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Skull base chordomas (SBC) are rare malignant tumors and few factors have been found to be reliable markers for clinical decision making and survival prognostication. The aim of the present work was to identify specific prognostic factors potentially useful for the management of SBC patients. A retrospective review of all the patients diagnosed and treated for SBC at the Fondazione IRCCS Istituto Neurologico “Carlo Besta” between January 1992 and December 2017 has been performed. Survival analysis was performed and a logistic regression model was used. Statistically significant predictors were rated based on their log odds in order to preliminarily build a personalized grading scale—the Peri-Operative Chordoma Scale (POCS). Fifty-nine primary chordoma patients were included. The average follow-up from the first treatment was 82.6 months (95% CI, 65.5–99.7). POCS was built over PFS and MR contrast enhancement (intense vs mild/no, value 4), preoperative motor deficit (yes vs no, value 3), and the development of any postoperative complications (yes vs no, value 2). POCS ranges between 0 and 9, with higher scores being associated with reduced likelihood of survival and progression-free state. Our results show that preoperative clinical symptoms (motor deficits), surgical features (extent of tumor resection and surgeon’s experience), development of postoperative complications, and KPS decline represent significant prognostic factors. The degree of MR contrast enhancement significantly correlated to both OS and PFS. We also preliminarily developed the POCS as a prognostic grading scale which may help neurosurgeons in the personalized management of patients undergoing potential adjuvant therapies.

Purpose/objective The purpose of this study is to assess the impact of the conversion scheme for relative biological effectiveness (RBE)-weighted dose (DRBE), implemented at our center, on treatment outcomes of adenoid cystic carcinoma (ACC) patients. Material/methods Treatment plans of 78 ACC patients, optimized with the Local Effect Model (LEM), were recalculated with the modified Microdosimetric Kinetic Model (mMKM). DRBE to 95%, 50% and 2% (DV%) of the clinical target volume (CTV), were selected as relevant parameters to compare LEM and mMKM DRBE. The pattern of failure of ACC treatments was analyzed in relation to uncertainties involved in the DRBE translation methodology. Results mMKM recalculations of LEM plans, optimized to a prescription dose of 68.8 Gy(RBE), showed a D50% 8% higher, on average, than the expected value (60.8 Gy(RBE)), closer to the most frequently used mMKM prescription DRBE (64 Gy(RBE)). D95% and D2% deviations, with respect to the optimization goals in the two RBE systems, increased of 0.5% and 14.2%, respectively, due to the steeper mMKM RBE variation along the beam path. Local recurrences were mainly (63%) reported in areas where CTV coverage was not satisfactory in the original LEM plan and the mMKM analysis showed that OARs constraints were too conservative. Conclusion No case of local recurrence could be explained by inadequate mMKM target coverage that was not already present in the LEM plan. New constraints have been defined for optic pathways and brainstem to improve target coverage with no expected increase in tissue complications.

Hadrontherapy has been in constant progress in the past decades. Due to the increasing interest in this field and the spreading of the technique in Italy and worldwide, the Italian Society of Radiation Oncology surveyed (by an online survey) its members regarding their perception of hadrontherapy. The survey outline addressed different items all related to hadrontherapy, such as: demographics (3 items), personal knowledge (5 items), actual use in clinical practice (5 items), and future perspectives and development (5 items). The survey was filled in by 224 radiation oncologists (RO). Among them, 74.6 % were RO with more than 5 years of clinical practice, and only 10.4 % RO in training. Median age was 46 years (range 27-77). 32.24 % admitted average knowledge about heavy particles radiobiology rationale and 32.42 % about the ongoing particle therapy clinical trials. Radioresistant tumors are perceived as-principal indications for carbon ions in 39.3 % of responders, and pediatric malignancies for protons in 37 %. Re-irradiation is highly recommended for 52.2 %. Strikingly, 38.8 % of participating ROs reported that, in the daily clinical practice, approximately less than 1 out of 10 patients asks to be referred for hadrontherapy. On the other side, 35.7 % claimed need for at least 3 up to 5 particle therapy centers in Italy. Overall, the results of the present survey highlight the interest of the Italian RO community for particle therapy among the other radiotherapy technique. Analysis of our results might picture the clinical attitude of the RO community towards hadrontherapy in Italy, and help in promoting targeted initiatives to spread clinical results and knowledge about technical innovations in this field.

Particle therapy (PT) has shown positive therapeutic results in local control of locally advanced pancreatic lesions. PT effectiveness is highly influenced by target localization accuracy both in space, since the pancreas is located in proximity to radiosensitive vital organs, and in time as it is subject to substantial breathing‐related motion. The purpose of this preliminary study was to quantify pancreas range of motion under typical PT treatment conditions. Three common immobilization devices (vacuum cushion, thermoplastic mask, and compressor belt) were evaluated on five male patients in prone and supine positions. Retrospective four‐dimensional magnetic resonance imaging data were reconstructed for each condition and the pancreas was manually segmented on each of six breathing phases. A k‐means algorithm was then applied on the manually segmented map in order to obtain clusters representative of the three pancreas segments: head, body, and tail. Centers of mass (COM) for the pancreas and its segments were computed, as well as their displacements with respect to a reference breathing phase (beginning exhalation). The median three‐dimensional COM displacements were in the range of 3 mm. Latero–lateral and superior–inferior directions had a higher range of motion than the anterior–posterior direction. Motion analysis of the pancreas segments showed slightly lower COM displacements for the head cluster compared to the tail cluster, especially in prone position. Statistically significant differences were found within patients among the investigated setups. Hence a patient‐specific approach, rather than a general strategy, is suggested to define the optimal treatment setup in the frame of a millimeter positioning accuracy. PACS number(s): 87.55.‐x, 87.57.nm, 87.61

To estimate the impact of dose calculation approaches adopted in different treatment planning systems (TPSs) on proton therapy dose delivered with pencil beam scanning (PBS). Treatment plans for six regular volumes in water and 15 clinical cases were optimized with Syngo-VC13 and exported for forward recalculation with Raystation-V7.0 pencil beam (RS-PBA) and Monte Carlo (RS-MC) algorithms and with the independent Fluka-MC engine. To verify clinical consistency between the two TPS dosimetric outcomes, the average percentage variations of clinical target volume (CTV) D 98%, D 50% and D 2%, adopted for plan prescription and evaluation, were considered. Ionization chamber measurements served as a further reference for comparison in homogeneous conditions. CTV dose volume histogram (DVH) analysis and gamma evaluation with 3 mm-3% agreement criteria quantified the dose deviation of TPS calculation algorithms, in heterogeneous conditions, against the Fluka-MC code. CTV D 50%, representing the plan dose prescription goal, was higher on average over H&N cases of (3.9 ± 0.9)% and (2.3 ± 0.6)% as calculated with RS-PBA and RS-MC, respectively, compared to Syngo. For tumors located in the pelvis district, average D 50% variations of (1.6 ± 0.7)% and (1.2 ± 0.7)% were found. Syngo underestimated target near maximum doses with respect to all computation systems. Calculation accuracy in heterogeneous conditions of RS-PBA H&N plans resulted poor when a range shifter was required. Target DVH and γ-analysis showed excellent agreement between RS-MC and Fluka-MC, with γ-pass rates >98% for all patient groups. Different TPS dose calculation approaches mainly affected dose delivered in H&N proton treatments, while minor deviations were found for pelvic tumors. RS-MC proved to be the most accurate TPS dose calculation algorithm when compared to an independent MC simulation code.

Purpose To derive personalized tumour control probability (TCP) models, using diffusion-weighted (DW-) MRI for defining initial tumour cellular density in skull-base chordoma patients undergoing carbon-ion radiotherapy (CIRT). Materials and methods 67 patients affected by skull-base chordoma were enrolled for a standardized CIRT treatment (70.4 Gy (RBE) prescription dose). Local control information was clinically assessed. For 20 of them, apparent diffusion coefficient (ADC) maps were computed from DW-MRI and then converted into cellular density. Radiosensitivity parameters (α, β) were estimated from the available data through an optimization procedure, taking advantage of a relationship observed between local control and the dose received by at least the 98% of the gross tumour volume. These parameters were fed into two poissonian TCP models, based on the LQ model, being the first (TCPLIT) computed from literature parameters and the second (TCPADC) enriched by a personalized initial cellular density derived from ADC maps. Results The inclusion of the cellular density derived from ADC into TCPADC yielded slightly higher dose values at which TCP = 0.5 (D50 = 38.91 Gy (RBE)) with respect to TCPLIT (D5034.16 Gy (RBE)). This suggested a more conservative approach, even if the prognostic power of TCPADC and TCPLIT, tested with respect to local control, was equivalent in terms of sensitivity (0.867) and specificity (0.600). Conclusions Both TCPADC and TCPLIT exhibited good agreement with a clinically validated information of local control, the former providing more conservative predictions.

Background and purpose Until now, carbon ion RT (CIRT) dose constraints for the optic nerve (ON) have only been validated and reported in the NIRS RBE-weighted dose (DNIRS). The aim of this work is to improve CNAO’s RBE-weighted dose (DLEM) constraints by analyzing institutional toxicity data and by relating it to DNIRS. Material and methods A total of 65 ONs from 38 patients treated with CIRT to the head and neck region in the period 2013–14 were analyzed. The absorbed dose (DAbs) of the treatment plans was reproduced and subsequently both DLEM and DNIRS were applied, thus relating CNAO clinical toxicity to DNIRS. Results Median FU was 47 (26–67) months. Visual acuity was preserved for the 56 ONs in which the old constraints were respected. Three ONs developed visual decline at DLEM|1% ≥71 Gy(RBE)/DLEM|20% ≥68 Gy(RBE), corresponding to DNIRS|1% ≥68 Gy(RBE)/DNIRS|20% ≥62 Gy(RBE). Dose recalculation revealed that NIRS constraints of DNIRS|1% ≤40 Gy(RBE)/DNIRS|20% ≤28 Gy(RBE) corresponded to DLEM|1% ≤50 Gy(RBE)/DLEM|20% ≤40 Gy(RBE). Reoptimization of treatment plans with these new DLEM constraints showed that the dose distribution still complied with NIRS constraints when evaluated in DNIRS. However, due to uncertainties in the method, and to comply with the EQD2-based constraints used at GSI/HIT, a more moderate constraint relaxation to DLEM|1% ≤45 Gy(RBE)/DLEM|20% ≤37 Gy(RBE) has been implemented in CNAO clinical routine since October 2018. Conclusion New DLEM constraints for the ON were derived by analyzing CNAO toxicity data and by linking our results to the experience of NIRS and GSI/HIT. This work demonstrates the value of recalculating and reporting results in both DLEM and DNIRS.

Purpose In particle therapy, conventional treatment planning systems rely on an imaging representation of the irradiated region to compute the dose. For irregular breathing, when an imaging dataset describing the actual motion is not available, a different approach for dose estimation is needed. To this aim, we validate a method for the estimation of physical dose variations in gated carbon ion treatments, providing also a demonstration of the feasibility of physical dose metrics to assess the method performance. Finally, we describe a sample use case, in which this method is used to assess plan robustness with respect to undetected irregular tumor motion. Methods The method entails the definition of a patient- and beam-specific water equivalent depth (WED) space, the simulation of motion as a translation equal to tumor displacement, and the reconstruction of the altered dose. We validated the approach using four-dimensional computed tomographies (4DCTs) and clinical plans in 12 patients, treated with respiratory gated carbon ion beams at the National Centre for Oncological Hadrontherapy (Pavia, Italy). Using the end-exhale CT and dose distribution as a reference, the physical dose delivered at the end-inhale tumor position was estimated and compared to the ground-truth dose recalculation on the end-inhale CT. Biologically effective and physical dose variations between the plan and the recalculation were compared as well. As a use case, we evaluated dose changes caused by simulated irregular tumor motion, that is, linear and nonlinear baseline shifts and/or amplitude variations with hysteresis. Results The ratio between biologically effective and physical equivalent uniform dose (EUD) variations due to end-exhale to end-inhale motion was less than one for 96% of investigated structures. In the validation study, we found a median error corresponding to a 14% EUD overestimation for the tumor and 4% EUD underestimation for a subgroup of organs at risk, together with a high EUD variation due to motion [median 352% EUD variation between end-exhale and end-inhale doses in the planning tumor volume (PTV)]. Considering relevant dose-volume histogram (DVH) metrics, the median difference between estimated and ground truth doses was ≤ 4%. Gamma analysis between estimated and recalculated dose distributions resulted in a pass rate > 80% for 83% of the target volumes. For the two patients selected for the sample use case, a patient-specific assessment of the method performance was performed on the 4DCT and it was possible to relate EUD variations of both tumor and organs at risk to the simulated target motion. Conclusions The physical dose distribution was found to be more sensitive to motion with respect to the biologically effective one, suggesting the suitability of the physical dose metrics for the WED-space method validation. We showed that the method can compensate for intra-fractional tumor motion with proper accuracy in the selected patient group, although its use is recommended when limited deformations are expected. In conclusion, the WED-space method can provide simulations of dose alteration due to irregular breathing when imaging data are lacking, and, once integrated with relative biological effectiveness (RBE) modeling, it would be useful in evaluating the robustness of carbon ion treatment plans.

Background: Liposarcomas are the most common soft-tissue sarcomas in adulthood. Orbital and spermatic cord liposarcomas are uncommon and there is no consensus on their management. The treatment of choice is wide excision, which may be destructive and lead to unacceptable morbidity. When surgery is declined by patients and in recurrent disease, management can be challenging. We report two cases of liposarcoma treated with carbon ion radiotherapy at the National Center for Oncological Hadrontherapy (Fondazione CNAO) in Italy. Case Report: A woman with orbital liposarcoma and a man with spermatic cord liposarcoma were referred to our Center and accepted for carbon ion radiotherapy. The treatment was well tolerated and late toxicities were mild. Good local control was achieved in patients. Conclusion: In our experience, carbon ion radiotherapy is an effective and safe option, especially in cases of tumor at high risk for local relapse, in patients with multiple local recurrences, and in patients who refuse destructive surgery.

Background/aim Glioblastoma is the most malignant and widespread brain tumor in adults, with a rapid clinical course. Recently, it has been hypothesized that L-DOPA plays a role in the diagnosis and treatment of glioblastoma. The aim of this study was to assess the effects of pretreatment with L-DOPA on the biological behavior of human T98G cells in vitro. Materials and methods T98G cells were treated with 50 μg/ml or 100 μg/ml of L-DOPA for 4 h and their morphology, growth rate, clonogenic survival and migratory capacity in basal conditions and after carbon ion irradiation were evaluated using standard methods. Results Treated cells showed a lower growth rate and an increased migratory capacity that correlated with the dose of tested L-DOPA. Treatment with L-DOPA increased the growth rate of carbon ion irradiated T98G cells compared to control non-treated cells exposed to the same radiation dose. Conclusion Our results open further questions about the overall advantage of L-DOPA treatment of glioblastoma.

Purpose At Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) ocular proton therapy (OPT) is delivered using a non-dedicated beamline. This paper describes the novel clinical workflow as well as technologies and methods adopted to achieve accurate target positioning and verification during ocular proton therapy at CNAO. Method The OPT clinical protocol at CNAO prescribes a treatment simulation and a delivery phase, performed in the CT and treatment rooms, respectively. The patient gaze direction is controlled and monitored during the entire workflow by means of an eye tracking system (ETS) featuring two optical cameras and an embedded fixation diode light. Thus, the accurate alignment of the fixation light provided to the patient to the prescribed gazed direction is required for an effective treatment. As such, a technological platform based on active robotic manipulators and IR optical tracking-based guidance was developed and tested. The effectiveness of patient positioning strategies was evaluated on a clinical dataset comprising twenty patients treated at CNAO. Results According to experimental testing, the developed technologies guarantee uncertainties lower than one degree in gaze direction definition by means of ETS-guided positioning. Patient positioning and monitoring strategies during treatment effectively mitigated set-up uncertainties and exhibited sub-millimetric accuracy in radiopaque markers alignment. Conclusion Ocular proton therapy is currently delivered at CNAO with a non-dedicated beamline. The technologies developed for patient positioning and motion monitoring have proven to be compliant with the high geometrical accuracy required for the treatment of intraocular tumors.

BACKGROUND: Skull-base chordomas are rare and malignant tumors that originate from remnants of the chorda dorsalis (notochord). Adjuvant radiotherapy (RT) is an important predictor of improved progression-free survival and it is recommended after surgery. Exclusive RT represents the treatment of choice for unresectable chordomas. Particle radiotherapy provides dosimetric advantages and higher biological effective dose especially for radioresistant tumors. The aim of the study was to evaluate local control (LC) and toxicity profile of patients (pts) with skull-base chordoma treated with exclusive or adjuvant particle therapy (proton therapy -PT- and carbon ion therapy -CIRT-) MATERIAL AND METHODS: Between September 2011 and December 2017, a total of 134 pts (79 men and 55 women) with a median age of 57 years (range 14–86) with histologically proven skull-base chordoma were treated with particle therapy at National Center of Oncological Hadrontherapy -CNAO. One-hundred and two (76%) pts had previous surgery and complete macroscopic resection was achieved only in 15 pts (20%). Sixty-one pts were treated with PT and 73 with CIRT. The particle choice (proton or carbon ion) was made on personalized basis. Median prescribed total dose was 70,4 Gy RBE (range 35,2-70,4 Gy RBE) in 8–22 fractions (median 16 fractions) of 3-4,4 Gy RBE (median 4,4 Gy RBE) for CIRT, and 74 Gy RBE (range 70–74 Gy RBE) in 27–37 fractions (median 37 fractions) of 2 Gy RBE for PT. Clinical outcome (LC, 3 year local relapse free- LRFS and overall -survival -OS-) and toxicity profile were evaluated. RESULTS: The median follow-up was 32 months (range, 2–64 months). LC was 83%. In pts that underwent complete macroscopic surgery followed by PT, LC was 100%, in pts with uncomplete resection/only biopsy and PT/CIRT, LC was 79%. The 3-year LRFS and OS were 80% and 90% respectively. In field recurrence occurred in 13% (18 pts). In 16 out of 18 cases of recurrences the tumor was in close contiguity to the brainstem. Out of field recurrence was found in 5 pts: 2 cases occurred within surgical way, attributable to surgical seeding, One case of histologically confirmed cervical lymph-node relapse, 2 cases of newly appeared nodules of recurrence. Six pts (4%) developed distant metastasis after a mean interval of 12 months. The toxicity profile was favorable. Only 2 pts developed acute radiation induced high grade toxicity: with oral mucositis (grade 3). High grade (G3-G4) late toxicity occurred in 4% of pts: 1 case of complete visual loss (G4) expected because of optic nerve in field, 1 case of soft tissue necrosis, 2 cases of cranial nerve neuropathy and 2 cases of pituitary dysfunction. CONCLUSION: Particle therapy is the most innovative and conformal RT for treatment of skull base chordomas. It allows to deliver higher (biologically effective) dose levels and to obtain high tumor control rates, minimizing radiation-related side effects.

Background/aim Cell migration and invasion are fundamental components of tumor cell metastasis that represent the biggest threat to the survival and quality of life of cancer patients. There is clear evidence that ionizing radiation can differently modulate migration and invasiveness of cancer cells depending on the cell lines, the doses and the radiation types investigated. This suggests that motile cells are able to adopt different migration strategies according to their molecular characteristics and external signals. Materials and methods In this study, a morphological analysis was performed on pancreatic cancer Aspc-1 cells to evaluate the amoeboid-mesenchymal mobility transition in several experimental conditions considering the role played by factors released by normal and tumor cells, in basal conditions and after low and high Linear Energy Transfer (LET) irradiation. Results and conclusion The migratory behavior of Aspc-1 cells is modulated by factors released by normal fibroblasts and tumor cells, and this is in turn modulated by both the radiation dose and the radiation quality.

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.

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

Particle therapy exploits the energy deposition pattern of hadron beams. The narrow Bragg Peak at the end of range is a major advantage but range uncertainties can cause severe damage and require online verification to maximise the effectiveness in clinics. In-beam Positron Emission Tomography (PET) is a non-invasive, promising in-vivo technique, which consists in the measurement of the β+ activity induced by beam-tissue interactions during treatment, and presents the highest correlation of the measured activity distribution with the deposited dose, since it is not much influenced by biological washout. Here we report the first clinical results obtained with a state-of-the-art in-beam PET scanner, with on-the-fly reconstruction of the activity distribution during irradiation. An automated time-resolved quantitative analysis was tested on a lacrimal gland carcinoma case, monitored during two consecutive treatment sessions. The 3D activity map was reconstructed every 10 s, with an average delay between beam delivery and image availability of about 6 s. The correlation coefficient of 3D activity maps for the two sessions (above 0.9 after 120 s) and the range agreement (within 1 mm) prove the suitability of in-beam PET for online range verification during treatment, a crucial step towards adaptive strategies in particle therapy.

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 The aim of this study was to evaluate the dosimetric impact caused by recently introduced carbon fiber reinforced polyetheretherketone (CF/PEEK) stabilization devices, in comparison with conventional titanium (Ti) implants, for post-operative particle therapy (PT). Methods As a first step, protons and carbon ions Spread-Out Bragg Peaks (SOBPs) were delivered to CF/PEEK and Ti screws. Transversal dose profiles were acquired with EBT3 films to evaluate beam perturbation. Effects on image quality and reconstruction artifacts were then investigated. CT scans of CF/PEEK and Ti implants were acquired according to our clinical protocol and Hounsfield Unit (HU) mean values were evaluated in three regions of interest. Implants and artifacts were then contoured in the sample CT scans, together with a target volume to simulate a spine tumor. Dose calculation accuracy was assessed by comparing optimized dose distributions with Monte Carlo simulations. In the end, the treatment plans of nine real patients (seven with CF/PEEK and two with Ti stabilization devices) were retrospectively analyzed to evaluate the dosimetric impact potentially occurring if improper management of the spine implant was carried out. Results As expected, CF/PEEK screw caused a very slight beam perturbation in comparison with Ti ones, leading to a lower degree of dose degradation in case of contouring and/or set-up uncertainties. Furthermore, CF/PEEK devices did not determine appreciable HU artifacts on CT images thus improving image quality and, as a final result, dose calculation accuracy. Conclusions CF/PEEK spinal fixation devices resulted dosimetrically more suitable than commonly-used Ti implants for post-operative PT.

Anal canal accounts for 2% of all cancer and its incidence increases with age with a predominance in woman. About 80% of all primary anal canal cancers are squamous; adenocarcinoma arising from the glands or glandular ducts shows a behaviour that is similar to that of the adenocarcinoma of the rectum. Risk factors includes sexually transmitted infection with Human Papillomavirus, cigarette smoking, immunosuppression, and sexual practices. The standard treatment for anal canal is chemo - radiation with a combination of fluoropyrimidines and mitomycin or cisplatin. Salvage surgery may be necessary for residual disease after radiotherapy or chemoradiation, for locoregional relapse and/or for sequelae. In the metastatic setting a multidisciplinary approach is preferred and includes medical treatment, surgery, and RT, if appropriate. Discussing these possible options in the initial stage is of most importance to ensure the best quality of life (QoL) for patients.

Purpose Around 10 centers worldwide treat ocular tumors with proton therapy, all with dedicated eyelines. Our synchrotron-based facility is equipped with general-purpose fixed beamlines; proton and carbon ion treatments are delivered with pencil beam scanning modality (range in water 3 ÷ 32 cm). Recently, our proton beamline was adapted to treat also ocular diseases. The main dosimetric properties of this new eyeline are described in this work. Methods A 3 cm water-equivalent range shifter (RS) was placed along the beamline to reach shallower penetration depths. In order to achieve steep lateral dose gradients, the position of the RS and patient-specific collimator were simulated using MonteCarlo (MC) FLUKA code. Lateral dose profiles were measured with gafchromic EBT3 films to evaluate lateral penumbra width and dose homogeneity. Several beam scanning patterns were tested. Depth-dose distributions (DDDs) were measured with the Peakfinder system. To obtain uniform dose distributions (Spread-Out Bragg Peaks, SOBPs), the weights of each DDD were optimized simulating different targets. Absorbed doses were then measured in water with an advanced Markus chamber. Neutron dose at the contralateral eye was also evaluated with passive bubble dosimeters. Results MC simulations and experimental results showed that maximizing the distance between RS and collimator reduces the lateral dose penumbra of the collimated beam and increases field transversal dose homogeneity. Therefore, RS and patient-specific collimator were placed at about 98 cm (behind beam monitors) and 6 cm from the isocenter, respectively. The lateral penumbra (distal fall-off) ranged between 1.0 and 1.8 mm (1.0 and 1.6 mm). The measured SOBP doses were in very good agreement with MC simulations, as shown in Fig. 1. The mean neutron dose at the contralateral eye was 68.8 ± 10.2 μSv/Gy. Conclusions Our eyeline satisfied the requirements to treat ocular tumors. The first ocular patient was treated in August 2016. Around 60 patients have been treated so far.

Objectives: Our aim was to assess FDG-PET/CT as a surrogate biomarker of the pathological complete response in locally advanced rectal cancer treated with neoadjuvant chemoradiation. Methods: T3–4 and/or N+ rectal cancer patients were treated prospectively with capecitabine-based chemoradiation and total mesorectal excision 7–8 weeks later. FDG-PET/CT uptake was obtained at baseline, after 2 weeks, and 6 weeks following treatment completion, calculating the maximum standardized uptake value (SUV) and percentage difference to identify the early and late metabolic ‘response index’. Results: Thirty-one patients were treated from January 2009 to January 2012 at the Istituto Nazionale dei Tumori of Milan. One patient was excluded due to surgery refusal. The pathological complete response rate was 30%. Early FDG-PET/CT was performed in 24 consenting patients and failed to show predictive utility. On the contrary, significant differences in late SUV value and response index were observed between complete and noncomplete pathological responders (p = 0.0006 and 0.03). In multivariate analysis including most relevant SUV parameters, none of them was independently associated with a pathological complete response. With receiver operating characteristic curve analysis, a late SUV threshold Conclusions: We evidenced a possible predictive role of late FDG-PET/CT for the assessment of pathological response in locally advanced rectal cancer following neoadjuvant chemoradiation.

At the Italian National Centre for Oncologic Hadrontherapy (CNAO) patients with upper-abdominal tumours are being treated with carbon ion therapy, adopting the respiratory gating technique in combination with layered rescanning and abdominal compression to mitigate organ motion. Since online imaging of the irradiated volume is not feasible, this study proposes a modelling approach for the estimation of residual motion of the target within the gating window. The model extracts a priori respiratory motion information from the planning 4DCT using deformable image registration (DIR), then combines such information with the external surrogate signal recorded during dose delivery. This provides estimation of a CT volume corresponding to any given respiratory phase measured during treatment. The method was applied for the retrospective estimation of tumour residual motion during irradiation, considering 16 patients treated at CNAO with the respiratory gating protocol. The estimated tumour displacement, calculated with respect to the reference end-exhale position, was always limited (average displacement is 0.32±0.65mm over all patients) and below the maximum motion defined in the treatment plan. This supports the hypothesis of target position reproducibility, which is the crucial assumption in the gating approach. We also demonstrated the use of the model as a simulation tool to establish a patient-specific relationship between residual motion and the width of the gating window. In conclusion, the implemented method yields an estimation of the repeatability of the internal anatomy configuration during gated treatments, which can be used for further studies concerning the dosimetric impact of the estimated residual organ motion.