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As the use of hypofractionation has spread in the setting of curative prostate radiotherapy, few data are available in the post-operative scenario. This study reports a mono-institutional experience of moderate post-operative hypofractionated radiotherapy for prostate cancer. In February 2021, we retrospectively assessed the outcomes of 129 patients who received between April 2013 and May 2020 hypofractionated post-operative radiotherapy using Helical Tomotherapy. Toxicity was assessed using CTCAE criteria v4.0. Survival endpoints were calculated with Kaplan–Meier method. Median age and follow-up were, respectively, 67 years and 43 months. Adjuvant and salvage treatment were delivered to 63.5% and 36.4% of patients to a median total dose of 63.8 Gy (61.6–65.25 Gy) in 29 fractions (2.12–2.25 Gy/fraction). Pelvic lymph-nodes irradiation was performed in 67.4% of cases. ADT was added in 50%. Acute toxicity was: G1 and G2 GU events in 36% and 9.3% of cases; G1 and G2 GI events in 29.4% and 13.9%. Late GU toxicity occurred in 12.4% of cases: 3.1% G1, 7.7% G2 and 1.5% G3 events; GI toxicity consisted of 1.5% G1 and 7.7% G2 events. Biochemical relapse occurred in 26.3% of cases, recording no significant differences between adjuvant and salvage (p = 0.67), with 4- and 5-years bRFS rates of 78.7% and 75.6%. Two patients died of progressive disease and eight for non-oncological causes resulting in 3-years overall survival and cancer-specific survival rates of 98% and 98.4%. Our experience supports the use of moderate hypofractionation for prostate bed radiotherapy, with minimal toxicity and promising results in terms of clinical outcomes.

Background/aim Medulloblastoma is a rare tumor of adult age, while it occurs more frequently in children. Given the rarity, there is a lack of evidence for the treatment of recurrent disease. Few data are available about salvage re-irradiation collecting very heterogeneous series. Case report A 51-year-old male presented with headache, nausea, double vision, and gait disorders. A contrast-enhanced brain-MRI showed the presence of multifocal medulloblastoma. After surgery, adjuvant craniospinal radiotherapy was performed, chemotherapy was stopped due to toxicity. After 27 months, a new MRI and a Methionine-PET revealed a late pontocerebellar relapse; multidisciplinary board decided for a SBRT treatment. The second course of RT was well tolerated and 14 months later, the patient is alive in good general conditions, with no evidence of disease. Conclusion Our experience supports the use of salvage stereotactic radiotherapy as a safe and effective treatment option.

Aims: To assess toxicity and clinical outcomes of moderately hypofractionated helical tomotherapy (HT) for the curative treatment of localized prostate cancer (PC). Methods: From December 2012 to May 2018, 170 patients were treated with definitive intent for PC. Thirty-four percent were low risk, 30% intermediate risk (IR) and 36% high risk (HR). All patients received 70Gy in 28 fractions to the prostate; 61.6Gy were delivered to the seminal vesicles for IR; pelvic lymph nodes irradiation for a total dose of 50.4Gy was added in the HR subgroup. Toxicity was assessed using CTCAE V4.0, and biochemical failure was defined following Phoenix criteria. Time-to-event data were analyzed using the Kaplan–Meier method and log-rank test. Results: The median follow-up was 36months (range 12–78); acute toxicity was as follows: G1 and G2 in 27.6% and 19.4% for GI; 53% and 24% for GU. No G ≥ 3 event was observed. For late toxicity, G ≥ 3 GI and GU rates were, respectively, 3% and 2.4% at 3years and 3% and 4.8% at 4years; no G4 occurred. A statistical correlation between acute or late G3 incidence and clinical or dosimetric parameters was not found. At the time of analysis, 2- and 3-year biochemical relapse-free survival rates were 90% and 87.5% and 2- and 3-year overall survival rates were 96.4% and 90%, respectively. The log-rank test revealed no difference between the risk groups in terms of biochemical control (p = 0.16). Conclusions: Moderately hypofractionated RT with HT for localized prostate cancer reported excellent outcomes with mild acute and late toxicity incidence, with promising biochemical control rates.

Predictive models based on radiomics and machine-learning (ML) need large and annotated datasets for training, often difficult to collect. We designed an operative pipeline for model training to exploit data already available to the scientific community. The aim of this work was to explore the capability of radiomic features in predicting tumor histology and stage in patients with non-small cell lung cancer (NSCLC). We analyzed the radiotherapy planning thoracic CT scans of a proprietary sample of 47 subjects (L-RT) and integrated this dataset with a publicly available set of 130 patients from the MAASTRO NSCLC collection (Lung1). We implemented intra- and inter-sample cross-validation strategies (CV) for evaluating the ML predictive model performances with not so large datasets. We carried out two classification tasks: histology classification (3 classes) and overall stage classification (two classes: stage I and II). In the first task, the best performance was obtained by a Random Forest classifier, once the analysis has been restricted to stage I and II tumors of the Lung1 and L-RT merged dataset (AUC = 0.72 ± 0.11). For the overall stage classification, the best results were obtained when training on Lung1 and testing of L-RT dataset (AUC = 0.72 ± 0.04 for Random Forest and AUC = 0.84 ± 0.03 for linear-kernel Support Vector Machine). According to the classification task to be accomplished and to the heterogeneity of the available dataset(s), different CV strategies have to be explored and compared to make a robust assessment of the potential of a predictive model based on radiomics and ML.

The strategy of vaccinating infants to prevent hepatitis B virus infection in adolescence or adulthood requires durable immunity. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children primed with three doses of either Hexavac® or Infanrix hexa® 10years earlier during infancy.This open-label, controlled, multicentre study conducted in Italy, enrolled 751 healthy pre-adolescents (aged 11-13years) who were given either Hexavac (n=409) or Infanrix hexa (n=342) at 3, 5 and 11months of life. All participants received a challenge dose of a monovalent hepatitis B vaccine (HBVaxPro® 5µg). The concentrations of antibodies to hepatitis B surface antigen (anti-HBs) were measured before and 1month after the challenge dose. The analysis was descriptive and no formal hypothesis was tested.One month post-challenge, 331 participants in the Hexavac cohort [83.6%, 95% CI: 79.6; 87.1] and 324 in the Infanrix hexa cohort [96.4%, 95% CI: 93.8; 98.1] had anti-HBs concentrations ≥10mIU/mL. Before the challenge dose, an anti-HBs concentration of ≥10mIU/mL was found in 94 children in the Hexavac cohort [23.9%, 95% CI: 19.7; 28.4] and in 232 children in the Infanrix hexa cohort [69%, 95% CI: 63.8; 74.0]. Among children with a pre-challenge anti-HBs concentration of10mIU/mL, 236 [78.7%, 95% CI: 73.6; 83.2] in the Hexavac cohort and 92 [88.5%, 95% CI: 80.7; 93.9] in the Infanrix hexa cohort achieved protective anti-HBs antibody concentrations. No evidence of active hepatitis B disease was observed in either group, and the HBVaxPro challenge dose was well tolerated.These data confirm that immune memory persists in a high percentage of children (80%) at least 10years after a two-dose primary and booster vaccination schedule with a hexavalent vaccine (Hexavac or Infanrix hexa).EudraCT Number: 2013-001602-28; clinicaltrials.gov: NCT02012998.

Objective: To report preliminary findings of a phase II study exploring the clinical outcomes of moderate hypofractionated radiotherapy performed with helical tomotherapy (HT) using computed tomography–magnetic resonance imaging–based planning for localized prostate cancer. Methods: The phase II prospective study received ethics approval from our institutional ethics committee. A dose of 60 Gy/20 fractions for low–intermediate risk prostate cancer by means of HT was explored. Primary endpoints of the study were acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. Secondary endpoints were quality of life and biochemical-free survival. Results: A total of 35 patients were included in this interim report. At the time of the analysis, median follow-up was 36 months (range, 13–62). Acute GI toxicity was recorded as follows: grade 1 in 34% and grade 2 in 14%; acute GU toxicity was grade 1 in 71% and grade 2 in 11%. For the entire population of the study, no acute toxicities ⩾ grade 3 occurred. A single case of late grade 3 GU toxicity was registered, whereas no late GI toxicity ⩾grade 3 was recorded. At the time of the final assessment, no biochemical failure was detected. Conclusions: The preliminary results of the present phase II trial, using HT for moderate hypofractionation in localized prostate cancer, are optimal. In fact, HT guaranteed an acceptable tolerability profile with low rates of GU and GI side effects and, more specifically, no acute severe adverse events were recorded. Long-term findings are warranted.

Purpose or objective: To evaluate toxicity and outcomes of moderately hypofractionated helical tomotherapy for the curative treatment of a cohort of patients aged ≥ 75years with localized prostate cancer (PC). Materials and methods: From January 2013 to February 2017, 95 patients with median age 77years (range 75–88) were treated for PC. 39% were low risk, 33% intermediate risk (IR), 28% high risk (HR). Median iPSA was 9.42ng/ml (1.6–107). Androgen deprivation was prescribed according to NCCN recommendations. All patients received 70Gy in 28 fractions to theprostate; 61.6Gy were delivered to the seminal vesicles for IR; whole pelvis irradiation with a total dose of 50.4Gy was added in the HR group.Toxicity evaluation was based on CTCAE V4.0 criteria, biochemical failure was defined following Phoenix criteria. Quality of Life was assessed with the EPIC-26 index. Overall survival and biochemical failure-free survival were analysed with Kaplan–Meier method. Results: With a median follow-up of 36months (range 24–73), acute and late toxicity were acceptable. No correlation between toxicity patterns and clinical or dosimetric parameter was registered. EPIC-26 showed a negligible difference in urinary and bowel function post-treatment that did not reach statistical significance. The 2- and 3-years OS were 93% and 87% with cancer specific survival of 97.9% and 96.2%. Conclusion: Moderate hypofractionated RT reported excellent outcomes in our cohort of older patients. Shorter schedules may be proposed regardless of chronological age facilitating the treatment compliance in the older population.

Background/aim Pineoblastoma of the adult age is an uncommon tumor with only 200 cases reported. A standardized approach for an optimal adjuvant strategy is currently lacking. The case presented herein also deals with the issue of central nervous system tumors in pregnancy. Case report A 21-year-old pregnant woman presented with massive hydrocephalus due to a mass in the pineal region detected with MRI. After positioning an urgent ventricular derivation, a cesarean section was performed. During a third ventriculocisternostomy, a biopsy revealed a pineoblastoma. After a maximal safe resection, postoperative craniospinal irradiation for a total dose of 36 Gy plus a sequential boost to the tumor bed to 54 Gy, and adjuvant chemotherapy with CDDP plus CCNU plus vincristine were performed. After one year, the patient is alive with no evidence of disease. Conclusion The use of adjuvant radio-chemotherapy provided excellent outcomes in our case. The advanced gestational age facilitated the choice of the therapeutic strategy.

To conduct a survey among Sicilian centers of radiation oncology belonging to Associazione Italiana di Radioterapia ed Oncologia Clinica (AIRO), to record the different methods of integration of radio-chemotherapy both in neoadjuvant and adjuvant settings, to evaluate surgical procedures in relation to the sphincter preservation and to report the different toxicity profiles of the treatment strategies. A questionnaire was sent at the end of 2017 to all the radiation oncology centers of Sicily region in order to collect the data from individual centers and the treatment characteristics retrospectively over the previous 5 years, from 2012 to 2016. The required data were collected from 13 centers out of 17 which, in relation to the single catchment areas, correspond to approximately 85% of the Sicilian population. The requested data concerned the type of integrated treatment (neoadjuvant vs adjuvant vs radical), combination with chemotherapy (induction, concomitant, adjuvant), type of surgical intervention (sphincter-saving vs abdomino-perineal resection), disease stage, schedule and radiotherapy technique adopted, as well as toxicity detected over the treatment period. A total of 784 pts (M/F: 509/275) were treated between 2012 and 2016, with a median age of 67 years (range 25–92). The majority of patients was treated in the neoadjuvant phase (62% of the total) compared to the adjuvant phase (31%) and to those treated radically (7%). Twenty-five percent of patients did not receive combination chemotherapy mainly for cardiovascular problems. Chemotherapy used concomitantly to radiotherapy was single-agent capecitabine (73% of patients) or 5-fluorouracil (27%). The use of chemotherapy alone before concomitant treatment is more common for patients treated in the adjuvant phase (64% of this subgroup), while 14% of patients treated in the neoadjuvant phase received induction chemotherapy before the concomitant phase; in both cases of chemotherapy alone, the majority of patients (91%) received oxaliplatin-based protocols (FOLFOX/XELOX/CAPOX). Few patients (3%) received chemotherapy alone after the concomitant phase. Information on the surgical treatment received is available for 88% of the sample. Of these, 93% received a surgical treatment. The overall rate of sphincter-saving surgery (anterior resection) was 72%, but the contribution of neoadjuvant treatment allowed to reach a rate of 83% in this subgroup (against 65% found in the subgroup of patients treated in adjuvant phase). Traditional radiotherapy schedule (45–50 Gy in 25–28 fractions) was used in 90% of patients, of which an intensified treatment in neoadjuvant phase (45 Gy + boost of 9–10 Gy) was used in 11% of patients. A short-course regimen (25 Gy in 5 fraction) in neoadjuvant setting was opted rarely (7%). Three-dimensional conformal technique was preferred over intensity-modulated ones (73% vs 27%). Toxicity was mainly of grade I–II CTCAE (skin 23%, gastrointestinal 39%, genitourinary 14%) compared to grade III (gastrointestinal 4%, genitourinary and hematological

Francesco Cuccia,1,2 Gianluca Mortellaro,2 Vincenzo Serretta,3 Vito Valenti,1,2 Antonella Tripoli,1,2 Marina Gueci,1,2 Nicoletta Luca,1,2 Antonio Lo Casto,4 Giuseppe Ferrera2 1Radiation Oncology School, University of Palermo, Palermo, Italy; 2Radiation Oncology, ARNAS-Civico Hospital, Palermo, Italy;3Section of Urology, Department of Surgical Oncological and Oral Science, University of Palermo, Palermo, Italy; 4Radiation Oncology School, Section of Radiological Sciences, DIBIMED, Università degli Studi di Palermo, Palermo, Italy Purpose: This is a mono-institutional study of acute and late toxicities and early biochemical control of a retrospective series of 75 prostate cancer patients treated with moderate postoperative hypofractionation delivered by helical tomotherapy (HT). Patients and methods: From April 2013 to June 2017, 75 patients received adjuvant (n=37) or salvage (n=38) treatment, delivering to prostate bed a total dose of 63.8 Gy (equivalent dose in 2-Gy fractions=67.4 Gy) using 2.2 Gy fractions. Whole-pelvis irradiation was performed in 63% of cases (median dose, 49.3 Gy; range, 48–55.1 Gy). Concurrent hormonal therapy was administered in 46% of cases. Common Terminology Criteria for Adverse Events (version 4.0) was adopted for acute and lategenitourinary (GU) and gastrointestinal (GI) toxicity evaluations. Biochemical progression was defined as PSA level increase of ≥0.2 or more above the postoperative radiotherapy (RT) nadir. Results: Acute GU toxicities were as follows: G1 in 46% and G2 in 4%, detecting no G≥3 events. For GI toxicity, we recorded G1 in 36% and G2 in 18%. With a median follow-up of 30 months (range, 12–58 months), we found late toxicity G2 GI in 6.6% and G≥2 GU in 5.3%, including two patients who underwent surgical incontinence correction. Acute GI≥2 toxicity and diabetes were found to be predictive of late GI≥2 toxicity (P=0.04 and P=0.0019). Actuarial 2- and 3-year biochemical recurrence-free survivals were 88% and 73%, respectively, for the entire population. Conclusion: In our experience, moderate hypofractionated postoperative RT with HT was feasible and safe, with reports of low incidence of toxicity and promising biochemical control rates. Keywords: prostate neoplasm, radiotherapy, hypofractionation, adjuvant, salvage

Background: Several experiences in the literature report SBRT as an effective treatment option for medically inoperable early stage non-small cell lung cancer (NSCLC) and oligometastatic disease. The optimal fractionation schedules and total dose remain controversial. In this study, we evaluated the safety in terms of toxicity and efficacy of using of 8–10 fractions schedules with Helical Tomotherapy (HT) for primary and metastatic lung lesions. Methods: Between March 2014 and May 2016, a total of 39 patients (median age 72 years, range 26–91) were treated with HT-SBRT for malignant lung lesions: 22 patients with early stage NSCLC, 17 with oligometastases. Patients received 8–10 fractions with lower daily dose for central and ultracentral lesions. Treatment-related toxicity was evaluated using CTCAE v 4.0 scale. Local control (LC), overall survival (OS) and toxicity rates were prospectively collected. Results: Median duration of RT was 15 days (range 10–26 days) and no interruption occurred. With a median follow-up of 13 months (range 3–29), we reported one G2 pneumonitis (2.6%) and one G2 chest pain (2.6%); no ≥ G2 esophagitis was registered. Actuarial local control rate was 95.5% both at 12 and 24 months for early stage NSCLC and 92.9% both at 12 and 24 months for metastatic patients. OS rate was 94.4 and 92.3% at 1 year, and 94.4 and 83.9% at 2 years in primary and metastatic group, respectively. Conclusions: The use of 8–10 fractions schedule HT-SBRT for lung malignancies results in high LC and OS rates with minimal toxicities reported.

Angiosarcoma of the scalp is a rare aggressive tumor that affects elderly patients. Chemoradiation is the treatment of choice for multicentric and extensive disease. The shape of the scalp represents a dosimetric challenge in terms of achieving a homogeneous concave dose distribution with coverage of the entire target volume and an acceptable organs-at-risk sparing. We report a case of an 81-year-old man with a multifocal angiosarcoma of the scalp treated with Helical TomoTherapy® (Accuray Inc., Sunnyvale, CA, USA) intensity modulated radiotherapy. This technique allows precise and daily verifiable coverage of the target keeping the dose to the organs at risk within the constraints.

Background This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. Methods In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. Results One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. Conclusions The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.

Purpose To evaluate the influence of radiation dose on tumor regression grade (TRG) and sphincter preservation rate in a series of cT3N0-1 rectal cancer patients treated with neoadjuvant chemoradiotherapy (CT-RT) with or without a sequential radiation boost. Materials and methods Between May 2002 and September 2013, 116 cases were eligible for retrospective evaluation. Radiotherapy was delivered for a total dose of 45 Gy (no boost arm) or 50.4 Gy (boost arm). TRG was evaluated with the Dworak scale. Results Median follow-up was 62 months (range, 12-138 months). The 5-year overall survival and local control rates were 72% and 93%, respectively. Fifty-five patients (47%) were treated with a sequential radiation boost and 61 (53%) without a boost. Eighty patients (72%) presented T3N0 disease and 32 (28%) T3N1 disease. Concomitant capecitabine was administered in 92 cases (79%) and intravenous 5-fluorouracil in 24 cases (21%). Sphincter preservation was performed in 82% of patients in the boost arm and 66% in the no-boost arm. A higher TRG was related to a longer interval between neoadjuvant treatment and surgery (pConclusions The long-term results from our single-center experience confirm literature data on the role of a sequential boost in tumor response after neoadjuvant CT-RT in a series of cT3N0-1 rectal cancer patients.

Introduction Multiple vaccination visits and administrations can be stressful for infants, parents and healthcare providers. Multivalent combination vaccines can deliver the required number of antigens in fewer injections and clinic visits, while vaccine co-administration can also reduce the number of visits. This non-inferiority study was undertaken to evaluate the feasibility of co-administering a combined measles-mumps-rubella-varicella (MMRV) vaccine with conjugated meningococcal C (MenC) vaccine in a large cohort of healthy Italian toddlers. Methods Healthy subjects aged 13–15 months were randomized (2:1:1) to receive single doses of either: co-administered MMRV + MenC at the same visit (MMRV + MenC group); or MMRV followed 42 days later by MenC (MMRV group); or MenC followed 42 days later by MMRV (MenC group). Blood samples were collected before and 43 days after vaccination. Antibody titers against MMRV were measured using ELISA. Functional-anti-meningococcal-serogroup activity (rSBAMenC) was assessed using a serum bactericidal test. Solicited local and general reactions were recorded for up to 4 and 42 days post-vaccination, respectively. Non-inferiority of MMRV + MenC to MMRV (post-dose-1 seroconversion rates) and MMRV + MenC to MenC (post-dose-1 seroprotection rates) was achieved if the lower limit (LL) of the 95% confidence interval (CI) for the group difference was ⩾−10% for each antigen. Results 716 subjects were enrolled in the study. At 42 days post-vaccination, the MMRV seroconversion rates were 99.3% (measles), 94.5% (mumps), 100% (rubella) and 99.7% (varicella) in the MMRV + MenC group, and 99.4%, 93.2%, 100% and 100%, respectively, in the MMRV group. The seroprotection rates against rSBA-MenC were 98.3% in the MMRV + MenC group and 99.3% in the MenC group. Non-inferiority was reached for all the vaccine antigens. The safety profiles were as expected for these vaccines. Conclusion The immune responses elicited by co-administered MMRV + MenC were non-inferior to those elicited by MMRV or MenC alone and support vaccination of children with both vaccines at a single visit. Clinical Trials registration: NCT01506193 .

Two doses of measles-mumps-rubella vaccine (MMR) are widely recommended and consideration is being given to a similar schedule for varicella vaccine. A combined measles-mumps-rubella-varicella vaccine (MMRV) could be considered for this second dose in children previously vaccinated separately with MMR and varicella vaccines. Healthy children (N=390) aged 15-75 months (median 54 months) previously immunized with MMR and varicella vaccines were randomly allocated to receive MMRV or separate injections of MMR and varicella vaccines. Before administration of study vaccines, seropositivity rates were 96.4% for measles, 94.3% for mumps, 99.5% for rubella, and 97.9% for varicella. Post-immunization, seropositivity rates were 99.5% for measles and mumps and 100% for rubella and varicella in the MMR+varicella group and 100% for all four antigens in the MMRV group; a 26.2- and 27.2-fold increase in varicella titer was observed in the MMR+varicella vaccine and MMRV groups, respectively. Except for more frequent pain in the MMRV group (33.3% vs. 23.7%, p=0.043), there were no differences in the incidence of local and solicited symptoms between groups. In children primed with MMR and varicella vaccine, MMRV had non-inferior immunogenicity and similar safety profiles as a second dose of licensed MMR and varicella vaccine administered concomitantly.

Based on radiobiology evidence, hypofractionated radiotherapy has the potential of improving treatment outcome in prostate cancer patients. In this study, we evaluated the safety, in terms of acutetoxicity, of using moderate hypofractionated radiotherapy delivered with Helical Tomotherapy (HT) to treat prostate cancer patients. Between December 2012 and April 2014, 42 consecutive patients were treated with hypofractionated radiotherapy using HT. All patients received 70 Gy in 28 fractions to PTV1, which included the prostate. In the intermediate risk group, 61.6 Gy were delivered to PTV2, which included the seminal vesicles. In high risk patients, the pelvic nodes were added (PTV3) and received 50.4 Gy. Acute toxicity was recorded prospectively with RTOG and Common Terminology Criteria for Adverse Events 3.0, retrospectively with CTCAE 4.0. Expanded Prostate Cancer Index Composite (EPIC) was measured at baseline and 3 months after end of treatment, to investigate health related quality of life with regards to bladder and gastrointestinal function. Acute toxicity was acceptable, independently from the system used to score side effects. Moderate genitourinary toxicity was more frequent than gastrointestinal toxicity. No correlation between acute side effects and patients’ characteristics or physical dose parameters was registered. EPIC evaluation showed a negligible difference in urinary and bowel function post-treatment, that did not reach statistical significance. Our experience confirms the safety of moderate hypofractionation delivered with HT in prostate cancer patients with low, intermediate and high risk.

Intensity-modulated radiotherapy has been suggested as the technique of choice for locally advanced head and neck cancer patients. In the last decade, most radiotherapy departments have focused their efforts in programs to implement this technique. We report our experience for parotid gland and constrictor muscle sparing with intensity-modulated radiotherapy in head and neck cancer using a step-and-shoot technique. Thirty-four consecutive patients with squamous cell carcinoma of the nasopharynx, oropharynx and larynx treated between June 2008 and June 2011 were retrospectively evaluated. A simultaneous integrated boost was adopted to treat different volumes in 30 fractions over 6 weeks. Priority as organs at risk was given to the parotid glands as well as the constrictor muscle of the pharynx in 53 % (n = 18). Dysphagia and xerostomia were evaluated according to RTOG/EORTC scale at 6, 12 and 24 months. Outcomes were analysed using Kaplan–Meier curves. The median follow-up was 43 months. The 5-year overall survival was 70 %, and local control was 94 %. Grade 2 dysphagia and xerostomia at 6, 12 and 24 months were as follows: 26 % (n = 9), 23 % (n = 8), 23 % (n = 8) and 21 % (n = 7), 12 % (n = 4), 12 % (n = 4), respectively. No grade 3 or 4 toxicity was found. Ordinal logistic regression analysis demonstrated that hyposalivation was the main predictive factor for late dysphagia. Excellent loco-regional results were achieved with acceptable acute and late toxicities. The low rate of late dysphagia was related to parotid gland sparing; we did not observe a correlation between late dysphagia and dose to pharyngeal constrictors.

Background Concomitant administration of vaccines can facilitate vaccination uptake, provided that no clinically significant effect on either vaccine is identified. We investigated the concomitant administration, during the second year of life, of one dose of the combined measles, mumps, rubella and varicella vaccine (ProQuad(®)) with a booster dose of a hexavalent vaccine. Methods In this multicentre, open-label study, participants were randomized to 3 groups: Group 1, concomitant administration of one dose of ProQuad(®) and a booster of hexavalent vaccine; Group 2, one dose of ProQuad(®) alone; Group 3, a booster dose of hexavalent vaccine alone. Two serum samples were collected, within 7 days prior to vaccination and Days 42-56 post-vaccination for antibody testing. Results Antibody response rates to measles, mumps, rubella, varicella, hepatitis B and Haemophilus influenzae type b following concomitant administration of ProQuad(®) and hexavalent vaccine were non-inferior compared with those following the individual vaccines. Antibody response rates to these antigens were all >95% in all groups. Antibody titres for the pertussis antigens following concomitant administration were also non-inferior to those following the individual vaccines. Antibody titres for the other valences were numerically comparable between groups with the exception of hepatitis B, Haemophilus influenzae type b, tetanus and poliomyelitis, which were higher in the concomitant than in the non-concomitant groups. The safety profiles of each vaccination regimen were comparable, with the exception of solicited ProQuad(®)-related injection-site reactions (Days 0-4), which occurred more frequently in the concomitant than in the non-concomitant groups. Conclusion These immunogenicity data support the concomitant administration of ProQuad(®) with a hexavalent vaccine. The safety profile of concomitant ProQuad(®) and hexavalent vaccination was also in line with that of the individual Summaries of Product Characteristics.

The anamnestic response to a challenge dose of vaccine can assess immune memory and protection against hepatitis B infection. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children immunised with three doses of either Hexavac or Infanrix-Hexa during infancy.This open-label, randomised, controlled, four-arm study enrolled 410 healthy children aged 4-7 years who had received either Hexavac (n=201) or Infanrix-Hexa (n=209) at 3, 5 and 11 months of life. Children received a single intramuscular challenge dose of either hepatitis B vaccine, HBVaxPro (Hexavac, n=34; Infanrix-Hexa, n=28) or Engerix-B (Hexavac, n=167; Infanrix-Hexa, n=181). Hepatitis B surface antibody (anti-HBs) concentrations were measured before and 1 month after the challenge vaccine dose. The analysis was descriptive and no formal hypothesis was tested.One month post-challenge, 91.2% of children in the Hexavac group (95% confidence interval [CI] 86.3, 94.8) and 98.0% (95% CI 94.9, 99.4) in the Infanrix-Hexa group had anti-HBs concentrations ≥10 mIU/ml (primary endpoint). In a post hoc analysis, most children with pre-challenge anti-HBs concentration10 mIU/ml achieved anti-HBs concentrations ≥10 mIU/ml (Hexavac group, 85.3% [95% CI 77.6, 91.2]; Infanrix-Hexa group, 91.9% [95% CI 78.1, 98.3]). Both challenge vaccines were well tolerated.These data suggest that immune memory persists for long-term (5 years) after a primary vaccination in infancy with a hexavalent vaccine (Hexavac or Infanrix-Hexa).

A 13-valent pneumococcal conjugate vaccine (PCV13) has been developed to improve protection against pneumococcal disease beyond that possible with the licensed 7-valent vaccine (PCV7). This study compared the safety and immunogenicity of PCV13 with those of PCV7 when given as part of the pediatric vaccination schedule recommended in Italy. A total of 606 subjects were randomly assigned to receive either PCV13 or PCV7 at 3, 5, and 11 months of age; all subjects concomitantly received diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzaetype B (DTaP-HBV-IPV/Hib) vaccine. Vaccine reactions were monitored. Antibody responses to DTaP-HBV-IPV/Hib antigens, serotype-specific anticapsular polysaccharide IgG responses, and antipneumococcal opsonophagocytic assay (OPA) activity were measured 1 month after the two-dose primary series and 1 month after the toddler dose. Overall, the safety profile of PCV13 was similar to that of PCV7. The response to DTaP-HBV-IPV/Hib antigens was substantially the same with both PCV13 and PCV7. PCV13 elicited antipneumococcal capsular IgG antibodies to all 13 vaccine serotypes, with notable increases in concentrations seen after the toddler dose. Despite a lower immunogenicity for serotypes 6B and 23F after the primary series of PCV13, responses to the seven common serotypes were comparable between the PCV13 and PCV7 groups when measured after the toddler dose. PCV13 also elicited substantial levels of OPA activity against all 13 serotypes following both the infant series and the toddler dose. In conclusion, PCV13 appeared comparable to PCV7 in safety profile and immunogenicity for common serotypes, demonstrated functional OPA responses for all 13 serotypes, and did not interfere with immune responses to concomitantly administered DTaP-HBV-IPV/Hib vaccine.

The safety of a single injection of the refrigerator-stable formulation of varicella vaccine VARIVAX was assessed in a blind, randomized, cross-over trial. Five hundred seven healthy children aged 12 to 15 months received subcutaneous injections of VARIVAX on day 0 and the measles, mumps and rubella vaccine (M-M-R II) on day 42 or M-M-R II on day 0 and VARIVAX on day 42. To maintain blinding, injections were given by a study nurse not involved in safety assessments. M-M-R II acted as a reference to validate the safety assessment, as its safety profile is well known in this age range. Parents or legal guardians recorded adverse events for 42 days following each injection. Solicited injection-site reactions (erythema, swelling, pain) were recorded on days 0 to 4. Other injection-site reactions, daily temperature, rashes and systemic adverse events were recorded on days 0 to 42, and serious adverse events until the final study visit. The safety profile of M-M-R II was consistent with previous reports. Following VARIVAX administration, 47.7% of children had at least one vaccine-related adverse event. Solicited injection-site reactions were reported in 13.0% of children, and 17.2% had at least one other injection-site reaction between days 0 and 42. Most reactions were small (

Aim: To compare local control and toxicity in non melanoma skin cancer treated with electrons and Leipzig applicators. Methods: We evaluated 60 patients (pts) with non melanoma skin cancer treated using electrons and Leipzig applicators (microselectron-HDR afterloader). The lesions were: 30 basal cell cancer, 17 squamous cell cancer, 10 basosquamous cell cancer, 1 dermatofibrosarcoma, 1 keloid, 1 histiocytoma fibrosus. Median age was 54 (25-84). The lesions were localized on head and neck, except 1 in the sternum and 1 in posterior part of knee. 49 pts underwent surgery before radiation treatment with negative margin in 38 pts and positive margins in 11. 30 pts were treated with electrons to a total dose 40 to 50 Gy (2Gy/fr). Electrons beam energy was selected based on delivering the treatment to the 90% isodose line, using bolus when required to superficialize the depth of the dose. 30 pts, considering the size and the depth of the lesions (0.5-3cm) were treated with Leipzig applicators using a dose of 40 Gy in 8 fractions twice a week for 4 weeks. Results: Median follow up was 12 months in each group. Electrons group report 30 complete remissions of tumor lesion. Leipzig group reports 26 complete remissions and 4 partial remissions including keloid. Recurrences appeared in 5 pts with lesion size larger than 2 cm or depth> 3mm. Tolerance to the treatment was good in each group with no difficulties in compliance but longer treatment is not well tolerate by elderly pts for positioning. Acute toxicity was similar in both groups, with a low or mild skin toxicity according RTOG toxicity scale. Conclusions: Our experience suggests both Leipzig and Electrons treatment are feasible and well tolerate with a good or excellent cosmetic results. Yet Leipzig technique with surface applicators of different diameters, although the radiation is hightly direct on lesion covering it completly, radiation may leak through the backside of the applicators having uncertainties of dosimetric distributions. So we consider Leipzig a good treatment in few selected pts with a very small and superficial skin lesions ( Disclosure: All authors have declared no conflicts of interest.

The aim of this short communication is to present an extremely uncommon case of penile metastases from rectal adenocarcinoma treated with an external beam radiotherapy technique. A 76-year-old man affected by very painful priapism from penile metastases was treated with radiotherapy (30 Gy) for symptom relief. In the course of the radiotherapy treatment the patient reported gradual and continuous pain reduction. One month after the end of radiotherapy both the priapism and the pain had disappeared. Although the long-term prognosis remains poor, good quality of life was achieved in this patient.

Background: Pertussis occurs in older children, adolescents and adults due to waning immunity after primary vaccination. Booster vaccination for pre-school children has been recommended in Italy since 1999. In this study (NCT00871000), the immunogenicity, safety and reactogenicity of a booster dose of reduced-antigen content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (dTpa-IPV; GSK Biologicals Boostrix™-Polio; 3-component pertussis) vs. full-strength DTPa-IPV vaccine (sanofi-pasteur—MSD Tetravac™; 2-component pertussis) was evaluated in pre-school Italian children. Methods: Healthy children aged 5–6 y primed in a routine vaccination setting with three doses of DTPa-based vaccines were enrolled and randomized (1:1) in this phase IIIb, booster study to receive a single dose of dTpa-IPV or DTPa-IPV; the MMRV vaccine was co-administered. Antibody concentrations/titers against diphtheria, tetanus, pertussis and poliovirus 1–3 were measured before and one month post-booster. Reactogenicity and safety was assessed. Results: 305 subjects were enrolled of whom 303 (dTpa-IPV = 151; DTPa-IPV = 152) received booster vaccination. One month post-booster, all subjects were seroprotected/seropositive for anti-diphtheria, anti-tetanus, anti-PT, anti-FHA and anti-poliovirus 1–3; 99.3% of dTpa-IPV and 60.4% of DTPa-IPV subjects were seropositive for anti-PRN; 98–100% of subjects were seropositive against MMRV antigens post-booster. Pain at the injection site (dTpa-IPV: 63.6%; DTPa-IPV: 63.2%) and fatigue (dTpa-IPV: 26.5%; DTPa-IPV: 23.7%) were the most commonly reported solicited local and general symptoms, during the 4-d follow-up period. No SAEs or fatalities were reported. Conclusions: The reduced-antigen-content dTpa-IPV vaccine was non-inferior to full-strength DTPa-IPV vaccine with respect to immunogenicity. The vaccine was well-tolerated and can be confidently used as a booster dose in pre-school children.