © 2008 Elsevier Ireland Ltd. All rights reserved.

Purpose: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT + IORT). Methods and Materials: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative "flash" RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. Results: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p = 0.019). Conclusions: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (∼50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT + external RT). © 2008 Elsevier Inc. All rights reserved.

Purpose: The squamous cell carcinoma (SCC) antigen is still considered the most accurate serologic tumor marker in cervical carcinoma. We assessed the contribution of the SCC assay to the detection of recurrences in patients treated with radiotherapy. Methods and Materials: The pattern of recurrence and follow-up data were prospectively recorded for 135 patients. Of the 135 patients, 103 (76.3%) had primary cervical carcinoma and 32 (23.7%) had already experienced disease recurrence that had been successfully treated with surgery (n = 2), surgery plus radiotherapy (n = 2), radiotherapy (n = 5), or concomitant chemoradiotherapy (n = 23). The follow-up evaluations (chest X-ray, abdominopelvic magnetic resonance imaging, gynecologic examination with colposcopy, Papanicolaou smear, and SCC assay) were performed at 6-month intervals; the evaluation was done earlier if recurrent disease was suspected. The median follow-up time was 29 months (range, 6-131). The SCC serum levels were assayed, and a cost analysis was done. Results: A total of 481 SCC determinations were performed. Of the 135 patients, 43 (31.8%) experienced disease recurrence. The SCC levels were higher in those with recurrent disease than in the disease-free patients. Elevation of SCC was documented in 34 (79.1% sensitivity) of 43 recurrences before symptoms appeared. Of the 38 patients with serum SCC elevation, 34 developed a recurrence (positive predictive value, 89.5%). Of the 97 patients with negative SCC serum levels, 88 had negative findings at the clinicoradiologic evaluation (negative predictive value, 90.7%). A simplified approach (SCC plus gynecologic examination) was evaluated. Compared with the complete follow-up program, the rate of missed recurrence was 2.2%. The total projected cost per patient for 5 years of follow-up for the simplified procedure was approximately 12.2-fold lower than the standard approach. Conclusions: Our results have shown that a simplified diagnostic approach, including the SCC assay and gynecologic examination, can detect a high rate of recurrence from cervical cancer, with a very favorable cost-effective profile. © 2007 Elsevier Inc. All rights reserved.

This work reports the results of the application of a practical method to determine the in vivo dose at the isocenter point, D(iso), of brain thorax and pelvic treatments using a transit signal S(t). The use of a stable detector for the measurement of the signal S(t) (obtained by the x-ray beam transmitted through the patient) reduces many of the disadvantages associated with the use of solid-state detectors positioned on the patient as their periodic recalibration, and their positioning is time consuming. The method makes use of a set of correlation functions, obtained by the ratio between S(t) and the mid-plane dose value, D(m), in standard water-equivalent phantoms, both determined along the beam central axis. The in vivo measurement of D(iso) required the determination of the water-equivalent thickness of the patient along the beam central axis by the treatment planning system that uses the electron densities supplied by calibrated Hounsfield numbers of the computed tomography scanner. This way it is, therefore, possible to compare D(iso) with the stated doses, D(iso,TPS), generally used by the treatment planning system for the determination of the monitor units. The method was applied in five Italian centers that used beams of 6 MV, 10 MV, 15 MV x-rays and (60)Co gamma-rays. In particular, in four centers small ion-chambers were positioned below the patient and used for the S(t) measurement. In only one center, the S(t) signals were obtained directly by the central pixels of an EPID (electronic portal imaging device) equipped with commercial software that enabled its use as a stable detector. In the four centers where an ion-chamber was positioned on the EPID, 60 pelvic treatments were followed for two fields, an anterior-posterior or a posterior-anterior irradiation and a lateral-lateral irradiation. Moreover, ten brain tumors were checked for a lateral-lateral irradiation, and five lung tumors carried out with three irradiations with different gantry angles were followed. One center used the EPID as a detector for the S(t) measurement and five pelvic treatments with six fields (many with oblique incidence) were followed. These last results are reported together with those obtained in the same center during a pilot study on ten pelvic treatments carried out by four orthogonal fields. The tolerance/action levels for every radiotherapy fraction were 4% and 5% for the brain (symmetric inhomogeneities) and thorax/pelvic (asymmetric inhomogeneities) irradiations, respectively. This way the variations between the total measured and prescribed doses at the isocenter point in five fractions were well within 2% for the brain treatment, and 4% for thorax/pelvic treatments. Only 4 out of 90 patients needed new replanning, 2 patients of which needed a new CT scan.

Objective: To investigate the feasibility and determine the recommended pre-operative intensity-modulated radiotherapy (IMRT) dose of extended-field chemoradiation along with simultaneous integrated boost (SIB) dose escalation. Methods: A radiation dose of 40Gy over 4 weeks, 2Gy/fraction, was delivered to the tumour and the lymphatic drainage (planning target volume, PTV3), which encompassed a volume larger than standard (common iliac lymphatic area up to its apex, in front of the L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the pelvis (PTV2) and to the macroscopic disease (PTV1) with the SIB-IMRT strategy. Three dose levels were planned: Level 1 (PTV3: 40/2Gy; PTV2: 40/2Gy; PTV1: 45/2.25Gy), Level 2 (PTV3: 40/2Gy; PTV2: 45/2.25Gy; PTV1: 45/2.25Gy) and Level 3 (PTV3: 40/2Gy; PTV2: 45/2.25Gy; PTV1: 50/ 2.5Gy). All treatments were delivered in 20 fractions. Patients were treated in cohorts of between three and six per group using a Phase I study design. The recommended dose was exceeded if two of the six patients in a cohort experienced dose-limiting toxicity within 3months fromtreatment. Results: 19 patients [median age: 46 years; The International Federation of Gynecology and Obstetrics (FIGO) stage IB2: 3, IIB: 10, IIIA-IIIB: 6] were enrolled. Median follow-up was 24 months (9-60 months). The most common grade 3/4 toxicity was gastrointestinal (GI) (diarrhoea, mucous discharge, rectal/abdominal pain). At Levels 1 and 2, only one grade 3 GI toxicity per level was recorded, whereas at Level 3, two grade 3 GI toxicities (diarrhoea, emesis and nausea) were recorded. Conclusion: The SIB-IMRT technique was found to be feasible and safe at the recommended doses of 45Gy to PTV1 and PTV2 and 40Gy to PTV3 in the pre-operative treatment of patients with locally advanced cervical cancer. Unfortunately, this complex technique was unable to safely escalate dose beyond levels already achieved with three-dimensional conformal radiotherapy technique given acute GI toxicity. Advances in knowledge: A Phase I radiotherapy doseescalation trial with SIB-IMRT technique is proposed in cervical cancer. This complex technique is feasible and safe at the recommended doses.

Craniopharyngiomas (CPs) are rare benign suprasellar tumors. The standard treatment for CP is complete surgical resection or partial resection followed by adjuvant radiotherapy (RT). Adjuvant RT is typically administered at a total dose of 54 Gy with 1.8 Gy/fraction. The current study reported the case of a young patient affected by recurrent craniopharyngioma, who was treated with irradiation subsequent to several surgical resections. Image fusion and intensity-modulated radiation therapy techniques were employed to deliver a high total dose (63 Gy with 2.1 Gy/fraction) with no severe acute toxicities recorded. At the 6-year follow-up, no radiological or clinical signs of disease progression or late sequelae were observed.

Complete pathological response after chemo-radiation in anaplastic thyroid cancer: A report of two cases

none 13 Purpose: Non melanoma skin cancers (NMSC) of eyelid are uncommon. Many treatments approach are available with surgery being considered as the gold standard. Radiotherapy is an effective alternative in patients unfit for surgery. Brachytherapy (BT) might be a better therapeutic option due high radiation dose concentration to the tumor and rapid dose fall-off resulting in normal tissues sparing. The aim of this review is to evaluate local control, toxicity, and functional cosmetic outcome of BT in NMSC of eyelid. Material and methods: A systematic search of the bibliographic databases PubMed, Scopus, and Cochrane Library from the earliest possible date through October 2015 was performed. Only studies published in English were included. Results: Six articles fulfilled the selection criteria and were included in our review. Due to high risk of bias, all studies were classified to provide a low level of evidence (according to Scottish Intercollegiate Guidelines Network Classification). No randomized controlled trials or case control studies were founded. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 95.2%). Functional and cosmetic outcome were reported in five study as acceptable good functional-cosmetic outcome (median: 100%). Conclusions: To date, few evidences are available on the role of BT in eyelid NMSC, and they show satisfactory results in terms of local control and functional cosmetic outcome. Therefore, prospective controlled trials are justified. Frakulli, Rezarta; Galuppi, Andrea; Cammelli, Silvia; Macchia, Gabriella; Cima, Simona; Gambacorta, Maria A.; Cafaro, Ines; Tagliaferri, Luca; Perrucci, Elisabetta; Buwenge, Milly; Frezza, Giovanni; Valentini, Vincenzo; Morganti, Alessio G. Frakulli, Rezarta; Galuppi, Andrea; Cammelli, Silvia; Macchia, Gabriella; Cima, Simona; Gambacorta, Maria A.; Cafaro, Ines; Tagliaferri, Luca; Perrucci, Elisabetta; Buwenge, Milly; Frezza, Giovanni; Valentini, Vincenzo; Morganti, Alessio G.

AIM: To present a systematic review of techniques and clinical results. METHODS: A systematic review of published literature was performed. Only studies reporting patient outcome after radiosurgery (single fraction) delivered with robotic devices [i.e., robotic radiosurgery (RRS)] have been analyzed. RESULTS: A total of 96 patients from 5 studies were included. The studies are characterized by small series and different methods in terms of dose, target definition, combination with chemotherapy and/or standard fractionated radiotherapy and evaluation modalities. Preliminary results are positive in terms of tumor response (ORR = 56%) and local control of the tumor (crude rate of local progressions: 19.5%). Results for median overall survival (11.4 mo) seem comparable with the ones of prolonged chemoradiation (range: 8.6-13.0 mo). However, gastrointestinal toxicity seems to be the main limitation of RRS, especially at the duodenal level. CONCLUSION: RRS allows for local treatment in a shortened time (1 fraction) compared to traditional treatments (about 1 mo), providing the possibility for an easy integration with systemic therapies. Preliminary results did not show any outcome differences compared to standard chemoradiation. Thus, further efforts to reduce gastrointestinal toxicity are strongly needed.

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014). Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

Introduction: The aim of this phase II study was to evaluate response and toxicity of a prolonged chemoradiation regimen in patients with locally advanced cervical cancer. Patients and Methods: Three cycles of concomitant chemotherapy were used with cisplatin (20 mg/m2, 2-hour intravenous infusion, days 1-4) and 5-fluorouracil (1000 mg/m2, 24-hour continuous intravenous infusion, days 1-4) administered at weeks 1, 5, and 9 of radiotherapy. In combination, radiotherapy was delivered to a planning target volume (PTV) defined as the CTV (clinical target volume) plus 8 mm. The CTV was defined as follows: gross tumor volume, upper half of the vagina (if not involved) or the whole vagina (if clinically involved), uterus, obturator nodes, external iliac nodes, internal iliac nodes, and the presacral nodes (cranial to S2). The prescribed dose to the PTV was 50 Gy, 2 Gy/fraction (ICRU 62) delivered in 25 fractions with a 2-week break at 20Gy and 40 Gy (split-course technique). Early and late toxicity was assessed according to the RTOG and RTOG/ EORTC toxicity scales. Perioperative toxicity was evaluated according to the Chassagne classification of surgical complications. Results: A total of 25 patients were included in this study. Median age was 52 years (range, 28-69). Clinical stage was: IB2-II: 19 patients (76%), III-IVA: 6 patients (24%). All patients completed the prescribed dose of chemoradiation and were evaluated 4 weeks after the end of treatment. Complete and partial clinical local response was observed in 4 and 19 patients, respectively (totaling 92% of clinical responses). About 32% of patients experienced grade 3 to 4 toxicity, in particular, grade 3 or 4 hematological toxicity was observed in 7 patients and 1 patient developed grade 3 genitourinary toxicity. No patients developed grade 3 gastrointestinal toxicity or skin toxicity. Of total, 22 patients (88%) underwent radical hysterectomy. Seven patients (28%) showed a complete response (CR) to treatment, and 7 patients (28%) showed microscopic residual disease (=PR), totaling 14 patients (56%) complete/partial microscopic responses. Perioperative morbidity was higher than reported in historical controls especially in terms of tissue fibrosis (64%) and perioperative urinary toxicity (14%). Actuarial 2-year local control, disease-free survival, and overall survival were 65.5%, 61.8%, and 80.8%, respectively. Conclusion: A prolonged treatment with more chemotherapy courses does not improve tumor response and increases the risk of perioperative complication. This treatment regimen, considering the low incidence of acute gastrointestinal toxicity, might be tested in the adjuvant setting. © 2010 by Lippincott Williams & Wilkins.

Purpose: To evaluate the efficacy of gemcitabine-based chemoradiation (CT-RT) in treating patients (pts) affected by locally advanced pancreatic cancers (LAPC). Methods and Materials: Weekly gemcitabine (100 mg/m2) was given as a 24-hour infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). After CT-RT, pts received five cycles of sequential chemotherapy with gemcitabine (1000 mg/m2; 1, 8, q21). Response rate was assessed according to World Health Organization criteria 6 weeks after the end of CT-RT. Local control (LC), time to progression (TTP), metastases-free survival (MFS), and overall survival (OS) were analyzed by the Kaplan Meier method. Results: Forty pts (male/female 22/18; median age 62 years, range, 36-76) were treated from 2000 to 2005. The majority had T4 tumour (n = 34, 85%), six pts (15%) had T3 tumour. Sixteen pts (40%) were node positive at diagnosis. Grade 3-4 acute toxicity was observed in 21 pts (52.5%). Thirty pts (75%) completed the treatment schedule. A clinical response was achieved in 12 pts (30%). With a median follow-up of 76 months (range, 32-98), 2-year LC was 39.6% (median, 12 months), 2-year TTP was 18.4% (median, 10 months), and 2-year MFS was 29.7% (median, 10 months). Two-year OS (25%; median, 15.5 months) compared with our previous study on 5-fluorouracil-based CT-RT (2.8%) was significantly improved (p

Background and purpose: To evaluate the results in terms of dosimetric parameters and acute toxicity of two clinical studies (MARA-1 and MARA-2) on accelerated IMRT-based postoperative radiotherapy. These results are compared with historical control group (CG) of patients treated with "standard" 3D postoperative radiotherapy. Materials and methods: Prescribed dose to the breast was 50.4 Gy in the CG, 40 Gy in MARA-1 (low risk of local recurrence), and 50 Gy in MARA-2 (medium-high risk of recurrence). The tumor bed total dose was 60.4 Gy (sequential 10 Gy electron boost), 44 Gy (concomitant 4 Gy boost), and 60 Gy (concomitant 10 Gy boost) in CG, MARA-1 and MARA-2 studies, respectively. Overall treatment time was of 32 fractions for CG (6.4 weeks); 16 fractions for MARA-1 study (3.2 weeks) and 25 fractions for MARA-2 study (5 weeks). Results: Three hundred and thirty two patients were included in the analysis. Dosimetric analysis showed Dmax and V107% reduction (p < 0.001) and Dmin improvement (p < 0.001) in the PTV in patients treated with IMRT. Grade 2 acute skin toxicity was 33.6%, 13.1%, and 45.1% in the CG, MARA-1, and MARA-2, respectively (p < 0.001), and grade 3 acute skin toxicity was 3.1%, 1.0%, and 2.0%, respectively. Similarly, larger PTV and use of chemotherapy with anthracyclines and taxanes were associated with a greater acute toxicity. With a median follow-up of 31 months, no patients showed local or nodal relapse. Conclusions: A simplified step and shoot IMRT technique allowed better PTV coverage and reduced overall treatment time (CG, 6.6 weeks; MARA-1, 3.2 weeks; MARA-2, 5 weeks) with acceptable short-term toxicity. © 2008 Elsevier Ireland Ltd. All rights reserved.

Purpose: Given the high cost and side effects of radioprotective agents such as amifostine, attention has been focused on potentially equally effective but less expensive and toxic natural substances. We evaluated the potential radioprotective effects of wine in preventing skin toxicity in patients with breast cancer. Methods and Materials: Before treatment, the medical history and habits of patients were assessed and the information recorded in their clinical folders. Patients were divided into three groups based on the dose/fractionation scheme used: control group, 60.4 Gy (standard technique); Modulated Accelerated Radiotherapy in Adjuvant treatment of breast cancer (MARA)-1 protocol group, 44 Gy (concomitant boost to tumoral bed); and MARA-2 protocol group, 60 Gy (concomitant boost to tumoral bed). The impact of the following variables on acute skin toxicity was evaluated by chart review: radiotherapy protocol, planning target volume (PTV), comorbidity (e.g., hypertension and diabetes), hemoglobin level before therapy, adjuvant hormone therapy, adjuvant chemotherapy, cigarette smoking, and drinking habits. Results: The study population consisted of 348 patients. More severe skin toxicity was significantly associated with the radiotherapy protocol (p < 0.001) and median PTV (p = 0.005). In addition, the incidence of acute toxicity of Grade 2 or greater was higher in patients without alcohol intake (38.4% vs. 22.3%, p = 0.021). The daily amount of alcohol intake also influenced the incidence of skin toxicity, with an incidence of 38.4% in patients with no wine intake, 31.8% in patients drinking half a glass per day, 13.6% in patients drinking one glass per day, and 35.0% in patients drinking two glasses per day. Multivariate analysis showed that wine intake, PTV, and radiotherapy protocol were all significantly correlated with acute toxicity. Conclusions: Our results indicate that wine may have a radioprotective effect; however, prospective studies are needed to confirm this beneficial effect of wine and its components. © 2009 Elsevier Inc. All rights reserved.

Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed ± enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade ≥3 or any hematological toxicity rated as ≥4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg. © 2010 Elsevier Inc. All rights reserved.

Purpose: A joint analysis of data from five contributing centers within the ISIORT-Europe program was performed to investigate the main contributions of intra-operative radiotherapy (IORT) to the multidisciplinary treatment of pancreatic cancer. Materials and methods: Patients with a histologic diagnosis of carcinoma of the pancreas, with an absence of distant metastases, undergoing surgery with radical intent and IORT were considered eligible for participation in this study. Results: From 1985 to 2006, a total of 270 patients were enrolled in the study from five European Institutions. Surgery was performed in 91.5% of cases and complicated by adverse events in 59 cases. External radiotherapy (ERT) preceded surgery in 23.9% of cases. One-hundred and six patients received further ERT. After surgery + IORT, median follow-up was 96 months (range 3-180). Median local control was 15 months, 5-year local control was 23.3%. Median overall survival was 19 months, while 5-year survival was 17.7%. A significantly greater local control and survival were observed in patients undergoing preoperative radiotherapy (LC: median not reached; OS: median 30 months) compared to patients treated with postoperative ERT alone (LC: median 28 months; OS: median 22 months), and to patients submitted to IORT exclusively (LC: median 8 months; OS: median 13 months) (p < 0.0001). Conclusion: From this joint analysis emerges the fact that preoperative radiotherapy increases the effects of IORT in terms of local control and overall survival. The 5-year local control of 23.3% confirms the beneficial "sterilizing" effect of IORT on the tumor bed. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 91 (2009) 54-59

Introduction. The breath-hold is one of the techniques to obtain the dose escalation for lung tumors. However, the change of the patient's breath pattern can influence the stability of the inhaled air volume, IAV, used in this work as a surrogate parameter to assure the tumor position reproducibility during dose delivery. Materials. and method. In this paper, an Elekta active breathing coordinator has been used for lung tumor irradiation. This device is not an absolute spirometer and the feasibility study here presented developed (i) the possibility to select a specific range ε of IAV values comfortable for the patient and (ii) the ability of a transit signal rate Ṡt, obtained by a small ion-chamber positioned on the portal image device, to supply in real time the in vivo isocenter dose reproducibility. Indeed, while the selection of the IAV range depends on the patient's ability to follow instructions for breath-hold, the Ṡt monitoring can supply to the radiation therapist a surrogate of the tumor irradiation reproducibility. Results. The detection of the Ṡt in real time during breath-hold was used to determine the interfraction isocenter dose variations due to the reproducibility of the patient's breathing pattern. The agreement between the reconstructed and planned isocenter dose in breath-hold at the interfraction level was well within 1.5%, while in free breathing a disagreement up to 8% was observed. The standard deviation of the Ṡt in breath-hold observed at the intrafraction level is a bit higher than the one obtained without the patient and this can be justified by the presence of a small residual tumor motion as heartbeat. Conclusion. The technique is simple and can be implemented for routine use in a busy clinic. © 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS).

Objective: We investigated the role of squamous cell carcinoma (SCC) at presentation (pre-SCC) and after treatment (post-SCC) as predictor of pathological response and outcome in locally advanced cervical cancer (LACC) patients undergoing preoperative chemoradiation. Methods: One hundred and twenty-three consecutive LACC patients underwent preoperative chemoradiation including cisplatin and 5-fluorouracil plus external radiotherapy to the whole pelvic region. Clinical responders underwent radical surgery. SCC levels were expressed in nanograms/milliliter. Results: Ninety-five of 123 (77.2%) and 15/113 (13.3%) cases were classified as having high pre-SCC and high post-SCC levels. Complete pathological response was documented in 51 cases (41.5%), while persistence of microscopic foci was shown in 40 cases (32.5%). In the univariate analysis, FIGO (International Federation of Gynecology and Obstetrics) stage, clinical response to treatment and post-SCC levels were associated with pathological response to chemoradiation. In the multivariate analysis, only clinical response to treatment and post-SCC levels retained an independent role as predictors of pathological response to treatment. Cases with high post-SCC status had a shorter disease-free survival than cases with low post-SCC levels (p = 0.028). In the multivariate analysis, lack of a pathological complete response/persistence of microscopic foci to treatment retained an independent negative prognostic role for disease-free survival. Conclusions: Post-SCC identifies LACC patients with a poor chance of pathological response to chemoradiation and an unfavorable outcome.

Purpose: To prospectively compare the rates of pathologic response, acute toxicity, and sphincter preservation with two different schedules of preoperative chemoradiotherapy in patients with cT3 mid-distal rectal cancer. Methods and Materials: Patients with cT3 and/or N+ resectable rectal carcinoma were randomized to receive one of the two following chemoradiotherapy regimens: cisplatin, 5-fluorouracil, and radiotherapy (PLAFUR) or raltitrexed, oxaliplatin, and radiotherapy (TOMOX-RT). For PLAFUR, cisplatin (60 mg/m2) was given on Days 1 and 29, with a prolonged infusion of 5-fluorouracil (1,000 mg/m2) on Days 1-4 and 29-32, plus concurrent radiotherapy (50.4 Gy in 1.8-Gy fractions daily). For TOMOX-RT, raltitrexed (3 mg/m2) and oxaliplatin (130 mg/m2) was given on Days 1, 19, and 38 with the same radiotherapy regimen as used for PLAFUR. Surgery was performed 6-8 weeks after completion of chemoradiotherapy. All pathologic specimens were reviewed by a designated expert pathologist. The primary endpoint of this study was pathologic tumor downstaging (defined as tumor regression grade 1-2). Secondary endpoints included the incidence of ypT0, clinical tumor downstaging, sphincter-saving surgery, and acute treatment-related toxicity. Results: Between 2002 and 2005, 164 patients were accrued in 10 Italian centers, 83 patients in the PLAFUR arm and 81 in the TOMOX-RT arm. Overall, tumor regression grade 1-2 was observed in 76 patients (46.4%) and ypT0 in 49 (29.9%). The tumor regression grade 1-2 rate was 41.0% vs. 51.9% (p = 0.162) and the ypT0 rate was 24.1% vs. 35.8% (p = 0.102) for the PLAFUR vs. TOMOX-RT arm, respectively. The overall rate of tumor regression grade 1 and ypN+ was 4.6%. The occurrence of ypT downstaging was significantly greater in the TOMOX-RT arm (p = 0.035). Grade 3-4 acute toxicity occurred in 19 patients (11.6%): 7.1% in the PLAFUR arm vs. 16.4% in the TOMOX-RT arm. Sphincter-saving surgery was performed in 143 patients (87.2%) overall: 87.9% in the PLAFUR arm and 86.4% in the TOMOX-RT arm. Conclusions: Compared with the PLAFUR regimen, TOMOX-RT achieved a greater incidence of downstaging but was associated with a correspondingly greater rate of acute Grade 3+ toxicity. With longer follow-up, the local control and survival rates might offer additional guidance as to the choice of regimen. © 2008 Elsevier Inc. All rights reserved.

Aims and Background The aim of the study was to analyze the feasibility of a setting up of a radiotherapy department using videoconferencing technology. Material and Methods A videoconferencing network was started to link an academic center of radiotherapy to a peripheral center of research at the start of its activity. Two years of data of involved professionals, subjects of links, audio, video link problems and running costs were recorded. Results A total of 418 links was established for an overall duration of 458 hours. The participants included all departmental staff. Videoconferencing involved teaching, ward organization, medical care and scientific subjects. In the second year of experience, the number of videoconferencing links was higher than the first (232 vs 186). Link times were reasonable for both skilled and unskilled operators. Overall, the cost per minute of link was 0.2 Euro, and the mean cost per link was 13 Euros. Videoconferencing was integrated with fax and computer networks to enhance sharing paper and electronic documents. Audio-video technical problems progressively decreased: the link was definitively interrupted or its activation unfeasible in only 1.0% of cases. Conclusions Our experience suggests that the establishment of a link between radiotherapy departments addressed to these aims is feasible by a videoconferencing network.

The case is reported of a patient with locally recurrent carcinoma of the tongue treated with intensity-modulated radiotherapy (IMRT) (simultaneous integrated boost) plus concurrent chemotherapy, who during the third week of radiotherapy developed grade 3 mucositis. Treatment was interrupted for 10 days until significant resolution of the symptoms. At the time of treatment resumption the patient showed 8% weight loss, and in vivo portal dose verification revealed large discrepancies between the computed and measured doses. A new CT scan showed marked tumor shrinkage and modifications to the critical structures. The comparison between the original plan and the hybrid IMRT showed a minimal dose increase in the new target volumes and a marked dose increase in the organs at risk. This case confirms the need for a robust quality assurance program when using IMRT, the feasibility and efficacy of in vivo dosimetry to detect significant discrepancies between planned and delivered dose, and the need to combine IMRT with 4-dimensional radiotherapy, at least for head and neck cancer.