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Adjuvant radiotherapy (aRT) has been shown to reduce the risk of local relapse in vulvar cancer (VC). In this multicentre study (OLDLADY-1.2), several Institutions have combined their retrospective data on VC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of aRT.The primary study end-point was the 2-year-local control, secondary end-points were the 2-year-metastasis free-survival, the 2-year-overall survival and the rate and severity of acute and late toxicities. Participating centres were required to fill data sets including age, stage, tumor diameter, type of surgery, margin status, depth of invasion, histology, grading as well technical/dosimetric details of radiotherapy. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected.One hundred eighty-one patients with invasive VC from 9 Institutions were retrospectively identified. The majority of patients were stage III (63%), grade 2 (62.4%) squamous carcinoma (97.2%). Positive nodes were observed in 117 patients (64.6%), moreover tumor diameter 4 cm, positive/close margins and depth of invasion deeper than 5 mm were found in 59.1%, 38.6%, 58% of patients, respectively. Sixty-one patients (33.7%) received adjuvant chemoradiation, and 120 (66.3%) received radiotherapy alone. aRT was started 3 months after surgery in 50.8% of patients. Prescribed volumes and doses heterogeneity was recorded according to margin status and nodal disease. Overall, 42.5% locoregional recurrences were recorded. With a median follow-up of 27 months (range 1-179), the 2-year actuarial local control rate, metastasis free and overall survival were 68.7%, 84.5%, and 67.5%, respectively. In term of safety, aRT leads to a prevalence of acute skin toxicity with a low incidence of severe toxicities.In the context of aRT for VC the present study reports a broad spectrum of approaches which would deserve greater standardization in terms of doses, volumes and drugs used.

Background: Individuals with Down syndrome (DS) require more time to develop motor and/or cognitive skills. Neuromodulation is used to assist in this development. However, there is a gap in the literature on neurophysiological changes that may occur in the primary motor cortex in individuals with DS following neuromodulation. Objective: Our objective was to investigate possible neurophysiological changes in brain wave behavior of the primary motor cortex following the administration of anodal transcranial direct current stimulation combined with sensorimotor training. Methods: The study involved 12 participants with DS. EEG equipment was used to investigate brain activity. The participants received neuromodulation involving anodal tDCS for 20 minutes with a current of 1 mA combined with virtual reality (VR) training three times a week for a total of ten sessions. We analyzed EGG signals and 3D movement during a reaching movement of the dominant upper limb before and after the ten-session protocol. Results: Significant differences in event-related desynchronization and event-related synchronization of the alpha and beta rhythms were found throughout the evaluations. Brain mapping revealed reductions in power and frequency, demonstrating changes in the patterns of these rhythms in the cerebral cortex. Revealed reorganization of the behavior of alpha and beta waves, as demonstrated by distribution of synchronization and desynchronization of these waves among the regions of the brain. Conclusion: The results suggest that anodal tDCS promotes the reorganization of brain impulses, redirecting these impulses to the required regions more efficiently and contributing to better motor planning.

In the randomised, phase 3 equivalence trial on electron intraoperative radiotherapy (ELIOT), accelerated partial breast irradiation (APBI) with the use of intraoperative radiotherapy was associated with a higher rate of ipsilateral breast tumour recurrence (IBTR) than whole-breast irradiation (WBI) in patients with early-stage breast cancer. Here, we aimed to examine the planned long-term recurrence and survival outcomes from the ELIOT trial.This single-centre, randomised, phase 3 equivalence trial was done at the European Institute of Oncology (Milan, Italy). Eligible women, aged 48-75 years with a clinical diagnosis of a unicentric breast carcinoma with an ultrasound diameter not exceeding 25 mm, clinically negative axillary lymph nodes, and who were suitable for breast-conserving surgery, were randomly assigned (1:1) via a web-based system, with a random permuted block design (block size of 16) and stratified by clinical tumour size, to receive post-operative WBI with conventional fractionation (50 Gy given as 25 fractions of 2 Gy, plus a 10 Gy boost), or 21 Gy intraoperative radiotherapy with electrons (ELIOT) in a single dose to the tumour bed during surgery. The trial was open label and no-one was masked to treatment group assignment. The primary endpoint was the occurrence of IBTR. The trial was designed assuming a 5-year IBTR rate of 3% in the WBI group and equivalence of the two groups, if the 5-year IBTR rate in the ELIOT group did not exceed a 2·5 times excess, corresponding to 7·5%. Overall survival was the secondary endpoint. The main analysis was done by intention to treat. The cumulative incidence of IBTR events and overall survival were assessed at 5, 10, and 15 years of follow-up. This trial is registered with ClinicalTrials.gov, NCT01849133.Between Nov 20, 2000, and Dec 27, 2007, 1305 women were enrolled and randomly assigned: 654 to the WBI group and 651 to the ELIOT group. After a median follow-up of 12·4 years (IQR 9·7-14·7), 86 (7%) patients developed IBTR, with 70 (11%) cases in the ELIOT group and 16 (2%) in the WBI group, corresponding to an absolute excess of 54 IBTRs in the ELIOT group (HR 4·62, 95% CI 2·68-7·95, p0·0001). In the ELIOT group, the 5-year IBTR rate was 4·2% (95% CI 2·8-5·9), the 10-year rate was 8·1% (6·1-10·3), and the 15-year rate was 12·6% (9·8-15·9). In the WBI group, the 5-year IBTR rate was 0·5% (95% CI 0·1-1·3), the 10-year rate was 1·1% (0·5-2·2), and the 15-year rate was 2·4% (1·4-4·0). At final follow-up on March 11, 2019, 193 (15%) women had died from any cause, with no difference between the two groups (98 deaths in the ELIOT group vs 95 in the WBI group; HR 1·03, 95% CI 0·77-1·36, p=0·85). In the ELIOT group, the overall survival rate was 96·8% (95% CI 95·1-97·9) at 5 years, 90·7% (88·2-92·7) at 10 years, and 83·4% (79·7-86·4) at 15 years; and in the WBI group, the overall survival rate was 96·8% (95·1-97·9) at 5 years, 92·7% (90·4-94·4) at 10 years, and 82·4% (78·5-85·6) at 15 years. We did not collect long-term data on adverse events.The long-term results of this trial confirmed the higher rate of IBTR in the ELIOT group than in the WBI group, without any differences in overall survival. ELIOT should be offered to selected patients at low-risk of IBTR.Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, Umberto Veronesi Foundation, American Italian Cancer Foundation, The Lombardy Region, and Italian Ministry of Health.

Objective: During 2020, medical clinical activities were dramatically modified by the coronavirus disease 2019 (COVID-19) emergency. We aim to evaluate the impact of COVID-19 on radiotherapy (RT) practice in a hub cancer center. Methods: Retrospective data collection of patients with suspected COVID-19 infection, identified by pathognomonic symptoms feedback at triage realized at the entrance to RT division. Inclusion criteria were diagnosis of oncologic disease, COVID-19–related symptoms, and signed written informed consent. Results: Between 1 March and 30 June 2020, 1,006 patients accessed our RT division for RT simulation or treatment. Forty-four patients matched inclusion criteria (4.4% of all patients): 29 women and 15 men. Seventeen patients had metastatic disease. Twenty-one patients reported fever, 6 presented dyspnea, 4 complained of ageusia and anosmia, and 3 developed conjunctivitis. Thirty-six patients underwent nasal swab, with 7 positive results. From our cohort, 4 cases of pneumonia were diagnosed with computed tomography scan imaging: 3 were related to COVID-19 infection, while the fourth was evaluated as an RT adverse event. From the entire series, 4 patients died: 3 during hospitalization in intensive care unit of complications of COVID-19 and 1 of other causes neither COVID-19 nor cancer-related. Conclusions: Cancer hub allows for safe RT practice continuation while minimizing the spread of contagion in this frail patient population. A challenge for the future will be to understand pandemic consequences in cancer natural history and manage its clinical impact.

Introduction: During the COVID-19 pandemic, Lombardy (Northern Italy) Regional Health Council created hubs for cancer care, meant to be SARS-CoV-2-free pathways for cancer patients. The workflow of breast cancer (BC) radiotherapy (RT) in one of the hubs is presented here. Methods: Candidates to adjuvant RT during the pandemic peak of March-April 2020 were compared to those treated in the same period of 2019, and patient volume, deferral rate, and type of RT were analyzed. Statistics were calculated with χ2 or Fisher exact tests for categorical variables, and the Wilcoxon rank test for continuous variables. Results: In March-April 2020 the BC patient volume increased by 28% compared to the same period in 2019 (scheduled patients: 175 vs. 137) and amid travel restrictions it was kept high (treated patients: 136 vs. 133), mainly due to an influx from across Lombardy. RT schemes basically did not change, being already centered on hypofractionation. The increase of median time (67 vs. 74.5 days in 2019 and 2020, respectively) to the commencement of RT for low-risk patients was clinically negligible yet statistically significant (p = 0.03), and in line with the pertinent recommendations. No significant difference was found in the time interval between treatments and RT for high-risk patients. Concomitant chemoradiotherapy was avoided throughout the pandemic peak. Twenty-one women (13.6%) delayed either computed tomography simulation or RT commencement mainly because of COVID-19-related concerns and mobility restrictions. Conclusion: The workload for BC was high during the pandemic peak. Hubs allowed the continuation of oncologic treatments, while mitigating the strain on frontline COVID-19 hospitals.

Perineal seeding of tumor cells from prostate cancer (PCa) is very rare, and no standard treatment exists for this atypical presentation with no evidence of distant metastases. Local excision or external beam radiotherapy are used as local salvage treatments for such perineal masses, including those occurring after biopsy, surgery, or interstitial brachytherapy. We report on a patient who presented no evidence of disease and no late urinary or gastrointestinal toxicities at 58 months after receiving high-dose-rate brachytherapy (HDR-BT) for perineal recurrence of PCa after radical prostatectomy and salvage external beam radiotherapy. To the best of our knowledge, this is the first case treated with HDR-BT in this scenario.

BackgroundStereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer.Primary ObjectiveThe MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment.Study HypothesisRadiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response.Trial DesignAll patients accrued will be treated with a radiotherapy dose in the range of 30–50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months.Major Inclusion/Exclusion CriteriaThe study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal.Primary EndpointThe primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis.Sample SizeApproximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions).Estimated Dates for Completing Accrual and Presenting ResultsFifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023.Trial RegistrationNCT04593381.

Introduction/Background* Vulvar cancer (VC) is a rare gynaecologic malignancy. The study aims to evaluate in a retrospective, multicentred, real-world dataset of patients affected by VC efficacy and safety of adjuvant (chemo)radiotherapy (aRT), focusing especially to the treatment prescription among participant centers joining the Observational itaLian stuDy on vuLvar cAncer adjuvant raDiotherapY (OLDLADY) project endorsed by the GYN study group of the AIRO (Italian Association of Radiotherapy and Clinical Oncology). Methodology Patients affected by VC and treated by eRT from January 2010 to December 2018 in Nine Italian radiotherapy centers were retrospectively included and clinical data were collected, analysing tumour staging, treatment prescription, clinical and toxicity outcomes. Result(s)* The multicentred retrospective cohort was composed by 181 patients (patient populations shown in table 1), with a median age of 71.5 years (range 17-90). A considerable heterogeneity was found in the treatment prescription, radiotherapy doses and concomitant chemotherapy schedules. The most relevant acute toxicity revealed for the patient cohort was skin toxicity (22.1%); instead, the rate of severe chronic lymphoedema was 1.1%. After a median follow-up of 30 months (range 1-185), the 2-year actuarial local control rate (LC), the 2-year disease free survival rate (DFS) and the overall survival rate (OS) were 57.2%, 49.4%, and 55.1%, respectively. Kaplan-Meier curves were computed and reported in figure 1. Conclusion* A diverse spectrum of radiotherapy options to exclusively treat patients affected by VC was reported. To achieve higher treatment standardisation, in terms of prescribed doses and volumes, this study suggest further cooperative prospective studies.

Introduction/Background* Vulvar cancer (VC) is a rare gynaecologic cancer with poor outcomes in locally advanced disease. This study aims to evaluate in a retrospective, multicentred, real-world dataset of patients affected by VC efficacy and safety of exclusive (chemo)radiotherapy (eRT), focusing especially to the treatment prescription among participant centers joining the Observational itaLian stuDy on vuLvar cAncer radical raDiotherapY (OLDLADY) project endorsed by the GYN study group of the AIRO (Italian Association of Radiotherapy and Clinical Oncology). Methodology Patients affected by VC and treated by eRT from January 2010 to December 2018 in Seven Italian radiotherapy centers were retrospectively included and clinical data were collected, analysing tumour staging, treatment prescription, clinical and toxicity outcomes. Result(s)* The multicentred retrospective cohort was composed by 90 patients (patient populations shown in table 1), with a median age of 76 years (range 32-92). A considerable heterogeneity was found in the treatment prescription, radiotherapy doses and concomitant chemotherapy schedules. The most relevant acute toxicity revealed for the patient cohort was skin toxicity (26%); instead, the rate of severe skin fibrosis was 4.4%. After a median follow-up of 10 months (range 1-199), the 2-year actuarial local control rate (LC), the 2-year disease free survival rate (DFS) and the overall survival rate (OS) were 42.2%, 40%, and 36.7%, respectively. Kaplan-Meier curves were computed and reported in figure 1. Conclusion* A diverse spectrum of radiotherapy options to exclusively treat patients affected by VC was reported. Clinical outcomes are still confirmed to be poor. The results suggest the clinical evaluation of the impact of treatment standardisation, in terms of doses and volumes, in a further perspective study.

Soil transmitted helminthiasis (STHs) are endemic in Nepal but since the country territory is extremely heterogeneous, a multidisciplinary assessment is required to evaluate the risk of infection in different areas. Prevalence data were retrieved with systematic literature search and geographical coordinates were assigned to each survey site. Spatial stratification was then implemented considering land use and ecological parameters. STH transmission boundaries were tested after reference criteria and elevation was evaluated as additional predictor: the elevation threshold of 3057 m above sea level is demarking the STH transmission limit. Areas above this threshold are safe, but since lodging in at-risk sites is a compulsory stopover for international travelers, STH risk exposure should be considered for every travel to the country.

Purpose To analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution. Material and methods Between March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) - European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria. Results Two patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy. Conclusions Our study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

Background: Children with Down Syndrome have poorer functional and sensory skills compared to children with typical development. Virtual reality training could help improve these skills. Moreover, transcranial direct current stimulation has achieved promising results in terms of enhancing the effects of physical and sensory therapy by modulating cortical excitability. Methods/design The sample will be defined after conducting a pilot study with the same methodology as that to be used in the main study. The study will involve individuals with Down Syndrome with a cognitive age of six to 12 years according to the Wechsler Abbreviated Intelligence Scale. Will be randomly allocated into two groups: Group 1 AtDCS combined with a virtual reality game and a manual motor task. Group 2 sham AtDCS with a virtual reality game and a manual motor task. The training protocol will involve 10 sessions of AtDCS during memory and motor task games. Three 20-minute sessions will be held per week for a total of 10 sessions. Evaluations will be performed on three different occasions: pre-intervention, post-intervention (after session 10) and follow-up (one month after the proposed training). The evaluations will consist of an analysis of electroencephalographic signals, electromyographic signals of the biceps and triceps brachii and the three-dimensional reconstruction of the reaching movement. The results will be analyzed statistically, with the significance level set at 5% (p ≤ 0.05). Discussion: The optimization of the results obtained is believed to be related to interactive training with a wide range of activities and scenarios involving multiple sensory channels and the creation of exercises, the intensity of which can be adjusted to the needs of individuals. Therefore, the proposed study aims to complement the literature with further information and different variables to provide the scientific community with clinical data on this combination of interventions. Trial Registration: REBEC protocol number RBR-43pk59 registered on 2019/03/27 and Human Ethics Committee number 3.608.521 approved on 2019/09/30.

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Over 5200 new cases of this tumor are diagnosed yearly in Italy, resulting in more than 3600 deaths. In terms of molecular biology, five different ovarian cancer subtypes should be distinguished. Method: This article summarizes the evidence-based guidelines that the Italian Medical Oncology Association (AIOM) has developed with a multidisciplinary panel of experts, including pathologists, gynecologic oncologists, medical oncologists, and radiotherapists, with the support of methodologists, to help clinicians involved in the management of patients with ovarian cancer in their daily clinical practice. Results: The most relevant randomized clinical trials regarding surgery, chemotherapy, and molecularly targeted agents (bevacizumab and PARP inhibitors) in early, advanced, and recurrent disease have been critically analyzed. The levels of evidence and strength of recommendation have been reported for any issue. Conclusion: Women with a clinical suspicion of ovarian cancer should be centralized in referral centers. The BRCA test should be requested for all women with nonmucinous and nonborderline tumors, regardless of age and family history. BRCA testing could be preferentially performed on neoplastic tissue. In the presence of a positive tumor test, a genetic test should always be performed on a blood sample to differentiate between germline mutations, which require counseling and genetic testing of family members, and somatic mutations.

This review analyzes the experience and trends in external beam radiotherapy for delivering a boost in locally advanced cervical cancer, identifying whether radiation therapy modalities impact clinical outcomes with the ultimate aim of evaluating alternatives to brachytherapy. Three independent Italian radiation oncologists conducted a literature search on different external beam radiotherapy boost modalities in locally advanced cervical cancer. The search yielded 30 studies. Eight dosimetric studies, evaluating target coverage and dose to organs at risk, and nine clinical investigations, reporting clinical outcomes, were analyzed. Dosimetric studies comparing external beam radiotherapy boost with brachytherapy produced divergent results, while clinical studies were limited by their retrospective nature, heterogeneous doses, radiation schedules, volumes and techniques, diverse follow-up times, and small cohorts of patients. Evidence emerged that high-tech external beam radiotherapy seemed no better than image-guided brachytherapy for delivering a boost in locally advanced cervical cancer. Prospective clinical studies comparing high-tech external beam radiotherapy and image-guided brachytherapy should be encouraged.

Background Management of head and neck cancers (HNC) in radiation oncology in the coronavirus disease 2019 (COVID‐19) era is challenging. Aim of our work is to report organization strategies at a radiation therapy (RT) department in the first European area experiencing the COVID‐19 pandemic. Methods We focused on (a) dedicated procedures for HNC, (b) RT scheduling, and (c) health care professionals' protection applied during the COVID‐19 breakdown (from March 1, 2020 to April 30, 2020). Results Applied procedures are reported and discussed. Forty‐three patients were treated. Image‐guided, intensity modulated RT was performed in all cases. Median overall treatment time was 50 (interquartile range: 47‐54.25) days. RT was interrupted/delayed in seven patients (16%) for suspected COVID‐19 infection. Two health professionals managing HNC patients were proven as COVID‐19 positive. Conclusion Adequate and well‐timed organization allowed for the optimization of HNC patients balancing at the best of our possibilities patients' care and personnel's safety.

Soft tissue sarcomas (STS) are uncommon, heterogeneous malignant tumors of mesodermal origin. Other than conservative surgery (CS), neoadjuvant or adjuvant radiotherapy (RT) is recommended when the risk of local recurrence is high. The aim of this study is to present our Institutional experience in adjuvant RT for treatment of STS of extremities and trunk (with either brachytherapy (BRT), external beam RT (EBRT), or both) and to provide an insight of toxicity and oncological outcomes for each RT modality. According to the RT treatment approach, patients were divided into three categories: 1) BRT alone; 2) EBRT alone; 3) combined BRT+EBRT. Differences among the three groups were assessed by the Chi-squared test. Patients' follow-up was performed every 6 months for the first two years after the end of RT and then once a year. Data from 90 patients were analyzed. The overall 3-year distant relapse-free survival (DRFS), progression-free survival (PFS), and overall survival (OS) were 84%, 80%, and 97%, respectively. Acute erythema was the most frequent side effect, although severe grade 3 toxicity was present in 5 patients. Chronic toxicity of any grade was reported in 14 patients. The incidence of chronic toxicity did not show any association with treatment modality. Multivariate analysis suggested a significant correlation between acute toxicity and tumor size, RT modality, and RT dose. In conclusion, good local control and toxicity profile were observed, despite negative patients' selection at baseline. Further investigation on wider series is warranted in order to define the optimal combination with systemic therapy.

Purpose To evaluate clinical results of catheter-based interstitial high-dose-rate (HDR) brachytherapy (BT) as adjuvant treatment in previously irradiated recurrent breast cancer. Material and methods Between January 2011 and September 2015, 31 consecutive patients with histologically confirmed recurrent breast cancer after conservative surgery and conventional whole breast radiotherapy, were retreated with a second conservative surgical resection and reirradiated with adjuvant interstitial HDR-BT. None of the brachytherapy implant was performed during the quadrantectomy procedure. A dose of 34 Gy in 10 fractions, 2 fractions per day, with a minimal interval of 6 hours was delivered. Results At the time of the implant, the median age of patients was 59.7 years (range, 39.3-74.9 years). The median time from first treatment until BT for local recurrence was 11.9 years (range, 2.5-27.8 years). The median interval between salvage surgery and BT was 3.6 months (range, 1-8.2 months). No acute epidermitis or soft tissue side effects higher than grade 2 were recorded, with good cosmetic results in all patients. Most of the patients presented grade 1-2 late side effects. Only one patient developed grade 3 liponecrosis. After a median follow-up of 73.7 months (range, 28.8-102.4 months), the overall survival and cancer specific survival were 87.1% and 90.3%, respectively; 5-year local control and 5-year progression-free survival rate were 90.3% and 83.9%, respectively. Conclusions Our preliminary analysis showed that HDR-BT is a feasible treatment for partial breast reirradiation offering very low complications rate and fast procedure. Higher patients' cohort is warranted in order to define the role of this treatment modality in the breast conservative management of local recurrence.

Background: Recent studies have reported improvement of outcomes (progression-free survival, overall survival, and prolongation of androgen deprivation treatment-free survival) with stereotactic body radiotherapy (SBRT) in non-small cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT-01) was to define activity and safety of SBRT in a very large, real-world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR-OC). Materials and Methods: The endpoints of the study were the rate of complete response (CR) to SBRT and the 24-month actuarial local control (LC) rate on “per-lesion” basis. The secondary endpoints were acute and late toxicities and the 24-month actuarial late toxicity-free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni- and multivariate analysis of factors predicting clinical CR and actuarial outcomes. Results: CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm3, lymph node disease, and biologically effective dose α/β10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow-up of 22 months (range, 3–120), the 24-month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24-month late toxicity-free survival rate was 95.1%. Conclusions: This study confirms the activity and safety of SBRT in patients with MPR-OC and identifies clinical and treatment parameters able to predict CR and LC rate. Implications for Practice: This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR-OC). Patient age 70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR-OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.

ObjectiveStandard treatment in locally-advanced cervical cancer is external beam radiotherapy concomitant with platinum-based chemotherapy, followed by brachytherapy. The goal of our study was to determine whether an intensity modulated radiation therapy (IMRT) boost is feasible in patients unfit for brachytherapy.MethodsWe retrospectively analyzed data of 25 patients unfit for brachytherapy with median age 55 years (range, 30–82) with locally-advanced/metastatic cervical cancer who underwent external beam radiotherapy to pelvis ±para-aortic lymph nodes and sequential IMRT boost between July 2014 and December 2017. Total dose of 45–50.4 Gy in 25–28 fractions (1.8 Gy/fraction) was administered to the cervix, uterus, parametria, ovaries, vaginal tissues (based on vaginal extension), involved lymph nodes, or relevant draining lymph-nodal groups. Para-aortic nodes were included if involved at radiological staging or if common iliac nodes were positive. The IMRT boost included all residual tumor after external beam radiotherapy identified on MRI. The Kaplan–Meier method was used to calculate 2 years' overall survival, 2 years' progression-free survival, and 2 years' local control. Overall survival- and progression-free survival were calculated considering the starting of radiotherapy or neo-adjuvant chemotherapy if prescribed, while local control was calculated from the end of radiotherapy.ResultsMedian radiation dose to pelvis ±para-aortic lymph nodes was 50.4 Gy (45–50.4), boost treatment was homogeneously performed to a total dose of 25 Gy in five fractions every other day.After a median follow-up of 26 months (range, 4–77), tumor persistence at cervix at 6 months from the end of radiotherapy or local recurrence occurred in five women (20%), eight (32%) experienced a further distant progression (two of them had also tumor persistence). Two-year local control and overall survival rates for all stages were 78% and 67%, respectively. According to Common Terminology Criteria for Adverse Events v.4 scoring criteria, 10 patients experienced gastrointestinal and/or genitourinary grade G1-2 acute toxicity. G2 rectal late toxicity requiring laser-coagulation was registered in two patients, there were no gastrointestinal and/or genitourinary acute or late toxicities≥G3.ConclusionThe combination of external beam radiotherapy and brachytherapy remains the standard of care, however our preliminary data show the feasibility of IMRT boost in terms of toxicity with promising results in terms of local control and overall survival.

Purpose To evaluate stereotactic body radiation therapy (SBRT) for metachronous oligometastatic ovarian cancer patients in terms of local control, delay of systemic treatment, survival outcomes, and toxicity. Methods and Materials Retrospective data collection from a single institution was performed. The inclusion criteria were as follows: (1) oligorecurrent or oligoprogressive disease in ovarian cancer patients during or after systemic therapy; (2) surgery or other local therapies not feasible; and (3) relative contraindication to systemic therapy for reasons such as unavailability of additional chemotherapy lines or refusal of the patient. Tumor response and toxicity were evaluated using the Response Evaluation Criteria in Solid Tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. A new systemic therapy regimen was started after an SBRT treatment course in 57 of 109 cases (52.3%). Local progression–free survival, progression-free survival, and overall survival were calculated via the Kaplan-Meier method. The systemic treatment–free interval was calculated in cases without concomitant systemic therapy. Results Between May 2012 and December 2016, 82 patients (156 lesions) underwent SBRT with a median dose of 24 Gy in 3 fractions. The median follow-up period was 17.4 months. Patients received a median of 3 systemic therapy regimens prior to SBRT. Concomitant systemic therapy was performed for 29 lesions (18.6%). Among 152 evaluable lesions, a complete radiologic response, partial response, stabilization, and progressive disease were observed in 91 (60%), 26 (17%), 24 (16%), and 11 (7%), respectively. No grade 3 or 4 acute or late toxicities were observed. The median systemic treatment–free interval after SBRT was 7.4 months, and 1 of 3 patients was disease free at 1 year after SBRT. The actuarial 2-year local progression–free survival, progression-free survival, and overall survival rates were 68%, 18%, and 71%, respectively. The pattern of failure was predominantly out of field. Conclusions SBRT for oligometastatic ovarian cancer showed good local control and a good toxicity profile. It might be an appealing alternative to other invasive local therapies to delay systemic therapy in the case of chemorefractory disease or intolerance to systemic agents.

Purpose To evaluate inter-fraction tumor localization errors (TE) in the RapidArc® treatment of pelvic cancers based on CBCT. Appropriate CTV-to PTV margins in a non-IGRT scenario have been proposed. Methods Data of 928 patients with prostate, gynecological, and rectum/anal canal cancers were retrospectively analyzed to determine systematic and random localization errors. Two protocols were used: daily online IGRT (d-IGRT) and weekly IGRT. The latter consisted in acquiring a CBCT for the first 3 fractions and subsequently once a week. TE for patients who underwent d-IGRT protocol were calculated using either all CBCTs or the first 3. Results The systematic (and random) TE in the AP, LL, and SI direction were: for prostate bed 2.7(3.2), 2.3(2.8) and 1.9(2.2) mm; for prostate 4.2(3.1), 2.9(2.8) and 2.3(2.2) mm; for gynecological 3.0(3.6), 2.4(2.7) and 2.3(2.5) mm; for rectum 2.8(2.8), 2.4(2.8) and 2.3(2.5) mm; for anal canal 3.1(3.3), 2.1(2.5) and 2.2(2.7) mm. CTV-to-PTV margins determined from all CBCTs were 14 mm in the AP, 10 mm in the LL and 9–9.5 mm in the SI directions for the prostate and the gynecological groups and 9.5–10.5 mm in AP, 9 mm in LL and 8–10 mm in the SI direction for the prostate bed and the rectum/anal canal groups. If assessed on the basis of the first 3 CBCTs, the calculated CTV-to-PTV margins were slightly larger. Conclusions without IGRT, large CTV-to-PTV margins up to 15 mm are required to account for inter-fraction tumor localization errors. Daily IGRT should be used for all hypo-fractionated treatments to reduce margins and avoid increased toxicity to critical organs.

AIM To ascertain whether cholestasis affects the expression of two CYP3A isoforms (CYP3A1 and CYP3A2) and of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). METHODS Cholestasis was induced by bile duct ligation in 16 male Wistar rats; whereas 8 sham-operated rats were used as controls. Severity of cholestasis was assessed on histological examination of liver sections, and serum concentrations of albumin, AST, ALT, GGT, ALPK and bilirubin. Gene and protein expressions of PXR, CAR, CYP3A1 and CYP3A2 were assessed by means of qRT-PCR and Western blot, respectively. Alterations in CYP3A activity were measured by calculating the kinetic parameters of 4-OH and 1’-OH-midazolam hydroxylation, marker reactions for CYP3A enzymes. RESULTS The mRNA and protein expression of CYP3A1 increased significantly in mild cholestasis (P < 0.01). At variance, mRNA and protein expression of CYP3A2 didn’t change in mild cholestasis, whereas the expression and activity of both CYP3A1 and CYP3A2 decreased dramatically when cholestasis became severe. Consistently with these observations, the nuclear expression of both PXR and CAR, which was measured because they both translocate into the cell nucleus after their activation, virtually disappeared in the late stage of cholestatic injury, after an initial increase. These results indicate that early- and late-stage cholestasis affects CYP3A-mediated drug metabolism differently, probably as consequence of the different activation of PXR and CAR. CONCLUSION Early- and late-stage cholestasis affects CYP3A-mediated drug metabolism differently. PXR and CAR might be targeted therapeutically to promote CYP3A-mediated liver detoxification.

To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC).From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control.Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control.Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control.

Purpose Mathematical modeling is a powerful and flexible method to investigate complex phenomena. It discloses the possibility of reproducing expensive as well as invasive experiments in a safe environment with limited costs. This makes it suitable to mimic tumor evolution and response to radiotherapy although the reliability of the results remains an issue. Complexity reduction is therefore a critical aspect in order to be able to compare model outcomes to clinical data. Among the factors affecting treatment efficacy, tumor oxygenation is known to play a key role in radiotherapy response. In this work, we aim at relating the oxygenation dynamics, predicted by a macroscale model trained on tumor volumetric data of uterine cervical cancer patients, to vascularization and blood flux indices assessed on Ultrasound Doppler images. Methods We propose a macroscale model of tumor evolution based on three dynamics, namely active portion, necrotic portion, and oxygenation. The model parameters were assessed on the volume size of seven cervical cancer patients administered with 28 fractions of intensity modulated radiation therapy (IMRT) (1.8 Gy/fraction). For each patient, five Doppler ultrasound tests were acquired before, during, and after the treatment. The lesion was manually contoured by an expert physician using 4D View® (General Electric Company - Fairfield, Connecticut, United States), which automatically provided the overall tumor volume size along with three vascularization and/or blood flow indices. Volume data only were fed to the model for training purpose, while the predicted oxygenation was compared a posteriori to the measured Doppler indices. Results The model was able to fit the tumor volume evolution within 8% error (range: 3-8%). A strong correlation between the intrapatient longitudinal indices from Doppler measurements and oxygen predicted by the model (about 90% or above) was found in three cases. Two patients showed an average correlation value (50-70%) and the remaining two presented poor correlations. The latter patients were the ones featuring the smallest tumor reduction throughout the treatment, typical of hypoxic conditions. Moreover, the average oxygenation value predicted by the model was close to the average vascularization-flow index (average difference: 7%). Conclusions The results suggest that the modeled relation between tumor evolution and oxygen dynamics was reasonable enough to provide realistic oxygenation curves in five cases (correlation greater than 50%) out of seven. In case of nonresponsive tumors, the model failed in predicting the oxygenation trend while succeeded in reproducing the average oxygenation value according to the mean vascularization-flow index. Despite the need for deeper investigations, the outcomes of the present work support the hypothesis that a simple macroscale model of tumor response to radiotherapy is able to predict the tumor oxygenation. The possibility of an objective and quantitative validation on imaging data discloses the possibility to translate them as decision support tools in clinical practice and to move a step forward in the treatment personalization.

Introduction/Background Re-irradiation of local recurrences of gynaecological cancer pose a difficult challenge to Oncologist. For their biological and physical characteristics particle therapy (PT) could be an interesting treatment. Methodology The aim of the study was to evaluate the feasibility and early clinical outcome in patients (pts) with gynaecological pelvic sidewall recurrence (PSWr). Between May 2014 to December 2018, 10 patients (median age 56) with PSWr within or at the edge of the previously irradiated field were treated using PT. They had recurrence of: cervical (5), endometrial (3), uterine (1) and ovarian (1) cancer. Previous radiotherapy prescription dose ranged from 46 to 59.4 Gy and 5 patients underwent brachytherapy (range: 7–28 Gy).Two patients, with marginal lymph node recurrence, were irradiated with protons with up to a total dose of 25 GyRBE and 51 GyRBE, respectively. The remaining women underwent carbon-ion radiotherapy (median total dose 50.4 GyRBE; range: 36–57) administered in a median number of 12 fractions. Six patients with PSWr received surgical spacer placement by open surgery to keep intestinal tracts apart from the tumour as the distance between tumour and nearest intestinal tracts was not sufficient. No pts received concurrent chemotherapy. Preliminary local control (LC) and toxicity profile (according to CTCAE V4.03 scale) were evaluated. Results All patients completed the planned treatment and no acute toxicities G>2 were observed. For the evaluable patients, 1 case of intermediate G≥3 toxicity was reported in women received sequential Bevacizumab (BV). For pts with a follow-up ≥3 months, median LC was 7 months (range: 3–14), median MFS was 4.5 months (range: 3–14,5) and median OS was 7 months (range: 3–14,5). 1 pt experienced local progression and 4 pts died for systemic progression. Data are still ongoing. Conclusion For pts with PSWr a PT approach seems to be feasible and our results showed a promising short-term outcome and limited radiation-related side effects. Longer follow-up and large patient accrual are required. Disclosure Nothing to disclose.

Introduction/Background We analyzed early clinical outcomes of carbon ion radiotherapy (CIRT) in the first patients with gynecological malignant mucosal melanoma(g-MMM) treated at CNAO. Methodology Between 2016 and 2018, 9 patients(pts) with g-MMM were treated with CIRT after surgery or in exclusive settings (table 1). They had 7 vaginal(VaM),1 cervical(CM) and 1 vulvar(VuM)MMM. One pt with VaM had been previously irradiated with photons;8 pts are considered inoperable and 1 pt underwent adjuvant CIRT on the small pelvic space after radical surgery without lymphadenectomy. Two pts underwent neoadjuvant and sequential anti-PD-1 immunotherapy. Because of the large volume of macroscopic disease,CM and VuM patients were irradiated with up to a total dose of 28 GyRBE(3 fractions) and 68.8 GyRBE(16 fractions), respectively, to the Clinical Target Volume (CTV) defined as the Gross Tumor Volume (GTV)+uterine cervix and corpus for the CM and GTV+vulva for the VuM. For inoperable VaM, small pelvic space including GTV was irradiated with up to a total dose of 38.7-43 GyRBE followed by a GTV boost of up to a total dose of 68.8 GyRBE in 16 fractions (figure 1). All patients were treated with synchrotron-based scanning carbon ion beams. Early clinical and toxicity profile(according to CTCAE V4.03) were evaluated. Results Treatment was well tolerated and no interruption was needed. For the evaluable pts, toxicity profile was favorable and no G≥2 acute/late toxicities were observed. Overall,for pts with a follow-up≥3 months,median LC ranged from 3 to 13 months( Conclusion Because of the high rate of distant metastasis and unsatisfactory survival benefit, a more conservative treatment approach, instead of extensive surgery, may be warranted. We think that CIRT may serve as a definitive treatment choice for patients with g-MMM. Disclosure Nothing to disclose.

Objectives The aim of this retrospective, multicenter study (MITO RT-01) was to define activity and safety of Stereotactic Body Radiotherapy (SBRT) in a very large, real life dataset of metastatic/persistent/recurrent ovarian cancer (MPR-OC) patients. Clinical and SBRT parameters have been analyzed in order to identify predictors of outcome. Methods The endpoints of the study were the rate of complete response (CR) to SBRT, and the 24-month actuarial local control (LC) rate on “per lesion” basis. The secondary end-points were acute and late toxicities, and the 24-month actuarial late toxicity free survival. Toxicity was evaluated by RTOG/EORTC and CTC-AE scales, according to center policy. Logistic and Cox regression were used for the uni- and multivariate analysis of factors predicting clinical CR and actuarial outcomes. Results CR, PR and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions. Patient age 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow-up of 22 months (range: 3–120), the 24-month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients. The 24- month late toxicity free survival rate was 95.1%. Conclusions This study confirms the activity and safety of SBRT in MPR-OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.

Background The role of radiotherapy and brachytherapy in the management of locally advanced cervical and endometrial cancer is well established. However, in some cases, intracavitary brachytherapy (ICBRT) is not recommended or cannot be carried out. We aimed to investigate whether external-beam irradiation delivered by means of intensity-modulated radiation therapy (IMRT) might replace ICBRT in gynaecological cancer when the standard ICBRT boost delivering cannot be administered for technical or clinical reasons. Materials and methods Fifteen already delivered treatments for gynaecological cancer patients were analysed. The treatments were performed through 3-dimensional conformal radiotherapy (3D-CRT) to the whole-pelvis up to the dose of 45-50.4 Gy followed by a boost dose administered with ICBRT in high-dose-rate or pulsed-dose-rate modality. For each patient, IMRT plans were elaborated to mimic the ICBRT. We analysed the ICBRT boost versus IMRT boost in terms of dosimetric and radiobiological aspects. Results Mean conformity index value calculated on boost volume was 0.73 for ICBRT and 0.97 for IMRT. Mean conformation number was 0.24 for ICBRT boost and 0.78 for IMRT boost. Mean normal tissue complication probability (NTCP) values for 3D-CRT plus ICBRT and for IMRT (pelvis plus boost) were, respectively, 28% and 5% for rectum; 1.5% and 0.1% for urinary bladder and 8.9% and 6.1% for bowel. Conclusions Our findings suggest that IMRT may represent a viable alternative in delivering the boost in patients diagnosed with gynaecological cancer not amenable to ICBRT.

To evaluate whether perfusion and diffusion parameters from staging MR in ovarian cancer (OC) patients may predict the presence of residual tumor at surgery and the progression-free survival (PFS) in 12 months. Patients who are from a single institution, candidate for OC to cytoreductive surgery and undergoing MR for staging purposes were included in this study. Inclusion criteria were: preoperative MR including diffusion-weighted imaging (DWI) and perfusion dynamic contrast-enhanced (DCE) sequence; cytoreductive surgery performed within a month from MR; and minimum follow-up of 12 months. Patients’ characteristics including the presence of residual tumor at surgery (R0 or R1) and relapse within 12 months from surgery were recorded. DWI parameters included apparent diffusion coefficient (ADC) of the largest ovarian mass (O-ADC) and normalized ovarian ADC as a ratio between ovarian ADC and muscle ADC (M-ADC). DCE quantitative parameters included were descriptors of tumor vascular properties such as forward and backward transfer constants, plasma volume and volume of extracellular space. Statistical analysis was performed, and p values

The authors' aim was to investigate the effects of continuous transcranial direct current stimulation (tDCS) combined with virtual reality training on static and functional balance in children with cerebral palsy (CP). Twenty children with CP (6 girls and 14 boys; M age = 7 years 6 months ± 2 years) were randomly allocated to two groups. The experimental group received active tDCS and the control group received sham stimulation during the 10 sessions of virtual reality mobility training protocols. The children were evaluated on 3 occasions (preintervention, postintervention, and 1-month follow-up). Static balance was evaluated using a force plate under 4 conditions: feet on force plate with (a) eyes open and (b) with eyes closed, and feet on foam mat with (c) eyes open and (d) with eyes closed. Functional balance was evaluated using the Pediatric Balance Scale and the Timed Up and Go Test. The analyses demonstrated statistically significant postintervention and follow-up effects favoring the experimental group over the control group with regard to the Pediatric Balance Scale, Timed Up and Go Test, and area of oscillation of the center of pressure when standing on the force plate with eyes open. The present findings suggest that tDCS can potentiate the effects of virtual reality training on static and functional balance among children with CP.

To report in-vivo dosimetry in the infraclavicular region, a potential site of a cardiac implantable electronic device (CIED) and to evaluate the absorbed dose from intraoperative radiotherapy with electrons (ELIOT). 27 non-cardiopathic breast cancer (BC) patients without CIED received quadrantectomy and ELIOT as partial breast irradiation. Before delivering ELIOT, two catheters, each containing eight thermoluminescent dosimeters (TLDs), were positioned in the infraclavicular region. TLDs internal catheter was located deep in the tumor bed while the external catheter was placed on patient’s skin. Data were available for 24/27 patients. The absorbed doses were referred to the dose of 21 Gy. Values measured by the external catheter were low, although statistically significant higher doses were found close to the applicator (mean values 0.26–0.49 Gy). External TLD doses in proximity of the applicator were lower than those detected by their internal counterparts. Values measured by the internal catheter TLDs varied according to the distance from the applicator while no correlation with tumor site and beam energy was found. The distance from the applicator to deliver

Background: The aim of this study was to confirm our preliminary results with in vivo dosimetry in non-pregnant breast cancer patients receiving electron beam intraoperative radiotherapy (ELIOT) and to report on the first treatment in a pregnant woman. Patients and Methods: Following our previous experience, 5 non-pregnant patients receiving ELIOT to the tumor bed after breast-conserving surgery (BCS) were studied with thermoluminescent dosimeters positioned in the subdiaphragmatic region, within the uterus, and in the ovarian region. In December 2011, the first pregnant breast cancer patient underwent BCS and ELIOT (21 Gy at 90% isodose) during the 15th week of gestation. Results: The mean dose to the subdiaphragmatic external region in the 5 non-pregnant patients was 5.57 mGy, while pelvic measurements were below 1 mGy. The actual dosimetry of the pregnant patient showed a mean subdiaphragmatic dose of 4.34 mGy, a mean suprapubic dose of 1.64 mGy, and mean ovarian doses of 1.48 mGy (right-sided) and 1.44 mGy (left-sided). The expected dose to the fetus was estimated as 0.84 mGy (0.004% of the prescribed dose). Conclusion: ELIOT as an anticipated boost to the breast could be considered in pregnant women in the early second trimester, postponing whole-breast irradiation after delivery.

Aim: We report on acute toxicity, which is the secondary endpoint of a phase II clinical trial specifically addressed to assess the chronic toxicity of a hypofractionated scheme including a simultaneous integrated boost, with intensity modulated radiotherapy. Materials and methods: From 2/2012 to 12/2013 194 patients with early breast cancer entered a phase II study on hypofractionated radiotherapy including a boost dose to the tumor bed. All patients were operated on conservatively. The whole breast and the tumor bed are planned to receive a dose of 45 Gy and 50 Gy, respectively, in 20 fractions, over 4 weeks. Treatment plans are generated using the TomoDirect modality,which is available on Tomotherapy Hi-Art System (Madison,WI). Acute toxicity was evaluated according to the RTOG acute toxicity scale, up to 6 months after the treatment. Afterwards, chronic toxicity is evaluated using LENT/SOMA scale. Results: 95% of the volume of the breast and boost PTVs received 99% and 100% of the planned dose, as median values, respectively and 0.1% (median value) of the entire breast volume received 100% of the boost dose. The median maximum dose to the breast and to the boost PTVs was 113% and 103.3 %, respectively. At the end of treatment, the acute toxicity, was distributed as follows. As far as erythema was concerned, at the end of treatment, 58% of the patients experienced grade 1 erythema, which dropped to 23% one month later. Grade 2 erythema affected 37% of the cases, and after one month, it decreased to 2%.Only 1 patient (0.5%) complained of Grade 3 erythema at the end of the treatment, which rapidly disappeared afterwards. With regard to breast oedema, at the end of treatment grade 1 was observed in 16% of the cases, for whom it tended to remain stable after one month, while grade 2 oedema was noted in 4% of the cases, decreasing to 1.5% on the first month- follow-up visit. Regarding desquamation, dry desquamation ( grade 1) was observed in less than 10% of cases at the end of treatment, but it tended to increase to 17% one month later. Patchy moist desquamation (grade 2) was present in 1.9% of the patients at the end of radiotherapy, and in 1% of them, one month afterwards. Confluent desquamation (grade 3) was noted only in 1 patient (0.5%), who was receiving concomitant chemotherapy with cyclophospamide, methotrexate and fluoruracil: it was still present 1 month after the radiotherapy completion, as the patient continued to be on chemotherapy. No significantly different side effects were observed between the whole breast and the boost area. No patients experienced any lung and cardiac symptoms. Conclusion: The clinical results of this SIB hypofractionated scheme showed low acute toxicity. In spite of the high dose per fraction, with the tumor bed receiving an even higher dose /per fraction, acute toxicity was within the limit acknowledged by literature for conventional fractionation. This non-rotational treatment option allows us to deliver treatment with a traditional tangent-like dose, without spreading low doses to the adjacent structures. Chronic toxicity will be assessed after 2 years. Therefore, a longer follow-up is needed to assess the effective tolerance to the SIB schedule. Citation Format: Maria Cristina Leonardi, Anna Morra, Federica Cattani, Luigi Santoro, Samantha Dicuonzo, Raffaella Cambria, Rosa Luraschi, Alessia Bazani, Roberta Lazzari, Veronica Dell'Acqua, Roberto Orecchia. Simultaneous integrated boost incorporated into a hypofractionated regimen using tomoDirect: Acute toxicity assessment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-07.

Purpose: To report long-term clinical results on breast cancer patients treated with a electron intraoperative boost followed by hypofractionated external beam radiotherapy (HEBRT) to the whole breast inside a clinical protocol. Materials and Methods: Between June 2004 and December 2008, 357 premenopausal women with a diagnosis of early-stage breast cancer were given breast conservative surgery (quadrantectomy and sentinel node biopsy +\- axillary dissection). During surgery, an electron intraoperative boost of 12 Gy was administered to the tumour bed. Within 4 weeks after having received the IORT boost, the whole breast was irradiated with hypofractionated scheme. HEBRT consisted of 13 daily fractions of 2.85 Gy up to a total dose of 37.05 Gy, with 3-D conformal technique. Median age was 42 years (24-48). Pathologic stages were distributed as follow: stage 0 4 (1.1%), I 192(53.8%), stage IIA 108 (30.3%), stage IIB 28 (7.8%), stage IIIA 18 (5%), stage IIIC 6 (1.7%), CR 1(0.3 %). The biomolecular classification included 33 triple negative patients. All patients but one received adjuvant systemic treatment, according to tumor features. Chemotherapy +/- endocrinotherapy was offered to 149 patients, while endocrinotherapy alone was given to 197 patients. In all cases, adjuvant chemotherapy commenced after the completion of HEBRT. Follow-up was carried out on a regular basis by breast surgeons and radiation oncologists. Results: Median follow-up was 83.1 months (range 9.1-118.9). 340 patients were alive and 317 were free of any disease (89%). Three patients (0.8%) had nodal regional recurrence, 12 patients (3.4%) had local recurrence, 26 patients (7.3%) had distant metastasis.13 patients (3.6%) developed contralateral breast cancer.12 patients (3.4%) had a new primary tumor in other site. 15 patients (4.2%) died due to progression of disease, while two died of other causes not related to the breast cancer. Conclusions: This shortened scheme including intraoperative anticipated boost and hypofractionated whole breast radiotherapy showed a good local control at 5 years follow-up. The patients’ compliance is very high and in patients who are in need of chemotherapy, the time gap between surgery and radiotherapy treatment is avoided. As follow-up length increases, a greater number of patients will achieve the minimum 5 -year period to receive the first long-term evaluation and the strength of the results on efficacy is bound to increase. Citation Format: Maria Cristina Leonardi, Anna Morra, Cristiana Fodor, Luigi Santoro, Samantha Dicuonzo, Roberta Lazzari, Veronica Dell'acqua, Elena Rondi, Federica Cattani, Floriana Pansini, Alberto Luini, Roberto Orecchia. Long-term outcome of electron intraoperative boost and hypofractionated external beam radiotherapy after breast-conserving surgery in premenopausal women [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-05.

Aim: The high likelihood of multicentricity and multifocality linked to lobular histology (ILC) has called into question the partial breast irradiation. Patients with ILC are categorized in the cautionary group according to ASTRO guidelines. We looked into the population treated with intraoperative radiotherapy with electrons (ELIOT) as full dose to investigate the impact of lobular compared to ductal histology (IDC) in terms of local recurrence. Matherials and methods: From 1999 to 2007, 2220 patients were treated with breast conserving surgery and intraoperatory radiotherapy with electrons ( 21 Gy at 90% isodose) as sole treatment. The study population includes both patients treated outside and inside the clinical randomized phase III trial ELIOT. Out of 2220 patients, 255 (11.5%) presented ILC. We compared this group with patients having IDC, treated in the same period. The rate of local recurrences has been analyzed, with a minimum follow-up of 5 years. The role of patients and tumor features on local control has been evaluated. Results: Compared to IDC group, patients with ILC were older (≥ 70, 20% vs. 11%), with no lymph node involvement( pN0, 79% vs. 70%), low grading( G1-2,86% vs.72%), absence of vascular invasion( 81% vs. 98%), higher hormonal receptor status (ER +, 97% vs. 88%), HER2 negativity (96% vs. 89%), low proliferative index( Ki-67, 23% vs. 44%). No differences were noticed with regard to the technical parameters of ELIOT. On the whole, the incidence of local relapse was 4.5% at 5 years (0.9/100 per year). Within the first 5 years of follow-up, no differences were observed between lobular and ductal histology, but after 5 years the difference became significant (p 0.05). Higher risk of local relapse was also observed in old patients ( over 60) with ILC. Regarding the biomolecular classification, lobular carcinomas belonging to Luminal A subtype had a more aggressive local behavior than Luminal A ductal carcinomas, showing a significantly higher rate of local relapse (p 0.0021). Conclusion: In spite of a favorable tumor profile, a greater incidence of local relapse occurred in tumors with ILC compared to ductal histology. When considering the anagraphic, histological and biomolecular variables, the old age (>60), the proliferative index and the luminal A subtype turned out to be significant. Interestingly, the incidence of local relapse becomes statistically significant 5 years after the treatment. This event points out the importance of an adequate follow-up length, especially in lobular histology for which other reports on whole breast irradiation in literature describe similar biological behavior . Citation Format: Maria Cristina Leonardi, Patrick Maisonneuve, Anna Morra, Nicole Rotmensz, Samantha Dicuonzo, Roberta Lazzari, Veronica Dell'acqua, Federica Cattani, Mauro Mastropasqua, Alberto Luini, Roberto Orecchia. Lobular histology and partial breast irradiation: To what extent is it a cautionary parameter? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-06.

Background Streptococcus pneumoniae (SP) is a major cause of morbidity and mortality worldwide in all age groups. Serious diseases often caused by pneumococci include pneumonia, meningitis and bacteremia. Objective The aim of this work was to estimate the hospitalization rate for SP in the Veneto region by investigating pneumococcal-related discharges. Material and methods This was a retrospective study based on hospital discharge data collected from 2008 to 2012 in the Veneto Region (north-east Italy). All hospitalizations for diseases potentially associated with SP were identified by searching the hospital discharge records, then the proportions of hospital admissions for pneumonia, meningitis and septicemia attributable to the infection were calculated. Comorbidities were also graded according to the Charlson Comorbidity Index (CCI). Data were analyzed using the chi square test and Student's t-test for unpaired data, as appropriate. Significant trends over the years considered were examined in terms of average annual percent changes (AAPC). A p value, Highlights • Estimated hospitalization rate was higher in children and the elderly • Overall fatality rate was 11.0%. • Economic burden of SP-HA was around €14.8 million a year in Veneto Region.