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Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( Clinicaltrial.gov identifier NCT02458508). The median progression-free survival (PFS) and median overall survival (OS) of these patients were 9.54 (95% CI 5.4-14.3) months and 24.9 (95% CI 17.8-34.6) months, respectively. The MC4R rs489693 AA genotype was significantly associated with a shorter PFS and OS. Indeed, with regard to PFS, patients harboring the rs489693 AA genotype had a median PFS of 2.99 months whereas patients with AC/CC genotypes had a median PFS of 10.82 months (P = 0.009). Interestingly, the rs489693 AA patients also had a lower median OS as compared with the median OS of the AC/CC genotypes (10.75 vs. 29.5 months, respectively, P = 0.0001). This study suggests that the MC4R rs489693 AA genotype is significantly associated with a shorter PFS and OS in patients treated with radiotherapy and temozolomide. These findings represent a relevant effort to identify novel clinical markers for RT-CT therapy in GBM to be validated in future pharmacogenetic clinical trials.

Introduction: The role of adjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma (PA) is controversial. In this study we aimed to assess the feasibility, disease-free survival (DFS) and overall survival (OS) of adjuvant chemoradiotherapy (gemcitabine based) in patients with resected PA and their correlation with prognostic factors., Methods: 122 resected patients (stage ≥IIa) treated between February 1999 and December 2013 were analyzed. Two cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15 every 28 days) were administered before concomitant radiotherapy (45 Gy/25 fractions) and chemotherapy (gemcitabine 300 mg/m2 weekly)., Results: Median follow-up was 22.7 months (range 4-109). Gastrointestinal toxicity (G3), neutropenia (G3-G4) and cardiac toxicity (G2-G3) were observed in 2.4%, 10.6% and 1.6% of patients, respectively. OS at 12, 24 and 60 months was 79%, 55% and 31%, respectively (median 25 months). Two-year OS in patients with postoperative Karnofsky performance status (KPS) ≤70 and ≥80 was 37.1% and 62.3%, respectively (p<0.0001). OS was better in the group of patients with a postoperative CA 19-9 level ≤100 U/mL (p = 0.014). Median DFS was 17 months., Conclusions: The combination of concomitant gemcitabine and radiotherapy in patients with radically resected PA was well tolerated and associated with a low incidence of local recurrences. Five-year OS was significantly influenced by postoperative KPS and CA 19-9 values.

Objective: To assess changes of CT perfusion parameters (ΔPCTp) of cervical lymph node metastases from head and neck cancer (HNC) before and after radiochemotherapy (RT-CT) and their association with nodal tumor persistence., Patients and Methods: Eligibility criteria included HNC (Stage III-IV) candidates for RT-CT. Patients underwent perfusion CT (PCT) at baseline 3 weeks and 3 months after RT-CT. Blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were calculated. PET/CT examination was also performed at baseline and 3 months after treatment for metabolic assessment., Results: Between July 2012 and May 2016, 27 patients were evaluated. Overall, only 3 patients (11%) experienced tumor persistence in the largest metastatic lymph node. A significant reduction of all PCTp values (p<0.0001), except MTT (from 6.3 to 5.7 s; p=0.089), was observed at 3 weeks post-RT-CT compared to baseline. All PCTp values including MTT were significantly lower at 3-month follow-up compared to baseline (p<0.05). Moreover, a statistically significant association was observed between nodal tumor persistence and high BF values (p=0.045) at 3 months after treatment that did not occur for the other parameters., Conclusions: Our preliminary findings show that all PCTp except MTT are significantly reduced after RT-CT. High BF values at 3 months post-RT-CT are predictive of nodal tumor persistence.

Purpose: Dysphagia is one of the most important treatment-related side effects in head and neck cancer (HNC), as it can lead to severe life-threating complications such as aspiration pneumonia and malnutrition. Intensity-modulated radiotherapy (IMRT) could reduce swallowing dysfunction by producing a concave dose distribution and reducing doses to the swallowing-related organs at risk (SWOARs). The aim of this study was to review the current literature in order to compare swallowing outcomes between IMRT and three-dimensional conformal radiotherapy (3DCRT)., Methods: A search was conducted in the PubMed and Embase databases to identify studies on swallowing outcomes, both clinically and/or instrumentally assessed, after 3DCRT and IMRT. Dysphagia-specific quality of life and objective instrumental data are summarized and discussed., Results: A total of 262 papers were retrieved from the searched databases. An additional 23 papers were retrieved by hand-searching the reference lists. Ultimately, 22 papers were identified which discussed swallowing outcomes after 3DCRT and IMRT for HNC. No outcomes from randomized trials were identified., Conclusion: Despite several methodological limitations, reports from the current literature seem to suggest better swallowing outcomes with IMRT compared to 3DCRT. Further improvements are likely to result from the increased use of IMRT plans optimized for SWOAR sparing.

Objective: To assess the association of clinicopathologic and molecular features with loco-regional recurrence (LRR) in post-mastectomy breast cancer patients with or without adjuvant radiotherapy (PMRT)., Patients and Methods: We retrospectively reviewed data of patients undergone to mastectomy followed or not by PMRT between January 2004 and June 2013. The patients were divided according to clinicopathologic and molecular sub-classification features. LRR and Cancer Specific Survival (CSS) were calculated using the Kaplan-Meier method; the prognostic factors were compared using long-rank tests and Cox regression model., Results: A total of 912 patients underwent to mastectomy of whom 269 (29.5%) followed by PMRT and 643 (70.5%) not; among the PMRT group, 77 underwent to the chest wall (CW) and 202 to the chest wall and lymphatic drainage (CWLD) irradiation. The median follow-up was 54 months (range, 3-118). No significant difference in terms of LRR and CSS was found between non-PMRT and PMRT group (p=0.175; and p=0.628). The multivariate analysis of LRR for patients who did not undergo PMRT showed a significant correlation with the presence of extracapsular extension (ECE) (p=0.049), Ki-67>30% (p=0.048) and triple negative status (p=0.001). In the PMRT group, triple negative status resulted as the only variable significantly correlated to LRR (p=0.006) at the multivariate analysis and T-stage also showed a trend to significance (p=0.073). Finally, no difference in LRR control was shown between CW and CWLD-PMRT (p=0.078)., Conclusions: After mastectomy ECE, a cut off of Ki-67>30% and triple negative status were strictly correlated with LRR regardless of clinicopathologic stage. PMRT has a positive impact in decreasing LRR in patients with this molecular profile. Besides, CW might represent a valid option for patients with one to three positive nodes.

Radiation necrosis (RN) of brain tissue is a serious late complication of brain irradiation and recently bevacizumab has been suggested as treatment option of RN. There is a lack of data in the literature regarding the effectiveness of bevacizumab for the treatment of RN. The purpose of this review was to perform a comprehensive analysis of all reported cases using bevacizumab for the treatment of brain RN. In September 2016, we performed a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane Library. The research for the review was conducted using a combination of the keywords "radiation necrosis", "radiotherapy" and "bevacizumab" alongside the fields comprising article title, abstract and keywords. Randomized trials, non-randomized trials, prospective studies, retrospective studies and single case reports were included in the review. Our research generated 21 studies and 125 cases where bevacizumab had been used for the treatment of RN. The median follow-up was 8 months and the most frequent bevacizumab dose used was 7.5 mg/kg for 2 weeks with a median of four cycles. Low-dose bevacizumab resulted in effectiveness with improvement in both clinical and radiographic response. The median decrease in T1 contrast enhancement and in T2/FLAIR signal abnormality was 64% and 60%, respectively. A reduction in steroidal therapy was observed in majority of patients treated. Based on the data of our review, bevacizumab appears to be a promising agent for the treatment of brain RN. Future prospective studies are required to evaluate the role of bevacizumab in RN and to define the optimal scheduling, dosage and duration of therapy.

Purpose: We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer., Methods and Materials: The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregional control (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions., Results: A total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval [CI] 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm., Conclusions: In patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of the present study is to evaluate the impact of extent of resection at initial and repeat craniotomy on overall survival of patients with recurrent glioblastoma. The authors retrospectively reviewed the records of all adults patients who underwent repeat resection of recurrent glioblastoma following radiation and chemotherapy at an academic tertiary-care institution between 2011 and 2015. We evaluated the survival outcomes with regard to extent of resection considering both the initial and repeat resections. The role of possible prognostic factors that may affect survival after repeat resection, including age, preoperative performance status, tumor location and adjuvant treatment, was evaluated using Cox regression analyses. Forty-eight patients were included in this study. The overall median survival of 14 patients who had subtotal resection at recurrence after initial subtotal resection did not statistically differ from seven patients who had gross-total resection at recurrence after initial subtotal resection (18 months vs. 22 months, p = 0.583). The overall median survival of 13 patients who had gross-total resection at recurrence after initial gross-total resection was significantly increased compared with survival of 13 patients who had subtotal resection at recurrence after initial gross-total resection (47 months vs. 14 months, p = 0.009). A Cox proportional hazards model was created demonstrating that preoperative performance status at recurrence (HR 0.418, p = 0.035) and the extent of repeat resection (HR 0.513, p = 0.043) were independent predictors of survival. Gross-total resection at repeat craniotomy is associated with longer overall survival and should be performed whenever possible in patients with recurrent glioblastoma and in good performance status.

Objective: The objective of this study was to assess the role of stereotactic body radiotherapy (SBRT) in the treatment of distantly recurrent, oligometastatic gynecological cancer., Methods: The hospital records of 45 patients with F-fluorodeoxyglucose (F-FDG) positron emission tomography positive, distantly recurrent, oligometastatic gynecological cancer were reviewed. All these patients had a number of target lesions less than 5, with largest diameter less than 6 cm. The treatment was delivered with a TrueBeam LINAC and RapidArc technique, using 10 or 6 MV FFF beams. A total of 70 lesions were treated, and lymph nodes represented the most common site of metastases, followed by lung, liver, and soft tissues. Twenty lesions were treated with one single fraction of 24 Gy and 5 lesions received 27 Gy delivered in 3 fractions, depending on the ability to fulfill adequate target coverage and safe dose/volume constraints for the organ at risk with either regimen., Results: Positron emission tomography scan 3 months after SBRT showed a complete response (CR) in 45 lesions (64.3%), a partial response in 14 (20.0%), a stable disease in 5 (7.1%), and a progressive disease in 6 (8.6%). No lesions in CR after SBRT subsequently progressed. Overall acute toxicity occurred in 13 (28.9%) patients. The most common grade 1 to 2 adverse event was pain (n = 9, 20.0%), followed by nausea and vomiting (n = 5, 11.1%). No grade 3 to 4 acute toxicities occurred, and no late toxicities were observed. Patients who failed to achieve a CR had a 2.37-fold higher risk of progression and a 3.60-fold higher risk of death compared with complete responders (P = 0.04 and P = 0.03, respectively)., Conclusions: Stereotactic body radiotherapy offers an effective and safe approach for selected cases of oligometastatic gynecological cancer.

Aim: To assess the role of stereotactic body radiotherapy (SBRT) in pulmonary metastases from colorectal cancer (CRC)., Patients and Methods: Thirty-three consecutive patients with pulmonary metastases from CRC who received SBRT were included in the analysis. The primary endpoints were local and systemic progression-free survival, a secondary endpoint was the safety profile of SBRT., Results: A total of 56 lesions were treated with SBRT. A single nodule was treated in 15 patients, two in 13 and three in five. The radiotherapy dose and the adopted fractionations were 24-27 Gy as a single fraction for 40 lesions and 27-42 Gy in three fractions (2-3 times a week) for the other 16 lesions. After a median follow-up of 22.8 months (range=1.3-45.7 months), the median progression-free survival of the irradiated sites was 13.4 months., Conclusion: SBRT can be considered as local therapy in patients with lung metastases from CRC., (Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Introduction: We assessed the clinical outcome and survival of 70 patients with primary vaginal squamous cell carcinoma undergoing radiotherapy (RT) at the Divisions of Radiotherapy, University of Pisa and ASST Cremona between January 1995 and June 2016., Methods: 58 patients received external beam RT (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose: 45-50.4 Gy). 29 patients (41.4%) received concomitant weekly cisplatin 40 mg/m2. 35 patients received an additional (15-36 Gy) high-dose-rate (HDR) brachytherapy (BT) boost and 13 received an additional (9-25 Gy) EBRT boost to the primary tumor site. 12 women exclusively received HDR-BT up to a total dose of (30-58 Gy)., Results: Median overall survival (OS) was 85 months. A total RT dose of > 60 Gy was significantly associated with a better OS (p = 0.015). There was a trend for a better OS for patients aged < 70 years and for those undergoing EBRT to the entire vagina and pelvis plus BT boost. The most common grade 1-2 acute toxicities were diarrhea (24.1%) and cystitis (20.7%); grade 3 cystitis only occurred in 2 patients (3.4%)., Conclusions: EBRT followed by BT boost seems to be the best treatment for vaginal carcinoma. The total dose of RT should be > 60 Gy., (© 2017 S. Karger GmbH, Freiburg.)

Background: The aim of this study was to assess the treatment benefit and patterns of recurrence for patients with high-risk vulvar squamous cell carcinoma treated with surgery followed by adjuvant radiotherapy (RT)., Patients and Methods: From January 1999 to June 2016, 51 patients underwent total or partial deep vulvectomy with inguinofemoral lymphadenectomy followed by adjuvant RT with 45-50 Gy in 25 fractions +/- a 4-10 Gy boost. 17 (33.3%) women received concomitant chemotherapy., Results: Median overall survival was 81 months. The 5-year disease-free survival and overall survival rates were 52 and 63%, respectively. In univariate and multivariate analysis, patients aged ≤ 76 years and those receiving an RT total dose of > 54 Gy had a significantly lower risk of progression (p = 0.044 and 0.045; p = 0.012 and 0.018, respectively) and death (p = 0.015 and 0.011; p = 0.015 and 0.026, respectively). There was a trend towards a lower risk of progression for patients with tumor size ≤ 4 (p = 0.098) and negative lymphovascular space involvement (p = 0.080). Also, there was a trend towards a higher risk of death (p = 0.075) for grade 3 tumors. Concomitant chemotherapy provided no significant benefit., Conclusion: Only age and RT total dose are significant prognostic variables for squamous cell carcinoma of the vulva treated with primary surgery and adjuvant RT to improve local and locoregional control., (© 2017 S. Karger GmbH, Freiburg.)

Purpose: The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT)., Material and Methods: Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/- adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02., Results: According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed., Conclusions: These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity.

Purpose: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. There are different treatment options and surgical excision is the most frequent treatment due to its low rates of recurrence. Radiotherapy is an effective alternative of surgery, and brachytherapy (BT) might be a better therapeutic option due to high radiation dose concentration to the tumor with rapid dose fall-off resulting in normal tissues sparing. The aim of this review was to evaluate the local control, toxicity, and cosmetic outcomes in NMSC treated with high-dose-rate BT (HDR-BT)., Material and Methods: In May 2016, a systematic search of bibliographic database of PubMed, Web of Science, Scopus, and Cochrane Library with a combination of key words of "skin cancer", "high dose rate brachytherapy", "squamous cell carcinoma", "basal cell carcinoma", and "non melanoma skin cancer" was performed. In this systematic review, we included randomized trials, non-randomized trials, prospective and retrospective studies in patients affected by NMSC treated with HDR-BT., Results: Our searches generated a total of 85 results, and through a process of screening, 10 publications were selected for the review. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 97%). Cosmetic outcome was reported in seven study and consisted in an excellent and good cosmetic results in 94.8% of cases., Conclusions: Based on the review data, we can conclude that the treatment of NMSC with HDR-BT is effective with excellent and good cosmetics results, even in elderly patients. The hypofractionated course appears effective with very good local disease control. More data with large-scale randomized controlled trials are needed to assess the efficacy and safety of brachytherapy.

Purpose: Aim of this work is the assessment of build-up and superficial doses of different clinical Head&Neck plans delivered with Helical TomoTherapy (HT) (Accuray, Sunnyvale, CA). Depth dose profiles and superficial dose points were measured in order to evaluate the Treatment Planning System (TPS) capability of an accurate dose modeling in regions of disequilibrium. Geometries and scattering conditions were investigated, similar to the ones generally encountered in clinical treatments., Methods: Measurements were performed with two dosimeters: Gafchromic® EBT3 films (Ashland Inc., Wayne, NJ) and a synthetic single crystal diamond detector (PTW-Frieburg microDiamond, MD). A modified version of the Alderson RANDO phantom was employed to house the detectors. A comparison with TPS data was carried out in terms of dose difference (DD) and distance-to-agreement (DTA)., Results: DD between calculated data and MD measurements are within 4% even in points with high spatial dose variation. For depth profiles, EBT3 data show a DDmax of 3.3% and DTAmax of 2.2mm, in low and high gradient regions, respectively, and compare well with MD data. EBT3 superficial points always results in measured doses lower than TPS evaluated ones, with a maximum DTA value of 1.5mm., Conclusions: Doses measured with the two devices are in good agreement and compare well with calculated data. The deviations found in the present work are within the reference tolerance level, suggesting that the HT TPS is capable of a precise dose estimation both in superficial regions and in correspondence with interfaces between air and PMMA., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Objective: To report the initial results of a prospective study aimed at evaluating the CT perfusion parameter changes (∆PCTp) of the primary tumour after radiochemotherapy (RCT) in head and neck cancer (HNC) and to correlate with positron emission tomography (PET)/CT response., Methods: Eligibility criteria included HNC (Stage III-IV) candidates for RCT. Patients underwent perfusion CT (PCT) at baseline and at 3 weeks and 3 months after treatment. Blood volume, blood flow, mean transit time (MTT) and permeability surface (PS) product were computed. Moreover, PET/CT was performed at baseline and 3 months after treatment. The ∆PCTp were evaluated between baseline and 3-week/3-month evaluations, whereas PET/CT response was based on the maximum standardized uptake value changes according to the European Organization for Research and Treatment of Cancer criteria., Results: Between July 2012 and July 2015, 25 patients were enrolled. A significant reduction of all CT tumour perfusion parameters (PCTp) was observed from the baseline to after RCT (p < 0.001). Specifically, a significant reduction was shown at 3 weeks for all PCTp except MTT (from 6.18 to 5.14 s; p = 0.722). Differently, a significant reduction of all PCTp (p < 0.001) including MTT (from 6.18 to 2.24 s; p = 0.001) was shown at 3 months. Moreover, the reduction of PS resulted in a significant prediction of PET/CT response at 3 months (p = 0.037) with the trend also at 3 weeks (p = 0.099) at the multivariate analysis., Conclusion: Our preliminary findings seem to show that almost all PCTp are significantly reduced after RCT, whereas PS seems to come out as the strongest factor in predicting the PET/CT response., Advances in Knowledge: This article provides information on the potential useful role of PCT in evaluating tumour response after both early and late RCT.

Background: The role of radiolabeled choline (Cho) in patients with biochemical recurrence after radical treatment for prostate cancer (PCa) is well established. Its widespread clinical use has prompted the depiction of incidentalomas, unusual sites of metastatic lesions, as well as false positive and negative cases. We reported a series of patients affected by biochemical recurrence of PCa imaged by [(18)F]Cho positron emission tomography/computed tomography (PET/CT) which resulted suspected for a second malignancy., Case Presentation: [(18)F]Cho PET/CT was performed in patients with biochemical PCa recurrence. From an internal clinical database we identified patients in which PET/CT resulted suspected for a second malignancy. A second malignancy was suspected in presence of "unusual" site of [(18)F]Cho uptake not consistent with clinical-instrumental history. Histology was used as reference standard for final diagnosis. Seven PCa patients (76 years, 71-84 years) with the suspicion of a second tumor based on [(18)F]Cho PET/CT findings were identified. Mean value of PSA at the time of [(18)F]Cho PET/CT was 2,37 ng/mL. The median time between PCa diagnosis and PET/CT was 6 years (range 0-14 years). In two cases history of a second malignancy (lung cancer and cutaneous basocellular carcinoma) was known (diagnosed 12 and 6 years after PCa, respectively). PET/CT identified 13 sites of [(18)F]Cho uptake (lung = 5, lymph node = 7, bone = 1). Final diagnosis was consistent with lung cancer in 5/7 cases (first diagnosis = 4/5, recurrence = 1/5), colorectal cancer and nodal metastases from melanoma in 1 case each., Conclusions: Although the clinical usefulness of Cho PET/CT for detecting cancer lesions other than prostate origin is known, for those patients who undergo this examination according to indication, the diagnosis of a second tumor has a significant impact on their therapeutic management.

Aim: To assess the outcome of 35 patients with vaginal carcinoma treated with different radiotherapy modalities., Materials and Methods: Thirty-one patients received external-beam irradiation (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose=45-50.4 Gy). Concomitant chemotherapy was used in 22 patients. Nineteen patients received additional 15-25 Gy high-dose-rate brachytherapy (BT) boost and eight received additional EBRT boost to the primary tumor site. Four women received exclusive 30-40 Gy high-dose-rate BT., Results: Median progression-free survival and median overall survival were 22 months and 89 months, respectively. Age <70 years, use of EBRT plus BT, and concomitant chemotherapy were associated with better progression-free (p=0.002, p=0.007, and p=0.02) and overall (p=0.01, p=0.009, p=0.009) survival., Conclusion: Concomitant EBRT and chemotherapy followed by BT is the best treatment for vaginal carcinoma., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: This study was undertaken to evaluate the association of individual parameters and outcome in patients with unresectable locally advanced head and neck cancer treated with radiochemotherapy., Materials and Methods: We retrospectively reviewed data from 126 patients treated in our Institution between 1998 and 2010 for a locally advanced head and neck cancer. Sixteen individual parameters were evaluated for association with specific outcomes such as overall survival, persistence of disease, disease-specific survival and disease-free survival., Results: Six factors influenced overall survival on Kaplan-Meier survival analysis and on univariate Cox regression analysis: smoking, body mass index, site, haemoglobin (Hb) nadir, total dose of radiotherapy and comorbidities. On a multivariate logistic model with stepwise selection, comorbidities, body mass index, total dose and site maintained significance. A significant association for persistence of disease was found with smoking, Hb nadir and site of cancer on univariate and multivariate analysis. Disease-free survival was correlated with performance status, Hb nadir and comorbidities using Kaplan-Meier survival analysis and on univariate Cox regression analysis. Only performance status maintained the significance on multivariate analysis. Disease-specific survival was correlated with five parameters: body mass index, site, Hb nadir, therapy interruption and total dose; on multivariate analysis, Hb nadir, therapy interruption and site maintained a statistically significant association., Conclusions: Hb nadir during treatment, body mass index, smoking, stage, comorbidities and performance status are prognostic factors of outcome and response to radical treatment with radiochemotherapy.

Purpose: No randomized trials have been conducted to directly compare radiotherapy (RT) with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced squamous cell carcinoma of the head and neck. In this randomized trial, we compared these two treatment regimens in terms of compliance, toxicity, and efficacy., Patients and Methods: Eligible patients were randomly assigned in a 1:1 ratio to receive either CDDP 40 mg/m(2) once per week or CTX 400 mg/m(2) as loading dose followed by CTX 250 mg/m(2) once per week concomitant to radical RT. For primary end points, compliance to treatment was defined as number of days of treatment discontinuation and drug dosage reduction. The acute toxicity rate was defined according to the National Cancer Institute Common Toxicity Criteria. Efficacy end points were local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival., Results: The study was discontinued early because of slow accrual after the enrollment of 70 patients. RT discontinuation for more than 10 days occurred in 13% of patients given CTX and 0% given CDDP (P = .05). Drug dosage reduction occurred in 34% given CTX and 53% given CDDP (difference not significant). Toxicity profiles differed between the two arms, with hematologic, renal, and GI toxicities more frequent in the CDDP arm, and cutaneous toxicity and the need for nutritional support more frequent in the CTX arm. Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the CTX arm (19% v 3%, P = .044). Locoregional control, patterns of failure, and survivals were similar between the treatment arms., Conclusion: CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT., (© 2015 by American Society of Clinical Oncology.)

Purpose: To report on single-fraction stereotactic body radiotherapy (RT) (SBRT) with flattening filter (FF)-free (FFF) volumetric modulated arc therapy (VMAT) for lung cancer and to compare dosimetric results with VMAT with FF., Methods and Materials: Overall, 25 patients were treated with 6-MV FFF VMAT (Varian TrueBeam STx LINAC) to a prescribed dose of 24Gy in a single fraction. Treatment plans were recreated using FF VMAT. Dose-volume indices, monitor units (MU), and treatment times were compared between FFF and FF VMAT techniques., Results: Dose constraints to PTV, spinal cord, and lungs were reached in FFF and FF plans. In FFF plans, average conformity index was 1.13 (95% CI: 1.07 to1.38). Maximum doses to spinal cord, heart, esophagus, and trachea were 2.9Gy (95% CI: 0.4 to 6.7Gy), 0.8Gy (95% CI: 0 to 3.6Gy), 3.3Gy (95% CI: 0.02 to 13.9Gy), and 1.5Gy (95% CI: 0 to 4.9Gy), respectively. Average V7Gy, V7.4Gy, and mean dose to the healthy lung were 126.5cc (95% CI: 41.3 to 248.9cc), 107.3cc (95% CI: 18.7 to 232.8cc), and 1.1Gy (95% CI: 0.3 to 2.2Gy), respectively. No statistically significant differences were found in dosimetric results and MU between FF and FFF treatments. Treatment time was reduced by an average factor of 2.31 (95% CI: 2.15 to 2.43) from FF treatments to FFF, and the difference was statistically significant., Conclusions: FFF VMAT for lung SBRT provides equivalent dosimetric results to the target and organs at risk as FF VMAT while significantly reducing treatment time., (Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Radionecrosis (RN) of brain tissue is a serious late complication of brain irradiation and historically has been treated with corticos-teroid therapy and alternatively surgical decompression. Recently, bevacizumab has been suggested for treatment of cerebral radiation necrosis. We present a case of a 73-years-old women affected by a primary non-small cell lung cancer with a single brain metastasis treated with radiosurgery. Two years after radiosurgery the patient referred neurological symptoms and a brain magnetic resonance confirmed the presence of RN. The patient refused surgical decompression so underwent at the treatment with bevacizumab 7.5 mg/kg/2 weeks for a total of 4 cycles. After two months of treatment the patient reported strumental and clinical improvement. Ten months after bevacizumab discontinuation the patient experienced a recurrence of RN with evident clinical manifestation and confirmed by radiological imaging. A new treatment with bevacizumab was not performed due to the systemic progression disease and the worsening of clinical status. Despite limited to only one clinical case, our study suggests the efficacy of bevacizumab to treat RN. Future studies are needed to confirm its mechanism and to properly define the optimal scheduling, dosage and duration of therapy.

Purpose: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. Basal cell carcinoma and squamous cell carcinoma are the two most common subtypes of NMSC. The aim of this study was to estimate tumour control, toxicity, and aesthetic events in elderly patients treated with high-dose-rate (HDR) brachytherapy (BT) using Valencia applicator., Material and Methods: From January 2012 to May 2015, 57 lesions in 39 elderly eligible patients were enrolled. All the lesions had a diameter ≤ 25 mm (median: 12.5 mm) and a depth ≤ 4 mm. The appropriate Valencia applicator, 2 or 3 cm in diameter was used. The prescribed dose was 40 Gy in 8 fractions (5 Gy/fraction) in 48 lesions (group A), and 50 Gy in 10 fractions (5 Gy/fraction) in 9 lesions (group B), delivered 2/3 times a week. The biological effective dose (BED) was 60 Gy and 75 Gy, respectively., Results: After median follow-up of 12 months, 96.25% lesions showed a complete response and only two cases presented partial remission. Radiation Therapy Oncology Group - European Organization for Research and Treatment of Cancer (RTOG/EORTC) G 1-2 acute toxicities were observed in 63.2% of the lesions: 56.3% in group A and 77.7% in group B. Late G1-G2 toxicities was observed in 19.3% of the lesions: 18.8% in group A and 22.2% in group B, respectively. No G3 or higher acute or late toxicities occurred. In 86% of the lesions, an excellent cosmetic result was observed (87.5% in group A and 77.8% in group B). Six lesions had a good cosmetic outcome and only 2.3% presented a fair cosmetic impact., Conclusions: The treatment of NMSC with HDR-BT using Valencia surface applicator is effective with excellent and good cosmetics results in elderly patients. The hypofractionated course appears effective and no statistical differences were observed between the two groups analysed.

Purpose: The aim of our study was to evaluate the usefulness of the four-dimensional computed tomography (4DCT) in accelerated partial breast irradiation (aPBI) planning., Materials and Methods: At our Institute, we have been treating the index quadrant with external intensity-modulated radiation therapy in a phase III trial. For this study, we selected a sample of 10 patients with right- or left-sided breast cancer and surgical clips at the excision site. Contouring of the target was performed both using three-dimensional computed tomography (3DCT) and 4DCT imaging. On both 3DCT and 4DCT, we recorded the clinical target volume (CTV) and the planning target volume (PTV) and the coordinates of the PTV centroid. We calculated the treatment plans, according to our protocol, using the contours drawn on the 3DCT and 4DCT and evaluated target coverage and sparing of organs at risk (OAR)., Results: Median age of the patients was 63.5 years (range 52-75). The comparison between the 3DCT and 4DCT PTV volumes was not statistically significant (p = 0.79). Concerning centroid coordinates, the average absolute differences were 0.1 mm in the latero-lateral, 0.7 mm in the antero-posterior and 0.3 mm in the supero-inferior direction. No statistically significant differences were observed both in PTV coverage and OAR sparing; the 4D PTV contour is adequately covered when the plan based on the 3D contours is used. Target coverage was reduced on average by 1 % and no statistically significant difference was observed (p = 0.93)., Conclusions: In our experience, no significant differences between PTV volumes, PTV coverage, OAR sparing and centroid position are evidenced when comparing 3DCT and 4DCT plans. Conventional 3DCT-based planning is adequate for aPBI.

Aim: The aim of this study was to compare surface imaging, portal imaging, and skin marker set-up in radiotherapy of thoracic and pelvic regions, using cone beam computed tomography (CBCT) data as the gold standard., Patients and Methods: Twenty patients were included in this study. CBCT, surface acquisition (SA), and two orthogonal portal images (PI) were acquired during the first four treatment sessions. Patient set-up corrections, obtained by registering the planning CT with CBCT, were used as the gold standard. Registration results of the PI and SA were evaluated and compared with those obtained with CBCT. The advantage derived from using SA or PI verification systems over a skin marker set-up was also quantified., Results: A statistically significant difference between PI and SA (in favour of PI) was observed in seven patients undergoing treatment of the pelvic region and in two patients undergoing treatment of the thoracic region. The use of SA or PI, compared with a skin marker set-up, improved patient positioning in 50% and 57% of the thoracic fractions, respectively. For pelvic fractions, the use of PI was beneficial in 73% of the cases, while the use of SA was beneficial in only 45%. Patient positioning worsened with SA, particularly along longitudinal and vertical directions., Conclusion: PI yielded more accurate registration results than SA for both pelvic and thoracic fractions. Compared with the skin marker set-up, PI performances were superior to SA for pelvic fractions while comparable results were obtained for thoracic fractions.

Aims and Background: We investigated efficacy, safety, and prognostic factors of reirradiation in patients with recurrent or second primary head and neck cancer., Methods: Records of 75 consecutive patients treated with reirradiation between August 2005 and December 2013 were reviewed., Results: Median overall survival (OS) and cancer-specific survival (CSS) were 29.5 and 33.6 months. Median local control (LC) and progression-free survival (PFS) were 21.7 and 16.2 months. Univariate analysis showed that patients younger than 70 years, with a Karnofsky Performance Status (KPS) &gt;90 or with 2 or less comorbidities at time of reirradiation, have a better OS; KPS &gt;90 and biological equivalent dose (BED) &gt;72 Gy positively influenced the PFS. At multivariate analysis, KPS at reirradiation was an independent predictive factor for OS, while BED was an independent predictive factor for CSS and OS. At univariate analysis, patients with planning target volume (PTV) &gt;221 mL had worse LC and PFS rates, with results confirmed at multivariate analysis. The rate of fatal treatment-related adverse events was 6.7% (3 carotid blowout, 1 soft tissue necrosis, and 1 thromboembolic event)., Conclusions: This study confirms the role and outcomes of reirradiation. A careful selection of patients could minimize acute and late side effects and influence survival: elderly patients, with significant medical comorbidities or poor KPS, are worse candidate for reirradiation. Total dose delivered with reirradiation and PTV appear to be other potential prognostic factors. Further studies of dose escalation are needed to establish the total dose that could achieve better LC rates with a safer toxicity profile.

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.

Background: Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC., Methods: This study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895., Findings: A total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045)., Interpretation: To our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: To assess the clinical utility of elective neck dissection in node-negative recurrent laryngeal carcinoma after curative radiotherapy for initial early glottic cancer., Methods: A retrospective review was undertaken of 110 consecutive early glottic cancer patients who developed laryngeal recurrence after radiotherapy (34 recurrent T1, 36 recurrent T2, 29 recurrent T3 and 11 recurrent T4a) and received salvage laryngeal surgery between 1995 and 2005., Results: Six patients presented with laryngeal and neck recurrence and underwent salvage laryngectomy with therapeutic neck dissection, 97 patients with recurrent node-negative tumours underwent salvage laryngeal surgery without neck dissection and only 7 underwent elective neck dissection. No occult positive lymph nodes were documented in neck dissection specimens. During follow up, only three patients with neck failure were recorded, all in the group without neck dissection. There was no significant association between the irradiation field (larynx plus neck vs larynx) and the development of regional failure. A higher rate of post-operative pharyngocutaneous fistula development occurred in the neck dissection group than in the group without neck dissection (57.2 per cent vs. 13.4 per cent, p = 0.01). Multivariate logistic regression analysis showed that early (recurrent tumour-positive, node-positive) or delayed (recurrent tumour-positive, node-negative) neck relapse was not significantly related to the stage of the initial tumour or the recurrent tumour. An age of less than 60 years was significantly associated with early neck failure (recurrent tumour-positive, node-positive)., Conclusion: Owing to the low occult neck disease rate and high post-operative fistula rate, elective neck dissection is not recommended for recurrent node-negative laryngeal tumours after radiation therapy if the initial tumour was an early glottic cancer.

Purpose: The aim of this study is to evaluate the evolution of supracricoid partial laryngectomy (SCPL) in indications, surgical techniques and outcomes through last decades., Materials and Methods: A retrospective analysis of 146 patients affected by laryngeal cancer treated with SCPL was carried on. We defined: (1) group A, 100 patients treated by cold instruments between 1995 and 2004; (2) group B, 46 patients treated by harmonic scalpel between 2005 and 2010. Complications rate, and functional and oncological results were documented and a comparison between the two groups was made; histopathological analysis of surgical margins was evaluated and correlated with local incidence of recurrence., Results: Significant differences in age mean-value (p=0.02), T classification (p=0.007), and in indication for more advanced-staged patients were found in group B (p=0.001). Surgical procedure was shorter in group B (p<0.001), with shorter swallowing recovery (p=0.003). Oncological outcomes did not report any significant differences. Group B showed a higher incidence of post- operative arytenoid edema (p=0.03) associated with a lower rate of pneumonia (p=0.038). Despite a higher rate of close or positive-margins found in group B no higher incidence of local-recurrence was reported (p=0.02) compared to group A., Conclusions: We documented changing in indications and surgical technique for SCPL because of the development of modern diagnostic techniques and the introduction of low-thermal injury device allowing a more challenging tumor excision as well as with a shorter swallowing recovery in our series., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We have previously shown that a subset of sinonasal intestinal-type adenocarcinomas (ITAC) shows activation of the epidermal growth factor-receptor (EGFR) pathway. In this study we examine the status of the EGFR, KRAS and BRAF genes in a series of sinonasal intestinal (ITAC) and non-intestinal type adenocarcinomas (non-ITAC). Eighteen ITACs and 12 non-ITACs were studied immunohistochemically for EGFR expression. Point mutations were analyzed for EGFR exons 19 and 21, KRAS exon 2 and BRAF exon 15 by direct sequencing. Non-ITACs showed significantly higher expression of EGFR (p = 0.015). Mutation analysis revealed one ITAC with EGFR and one ITAC with KRAS mutation, while two non-ITACs presented mutation of BRAF. We conclude that a subset of sinonasal adenocarcinomas shows overexpression of EGFR, while activating mutations of the signaling cascade downstream of EGFR are rare, suggesting that these tumors could be good candidates for anti-EGFR therapies.

Aims and Background: We report the toxicity and preliminary clinical outcome in patients affected by locally recurrent head and neck cancer treated with stereotactic re-irradiation., Methods: Between February 2012 and August 2013, 17 patients were treated with CyberKnife as stereotactic re-irradiation for locally recurrent head and neck cancer. All patients had previously received a full dose radiation treatment with radical intent, with a median total dose of 66 Gy (range, 50-70) delivered with standard fractionation. The median interval between the primary radiotherapy and re-irradiation was 24 months (range, 10-168)., Results: All patients completed the prescribed treatment, which was delivered in 5 fractions. The median tumor dose administered was 30 Gy (range, 25-35) prescribed to the 80% isodose line. Treatment sites were as follows: neck lymph nodes in 5 patients, paranasal sinuses in 5, oropharynx in 2, nasopharynx, and larynx, oral cavity, nasal fossa and parotid gland each in 1 patient. The median target volume treated was 58.7 cm3 (range, 8.5-211.3). Sixteen patients (94%) were evaluated for response. At a median follow-up of 7.5 months (range, 2-17), 4 patients achieved complete response (25%), 5 had partial response (31%) and 7 showed stable disease (44%). No patient showed in-field progression after re-irradiation. Grade 3 acute toxicity was noted in one patient only; no late side effect was observed during the follow-up., Conclusions: Stereotactic re-irradiation with CyberKnife is an appealing non-surgical salvage treatment for selected patients with local-regionally recurrent head and neck cancer.

After failure of curative radiotherapy (RT), surgery is the main therapeutic option to control recurrent laryngeal cancer. Recurrences after RT for T1-T2 tumours of the glottic larynx are often diagnosed at a more severe stage than the original disease and, thus, usually treated by radical approaches. Our aim is to investigate the feasibility of more conservative strategies for proper treatment of post-RT recurred glottic cancer. We collected and reviewed our files from 1990 to 2006, selecting 75 patients which matched the following inclusion criteria: (1) patient was originally diagnosed with early stage squamous cell carcinoma of the glottic larynx (stage I-II according to 2010 TNM), (2) patient was treated by RT with curative intent, (3) patient presented a recurrence of disease after RT which was surgically treated at our Institution. T stage at first diagnosis was T1a in 41 cases (55%), T1b in 12 (16%) and T2 in 22 (29%). At clinical examination of RT-recurred lesions, we documented advanced lesions (rT3-rT4) in 29 out of 75 patients (39%). Overall, an upstage was reported for 56% RT-recurred cancers, while 37.3% remained at the same stage than the original tumour and 6.7% were downstaged. Twelve patients (16%) underwent salvage partial laryngectomy (SPL), while 63 (84%) received a salvage total laryngectomy (STL). Multivariate analysis showed that rTNM according to the AJCC-UICC of 2010 was the only prognostic factor for both disease-free survival (p = 0.042) and overall survival (p = 0.004). Considering the prognostic impact of rT and rN we documented a statistical significance only in terms of overall survival for both factors (p = 0.004 and p = 0.04, respectively). Although STL remains the most frequent treatment choice for failures after RT in laryngeal carcinomas, SPL represents a valid option for selected patients with limited recurrence and can deliver good oncologic and functional results if performed according to careful indications.

Purpose: The aim of this study was to evaluate disease-free survival (DFS), overall survival and toxicity of patients who underwent preoperative therapy for soft tissue sarcoma., Materials and Methods: The data of 38 consecutive patients affected by soft tissue sarcoma were retrospectively analysed. Six (15.8 %) patients were treated only with neoadjuvant radiotherapy, and 32 (84.2 %) with neoadjuvant chemo-radiation therapy. Surgery was performed within 4-6 weeks after the completion of neoadjuvant treatment., Results: Median follow-up was 4.9 years (range 1-13.7 years). All patients received preoperative external beam radiotherapy (RT). Most patients (84.2 %) underwent neoadjuvant chemotherapy treatment associated with radiotherapy. After neoadjuvant treatment, the majority of patients underwent wide excision (32 out of 38) and five patients had marginal surgery; only one patient underwent amputation. Local recurrence was observed in only two patients (5.2 %). Fourteen (36.8 %) patients experienced metastatic relapse. At the time of our analysis 13 patients (34.2 %) had died due to metastatic spread of the disease. In our series, DFS in relation to distant metastases (DM) showed a significant result for lower limb involvement (p = 0.038) and marginal excision (p = 0.024), both predictors of a worse DFS, histology was statistically significant although it was not possible to evaluate the risk for specific histology due to the small number of events in the different subtypes., Conclusions: The results obtained from our study are encouraging with regard to the feasibility and efficacy of preoperative RT in the treatment of soft tissue sarcoma in view of the results obtained in terms of local control, limb sparing and safety.

Surgery is the main therapeutic option to control recurrent laryngeal cancer after radiotherapy (RT) relapse. Most RT-recurred cancer is treated aggressively; although, conservative laryngeal surgery was attempted in selected cases. Here, we report our experiences with salvage laryngeal surgery for early glottic cancers that did not respond to RT. We analyzed files from 1980 to 2006 and selected 173 patients surgically treated for a RT-failed early glottic carcinoma (stage I-II according to 2010 TNM: 114 T1N0, 59 T2N0). Among them, 47 patients (27%) underwent a salvage partial laryngectomy (SPL) and 126 (73%) had a salvage total laryngectomy (STL). When compared with initial T staging, we found 61% of lesions were up-staged, 31% had the same staged lesion, and only 8% were down-staged (according to rTNM). No statistically significant differences were found in terms of disease-free survival and overall survival when SPL and STL patients were compared. Univariate analysis showed that T, rT, and rTNM were prognostic factors for overall survival (p = 0.045, p = 0.028, and p = 0.037, respectively); yet, these significances were lost in multivariate analysis. Our results suggest that salvage surgery is feasible in most cases of RT-recurred early glottic cancer; although, a conservative approach achieves good oncological and functional results only in select RT-recurred patients.

External beam radiation therapy with conventional fractionation to a total dose of 76-80 Gy represents the most adopted treatment modality for prostate cancer. Dose escalation in this setting has been demonstrated to improve biochemical control with acceptable toxicity using contemporary radiotherapy techniques. Hypofractionated radiotherapy and stereotactic body radiation therapy have gained an increasing interest in recent years and they have the potential to become the standard of care even if long-term data about their efficacy and safety are not well established. Strong radiobiological basis supports the use of high dose for fraction in prostate cancer, due to the demonstrated exceptionally low values of α / β . Clinical experiences with hypofractionated and stereotactic radiotherapy (with an adequate biologically equivalent dose) demonstrated good tolerance, a PSA control comparable to conventional fractionation, and the advantage of shorter time period of treatment. This paper reviews the radiobiological findings that have led to the increasing use of hypofractionation in the management of prostate cancer and briefly analyzes the clinical experience in this setting.

Background and Objectives: Sparing internal jugular vein (IJV) in neck dissection for head and neck cancer is controversial. We aimed at evaluating the prognostic impact of IJV preservation., Methods: We examined 206 files of head and neck cancer patients who underwent radical or modified radical neck dissection at the Otolaryngology University of Florence. The site of primary tumor was larynx and hypopharynx in 44.66%, oropharynx in 25.24%, oral cavity in 23.3%, unknown in 4.85%, salivary glands and rhinopharynx in 0.97%. In 60.19% the IJV was resected, in 39.81% preserved. Prognostic impact of IJV preservation was assessed by Kaplan-Meier and multivariate analysis., Results: Neck recurrence occurred in 25.2%: the IJV was resected in 42.31%, in 57.69% preserved (P = 0.02). At multivariate analysis, neck recurrence resulted significantly associated to extracapsular spread (ECS) (P = 0.009), IJV preservation (P = 0.01), positive margins (P = 0.02). In ECS positive patients, a higher risk of neck recurrence was documented for IJV preservation (P = 0.012). A worse prognosis was observed for patients with IJV spared (P = 0.06)., Conclusions: IJV preservation is associated with an increased risk of neck failure and a worse outcome, mainly in patients with ECS of nodes., (© 2013 Wiley Periodicals, Inc.)

Objectives/hypothesis: To review toxicity and outcomes in patients with head and neck cancer treated with simultaneous integrated boost-intensity-modulated radiotherapy (SIB-IMRT)., Study Design: Review of experience with the SIB-IMRT technique., Methods: Fifty patients were treated with the SIB-IMRT technique. Two possible schedules of radiation therapy (RT) were used: SIB 70 (70/60/54 in 33 fractions) and SIB 66 (66/60/54 in 33 fractions). Forty-one patients also received chemotherapy., Results: All but two patients completed treatment as prescribed. No G4 acute toxicity has been reported in our series. We did not observe any G3 to G4 chronic toxicity, apart from one case of cutaneous necrosis. After a median follow-up of 23.3 months (range, 1-60 months), 41 patients (82%) were alive and negative for disease, and one patient (2%) was alive with distant metastases. Eight patients (16%) died, seven because of progressive disease and one for other causes., Conclusions: SIB-IMRT is a highly effective and safe technique of RT in the treatment of head and neck cancer., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

A case is presented of a patient with a skin basosquamous cell carcinoma of the frontal region infiltrating the cerebral tissue and with a widespread unresectable regional metastatic ulceration of the left parotid region. The patient underwent combined palliative treatment: surgical coverage of the ulceration by means of a pectoralis mayor flap transposition and radiotherapy. After 18 months of follow-up, no signs of tumour progression were noted, the patient is currently free from pain, no increase in trismus was seen, and a slight gain in weight was recorded. Unresectable cancer is mainly treated by concurrent chemoradiation; radiotherapy, however, is contraindicated in deep neoplastic ulcerations with exposure of large vessels. The data reported suggest that surgical coverage of an unresectable neoplastic ulcer is feasible, and combined with early administration of radiation permits a palliative approach in an otherwise untreatable condition.

Aims and background. To report the clinical outcome of linac-based or robotic, image-guided stereotactic body radiotherapy in patients affected by abdominal lymph node metastases from different primary cancers. Methods and methods. Twenty-six patients with 32 abdominal lymph node metastases were consecutively treated at the University of Florence between April 2011 and May 2012. The mean follow-up was 4.6 months (SD, 3.9; range, 0.3-13). The dose prescription ranged between 24 Gy and 36 Gy delivered in 1-5 fractions. Results. In terms of local control, complete response to stereotactic body radiotherapy was obtained in 18 cases (66.7%), partial response in 7 (25.9%), and stable disease in 2 (7.4%). At the Cox univariate regression analysis, an increased risk of partial response or absence of local response to radiotherapy was found for subjects of the female sex (P = 0.036), age less than 50 years (P = 0.022), primary tumor of the genital tract (P = 0.007), and previous chemotherapy (P = 0.057). An excellent local control rate (90.9%) was obtained in patients affected by abdominal lymph node metastases of prostatic origin. Conclusions. Stereotactic body radiotherapy for abdominal lymph node metastases is a safe and effective treatment in terms of high rates of local control, especially in a subset of patients affected by prostate cancer.

We report the case of a 48-year-old woman affected by inoperable primary angiosarcoma of the right atrium who was treated with 4 cycles of induction chemotherapy and radical radiotherapy. We present the application and the result of helical tomotherapy for this patient. We also describe the technical aspects of the simulation, planning, setup and delivery of radiotherapy. At 16 months after the diagnosis the patient is still in good condition without any symptoms and with a partial response of the lesion. This case shows the feasibility of treatment with high doses of radiation for a primary unresectable cardiac sarcoma.

Purpose: This study sought to evaluate acute toxicity and local control in patients who underwent extracranial stereotactic body radiation therapy (SBRT) for paracardiac and cardiac metastatic lesions, defined as such when located at a maximum distance of 1 cm from the heart or inside its parenchyma., Materials and Methods: Between January 2009 and May 2011, 16 patients with paracardiac and cardiac lesions were treated with SBRT. For dose specification, in 15 of 16 patients, the prescription dosage was 36 Gy in three fractions (70% isodose). In one patient, the target lesion was inside the heart, and the prescription dosage was 30 Gy in three fractions (70% isodose)., Results: Regarding response to stereotactic radiotherapy, we recorded one (6%) complete response (CR), six (37%) partial responses (PR), five (32%) stable disease (SD) and four (25%) local failures. Median interval to local failure was 5.2 (range, 3-12) months. The cause of death was distant progression of disease in all four patients. Compliance to treatment was excellent; no patient developed cardiological symptoms or electrocardiographic abnormalities, even months after SBRT., Conclusions: Results of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.

Purpose: The aim of this study was to evaluate the rate of pathological response (PR), disease control and safety of neoadjuvant chemotherapy using oxaliplatin (OX) and 5-fluorouracil (5-FU) with concurrent radiotherapy for treating locally advanced rectal cancer., Materials and Methods: Between November 2002 and December 2010, 90 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) were retrospectively analysed. All patients underwent preoperative radiotherapy (45 Gy in 1.8-Gy fractions) with concurrent OX (80 mg/m(2) i.v., day 1) and a 120-h continuous infusion of 5-FU (1,000 mg/m(2) per day). Surgery was performed within 6 weeks after completion of CRT treatment., Results: Complete pathological response was obtained in six patients (6.7%), and 39 (43.3%) had their disease downstaged. The median follow-up period was 4.7 years (6 months to 9 years). Local recurrence occurred in two patients (2.2%), one of whom developed also liver metastases. Distant metastases not associated with local relapse occurred in 23 (25.6%) patients. Overall (OS) and disease-free (DFS) survival were 62.9% and 52.8%, respectively. CRT was well tolerated, with only one grade 3 (1.2%) haematological toxicity (neutropaenia)., Conclusions: Neoadjuvant systemic chemotherapy based on OX and 5-UC associated with radiotherapy is well tolerated, with good results in terms of pathological response, disease control and survival, in rectal cancer patients.

Purpose: We conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years., Materials and Methods: We reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours., Results: At a median follow-up of 8.9 [range, 0.6-20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003)., Conclusions: In consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater pathological tumour size and positive nodal status as unfavourable features for survival in male breast cancer.

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.

Purpose: The aim of this paper is to investigate the accuracy of a laser∕camera surface imaging system (Sentinel) when used on patients treated in the thorax or pelvic regions and to evaluate system employment conditions and patient setup procedures that provide more accurate results., Methods: The system was tested on two groups of patients for whom different patient setup procedures and Sentinel employment conditions were considered. For the first group of 33 patients (FG) no changes to the usual setup procedures were made and a surface extension limited to the treated region was considered. For the second group of 14 patients (SG) the reproducibility of external body surfaces, including body parts not in close proximity to the treatment site, was optimized and a wider surface was captured. In all cases the system accuracy was evaluated comparing registration results from concurrent Sentinel and cone beam CT (CBCT) acquisitions for a total of 192 occasions. External body surfaces, extracted from planning CT studies, were used as reference in both cases, but for SG also surface data captured by Sentinel system at the first treatment were employed., Results: In the 90th percentile of the distributions reporting CBCT and Sentinel registration parameters, absolute differences for FG were less than 6.4 mm and 3.8°. Better performances were observed for SG (≤5.7 mm and 2°). Mean absolute differences between three translation and three rotation parameters of CBCT and Sentinel were: less than 3.5 mm and 2.1° and 3.7 mm and 1.3° in FG for thorax and pelvis, respectively, and less than 2.8 mm and 1° and 2.7 mm and 0.9° for pelvis and thorax, respectively, in SG. No advantage in considering surface data captured by Sentinel as a reference instead of the surface extracted from the planning CT was observed., Conclusions: The accuracy of Sentinel system in detecting errors is influenced by the extension and reliability of the surface used. When the reproducibility of external body surfaces was optimized differences between CBCT and Sentinel registration parameters resulted less than 5.7 mm and 2° in the 90% of the pelvis and thorax considered cases. No advantage in considering a Sentinel acquisition as reference was observed.

Purpose: Dysphagia is a debilitating complication in head and neck cancer patients (HNCPs) that may cause a high mortality rate for aspiration pneumonia. The aims of this paper were to summarize the normal swallowing mechanism focusing on its anatomo-physiology, to review the relevant literature in order to identify the main causes of dysphagia in HNCPs and to develop recommendations to be adopted for radiation oncology patients. The chemotherapy and surgery considerations on this topic were reported in recommendations only when they were supposed to increase the adverse effects of radiotherapy on dysphagia., Materials and Methods: The review of literature was focused on studies reporting dysphagia as a pre-treatment evaluation and as cancer and cancer therapy related side-effects, respectively. Relevant literature through the primary literature search and by articles identified in references was considered. The members of the group discussed the results and elaborated recommendations according to the Oxford CRBM levels of evidence and recommendations. The recommendations were revised by external Radiation Oncology, Ear Nose and Throat (ENT), Medical Oncology and Speech Language Pathology (SLP) experts., Results: Recommendations on pre-treatment assessment and on patients submitted to radiotherapy were given. The effects of concurrent therapies (i.e. surgery or chemotherapy) were taken into account., Conclusions: In HNCPs treatment, disease control has to be considered in tandem with functional impact on swallowing function. SLPs should be included in a multidisciplinary approach to head and neck cancer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background and Purpose: The mechanism of dissemination of locally advanced head and neck cancer (LAHNC) is far to be resolved. Circulating tumour cells (CTC) have been identified as a prognostic factor in metastatic breast and prostate cancer. This prospective multi-centric analysis studied the possible role of CTC identification in LAHNC., Materials and Methods: CTC were searched in 73 patients with LAHNC (oropharynx, n=39; nasopharynx, n=10; larynx, n=10; paranasal sinuses, n=6, of whom 3 with sinonasal undifferentiated carcinoma, SNUC; hypopharynx, n=5; oral cavity, n=3). All of them (apart from SNUC) had squamous cell cancers. The relationship between CTC positivity and other clinical prognostic factors has been investigated. Response to treatment and survival has been related with changes in CTC number during the treatment., Results: CTC were frequently identified in oro- and hypopharyngeal cancer and in SNUC. They were more frequent in stage IV than in stages I-III disease (18% versus 6%, p=NS (not significant)). Partial or complete response (CR) was related with the absence or disappearance of CTC during treatment (p=0.017). A decrease in the CTC number or their absence throughout the treatment seems also related with non-progressive disease, after both complete or incomplete remission and with the proportion of patients alive and NED (no evidence of disease) (p=0.009)., Conclusions: These preliminary data suggest a possible role of CTC determination in head and neck cancer. Additional and longer follow up data need to be collected to confirm these findings., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aims and Background: Waiting time for radiotherapy is a major problem in clinical practice. We developed a model to create a priority list of patients waiting for radiotherapy according to clinical criteria, where booking of patients is not on a "first-come, first-served" basis and where prioritization has not been left up to individual discretion., Methods: The system is based on an algorithm that assigns to each patient a personal code (priority code, PC) that can be used as a continuous variable to have a priority list. PCpatient = D0patient + PWTsubgroup of treatment. Palliative treatments were categorized according to the clinical urgency. Radical treatments were stratified by primary tumors, by the setting of treatment (preoperative, curative, postoperative) and by the main prognostic factors. Each subgroup of patients has a "priority waiting time" (PWT subgroup of treatment). Calculation of the PC starts from a differentiated date according to clinical scenario [Reference date (D0)], which is taken from the clinical history of the patient., Results: Patients are differentiated according to clinical criteria and according to time elapsed from diagnosis. The priority list can be automatically updated day by day. Delays in patient referral or imaging availability are minimized., Conclusions: The model represents a tool for an objective and automatic prioritization of the patients who are waiting for radiotherapy.

Background: Meningeal carcinomatosis (MC) is a rare complication in breast cancer (BC) with no efficient modality of treatment yet found; overall survival (OS) generally did not exceed six months. We reviewed the experience of the University of Florence focusing on prognostic factors and MC survival., Patients and Methods: We analyzed 33 patients treated for MC from BC between 2002 and 2010., Results: Mean OS from MC diagnosis was 4.9 months. At survival analysis clinical stage emerged as the only statistical significant parameter (P = 0.009) among BC diagnosis features. Among MC diagnosis parameters, more than three metastases at diagnosis (P = 0.037), multimodality treatment (P = 0.014) and poor performance status (P = 0.003) reached the statistical significance. At multivariate analysis only performance status at MC diagnosis maintained the statistical significance (P = 0.0047; HR: 3.34; CI 95% 1.45-7.73)., Conclusions: Our experience confirms that performance status is probably the most important prognostic factor in these patients. Multimodality approach is probably the best option.