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Introduction:: This retrospective study analyzes the safety and feasibility of concurrent chemoradiotherapy (CRT) in adjuvant treatment of soft tissue sarcoma (STS)., Methods:: A total of 158 patients with STS were retrospectively analyzed. Anthracycline-based computed tomography was performed in high-risk patients. Acute radiotherapy toxicity and chemotherapy-related toxicity were assessed according to the Common Terminology Criteria for Adverse Events 4.0; late radiotherapy toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria., Results:: Fifty-four (34.2%) patients received CRT. Mean follow up was 5.4 years (range .2-21.1 years). Local DFS-recurrence-free survival, distant DFS-relapse-free survival, and overall survival were 79.1%, 76.4%, and 64.6%, respectively, at last follow-up. Leukopenia occurred in 11.4% of patients. Skin acute toxicity developed in 60.1% of patients and determined interruption of radiotherapy treatment in 19 (12%) patients. Nineteen patients (12%) experienced moderate fibrosis (grade 2). Mild and moderate joint stiffness was recorded in 16 (10.1%) patients. Size ≥5 cm was the only predictor of local recurrence at multivariate analysis (hazard ratio [HR] 9.65, 95% confidence interval [CI] 1.28-72.83, p = .028). Age and stage resulted as independent distant relapse predictors (HR 4.77, 95% CI 1.81-12.58, p = .002 and HR 4.83, CI 1.41-16.57, p = .012, respectively). At Cox regression univariate analysis, Karnofsky Performance Status, size, and stage were significant survival predictors (HR 2.23, 95% CI 1.02-4.87, p = .045; HR 2.88, 95% CI 1.10-7.52, p = .031; HR 2.59, 95% CI 1.11-6.04, p = .028)., Conclusions:: Concurrent CRT is a well-tolerated treatment option with no additional toxicity compared to exclusive radiotherapy or sequential CRT.

Introduction: This study aimed to evaluate the diagnostic accuracy of panoramic radiography (PAN) for the detection of clinically/surgically confirmed apical periodontitis (AP) in root canal-treated teeth using cone-beam computed tomographic (CBCT) imaging as the reference standard., Methods: Two hundred forty patients with endodontically treated AP (diseased group) were detected via CBCT imaging using the periapical index system. They were divided into groups of 20 each according to lesion size (2-4.5 mm and 4.6-7 mm) and anatomic area (incisor, canine/premolar, and molar) in both the upper and lower arches. Another 240 patients with root filling and a healthy periapex (healthy group) were selected. All diseased and healthy patients underwent PAN first and a CBCT scan within 40 days. The periapical index system was also used to assess AP using PAN. Sensitivity, specificity, diagnostic accuracy, positive predictive value, and negative predictive value for PAN images with respect to CBCT imaging were analyzed. The k value was calculated to assess both the interobserver reliability for PAN and the agreement between PAN and CBCT., Results: PAN showed low sensitivity (48.8), mediocre negative predictive value (64.7), good diagnostic accuracy (71.3), and high positive predictive value (88.6) and specificity (93.8). Both interobserver reliability for PAN and agreement between PAN and CBCT were moderate (k = 0.58 and 0.42, respectively). The best identified AP was located in the lower canine/premolar and molar areas, whereas the worst identified AP was located in the upper/lower incisor area and upper molar area., Conclusions: PAN showed good diagnostic accuracy, high specificity, and low sensitivity for the detection of endodontically treated AP., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Invasive triple negative apocrine carcinoma (TNAC) of the breast is a rare type of triple negative breast cancer. Several studies reported significantly distinct prognosis for TNAC when compared with most of the non-apocrine triple negative (NATN) tumors. This is a case-control study reporting onoutcomes from our long-term single-center experience., Patients and Methods: We analyzed the clinicopathologic features of a series of 46 TNAC tumors treated in a 15-year period. Tumor characteristics and outcomes have been compared with a homogeneous control series of 43 NATN tumors treated during the same follow-up period. Local relapse-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS) have been evaluated., Results: LRFS in the TNAC group was 85% and 78% at 5 and 10 years, respectively. LRFS in the NATN group was 90% and 79% at 5 and 10 years, respectively (hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.41-3.19; P = .80). DMFS in the TNAC group was 85% and 85% at 5 and 10 years, respectively. DMFS in the NATN group was 85% and 75% at 5 and 10 years, respectively (HR, 0.39; 95% CI, 0.14-1.08; P = .071). OS in the TNAC group was 86% and 83% at 5 and 10 years, respectively. OS in the NATN group was 86% and 63% at 5 and 10 years, respectively. OS was significantly better in the TNAC group (HR, 0.45; 95% CI, 0.20-0.99; P = .049)., Conclusions: TNAC seems to represent a distinct group of triple negative breast cancer, characterized by a favorable long-term outcome when compared with NATN tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Candidemia is a major cause of in-hospital mortality. Antifungal stewardship programme (AFSP) providing infectious diseases consultation (IDC) might improve the outcome. We evaluate the impact on candidemia mortality of IDC as part of AFSP restricting the use of all antifungals with exception of fluconazole. We retrospectively reviewed the charts of patients with documented candidemia in our hospital during the period 2012-2014 evaluating the impact of several variables on 30-days in-hospital mortality. We reviewed data on 276 patients with documented candidemia: 200 (72%) were treated without IDC and 76 (28%) with IDC. In the group without IDC, 52 patients (26%) received no antifungal therapy. Antifungals used for treating candidemia were (no IDC/IDC): azoles (74%/42%); echinocandins (0%/46%); liposomal and lipidic complex amphotericin B (0%/12%). The 30-day in-hospital mortality was respectively (no IDC/IDC) 37% vs. 20% (p = 0.011). The multivariate analysis confirmed IDC as independent factor protecting from death (OR 0.511, 95% CI 0.251-0.994; p = 0.046), together with fungemia due to non-albicans Candida (OR 0.565, 95% CI 0.327-0.977; p = 0.042). Age >65 years was associated with a higher risk of death (OR 1.989, 95% CI 1.055-3.895; p = 0.038). The additional cost for the use of echinocandins driven by IDC in the study period was €207,000. IDC, as a part of a restrictive front-end antimicrobial stewardship programme (ASP), providing a timely right choice of antifungal therapy, increases the cost of antifungal drugs but might be a contributing protective factor from mortality due to candidemia. Efforts to increase the number of IDC in patients with candidemia seems to be warranted.

Objectives: Swallowing and voice dysfunctions are common side effects following head-and-neck squamous-cell carcinoma (HNSCC) treatment. Our aim was to analyze the relationships between quality of life, swallowing, and phonatory problems in patients with an advanced-stage HNSCC and to prospectively evaluate the effects of a prophylactic swallowing program., Methods: First, we retrospectively studied 60 advanced HNSCC patients treated with exclusive or adjuvant radiotherapy/chemoradiotherapy (RT/CRT). Subjects were classified according to general and clinical-therapeutic features. Outcome measures included EORTC QLQ-C30, EORTC QLQ-H&N35, Dysphagia Handicap Index (DHI), M.D.Anderson Dysphagia Inventory (MDADI), and Voice Handicap Index (VHI). Then, we conducted a prospective evaluation of a prophylactic swallowing counselling in 12 consecutive advanced-stage HNSCC patients by a two-arm case-control analysis. These patients were treated with exclusive or adjuvant RT/CRT., Results: 71% of the retrospective population studied reported swallowing dysfunction as a major side effect. No differences were detected in the severity of dysphagia or dysphonia according to type of treatment or staging of the primary tumour, while hypopharyngeal and laryngeal cancer patients showed significantly better swallowing ability and better QoL compared to oral cavity and oropharyngeal localisation (p < 0.05). In addition, a relevant correlation between swallowing and voice problems emerged (p < 0.05). In the prospective part, while no statistical correlation was evident before the start of RT/CRT in the experimental group compared to the control one, the former showed better performances at MDADI (p = 0.006) and DHI (p = 0.002) test 3 months after its end., Conclusion: Dysphagia is both an acute-and-long-term side effect which greatly affects QoL of HNSCC patients undergoing multimodality treatment. Our data show that a prophylactic swallowing program could actually produce a beneficial effect on patients' outcomes., Level of Evidence: 1b and 2b.

Background: Whole pelvic irradiation in prostate cancer patients might prevent metastatic spread of cancer cells through lymphatic drainages in patients eligible for definitive radiotherapy, but its use has declined in the last decades in favor of prostate-only irradiation (POI). The aim of our study is to assess the incidence of pelvic lymph nodal relapse and outcome in prostate cancer patients receiving POI., Materials and Methods: Data from 207 consecutive patients were collected. Clinical and treatment variables were collected. Biochemical relapse-free survival (BRFS), pelvic nodal relapse-free survival (PNRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) were calculated; analysis of prognostic variables was performed., Results: Five-year BRFS, PNRFS, DMFS, DSS and OS were, respectively, 90, 98, 96, 97 and 91%. On multivariate analysis, independent negative predictors of BRFS were Gleason score ≥ 7 (HR: 3.25) and PSA nadir ≥ 0.08 (HR: 4.86). Pelvic nodal relapse was not correlated to impaired outcome., Conclusions: Lymph nodal pelvic relapse occurs in 2% of patients at 5 years and does not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation. Tumor biology and response to treatment are the main determinants of outcome.

The primary aim of this review is to provide practical recommendations in terms of fractionation, dose, constraints and selection criteria to be used in the daily clinical routine. Based on the analysis of the literature reviewed, in order to keep the risk of severe side effects ≤3,5%, patients should be stratified according to the target volume. Thus, patients should be treated with different fractionation and total EQD2 (<12.5 ml: EQD2 < 65 Gy with radiosurgery; >12.5 ml and <35 ml: EQD2 < 50 Gy with hypofractionated stereotactic radiotherapy; >35 ml and <50 ml: EQD2 < 36 Gy with conventionally fractionated radiotherapy). Concurrent approaches with temozolomide or bevacizumab do not seem to improve the outcomes of reirradiation and may lead to a higher risk of toxicity but these findings need to be confirmed in prospective series., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Oral mucositis is a side effect of treatment regimens containing 5-fluorouracil (5-FU). The purpose of this study was to present our evaluation to see if rosiglitazone (RGZ) protected normal tissues from chemotherapy-induced oral mucositis., Methods: C57BL/6J mice were treated with 5-FU for 5 days, with or without RGZ. Mice were euthanized after 5, 8, 11, or 15 days, and mucosal segments were collected., Results: The RGZ did not affect the 5-FU-induced decrease in mouse body weight. The 5-FU caused loss of epithelial architecture, collagen fiber impairment, and inflammatory infiltration. The RGZ reduced leukocyte infiltration, preserved tissue structure, and dampened the 5-FU-induced expression of p53 and matrix metalloproteinase (Mmp)-2 after 5 days, and of Mmp-2 and interleukin (Il-1β after 15 days. The RGZ inhibited the 5-FU-induced increase of transforming growth factor-beta (TGF-β) and nuclear factor-kappa B (NF-κB) proteins and restored collagen protein levels., Conclusion: The RGZ had a protective effect on oral mucosa damaged by chemotherapy. These data encourage the further study of RGZ for the prevention of 5-FU-induced mucositis in patients with cancer., (© 2017 Wiley Periodicals, Inc.)

Introduction and Background: Head and neck squamous cell carcinoma (HNSCC) has been increasingly recognized as an immune suppressive malignancy. The efficacy of immune checkpoint inhibitors (ICI's) in the context of recurrent/metastatic (R/M) setting anticipates the possible integration of immunotherapy into the therapeutic armamentarium of locally advanced disease. Durvalumab (DUR) is a humanized monoclonal IgG1, anti-PD-L1 antibody with promising data in R/M HNSCC. The aim of our study is to test the antitumor activity of a combined regimen incorporating an immune checkpoint inhibitor into a conventional bio-radiation strategy for the cure of unfavorable locally advanced HNSCC., Methods/design: In this open label, multi-center, single-arm, phase I/II study, enrolled patients will receive Radiotherapy (RT) (69.9 Gy/2.12 Gy in 33 fractions) with concurrent Cetuximab (CTX) (400 mg/m 2 1 week before RT start followed by 250 mg/m 2 weekly) and DUR (fixed dose of 1500 mg every 4 weeks starting from RT-CTX week 1) followed by adjuvant DUR (to a maximum of 6 months after completion of RT-CTX). Primary endpoint of the study is 2-year progression-free survival (PFS). A safety run-in is planned after the enrollment of first 12, 24 and 36 patients. Patients affected by high-risk (≥N2a or ≥T3, any N) larynx, hypopharynx and HPV negative oropharynx or HPV-positive oropharynx (≥T2, ≥N2b, ≥10 pack/years) will be eligible., Discussion: Conventional intensification strategies failed to provide any benefit for the cure of locally advanced HNSCC. For the still prevalent HPV-negative population and the high risk-HPV positive disease, there is an unmet need for alternative treatment paradigms. Potentially, the inhibition of the PD-1/PD-L1 checkpoint may synergize with both CTX and RT through immunologic interplay, ultimately aiming to reverse the HNSCC-induced immune suppression. The DUCRO study will seek to demonstrate if such a strategy may be safe and active., Trial Registration: NCT number: NCT03051906Eudract number: 2016-004668-20.

Background and Purpose: There is currently no health-related quality of life (HRQoL) measure specific to anal cancer. Our objective was to develop an anal cancer HRQoL module to supplement the EORTC QLQ-C30 questionnaire using EORTC Quality of Life Group Guidelines., Materials and Method: In order to generate a list of HRQoL issues facing anal cancer patients treated with chemoradiotherapy (CRT), we systematically reviewed the literature and conducted semi-structured interviews with patients and health care professionals (HCPs). Our list was then operationalised into questions using the EORTC Item Library. The provisional question list was pilot tested alongside the EORTC QLQ-C30 with patients from 11 centres across 8 countries., Results: From our literature review and interviews with 43 patients, we generated a list of 197 issues. The list was then refined to 134 issues and reviewed by 34 HCPs and 10 patients. This review resulted in the retention of 65 issues which were used in the draft questionnaire tested by 100 patients. Our analyses led to the modification and removal of questions resulting in a 27 item questionnaire, the EORTC QLQ-ANL27., Conclusion: We have developed a 27 item questionnaire to supplement the EORTC QLQ-C30, for use with patients treated for anal cancer. This has been pilot tested and is now available upon request for use in clinical trials as well as clinical practice in 8 languages (http://groups.eortc.be/qol/)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife., Materials and Methods: Data from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03., Results: All patients received prior EBRT. The median EQD2 total dose was 74 Gy (60-80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of -77.1% (14.3-99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0-2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity., Conclusion: Focal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Stereotactic body radiotherapy (SBRT) emerged as a treatment option in oligometastatic (≤3 metastases) patients experiencing lymph node relapse from treated prostate cancer. No recommendations are available concerning dose schedule, and available studies report the use of multiple-fraction regimens due to theoretical lower toxicity and higher cumulative dose delivered to the target. The aim of the present study was to evaluate the safety and efficacy of a dose-intensive, single-fraction SBRT regimen., Patients and Methods: Retrospective data on outcome and toxicity from 27 treatments on 23 consecutive patients were collected. Statistical analysis was performed., Results: Median follow-up was 22 months (range 6-63, interquartile range 15-28). Biochemical progression-free survival (bPFS) at 6 months, 1 year, and 2 years were 65%, 40%, and 26%, respectively. In 2 cases acute toxicity of grade 1 were observed., Conclusion: Single-fraction SBRT for lymph node relapse of oligometastatic prostate cancer resulted in promising biochemical control with minimal toxicity., (© 2018 S. Karger GmbH, Freiburg.)

Purpose: The 11-gauge (11G) stereotactic vacuum-assisted breast biopsy (VABB) showed a better profile than 14G-VABB in terms of feasibility, safety, microcalcification sampling, and accuracy. Underestimation rates were significantly lower with 11G-VABB than with 14G-VABB. Thus, the introduction of an even larger needle at the VABB procedure could reduce this rate further. The purpose of this study was to compare the overall performance of stereotactic VABB with 8G and 11G needles., Materials and Methods: Four hundred and three VABBs performed between July 2012 and February 2015 at the Breast Diagnostic Unit of Careggi Hospital in Florence were retrospectively analyzed; 197 were performed with 11G-VABB and 206 with 8G-VABB. Lesions were classified according to mammographical patterns in microcalcifications, architectural distortions, or opacities, and all biopsy targets were classified according to BIRADS classification as BIRADS III, IV or V. Data were collected on radiological classification of targets, imaging presentation, procedure time, number of specimens per procedure, and microcalcification retrieval on histological findings. Surgery was always performed when high-risk or malignant lesions (B3 or B5) were detected; the final diagnosis was made on surgical pathology., Results: Compared to VABB with an 11G needle, 8G-VABB allows a reduction in the time needed to complete the procedure (20.6 versus 27.4, P < 0.00001) and the number of specimens collected per lesion (21.6 versus 12.2, P < 0.00001). Moreover, 8G-VABB resulted in the same diagnostic accuracy, and the underestimation rates were comparable between the two groups for both B3 and DCIS lesions., Conclusions: The 8G needle should be considered as a valid alternative option in VABB for breast lesions., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: Radiotherapy plus cetuximab is an effective combination therapy for locally advanced head and neck squamous cell carcinoma. The aim of our study was to determine the frequency of skin toxicity in patients receiving the combined treatment., Results: Forty-eight studies were included in our analysis, for a total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5-36.5) and 13.4% (SD: 11.5; 95% CI: 11.2-15.6), respectively. The majority of studies referred to CTCAE scales for reporting both side effects (85.7% and 92.1%, respectively). Data on the management of skin toxicity were available in only 35.4% of the reviewed literature., Conclusions: severe radiation dermatitis is a frequent side effect induced by the combination of radiotherapy and cetuximab in head and neck cancer. The lack of predictive biomarkers of toxicity hampers the possibilty to design preventive measures on a personalized basis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: The aim of our work was to report on the clinical outcome of a moderately hyprofractionated radiotherapy regimen in elderly patients affected by head and neck squamous cell carcinoma (HNSCC)., Material and Methods: HNSCC aged ≥65 deemed unsuitable for curatively-intended concurrent chemo-radiotherapy or high-dose radiotherapy by clinical judgement were further evaluated with the Geriatric 8 (G8) questionnaire and Charlson comorbidity index (CCI). In case of a G8 score ≤14, a de-intensified radiation schedule of 40 Gy delivered in 16 fractions was prescribed., Results: Thirty-six patients were treated between 2011 and 2016. The median age of the cohort was 77.5 (range: 65-91 years) with a combined ECOG PS of 2-3 in 77.8% and CCI of ≥8 in 25% patients, respectively. At a median follow-up of 13 months (range 2-62 months), the 6-month and 1-year rates of loco-regional control and progression-free survival were 42%, 28% and 36% and 20%, respectively. At univariate analysis, log-rank test showed that age >75 years (p=0.036), worse PS (ECOG≥2; p=0.027), lower G8 score (<9; p=0.027) and PTV volume greater than 200 cc (p=0.038) had a significant correlation with PFS. The negative impact of the PTV volume on PFS was the only parameter confirmed in the multivariate analysis (HR 2.68; 95% CI: 1.24-5.81, p=0.013). No grade 4-5 toxicity was observed, while 13/36 patients (36%) had G3 acute side effects., Conclusion: The hypofractionated radiation schedule evaluated provides clinical benefit with low toxicity in frail, elderly patients affected by locally advanced HNSCC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: This study aimed to evaluate the diagnostic accuracy of orthopantomography (OPT) for the detection of clinically/surgically confirmed apical periodontitis (AP) without endodontic treatment using cone-beam computed tomographic (CBCT) imaging as the reference standard., Methods: One hundred twenty patients without endodontically treated AP (diseased group) were detected via CBCT imaging using the periapical index system. They were divided into groups of 10 each according to the size of the lesion (2-4.5 mm and 4.6-7 mm) and the anatomic area (incisor, canine/premolar, and molar) in both the upper and lower arches. Another 120 patients with a healthy root and periapex (healthy group) were selected. Each diseased and healthy patient underwent OPT first and a CBCT scan within 40 days of the OPT. The periapical index system was also used to assess AP by OPT. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for OPT images with respect to CBCT imaging were analyzed. The k value was calculated to assess both the interobserver reliability for OPT and the agreement between OPT and CBCT imaging., Results: OPT showed low sensitivity (34.2), negative predictive value (59.3), and diagnostic accuracy (65.0) and high specificity (95.8) and positive predictive value (89.1). Interobserver reliability for OPT was substantial (k = 0.71), and agreement between OPT and CBCT imaging was fair (k = 0.30). The best and worst identified AP were located in the lower molar area and the upper/lower incisor area, respectively., Conclusions: OPT showed high specificity and positive predictive value. However, overall, it was not an accurate imaging technique for the detection of untreated AP, especially in the incisor area., (Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Ductal carcinoma in situ (DCIS) is a heterogeneous disease, for which the best adjuvant treatment is still uncertain. Many attempts of risk-groups stratification have been made over time, developing prognostic scores to predict risk of local recurrence (LR) on the basis of features such as age, final surgical margins (FSM) status, grade, and tumor size. The aim of our analysis was to evaluate the patterns of recurrence from a two large-institutional retrospective series., Patients and Methods: We collected data on 457 patients treated with BCS and adjuvant RT between 1990 and 2012. Final analysis was performed on 278 patients, due to missing data about hormonal status (HS). Patients were treated at the Radiation Oncology Unit of the University of Florence (n = 195), and S. Maria Annunziata Hospital (n = 83) (Florence, Italy)., Results: At a median follow up time of 10.8 years (range 3-25), we observed 20 LR (7.2%). The 5-year and 10-year LR rates were 4.9% and 10.2%, respectively. At Cox regression univariate analysis, estrogen receptor (ER) positive status (p = 0.001), HS positive (p = 0.003), and FSM <1 mm (p = 0.0001) significantly impacted on LR. At Cox regression multivariate analysis positive ER status maintained a protective role (p = 0.003), and FSM status <1 mm its negative impact (p = 0.0001) on LR rate., Conclusions: Our experience confirmed the wide heterogeneity of DCIS. Inadequate FSM and negative ER status negatively influenced LR rates. Tumor biology should be integrated in adjuvant treatment decision-making process., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Both endocrine and chemotherapy can be utilized for breast cancer patients' management, in multiple setting (i.e., primary systemic therapy, adjuvant, metastatic treatment). Health-related quality of life in breast cancer survivors can be significantly influenced by cognitive impairment, which has been related in several previously reported experiences to systemic therapies administration. However, although the growing body of literature, the impact of both chemo- and endocrine therapy on cognitive function is currently unclear, due to many confounding factors (i.e., multiple therapies, duration of therapy, comorbidity, age). The aim of the present review is to present an overview of the current literature concerning the possible influence of endocrine and systemic therapy on breast cancer patients' cognitive impairment.

Purpose: Radiosurgery (RS) is a well-established treatment in selected patients with brain metastasis. The aim of this study is to compare the differences between CyberKnife (CK) and TomoTherapy (HT) treatment plans of RS of single brain metastasis (BM) to define when HT should be used in cases beyond Cyberknife-when both systems are readily available for the radiation oncologist., Methods and Materials: Nineteen patients with single brain metastasis treated with CK were re-planned for radiosurgery using TomoTherapy Hi-ART system. Two planning approaches have been used for TomoTherapy plans: the classical one (HT) and the improved conformity (icHT) that produces dose distributions more similar to those of RS plans. PTV coverage, Conformity Index (CI), Paddick Conformity Index (nCI), Homogeneity Index (HI), Gradient Index (GI), and beam on time of CK, HT, and icHT plans were evaluated and compared., Results: A good coverage was found for CK, HT, and icHT plans. A difference between mean HI of CK and icHT plans was observed (p = 0.007). Better dose gradients compared to both icHT and HT modalities were observed in CK plans. icHT modality showed improved mean CI respect to HT modality, similar to that obtained in CK plans., Conclusions: CK plans show higher conformity and lower GI than icHT and HT plans. TomoTherapy demonstrates the advantage of being a device capable to reach different clinical objectives depending on the different planning modality employed. CyberKnife and TomoTherapy are both optimal RS devices, the choice to use one over another has to be clinically guided.

Over the years, thanks to the addition of new generation systemic agents, as well as the use of more advanced and precise radiotherapy techniques, it was able to obtain a high curability rate for breast cancer. Anthracyclines play a key role in the treatment of breast disease, with a well-known benefit on disease-free survival of patients with positive nodal status. Trastuzumab have shown a significant outcome advantage after 1-year administration in case of HER2-positive disease. Unfortunately, significant increase in cardiotoxicity has been observed after anthracyclines and trastuzumab therapies. Even though the cardiology and oncology community strongly recommend a cardiotoxicity prevention strategy for this subset of patients, there is still no consensus on the optimal patient's approach. We aimed to review the published and ongoing researches on cardioprevention strategies and to present the SAFE trial (CT registry ID: NCT2236806; EudraCT number: 2015-000914-23). It is a randomized phase 3, four-arm, single-blind, placebo-controlled study that aims to evaluate the effect of bisoprolol, ramipril or both drugs, compared to placebo, on subclinical heart damage evaluated by speckle tracking cardiac ultrasound in non-metastatic breast cancer patients.

Background: Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC). We recently published the 5-year results of the APBI-IMRT-Florence phase 3 randomised trial (NCT02104895), showing a very low rate of disease failure, with acute and early-late toxicity in favour of APBI. We present the early and 2-year follow-up health-related quality of life (HRQoL) results., Methods: Eligible patients were women aged more than 40 years with early BC suitable for breast-conserving surgery. APBI consisted of 30 Gy in five fractions delivered with IMRT technique. Standard whole breast irradiation (WBI) consisted of 50 Gy in 25 fractions plus a 10 Gy in five fractions boost on tumour bed. A total of 520 patients were enrolled in the phase 3 trial. Overall, 205 patients (105 APBI and 100 WBI) fully completed all the given questionnaires and were therefore included in the present analysis. As HRQoL assessment, patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30, and the BR23 questionnaires at the beginning (T0), at the end (T1) and after 2 years from radiation (T2)., Findings: No significant difference between the two arms at QLQ-C30 and BR23 scores emerged at T0. Global health status (p = 0.0001), and most scores of the functional and symptom scales of QLQ-C30 at T1 showed significant differences in favour of the APBI arm. Concerning the BR23 functional and symptom scales, the body image perception, future perspective and breast and arm symptoms were significantly better in the APBI group. Similar significant results emerged at T2: significant differences in favour of APBI emerged for GHS (p = 0.0001), and most functional and symptom QLQ-C30 scales. According to QLQ-BR23 module, among the functional scales, the body image perception and the future perspective were significantly better in the APBI group (p = 0.0001), whereas among the symptom scales significant difference emerged by breast and arm symptoms with better outcomes in APBI arm (p < 0.01)., Interpretation: Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. APBI should be strongly considered in the treatment choice for selected low-risk patients. Mature local control results from ongoing adequately powered randomised trials are awaited., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control. The aim of this review is to describe the principal mechanisms of immune modulation of response to radiation and investigational strategies to harness the potential of radiation-inducible immune response: radiation therapy is expected to be not just a local treatment but the cornerstone of a multimodal strategy that might achieve long-lasting tumor remission at the primary site and systemic efficacy metastatic lesions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical problem associated with a number of cytotoxic agents. OPERA ® (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule. The aim of this prospective study was to determine the efficacy and safety of OPERA ® supplementation in a series of patients affected by CIPN. We selected 25 subjects with CIPN evolving during or after chemotherapy with potentially neurotoxic agents. Patients were enrolled at the first clinical manifestation of neuropathy. CIPN was assessed at the enrollment visit and subsequently repeated every 3 weeks until 12 weeks. Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA ® . Analysis of VAS data showed reduction in pain perceived by patients. According to NCI-CTC sensor and motor score, mISS scale and TNSc scale, both pain and both sensor and motor neuropathic impairment decreased after 12 weeks of treatments. Treatment with OPERA supplement was well tolerated; no increase in the toxicity profile of any of the therapeutic regimen that the patients were undergoing was reported. OPERA ® was able to improve CIPN symptoms in a prospective series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. Prospective RCT in a selected patients' population is warranted to confirm its promising activity.

Objective: Because of its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-neoplastic properties, the PPAR-γ agonist rosiglitazone is an interesting drug for investigating for use in the prevention and treatment of radiation-induced intestinal damage. We aimed to evaluate the radioprotective effect of rosiglitazone in a murine model of acute intestinal damage, assessing whether radioprotection is selective for normal tissues or also occurs in tumour cells., Methods: Mice were total-body irradiated (12 Gy), with or without rosiglitazone (5 mg/kg/day). After 24 and 72 hours, mice were sacrificed and the jejunum was collected. HT-29 human colon cancer cells were irradiated with a single dose of 2 (1000 cells), 4 (1500 cells) or 6 (2000 cells) Gy, with or without adding rosiglitazone (20 µM) 1 hour before irradiation. HT-29-xenografted CD1 mice were irradiated (16 Gy) with or without rosiglitazone; tumour volumes were measured for 33 days., Results: Rosiglitazone markedly reduced histological signs of altered bowel structures, that is, villi shortening, submucosal thickening, necrotic changes in crypts, oedema, apoptosis, and inflammatory infiltrate induced by irradiation. Rosiglitazone significantly decreased p-NF-kB p65 phosphorylation and TGFβ protein expression at 24 and 72 hours post-irradiation and significantly decreased gene expression of Collagen1 , Mmp13 , Tnfα and Bax at 24 hours and p53 at 72 hours post-irradiation. Rosiglitazone reduced HT-29 clonogenic survival, but only produced a slight reduction of xenograft tumour growth., Conclusion: Rosiglitazone exerts a protective effect on normal tissues and reduces alterations in bowel structures and inflammation in a radiation-induced bowel toxicity model, without interfering with the radiation effect on HT-29 cancer cells. PPAR-γ agonists should be further investigated for their application in abdominal and pelvic irradiation.

Background: Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR gamma agonist rosiglitazone is of interest in prevention and therapy of radiation-induced toxicities. We aimed to evaluate the radioprotective effect of rosiglitazone in a mouse model of radiation-induced oral mucositis., Material and Methods: Oral mucositis was obtained by irradiation of the oral region of C57BL/6J mice, pretreated or not with rosiglitazone. Mucositis was assessed by macroscopic scoring, histology and molecular analysis. Tumor xenograft was obtained by s.c. injection of Hep-2 cells in CD1 mice. Tumor volume was measured twice a week to evaluate effect of rosiglitazone alone and combined with radiotherapy., Results: Irradiated mice showed typical features of oral mucositis, such as oedema and reddening, reaching the peak of damage after 12-15days. Rosiglitazone markedly reduced visible signs of mucositis and significantly reduced the peak. Histological analysis showed the presence of an inflammatory cell infiltrate after irradiation; the association with rosiglitazone noticeably reduced infiltration. Rosiglitazone significantly inhibited radiation-induced tnfα, Il-6 and Il-1β gene expression. Rosiglitazone controlled the increase of TGF-β and NF-kB p65 subunit proteins induced by irradiation, and enhanced the expression of catalase. Irradiation and rosiglitazone significantly reduced tumor volume as compared to control. Rosiglitazone did not protect tumor from the therapeutic effect of radiation., Conclusion: Rosiglitazone exerted a protective action on normal tissues in radiation-induced mucositis. Moreover, it showed antineoplastic properties on head-neck carcinoma xenograft model and selective protection of normal tissues. Thus, PPAR gamma agonists should be further investigated as radioprotective agents in head and neck cancer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: This study evaluates, for the first time, the safety of eribulin in metastatic breast cancer patients concomitantly treated with palliative radiotherapy (RT). Patients & materials: A total of 17 patients were pretreated for metastatic breast cancer. Patients received eribulin mesylate and bone RT., Results: The most frequent grade 3 hematologic adverse events were neutropenia (56%) and anemia (20%). Mean pain score decreased from 2 (baseline) to 0.7 (end of observation). Analgesic score remained stable (1.8 vs 1.6). Bone pain scores dropped within a few weeks and remained below baseline values throughout the analysis. The overall response rate was 29%, and the clinical benefit rate was 59%., Conclusion: Eribulin is characterized by a manageable safety profile also when combined with palliative RT.

Near 75% of all breast cancers (BC) express estrogen receptors (ER) and/or progesterone receptors (PgR), while up to 20% of BC show an overexpression/amplification of Human Epidermal Growth Factor Receptor 2 (HER2). Around 50% of all HER2-overexpressing BC show the coexistence of both HER2 overexpression/amplification and ER and/or PgR overexpression. Numerous in vitro and in vivo studies suggest the existence of a cross-talk between their downstream pathways, which seem to affect the natural history, response to therapy and outcome of patients affected by this subset of BC. Meta-analyses or subgroup analysis of numerous neo-/adjuvant trials demonstrated significant clinical implications deriving from ER/HER2 co-existence, consisting in a different pattern of relapse and dissimilar outcome in response to anti-HER2 therapy. However, only two randomized trials in early disease and three in advanced disease specifically addressed the issue whether a combined approach with both hormonal and anti-HER2 therapy would have a better therapeutic impact in this subset of BC compared to the lone anti-HER2 or hormonal therapies (HT). None of these trials demonstrated improvements in overall survival, even though several efficacy end-points such as progression free survival, in advanced setting, or pCR rates in neoadjuvant setting, often favored the combined hormonal and anti-HER2 therapeutic approach. In the next few years, a certain number of ongoing randomized trials, both in neoadjuvant and advanced setting, will evaluate the efficacy of new anti-HER2 drugs, T-DM1 and pertuzumab, in combination with HT, helping to improve the therapeutic strategy for this specific subtype of breast tumors., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: This study analyzes our single-center, retrospective experience on 63 premenopausal breast cancer patients treated with monthly triptorelin and concomitant chemotherapy., Patients & Methods: Concomitant chemotherapy and triptorelin were adopted as part of premature ovarian failure prevention strategy., Results: Age at diagnosis was the main factor influencing fertility preservation (p = 0.002). Compared with patients aged 41-45 years, the probability of menses resumption was almost threefold than for women aged 35-40 years, and significantly higher for women aged <35 years (hazard ratio: 9.0; p = 0.0001). The cumulative proportion among patients who resumed menses was 33.3% at 6 months, 75% at 12 months and 87.5% at 24 months. Seven patients attempted pregnancy, and five (71%) obtained healthy deliveries., Conclusion: We observed an acceptable rate of fertility preservation. Age at diagnosis influences fertility preservation.

Background: General paresis (GP) is a late form of parenchymal neurosyphilis causing dementia and neuropsychiatric disorders. The diagnosis is often difficult since the clinical signs are protean. So far, neuroimaging has played a minor role as radiological findings are not specific., Methods: We studied three immunocompetent patients, admitted to hospital for cognitive impairment. The diagnosis of neurosyphilis was formulated on the basis of serological texts and cerebrospinal fluid analysis. The patients underwent a 3 T MR examination including susceptibility-weighted imaging (SWI) sequence before and after the initiation of penicillin therapy., Results: In all patients, SWI revealed cortical hypointensity, mostly distributed in frontal and temporal lobes. In drug-naive patients, the hypointensity extended over the whole cortical thickness, from the cortical/subcortical junction to the pial surface. After starting the penicillin therapy, the cortical hypointensity partially reversed, involving only the deep cortical layers., Conclusions: The MRI pattern at SWI observed in patients with GP was not reported in other infectious or inflammatory disease of the central nervous system, thus we suggest it could be a peculiar radiological finding of the disease. On the basis of previous pathological data, we hypothesise that cortical SWI hypointensity could be expression of iron deposits within activated microglia., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aim: The present phase II study aimed to evaluate the tolerance and safety of Dixentil, a nutritional supplement based on zinc with the addition of prebiotics (galacto-oligosaccharides), tyndalized probiotics (Lactobacillus acidophilus and L. casei) and vitamins B1, B2 and B6, and nicotinamide), given as prophylaxis to patients undergoing pelvic radiotherapy and its efficacy in the prevention and reduction of radiation-related gastrointestinal disorders., Patients and Methods: Forty consecutive patients who were candidates for pelvic radiotherapy received Dixentil before starting and during radiotherapy. The primary end-point was to evaluate the safety and tolerance of Dixentil. Secondary end-points were incidence and severity of radiation-induced diarrhea and number of patients who discontinued radiotherapy because of diarrhea., Results: Radiation-induced enteritis occurred in 17 patients, grade I and grade II diarrhea was documented in 14 and 3 patients respectively; no grade III or IV diarrhea was observed. Radiotherapy was discontinued due to treatment-induced enteritis only in two patients for 6 days., Conclusion: Use of Dixentil is an easy, safe, and feasible approach to protect patients against the risk of radiation-induced diarrhea., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The purpose of this study was to report the efficacy and the safety profile on the subset of selected early breast cancer (BC) patients aged 70 years or older from a single-center phase 3 trial comparing whole breast irradiation (WBI) to accelerated partial breast irradiation (APBI) using intensity-modulated radiation therapy technique. Between 2005 and 2013, 520 patients aged more than 40 years old were enrolled and randomly assigned to receive either WBI or APBI in a 1:1 ratio. Eligible patients were women with early BC (maximum diameter 2.5 cm) suitable for breast conserving surgery. This study is registered with ClinicalTrials.gov, NCT02104895. A total of 117 patients aged 70 years or more were analyzed (58 in the WBI arm, 59 in the APBI arm). At a median follow-up of 5-years (range 3.4-7.0), the ipsilateral breast tumor recurrence (IBTR) rate was 1.9 % in both groups. No significant difference between the two groups was identified (log-rank test p = 0.96). The 5-year disease-free survival (DFS) rates in the WBI group and APBI group were 6.1 and 1.9 %, respectively (p = 0.33). The APBI group presented significantly better results in terms of acute skin toxicity, considering both any grade (p = 0.0001) and grade 2 or higher (p = 0.0001). Our subgroup analyses showed a very low rate and no significant difference in terms of IBTR, using both WBI and APBI. A significant impact on patients compliance in terms of acute and early late toxicity was shown, which could translate in a consistent improvement of overall quality of life.

Aims and Background: Radiobiological and technical considerations have traditionally limited the role of radiation therapy in the context of primary and secondary cardiac malignancies. Stereotactic body radiotherapy (SBRT) is a promising modality for the delivery of focused high-dose radiation with ablative potential to complex targets such as small, deep-seated, moving lesions, allowing also for re-irradiation., Methods: Between January 2013 and October 2013, 3 patients underwent SBRT for cardiac lesions: 2 patients had recurrent, previously irradiated cardiac angiosarcomas (PCA) and 1 patient had a cardiac metastasis from melanoma. They were treated with fiducial-guided robotic radiotherapy with CyberKnife. As for dose prescription, 24 Gy in 3 fractions (80% isodose) and 30 Gy in 5 fractions (80% isodose) were administered to the recurrent PCAs and cardiac metastasis, respectively., Results: At 2 months after SBRT, cardiac MRI showed a partial response in the patients treated for recurrent PCA while the cardiac metastasis remained stable. In all cases, absence of local progression was subsequently confirmed by contrast-enhanced cardiac MRI after 6 months, without any evidence of treatment-related side effects., Conclusions: Fiducial-guided SBRT proved to be feasible and effective in preventing local disease progression in selected patients with cardiac malignancies.

In total parenteral nutrition (TPN), especially in the case of preterm infants, simultaneous administration of vitamins and trace elements is still a problematic issue: guidelines put in evidence the lack of specific documentation. In this work NMR spectroscopy was applied to the study of vitamins (pyridoxine hydrochloride, thiamine nitrate, riboflavin-5'-phosphate and nicotinamide) stability in presence of salts and trace elements. Vitamins in D2O were first analyzed by (1)H NMR spectroscopy in absence of salts and trace elements; changes in chemical shifts or in diffusion coefficients, measured by NMR DOSY technique, were analyzed. The effects of salts and trace elements on single vitamins and on their admixtures were then investigated by performing quantitative analyses during 48h. Selected vitamins are subject to intermolecular interactions. No degradative effects were observed in presence of salts and trace elements. Only riboflavin-5'-phosphate is subject to precipitation in presence of divalent cations; however, at low concentration and in presence of other vitamins this effect was not observed. Solutions analyzed, in the condition of this study, are stable for at least 48h and vitamins and trace elements can be administered together in TPN., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The tumor status of the axillary lymph nodes is one of the most important prognostic factors in women with early breast cancer (BC). Sentinel lymph node (SLN) biopsy has become the standard staging procedure for patients with invasive BC, largely replacing axillary lymph nodes dissection (ALND). The exact impact on prognosis of SLN tumor burden is still object of controversy. The aim of this study was to correlate the tumor burden in the SLN with the outcome in a large cohort of women., Patients and Methods: 1040 consecutive patients with clinical stage I-III invasive BC were prospectively collected on our Institutional BC database from January 2001 to January 2007. Patients were stratified into the following four groups based on the tumor burden of the SLN: macrometastases, tumor deposit ≥2 mm; micrometastases, tumor deposit ≥0.2 mm and <2 mm; isolated tumor cells (ITC), isolated tumor cells or tumor deposit <0.2 mm; negative, in case of patients with no evidence of tumor., Results: At a median follow-up of 8.5 years, the tumor burden of SLN metastases resulted significant predictor of DFS (P < 0.0001) and OS (P = 0.042). Multivariate analysis showed that the tumor burden of SLN metastases and Ki 67 proliferative index maintained the statistical significance., Conclusion: Patients with SLN micrometastases or ITC, do not seem to have a worse DFS or OS compared with SLN negative cases. There is a significant decrease in DFS and OS in patients with macrometastatic disease in the SLN., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A 22-year-old man with acute lymphoblastic leukaemia was referred to our observation for headache, cervical pain and sopor. A computed tomography study revealed triventricular obstructive hydrocephalus due to a left cerebellar hyperdense mass impinging on the fourth ventricle. A magnetic resonance study demonstrated an area of hyperintensity on T2-weighted images, hypointensity on T1, restricted diffusivity and contrast enhancement involving the left hemispherical cerebellar cortex and the vermis and causing cerebellar herniation. After surgical excision of the lesion, histological examination revealed an infiltrate of lymphoblastic leukaemia with B cells. Leukaemic intracranial masses are rare. Our report describes a case presenting a cerebellar mass of leukaemic tissue characterized by high cellularity and low apparent diffusion coefficient value comparable to acute ischaemia. Therefore leukaemic intracranial mass has to be considered in the differential diagnosis of cerebellar masses.

Aims and Background: Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy., Methods and Study Design: A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy., Results: With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34)., Conclusions: Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

Purpose: In lung cancer, a high radiation dose to the target area correlates with better local control but is frequently counterbalanced by a higher risk of lung toxicity. Several methods exist to coordinate respiratory motion in lung radiotherapy. We aimed to investigate the impact of a breathing-control system on irradiated volumes and dosimetric parameters in three-dimensional conformal radiotherapy (3D-CRT) and stereotactic radiotherapy (SRT) treatments., Materials and Methods: Twelve patients were scheduled for radical radiotherapy: five for SRT and seven for 3D-CRT. For each patient, in addition to the free-breathing computed tomography (CT) scan, four additional sets of CT slices were acquired using the Active Breathing Coordinator device (ABC, Elekta Oncology Systems Ltd., UK)., Results: The volumes acquired with the ABC device were significantly smaller than the free-breathing volumes [23 % reduction of planning tumour volume (PTV), p = 0.002]. ABC allowed a reduction of all dosimetric parameters [2.28 % reduction of percentage volume of lung treated to a dose of ≥ 20 Gy (V20), p = 0.004; 10 % reduction of mean lung dose (MLD), p = 0.009]. Significant differences were found both in SRT and in 3D-CRT, in peripheral and apical lesions., Conclusion: In our experience, ABC has the potential to reduce lung toxicity in the treatment of lung cancer; alternatively, it can allow the prescribed dose to be increased while maintaining the same risk of lung toxicity.

For the first time we describe and interpret Susceptibility Weighted Imaging (SWI) and Perfusion Weighted Imaging (PWI) findings in a case of Chronic Lymphocytic Inflammation with Perivascular Pontine Enhancement Responsive to Steroids (CLIPPERS). The diagnosis of the disease was formulated on the basis of typical Magnetic Resonance (MR) findings and its responsiveness to steroids in a 40-year-old man with acute onset of dizziness, ataxia and diplopia. The patient underwent a 3 tesla (T) MR examination including SWI and PWI sequences. SWI revealed prominent veins and multiple hypointense lesions of different size widely distributed in brainstem and cerebellum, which could be expression of iron deposition or cellular infiltrates. PWI demonstrated global infratentorial hypoperfusion. SWI and PWI provide new information on CLIPPERS that might be helpful to understand the physiopathology of the disease. Further observations are needed to evaluate if these findings are peculiar for CLIPPERS and if they might have a role in a non-invasive diagnosis of the disease., (© 2013.)

Purpose: To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS)., Methods and Materials: A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive., Results: After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence., Conclusions: Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Primary angiitis of the central nervous system (PACNS) is a rare disease characterized by an inflammatory process of intracranial vessels. Magnetic resonance angiography (MRA) (3 T) offers increased signal-to-noise ratio and background suppression, leading to better depiction of the intracranial vessels. The aim of our work was to compare the sensitivity of 3-T MRA to that of 1.5-T MRA in the diagnosis of PACNS., Methods: Eight patients with PACNS and signs of angiitis at digital subtraction angiography (DSA) underwent MRA at 1.5 and 3 T. Magnetic resonance angiograms obtained with time-of-flight (TOF) technique were evaluated for the presence of stenosis with respect to DSA., Results: In PACNS patients, DSA identified 827 intracranial stenoses. Sensitivity for vessel stenosis of 3-T TOF MRA was 47% and 14% for 1.5-T TOF., Conclusions: Time-of-flight MRA at 3 T improved the sensitivity of MRA in the noninvasive preliminary evaluation of patients with PACNS.

Inflammatory breast cancer represents a rare and extremely aggressive subtype of breast cancer. Due to its rarity, prospective studies are a difficult goal to obtain in this field. Nowadays a multimodal approach seems to be the standard approach. Role and timing of surgery, radiotherapy and chemotherapy are still debated issues. In this scenario interest is rising in molecular and target therapies. We performed a review analyzing the management of this unfavorable disease focusing on the role of radiotherapy, with particular emphasis on levels of evidence., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The aim of our analysis was to report the outcome and safety of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2-negative metastatic breast cancer. Between February 2009 and August 2011, 62 consecutive patients received paclitaxel 90 mg/m(2) on days 1, 8, and 15 and bevacizumab (BV) 10 mg/kg intravenously on days 1 and 15, every 28-day cycle. After 6 cycles of combined treatment, patients were given maintenance BV every 3 weeks (15 mg/kg) until progression disease or unacceptable toxicity. At time of analysis, median overall survival was 12.3 months (range 4.6-44.8 months), progression-free survival was 8.1 months (range 2.3-33.2 months), and time to treatment failure was 8.4 months (range 2.3-33.2 months). Our results confirmed the efficacy and the acceptable toxicity profile of bevacizumab plus paclitaxel as first-line regimen for metastatic breast cancer.

We report a case of a 30 years old male affected by synchronous bilateral germ cell tumor with a history of unilateral cryptorchidism; the patient underwent surgical treatment followed by adjuvant radiotherapy on paraaortic and iliac lymphnodes. Patients with synchronous tumors usually present with a higher stage disease in contrast to those with unilateral testicular carcinoma, yet the prognosis remains equally favorable.

Aims and Background: Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control., Methods and Study Design: We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence., Results: A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients., Conclusions: Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.

Background: The aim of this study was to review the treatment, toxicity, and outcomes in patients with stage I seminoma after orchidectomy., Patients and Methods: A retrospective chart review of all patients with stage I seminoma referred for initial treatment during the last 49 years was performed. Initial treatment approaches, toxicity, and outcomes were analyzed., Results: A total of 320 patients were seen between 1960 and 2009. Median age at diagnosis was 37 years (range: 20-72), with a median follow-up of 22.7 years (range: 1-48). All patients but 12 were treated with adjuvant radiotherapy. Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade 2. The 10-year disease-specific survival and relapse-free survival were 97.7 and 97.6%, respectively. 8 patients (2.7%) developed a relapse and were managed with chemotherapy. 10 patients died, 6 of the disease and 4 from other causes (disease-free at time of death)., Conclusion: In the management of stage I seminoma, 3 treatment options are available; currently in the European Consensus, surveillance is the first choice, considering the overall comparable outcome and the low acute and late toxicity. Adjuvant radiotherapy and adjuvant chemotherapy should be considered as alternative options only if the patient declines the surveillance strategy., (2011 S. Karger AG, Basel.)

The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 10(7) lymphocytes. Thirty patients with stage I-IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.