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Purpose: Professional quality of life (QoL) is crucial for healthcare workers as it affects performance at work and interaction with patients, but little is known about stressors influencing radiation oncology professionals. The present study aims to explore the professional QoL of radiation oncologists (ROs) and radiation therapists (RTTs) in an Italian radiotherapy department and to report data about the possible impact of personality factors, such as alexithymia and empathy., Material and Methods: Participants filled out three validated questionnaires measuring the professional QoL, alexithymia, and empathy: (i) Professional Quality of Life Scale (ProQOL); (ii) Toronto Alexithymia Scale (TAS-20); (iii) Interpersonal Reactivity Index (IRI). Correlation, regression analyses and non-parametric tests were run., Results: A total of 48 professionals completed the survey (66.7% ROs, 33.3% RTTs). Considering the ProQOL dimensions, moderate levels of risk for burnout (BO) and secondary traumatic stress (STS) were found. BO was found to be predictive by TAS-20 total score (β=.37, p =.010), while STS resulted to be predictive by TAS-20 total score (β=.54, p <.001) and IRI Empathic Concern subscale (β=.45, p <.001). No significant differences were found between ROs and RTTs for all the considered variables, except for TAS-20 total score ( p =.032), higher for RTTs., Conclusions: Results showed no evidence of high risk of burnout and no intrinsic differences regarding the professional QoL between ROs and RTTs. Findings suggest a significant role of alexithymia and empathy predicting professional QoL. These results underscore the importance of promoting a positive work environment and emotional competencies to prevent high stress levels., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The Division of Radiation Oncology of IEO received research funding from AIRC (Italian Association for Cancer Research), Fondazione IEO-CCM (Istituto Europeo di Oncologia-Centro Cardiologico Monzino), ACCURAY, IBA (Ion Beam applications), all outside the current project. BAJF received speakers’ fees from Bayer, Accuray, Astellas, Iba, Ipsen, Astra Zeneca, Tecnologie Avanzate, Recordati, Novartis; BAJF participated to Advisory Board of Accuray, Bayer, Seagen, all outside the current project. The remaining authors declare no conflicts of interest that are relevant to the content of this article.

Purpose/objective: To perform a dosimetric and a normal tissue complication probability (NTCP) comparison between intensity modulated proton therapy and photon volumetric modulated arc therapy in a cohort of patients with parotid gland cancers in a post-operative or radical setting., Materials and Methods: From May 2011 to September 2021, 37 parotid gland cancers patients treated at two institutions were eligible. Inclusion criteria were as follows: patients aged ⩾ 18 years, diagnosis of parotid gland cancers candidate for postoperative radiotherapy or definitive radiotherapy, presence of written informed consent for the use of anonymous data for research purposes. Organs at risk (OARs) were retrospectively contoured. Target coverage goal was defined as D95 > 98%. Six NTCP models were selected. NTCP profiles were calculated for each patient using an internally-developed Python script in RayStation TPS. Average differences in NTCP between photon and proton plans were tested for significance with a two-sided Wilcoxon signed-rank test., Results: Seventy-four plans were generated. A lower Dmean to the majority of organs at risk (inner ear, cochlea, oral cavity, pharyngeal constrictor muscles, contralateral parotid and submandibular gland) was obtained with intensity modulated proton therapy vs volumetric modulated arc therapy with statistical significance (p < .05). Ten (27%) patients had a difference in NTCP (photon vs proton plans) greater than 10% for hearing loss and tinnitus: among them, seven qualified for both endpoints, two patients for hearing loss only, and one for tinnitus., Conclusions: In the current study, nearly one-third of patients resulted eligible for proton therapy and they were the most likely to benefit in terms of prevention of hearing loss and tinnitus., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The Division of Radiation Oncology of IEO received Institutional grants from Accuray InC. and Ion Beam Applications (IBA). BAJF received speakers’ fees from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, IBA and Astra Zeneca (all outside the current project). The remaining authors declare no conflicts of interest.

Aim: The study aims to report the feasibility and safety of palliative hypofractionated radiotherapy targeting macroscopic bladder tumors in a monocentric cohort of frail and elderly bladder cancer patients not eligible for curative treatments., Methods: Patients who underwent hypofractionated radiotherapy to the gross disease or to the tumor bed after transurethral resection of bladder tumor from 2017 to 2021 at the European Institute of Oncology IRCCS, were retrospectively considered. Schedules of treatment were 30 and 25 Gy in 5 fractions (both every other day, and consecutive days). Treatment response was evaluated with radiological investigation and/or cystoscopy. Toxicity assessment was carried out according to RTOG/EORTC v2.0 criteria., Results: A total of 16 patients were included in the study, of these 11 received hypofractionated radiotherapy on the macroscopic target volume and five on the tumor bed after transurethral resection of bladder tumor. No grade (G) >2 acute toxicities were described after treatment for both groups. Only one patient in the group receiving radiotherapy on the macroscopic disease reported G4 GU late toxicity. Ten patients had available follow-up status (median FU time 18 months), of them six had complete response, one had stable disease, and three had progression of disease. The overall response rate and disease control rate were 60% and 70%, respectively., Conclusion: Our preliminary data demonstrate that palliative hypofractionated radiotherapy for bladder cancer in a frail and elderly population is technically feasible, with an acceptable toxicity profile. These outcomes emphasize the potential of this approach in a non-radical setting and could help to provide more solid indications in this underrepresented setting of patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Hippocampal sparing whole-brain radiotherapy (HS-WBRT) showed significantly lower long-term side effects compared to standard WBRT. Aim of this study is to describe a HS-WBRT real-world monoinstitutional experience within a retrospective cohort., Methods: Patients who completed HS-WBRT course, with Karnofsky Performance Status ⩾ 60 and radiological diagnosis of brain metastases (BMs) were enrolled. Treatment was performed using helical Tomotherapy scheduled in 30 Gy in 10 or 12 fractions or 25 Gy in 10 fractions. Oncological outcomes were clinically and radiologically assessed every three months. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.3., Results: One hundred and nineteen patients from 2016 to 2020 met inclusion criteria; after a median follow-up of 18 months, 29 patients were alive; 6- and 12-months overall survival rates were 66% and 41%, respectively. HS-WBRT response was assessed for 72 patients. Median time to any progression and intracranial failure (IF) was 4.5 and 13.7 months, respectively. The 6- and 12-month IF rates were 85% and 57%. Among 40 patients (34%) who experienced IF, 17 (42%) were oligometastatic, 23 (58%) polymetastatic and 15/40 developed IF within the hippocampi avoidance zone. No grade (G) ⩾ 2 acute toxicities were reported and one G2 (dizziness) late toxicity was described., Conclusions: HS-WBRT is well tolerated, and despite the hippocampal sparing region, the oncological control is satisfying. Further investigation is warranted to find patients who could most benefit from a HS-WBRT approach., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study quantified the incidental dose to the first axillary level (L1) in locoregional treatment plan for breast cancer. Eighteen radiotherapy centres contoured L1-L4 on three different patients (P1,2,3), created the L2-L4 planning target volume (single centre planning target volume, SC-PTV) and elaborated a locoregional treatment plan. The L2-L4 gold standard clinical target volume (CTV) along with the gold standard L1 contour (GS-L1) were created by an expert consensus. The SC-PTV was then replaced by the GS-PTV and the incidental dose to GS-L1 was measured. Dosimetric data were analysed with Kruskal-Wallis test. Plans were intensity modulated radiotherapy (IMRT)-based. P3 with 90° arm setup had statistically significant higher L1 dose across the board than P1 and P2, with the mean dose (Dmean) reaching clinical significance. Dmean of P1 and P2 was consistent with the literature (77.4% and 74.7%, respectively). The incidental dose depended mostly on L1 proportion included in the breast fields, underlining the importance of the setup, even in case of IMRT., Competing Interests: Declaration of Conflicting InterestThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Division of Radiotherapy IEO received research funding from AIRC (Italian Association for Cancer Research) and Fondazione IEO-CCM (Istituto Europeo di Oncologia-Centro Cardiologico Monzino) (all outside the current project). BAJF received speakers fee from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, IBA Astra Zeneca (all outside the current project). MCL received a speaker fee from Accuray Inc (outside the current project). SD received speakers fee from Accuray Asia (outside the current project). MGV was supported by a research fellowship from AIRC entitled “Radioablation ± hormonotherapy for prostate cancer oligorecurrences (RADIOSA trial): potential of imaging and biology”, registered at ClinicalTrials.gov NCT03940235, approved by the Ethics Committee of IRCCS Istituto Europeo di Oncologia and Centro Cardiologico Monzino (IEO-997). IEO, the European Institute of Oncology IRCCS, was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds and by institutional grants from Accuray Inc. The sponsors did not play any role in the study design, collection, analysis and interpretation of data, nor in the writing of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors declare no conflict of interest that are relevant to the content of this article.

Background: The impact of radiotherapy (RT) in neuroendocrine neoplasms is still unknown, and outcomes could be improved by a better insight in RT response predictors. This retrospective analysis investigates the potential correlation between Ki-67 and RT response to evaluate its role as biological marker of radiosensitivity., Material and Methods: Data from patients treated at an Italian NET-referral center between 2015 and 2020 were retrieved. Inclusion criteria included: histologically-proven diagnosis of NEN, Ki-67 status, indication (symptomatic and/or ablative) and at least one post-RT radiological assessment., Results: Forty-two patients and 63 different treatment lines were included. Primary tumors presented Ki-67 values < 3% in 21% of cases, between 3 and 20% in 45% and >20% in the remaining 33%. Almost all patients were metastatic at the time of RT, which was performed with symptomatic purpose in 43% of cases. At a median time of three months, a complete response on the target lesion was observed in nine cases (14%), a partial response in 17 (27%), stability in 23 (37%) and local progression in 14 (22%). With median FU of 22.8 months, OS does not show statistically significant differences among three Ki-67 groups. Considering all lines of therapy, the relationship between ORR and Ki-67, did not show statistically significant differences, even following adjustments for drug types and delivered RT doses., Conclusion: No association between Ki67 and local tumor response to RT could be observed in the present cohort, regardless of whether the evaluation was performed on a categorical or continuous scale.

Objective: To compare different stereotactic body techniques-intensity-modulated radiotherapy with photons and protons, applied to radiotherapy of prostatic cancer-with simultaneous integrated boost (SIB) on the dominant intraprostatic lesion (DIL)., Methods: Ten patients were selected for this planning study. Dosimetric results were compared between volumetric modulated arc therapy, intensity-modulated radiation therapy (IMRT), and intensity-modulated proton therapy both with two (IMPT 2F) and five fields (IMPT 5F) planning while applying the prescription schemes of 7.25 Gy/fraction to the prostate gland and 7.5 Gy/fraction to the DIL in 5 fractions., Results: Comparison of the coverages of the planning target volumes showed that small differences exist. The IMPT-2F-5F techniques allowed higher doses in the targets; conformal indexes resulted similar; homogeneity was better in the photon techniques (2%-5%). Regarding the organs at risk, all the techniques were able to maintain the dose well below the prescribed constraints: in the rectum, the IMPT-2F-5F and IMRT were more efficient in lowering the intermediate doses; in the bladder, the median dose was significantly better in the case of IMPT (2F-5F). In the urethra, the best sparing was achieved only by IMPT-5F., Conclusions: Stereotactic radiotherapy with SIB for localized prostate cancer is feasible with all the investigated techniques. Concerning IMPT, the two-beam technique does not seem to have a greater advantage compared to the standard techniques; the 5-beam technique seems more promising also accounting for the range uncertainty.

Lombardy has represented the Italian and European epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Although most clinical efforts within hospitals were diverted towards the care of virally infected patients, therapies for patients with cancer, including radiotherapy (RT), have continued. During both the first and second pandemic waves, several national and regional organizations provided Italian and Lombardian RT departments with detailed guidelines aimed at ensuring safe treatments during the pandemic. The spread of infection among patients and personnel was limited by adopting strict measures, including triage procedures, interpersonal distance, and adequate implementation of personal protective equipment (PPE). Screening procedures addressed to both the healthcare workforce and patients, such as periodic nasopharyngeal swabs, have allowed the early identification of asymptomatic or pauci-symptomatic COVID-19 cases, thus reducing the spread of the infection. Prevention of infection was deemed of paramount importance to protect both patients and personnel and to ensure the availability of a minimum number of staff members to maintain clinical activity. The choice of treating COVID-19-positive patients has represented a matter of debate, and the risk of oncologic progression has been weighted against the risk of infection of personnel and other patients. Such risk was minimized by creating dedicated paths, reserving time slots, applying intensified cleaning procedures, and supplying personnel and staff with appropriate PPE. Remote working of research staff, medical physicists, and, in some cases, radiation oncologists has prevented overcrowding of shared spaces, reducing infection spread.

Aim: Since 20 February 2020, Lombardy has been one of the most affected areas worldwide by the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate work and psychological impact of COVID-19 on Lombardy radiation therapy (RT) residents in the first 3 months of the outbreak (first lockdown)., Methods: An online questionnaire (22 multiple choice questions) via Microsoft Forms was administered on 30 May 2020 to RT residents., Results: Nineteen Lombardy RT residents responded to the survey. Nineteen percent of residents underwent a nasal swab and 11% were quarantined. Seventeen residents (89%) reported an increase in workload. Twelve residents (63%) did not find any difference in terms of work distress; worsening was highlighted in 5 cases (26%). The majority has never considered the possibility of stopping work due to excessive stress (89%). Almost all the residents experienced self- or relative-referred apprehension (95%). Ninety-five percent reported having missed extra-work social relationships. Most of the sample noted worsening sleep quality and difficulty concentrating (69%). No residents requested psychological support, even if provided by the hospital., Conclusion: Overall, the residents adapted to the new workplace scenario, although some health risks and well-being challenges have been reported. An extension of the survey to all Italian RT residents endorsed by Italian Association of Radiotherapy and Clinical Oncology "Young AIRO" will allow an evaluation of COVID-19 impact on a national level. A second survey is planned to underline differences between the first lockdown and the current situation of the pandemic.

The presence of a neobladder constitutes a limitation for the radiation oncologist, as there is no clear evidence about its tolerance to radiotherapy (RT). The limited literature only concerns the conventional postoperative treatment in patients with bladder cancer after cystectomy. Here we report a case of a patient with neobladder who underwent a stereotactic RT for a pelvic recurrence of disease, with response to treatment and no toxicity to the neobladder. This case represents a promising example of the chance to perform RT with ablative intent, using advanced techniques, even on lesions close to the neobladder.

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.

Objective: To review the therapeutic strategy in Merkel cell carcinoma (MCC) treated with radiotherapy (RT) discussed in a multidisciplinary tumour board., Methods: Clinical records of patients with a diagnosis of MCC and with an indication to undergo RT at the European Institute of Oncology between 2003 and 2018 were reviewed retrospectively., Results: Twenty-six patients were included in the analysis (median age 65 years, range 42-87). Nineteen received adjuvant RT, 4 exclusive RT, and the remainder palliative RT. Intensity-modulated RT was used in 13 cases, a 3D conformal technique in 11 cases, and stereotactic RT in 2 cases. No major toxicities were recorded. The median relapse-free survival (RFS) after adjuvant RT was 20.5 months, while for unknown primary MCC, it was 23 months. In the adjuvant setting, median polyomavirus-positive RFS was 21.5 months (range 1-49) and median polyomavirus-negative RFS was only 14 months (range 4-45). Overall, RFS of polyomavirus-positive and polyomavirus-negative patients was 10.5 and 8 months, respectively. After adjuvant RT, only 1 out of 10 patients had a recurrence in the RT field. At the time of data collection, 16 patients were alive with no evidence of disease, 1 patient was alive with advanced status of disease, 8 patients died of disease progression, and 1 patient died of other causes., Conclusions: The management of unknown primary and polyomavirus-positive cases, which had a better prognosis in our series, may benefit from a multidisciplinary approach, given the limited data available regarding optimal treatment.

Objective: To report treatment times (door to door) of adjuvant treatments of breast cancer (BC) with intensity-modulated radiotherapy (IMRT)., Methods: Treatment times of 62 patients with BC on the TomoTherapy Hi-Art System were collected for the analysis. Patients underwent either locoregional radiotherapy (postmastectomy radiotherapy [PMRT]) with helical modality (TomoHelical) or whole breast radiotherapy (RT) with simultaneous integrated boost (WBRT-SIB) with direct modality (TomoDirect). Door-to-door time was broken down into different steps, which were crucial to RT session., Results: A total of 594 treatment fractions were monitored. Median treatment time was 22.4 minutes (17.2-30.8) for PMRT and 14.4 minutes (10.9-23.5) for WBRT-SIB. The mean beam-on time accounted for 61.36% of the overall treatment time for PMRT compared to 57% for WBRT-SIB. The beam-on time was a much more time-consuming process., Conclusion: This treatment times analysis on the use of IMRT for BC might be useful to organize and improve the workflow efficiency in RT facilities.

Objective: Postoperative radiotherapy (PORT) is indicated in almost two-thirds of patients treated with transoral robotic surgery (TORS) for head and neck tumors. The aim of this study was to quantify the toxicity profile of patients treated with PORT after TORS in oropharyngeal and supraglottic laryngeal cancer focusing on soft tissue necrosis (STN)., Methods: We retrospectively reviewed 28 patients. Acute and late toxicity were examined. Incidence and severity of STN were recorded., Results: No patient experienced acute grade 3 skin or mucosal toxicity; 1 patient had grade 3 dysphagia. At 12 months, no evaluated patient required enteral nutrition and 2 patients had tracheostomy. STN occurred in 4 (14%) patients: 3 out of 4 (75%) patients with STN had diabetes, whereas 6 out of 13 (25%) patients without STN had diabetes ( p = 0.05)., Conclusion: We found an acceptable toxicity profile of PORT performed after a TORS procedure. Diabetes mellitus might be a risk factor for STN.

Introduction: In case of pelvic recurrence of colorectal cancer, reirradiation of previously irradiated patients may increase the rate of salvage radical resection. Due to the high cumulative dose, one of the main concerns is radiation-induced lumbosacral plexopathy. This report describes multiple irradiations of a lesion adjacent to the lumbosacral plexus, using a highly selective technique, which allows optimal sparing of such a critical structure., Case Description: A 53-year-old woman treated in 2008 for a locally advanced rectal adenocarcinoma with preoperative pelvic irradiation and concomitant chemotherapy followed by surgery had disease recurrence in 2011 and underwent a second course of pelvic radiotherapy. In December 2015, magnetic resonance imaging showed a single local recurrence infiltrating the muscle next to the right lumbosacral plexus and close to the cauda equina. Repeat reirradiation was planned. The total dose deriving from the previous treatment plans was assessed by nonrigid image registration using the dedicated tool implemented in MIM 6.1.7 (MIMvista Corp., Cleveland, OH). The treatment was performed with Cyberknife (Accuray, Sunnyvale, CA) with a schedule of 20 Gy in 5 fractions (4 Gy per fraction). The dose was prescribed to 70% isodose and target coverage was 97%. Two months after the treatment, magnetic resonance imaging showed a decreased signal and stable disease with no change in tumor size., Conclusions: This case report suggests that pelvic re-reirradiation might be a possibility in very carefully selected cases of rectal cancer, using high-precision radiation modalities.

Introduction:: Several efforts are being implemented at the European level to measure provision of up-to-date radiation treatments across the continent., Methods:: A snapshot survey involving all radiation oncology centers within Lombardy, Italy, was performed in 2012 and repeated in 2014 and 2016, in cooperation with regional governmental officers. Centers were asked to provide detailed information concerning all individual patients being treated on the index day, and to report data on available local resources., Results:: We observed an increase in the number of centers and of megavoltage units (MVU) (from 76 to 87, i.e., 8.7 MVU per million inhabitants in 2016). Mean number of MVU per center was 2.5. Average age of MVU increased from 5.3 to 7.5 years and patients on the waiting list also increased. Conformal 3D radiotherapy (RT) treatments decreased from 56% to 42% and were progressively replaced by intensity-modulated RT treatments (from 39% to 49%). Waiting times were overall satisfactory. Radiation oncologists treated on average 152 and radiation therapists 100 RT courses per year. Average reimbursement per course was €4,879 (range €2,476-€8,014)., Conclusions:: The methodology of snapshot survey proved feasible and provided valuable information about radiation oncology provision and accessibility in Lombardy.

Background: This study was based on a survey to investigate perceptions of hadrontherapy of the members of the Italian Association of Medical Physics (AIFM). The survey was digitally submitted to the 991 members between the end of January and the beginning of April 2016., Methods: A 19-item questionnaire was designed focusing on advantages and disadvantages of hadrontherapy, current status and possible future improvements, and need and opportunities for future investments in Italy and abroad. Information about professional qualifications, main fields of clinical involvement and specific competencies of the respondents was also collected., Results: The survey was completed by 121 AIFM members (response rate 12.2%). In the answers collected, it was shown that medical physicists expressed interest in hadrontherapy mainly for reasons of personal interest rather than for professional needs (90% ± 2.5% vs. 52% ± 4.3% of the respondents, respectively), with a good knowledge of the related basic aspects as well as of the pros and cons of its application. However, poor knowledge of the current status of hadrontherapy was observed among the medical physicists not directly involved at a professional level, who were less than 3% of the physicists working in radiotherapy., Conclusions: In light of these results, the implementation of new training and education initiatives should be devised to promote a deeper and global knowledge of hadrontherapy-related issues, not only from a theoretical point of view but also in practical terms. Moreover, a close collaboration between highly specialized medical physicists employed in hadrontherapy centers and others in oncology hospitals should be -encouraged.

Purpose: Definition of the optimal treatment schedule for high-risk prostate cancer is under debate. A combination of photon intensity modulated radiotherapy (IMRT) on pelvis with a carbon ion boost might be the optimal treatment scheme to escalate the dose on prostate and deliver curative dose with respect to normal tissue and quality of dose distributions. In fact, carbon ion beams offer the advantage to deliver hypofractionated radiotherapy (RT) using a significantly smaller number of fractions compared to conventional RT without increasing risks of late effects., Methods: This study is a prospective phase II clinical trial exploring safety and feasibility of a mixed beam scheme of carbon ion prostate boost followed by photon IMRT on pelvis. The study is designed to enroll 65 patients with localized high-risk prostate cancer at 3 different oncologic hospitals: Istituto Europeo di Oncologia, Fondazione IRCCS Istituto Nazionale dei Tumori, and Centro Nazionale di Adroterapia Oncologica. The primary endpoint is the evaluation of safety and feasibility with acute toxicity scored up to 1 month after the end of RT. Secondary endpoints are treatment early (3 months after the end of RT) and long-term tolerability, quality of life, and efficacy., Results: The study is not yet recruiting; in silico studies are ongoing and we expect to start recruitment by 2017., Conclusions: The present clinical trial aims at improving the current treatment for high-risk prostate cancer, evaluating safety and feasibility of a new RT mixed-beam scheme including photons and carbon ions. Encouraging results are coming from carbon ion facilities worldwide on the treatment of different tumors including prostate cancers. Carbon ions combine physical properties allowing for high dose conformity and advantageous radiobiological characteristics. The proposed mixed beam treatment has the advantage to combine a photon high conformity standard of care IMRT phase with a hypofractionated carbon ion RT boost delivered in a short overall treatment time.

Introduction: Of the different treatments for early prostate cancer, hypofractionated external-beam radiotherapy is one of the most interesting and studied options., Methods: The main objective of this phase II clinical study is to evaluate the feasibility, in terms of the incidence of acute side effects, of a new ultra-hypofractionated scheme for low- or intermediate-risk prostate cancer patients treated with the latest imaging and radiotherapy technology, allowing dose escalation to the dominant intraprostatic lesion identified by multiparametric magnetic resonance imaging. Secondary endpoints of the study are the evaluation of the long-term tolerability of the treatment in terms of late side effects, quality of life, and efficacy (oncological outcome)., Results: The study is ongoing, and we expect to complete recruitment by the end of 2016., Conclusions: Like in previous studies, we expect ultra-hypofractionated radiation treatment for prostate cancer to be well tolerated and effective., Trial Registration: ClinicalTrials.gov identifier: NCT01913717.

Aims and Background: This study evaluates 3 different imaging modalities--ultrasound (US), stereoscopic X-ray imaging of implanted markers (Visicoils) (X-ray), and kV cone-beam computed tomography (CBCT)--to assess interfraction and intrafraction localization error during conformal radiation therapy of prostate cancer., Methods and Study Design: The study population consisted of 186 consecutive prostate cancer patients treated with an image-guided radiotherapy (IGRT) hypofractionated protocol using 3 techniques: 32 with X-ray, 30 with CBCT, and 124 with US. Treatment dose of 70.2 Gy was delivered in 26 fractions with a conformal dynamic arcs technique. Interfraction prostate localization errors were determined for the 3 techniques. Moreover, interfraction and intrafraction prostate motion in terms of translations and rotations, as well as residual errors, were determined with X-ray., Results: The systematic and random components of the prostate localization errors were as follows: (1) with X-ray 3.0 ± 3.4, 2.3 ± 2.7, 1.8 ± 2.3 mm in anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions and 1.8° ± 1.2°, 2.3° ± 1.5°, 2.7° ± 3.1°, for the yaw, roll, and pitch rotations; (2) with CBCT 3.5 ± 4.2, 3.3 ± 3.3, 2.5 ± 3.1 mm in AP, SI, and LR directions; (3) with US 3.7 ± 4.7, 3.4 ± 4.3, 2.3 ± 3.5 mm in AP, SI, and LR directions. Residual errors with X-ray were less than 1 mm in all directions. Intrafraction prostate motion of less than 0.5 mm in LR and of the order of 1 mm in AP and SI directions was found. This led to a significant reduction of the margins, potentially important for dose escalation studies., Conclusions: Daily on-line IGRT with stereoscopic X-ray imaging allowed a consistent PTV margin reduction considering residual interfraction prostate localization error and intrafraction motion. X-ray offers the best compromise among accuracy, reliability, dose to the patient, and time investment for daily IGRT treatment of prostate.

Aims and Background: Bladder preservation is a treatment option in muscle-invasive bladder carcinoma. The most investigated approach is a trimodality schedule including maximum transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy. Our aim was to evaluate the use of bladder preservation by radiation oncologists of the Lombardy region in Italy., Methods and Study Design: A survey with 13 items regarding data of 2012 was sent to all 32 radiotherapy centers within the collaboration between the Lombardy Oncological Network and the Lombardy Section of the Italian Society of Oncological Radiotherapy., Results: Thirteen centers (41%) answered the survey; the presented data come from 11 active centers. In these centers, 11,748 patients were treated with external-beam radiotherapy in 2012, 100 of whom having bladder cancer (0.9%). 74/100 patients received radiotherapy as palliative treatment for T, N or M lesions. A further 9 and 5 patients received radiotherapy for oligometastatic disease (ablative doses to small volumes) and postoperatively, respectively. Bladder preservation was performed in 12 cases and included trimodality and other strategies (mainly TURBT followed by radiotherapy). A multidisciplinary urology tumor board met regularly in 5 of 11 centers. All responders declared their interest in the Lombardy multicenter collaboration on bladder preservation., Conclusions: Our survey showed that bladder preservation is rarely used in Lombardy despite the availability of the latest radiotherapy technologies and the presence of an urology tumor board in half of the centers. The initiative of multicenter and multidisciplinary collaboration was undertaken to prepare the platform for bladder preservation as a treatment option in selected patients.

Purpose: To evaluate the tolerance of concomitant administration of anthracycline-based chemotherapy (CHT) and 3-dimensional conformal radiotherapy (RT) after breast-conserving surgery., Methods and Materials: Sixty-seven patients, treated with conservative surgery followed by 3-dimensional whole breast RT and concomitant CHT regimens including “Canadian modified” CEF (5-fluorouracil, epirubicin, cyclophosphamide) or AC (doxorubicin, cyclophosphamide) were evaluated for toxicity. They were compared in terms in compliance and acute toxicity with 67 patients irradiated sequentially after having received anthracyclines., Results: Acute grade ≥2 skin toxicity was significantly higher in the concomitant group compared to the sequential group, although the incidence of Grade 3 desquamation showed no statistical difference (9% vs. 3%, p = 0.14). Haematological toxicity represented the main cause of treatment discontinuation, reporting higher rate of grade 3-4 leuco-neutropenia in the concomitant group (20.9% vs. 6%, p = 0.01). Mean RT duration was longer in the concomitant group (51 days vs. 45 days) owing to RT breaks. Late toxicity was acceptable. No symptomatic lung and heart events were reported. Radiological lung hyperdensity was detected in 27.7% of the patients in the concomitant group. Post-treatment left ventricular ejection fraction significantly decreased compared with baseline, but cardiac function remained within the normal range, without any difference between left or right-sided RT., Conclusions: Although there was more acute grade ≥2 skin toxicity in the concomitant group, the rate of grade 3 dermatitis was lower than expected, suggesting some advantages of 3-D CRT over older techniques. Haematological toxicity exerted a significant impact on both RT and CHT delivery.

Aims and Background: To achieve the goal of organ preservation, both a chemoradiotherapy and a conservative surgical approach can be proposed. The aim of the study was to review all patients treated in our Institute with conservative surgery and postoperative radiotherapy for locally advanced supraglottic tumor., Methods and Study Design: A retrospective analysis of 32 patients treated between 2000 and 2010 was performed. Overall survival, disease-free survival and late laryngeal toxicity were evaluated. The impact of surgical procedures, radiotherapy characteristics and addition of chemotherapy on late laryngeal toxicity was studied., Results: The median follow-up was 38 months. Overall survival and disease-free survival at 5 years were 73% and 66%, respectively. Three (9%) patients experienced local recurrence (after 22, 25 and 40 months, respectively) and were treated with total laryngectomy. The larynx preservation rate was 93%. Severe treatment-related late laryngeal toxicity (grade 3 and 4 laryngeal edema, laryngeal stenosis, presence of tracheotomy at last follow-up because of treatment-related toxicity, and the need for enteral nutrition) was experienced by 34% of patients. The functional larynx preservation rate was 81%. The statistically significant risk factors for severe late toxicity were: female gender, extension of the surgical procedure, removal of one arytenoid and association with concomitant chemotherapy., Conclusions: We confirmed literature data on the feasibility and efficacy of a surgical organ preservation strategy. However, the high incidence of severe late toxicity requires further studies to improve patient selection and to reduce side effects.

Aims and Background: To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies. MATERIAL AND STUDY DESIGN: A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed. Minimum 5-year follow-up was required. Each index case was matched with 5 controls by 1) year of birth, 2) year of radiotherapy and 3) follow-up duration. Peridose-software was used to calculate peripheral dose., Results: 195 second cancers were registered (19% [corrected] of all patients treated with adjuvant irradiation). Several methodological limitations of the Peridose calculation were encountered including impossibility to calculate the peripheral dose in the patients treated with intraoperative or external electron beam radiotherapy, in case of second tumors located at <15 cm from the radiotherapy field etc. Moreover, Peridose requires full radiotherapy data and the distance between radiotherapy field and second primary site. Due to these intrinsic limitations, only 6 index cases were eligible for dose calculation. Calculated doses at the second cancer site in index cases and in an analogous site in controls ranged between 7.5 and 145 cGy. The mean index-control dose difference was -3.15 cGy (range, -15.8 cGy and +2.7 cGy)., Conclusions: The calculated peripheral doses were low and the index-control differences were small. However, the small number of eligible patients precludes a reliable analysis of a potential dose-response relationship. Large patient series followed for a long period and further improvement in the methodology of the peripheral dose calculation are necessary in order to overcome the methodological challenges of the study.

Aims and Background: To evaluate clinical outcome and toxicity using high-dose-rate brachytherapy as monotherapy in head and neck carcinomas., Methods: Between September 2004 and April 2010, a series of 12 patients with lip (7 patients) or buccal mucosa (5 patients) cancers were treated by exclusive interstitial high-dose-rate brachytherapy. The median age of the patients was 71.5 years (range, 47-87). Stages were T1N0M0 and T2N0M0 in 6 and 6 patients, respectively. A dose of 27 to 54 Gy in 9 to 16 fractions, 3 to 4.5 Gy per fraction, 2 fractions per day with a minimal gap of 6 h in between was delivered., Results: After a median follow-up of 46 months (range, 10-85), the disease-free and overall survival was 83% (10 of 12 patients) and 50% (6 of 12 patients), respectively. The crude local control in the lip cancer patients was 100% and in the buccal mucosa cancer patients was 60%. No severe toxicity was registered., Conclusions: High-dose-rate brachytherapy is feasible and safe and offers the possibility to treat patients in an outpatient regimen.

Aims and Background: Salivary gland malignancies are rare. The aim of our study was to investigate radiotherapy-related toxicity and clinical outcome in patients treated at our division with postoperative radiotherapy (pRT) for parotid tumors., Methods and Study Design: Forty-three consecutive patients (32 with primary parotid tumors, 9 with parotid metastases and 2 with recurrent benign diseases) were retrospectively analyzed., Results: The median follow-up was 28 months. Twenty and 5 patients had a follow-up longer than 2 and 5 years, respectively. Thirty-seven patients were alive and most of them (78%) were free from disease. The local and distant control rates were higher in patients with primary parotid tumors (94% and 87.5%) than in patients with parotid metastases (87.5% and 75%). Grade 3 radiotherapy-related acute toxicity of skin and mucosa was recorded in 20.9% and 28% of patients, respectively. Two patients (4.7%) had grade 4 skin toxicity. Late toxicity data were available for 33 (77%) patients. None of the patients developed severe (grade 3 and 4) late toxicity of soft tissues, skin or temporomandibular joints., Conclusions: Postoperative radiotherapy is a feasible treatment that was found to be effective mainly in patients with primary parotid tumors. Toxicity was acceptable but could probably be further reduced using more advanced radiotherapy techniques. Longer follow-up is required to achieve definitive results.

Aims and Background: To evaluate the feasibility, toxicity and patient outcome of hypofractionated 3-dimensional conformal radiotherapy for low- and intermediate-risk prostate cancer, using daily an ultrasound targeting system (BAT)., Methods: Between May 2005 and October 2006, 25 patients (cT1-T2, GS < or = 7, mean initial PSA = 7.06 ng/ml) received a dose of 72 Gy in 30 fractions. Only the prostate was included in the clinical target volume. Immediately before each radiotherapy session, BATTM ultrasound alignment was performed. Acute and late toxicity was evaluated according to the Radiation Therapy Oncology Group criteria; the Phoenix definition (PSA = nadir + 2 ng/ml) was applied to define biochemical failure. BAT localization data were provided for 300 out of 750 procedures., Results: No interruptions in 3-dimensional conformal radiotherapy due to toxicity were registered. There was no acute rectal toxicity in 52% of patients; 28% had G1, 16% had G2, and 1 patient had a G3 event. No acute urinary toxicity was observed in 28% of the patients. G1 toxicity occurred in 40%, G2 in 28%, and G3 in 1 patient; no G4 event was observed. With an average follow-up of 45 months, one biochemical relapse was observed; late toxicity showed an excellent profile: 78% of the patients had no rectal toxicity, 16% had G1, and 1 patient had G2 toxicity. Most of the patients (68%) had no late urinary complications, whereas 32% had G1 toxicity. Localization data showed systematic and random errors in relation to some procedure biases., Conclusions: Promising tumor control and toxicity profile were observed with this mildly hypofractionated BAT-based 3-dimensional conformal radiotherapy.

Aims and Background: Technological advances in treatment planning and execution are providing new potential opportunities in the treatment of recurrent prostate cancer. This study was conducted to evaluate the feasibility and safety of reirradiation with image-guided radiosurgery using CyberKnife, a robotic arm-driven compact linear accelerator, for intraprostatic recurrence after external beam radiotherapy (EBRT)., Methods: Between September 2007 and May 2008, 6 patients diagnosed with locally recurrent prostate cancer after EBRT were treated using the CyberKnife system. The total reirradiation dose was 30 Gy in five fractions. Prior to radiosurgery four patients were treated with androgen-deprivation therapy. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and the Houston-Phoenix definition (PSA nadir + 2 ng/mL) were used for toxicity and biochemical failure evaluation, respectively., Results: After a median follow-up of 11.2 months (range, 9.6-18.6 months), all patients are alive with no evidence of severe urinary or rectal acute morbidity. Local control cannot be exactly determined due to the short follow-up and the bias of the use of androgen ablation. Four patients had biochemical failure, three of them with clinical failure evidence (lymph node, bone and lung metastasis, respectively): none of these patients had clinical evidence of tumor persistence in the prostate., Conclusions: Salvage radiosurgery with CyberKnife after irradiation is feasible with low urinary and rectal morbidity. A longer follow-up and a larger number of patients are necessary to evaluate its effectiveness and optimal patient selection criteria.

No standard treatment exists for locally relapsed prostate cancer after primary external beam radiotherapy with no evidence of distant metastases. Radical prostatectomy, brachytherapy, cryotherapy and high-intensity focused ultrasound are currently used as local salvage treatments. Data on the safety and effectiveness of high dose rate (HDR) brachytherapy in this scenario are limited. We report on a patient who has no evidence of disease and no late urinary or gastrointestinal toxicity 33 months after receiving HDR treatment for recurrent prostate cancer.

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine skin carcinoma. It usually affects sun-exposed skin of white elderly people. MCC is characterized by a high incidence of early locoregional relapse and distant metastases. Because of its rarity and the resulting lack of prospective randomized trials, data regarding the optimal treatment of MCC are limited. Despite aggressive multimodality treatment, the prognosis of patients bearing MCC is often poor. We report three cases of lymph node metastases of MCC with unknown primary sites. Two patients died 17 and 28 months after diagnosis due to brain and pancreatic metastases, respectively, without evidence of cutaneous disease. The third patient is alive and free of tumor at 16 months from the diagnosis. After an accurate diagnosis of lymph node metastases from MCC, the absence of a primary tumor at complete initial evaluation and during adequate follow-up can confirm this particular clinical scenario. The prognosis seems to be analogous to that of cases with similar disease stage (lymph node involvement) but a known primary site.

Delineation of target volumes is increasingly recognized as the most crucial step within the process of modern conformal radiotherapy. In the field of head and neck radiation oncology, the need for a standardized methodology in the delineation of nodal regions of the neck on computed tomography (CT) images has recently emerged. To address this issue, a consensus document has been prepared by the Head and Neck Working Party of the AIRO-Lombardia Cooperative Group, based on the proceedings of multidisciplinary meetings and on literature findings. The document contains detailed guidelines for the delineation on CT images of the nodal regions of the neck, including for each nodal region (1 to 7) the description of anatomical limits as seen on CT images.

Acute and chronic radiotherapy-related fatigue occurs in up to 80% and 30%, respectively, of patients undergoing irradiation for cancer. Frequently, the symptom is not expected by the patients and is underestimated by medical and nursing staff. Fatigue can affect global quality of life more than pain, sexual dysfunction and other cancer- or treatment-related symptoms. Its etiology and correlates are not clear. Published reports are mainly descriptive, and in many of them numerous methodological biases are present. One of the limitations is lack of a standard method of assessment that could simplify the comparison between different series. In the last decade, modern instruments have been designed to measure fatigue. They include uni- and multidimensional tools. Use of these specific instruments is highly recommended for research on radiation-related fatigue. In daily practice when time is limited, simple assessment is necessary. For example, systemic use of plain and easily understandable questions about fatigue, its level and impact on daily life could be sufficient and reliable. Therapeutic strategies for radiotherapy-induced fatigue have not yet been clearly defined, but a few randomized studies have been recently published. Physical exercise, group psychotherapy and relaxation therapy have been demonstrated to be effective. Moreover, pharmacological treatment of concomitant disturbances (anemia, pain, insomnia, depression, dehydration, infection, malnutrition) and other radiotherapy side effects (diarrhea, hormonal insufficiency etc.) should be considered. Further methodologically correct studies are warranted to better define the causes, optimal prevention, assessment and management of this symptom.