Omentum flap as a spacer before carbon ion radiotherapy for gynecological recurrences. A technical note.

Re-irradiation of pelvic recurrent gynecological cancer is a challenge due to the proximity of high-radiation-sensitive organs, such as the bowel and the urinary tract. Hadrontherapy for re-irradiation emerges as a safe and effective treatment with a mild rate of morbidity of surrounding normal tissue. To improve the dose to the tumor, a prophylactic displacement of organs at risk is needed, and a multidisciplinary approach is recommended. In this technical note, we report a surgical technique of omentum spacer placement for patients enrolled for carbon ion radiotherapy as re-irradiation for recurrent gynecological tumors.

Dosimetric effect of variable rectum and sigmoid colon filling during carbon ion radiotherapy to sacral chordoma.

PURPOSE: Carbon ion radiotherapy (CIRT) is sensitive to anatomical density variations. We examined the dosimetric effect of variable intestinal filling condition during CIRT to ten sacral chordoma patients. METHODS: For each patient, eight virtual computed tomography scans (vCTs) were generated by varying the density distribution within the rectum and the sigmoid in the planning computed tomography (pCT) with a density override approach mimicking a heterogeneous combination of gas and feces. Totally full and empty intestinal preparations were modelled. In addition, five different intestinal filling conditions were modelled by a mixed density pattern derived from two combined and weighted Gaussian distributions simulating gas and feces respectively. Finally, a patient-specific mixing proportion was estimated by evaluating the daily amount of gas detected in the cone beam computed tomography (CBCT). Dose distribution was recalculated on each vCT and dose volume histograms (DVHs) were examined. RESULTS: No target coverage degradation was observed at different vCTs. Rectum and sigma dose degradation ranged respectively between: [-6.7; 21.6]GyE and [-0.7; 15.4]GyE for D50%; [-377.4; 1197.9] and [-95.2; 1027.5] for AUC; [-1.2; 10.7]GyE and [-2.6; 21.5]GyE for D1%. CONCLUSIONS: Variation of intestinal density can greatly influence the penetration depth of charged particle and might compromise dose distribution. In particular cases, with large clinical target volume in very close proximity to rectum and sigmoid colon, it is appropriate to evaluate the amount of gas present in the daily CBCT images even if it is totally included in the reference planning structures.

Development and validation of a new set-up simulator dedicated to ocular proton therapy at CNAO.

An Eye Tracking System (ETS) is used at CNAO for providing a stable and reproducible ocular proton therapy (OPT) set-up, featuring a fixation light (FL) and monitoring stereo-cameras embedded in a rigid case. The aim of this work is to propose an ETS set-up simulation algorithm, that automatically provides the FL positioning in space, according to patient-specific gaze direction and avoiding interferences with patient, beam and collimator. Two configurations are provided: one in the CT room for acquiring images required for treatment planning with the patient lying on a couch, and one related to the treatment room with the patient sitting in front of the beam. Algorithm validation was performed reproducing ETS simulation (CT) and treatment (room) set-up for 30 patients previously treated at CNAO. The positioning accuracy of the device was quantified through a set of 14 control points applied to the ETS case and localizable both in the CT volume and in room X-ray images. Differences between the position of ETS reference points estimated by the algorithm and those measured by imaging systems are reported. The corresponding gaze direction deviation is on average 0.2° polar and 0.3° azimuth for positioning in CT room and 0.1° polar and 0.4° azimuth in the treatment room. The simulation algorithm was embedded in a clinically usable software application, which we assessed as capable of ensuring ETS positioning with an average accuracy of 2 mm in CT room and 1.5 mm in treatment room, corresponding to gaze direction deviations consistently lower than 1°.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

Reirradiation of salivary gland tumors with carbon ion radiotherapy at CNAO.

AIMS: To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. METHODS: From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. RESULTS: Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. CONCLUSIONS: CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

Carbon ions therapy as single treatment in chordoma of the sacrum. Histologic and metabolic outcome studies.

OBJECTIVE: Even though carbon ions treatment (CIRT) of sacral chordoma (SC) substantially reduces tumor mass, tumor remnants are observed in most patients. Differentiating tumor remnants from necrosis is challenging, expensive in terms of imaging and time-consuming. So far, there has not been a systematic histological and metabolic analysis of post-CIRT lesions. We designed a prospective study aiming to histologically a metabolically differentiate between viable tumor and foci of necrosis and of fibrosclerosis after CIRT and correlate these findings to clinical outcome in patients with SC. PATIENTS AND METHODS: Between January 2013 and December 2016 18 patients, 12 males and 6 females, with histological confirmation of sacral chordoma, underwent CIRT. The total dose was 70.4 GyE, with a daily fraction of 4.4 GyE, for 4 weeks. MRI was performed every three months after treatment. FDG PET-CT scan and CT-guided needle biopsy were performed 6-12 months after CIRT. The incidence of complications (intraoperative and postoperative), local control (LC), overall survival (OS) and progression-free survival (PFS), changes in neurological status, clinical outcomes and toxicity were considered. RESULTS: All histological analysis but 2 reported signs of necrosis and of fibrosclerosis after CIRT. One of these 2 patients turned into a dedifferentiated chordoma. Radiological partial response (PR) was observed in 10 patients (56.3%) and stable disease (SD) in 5 patients (28.3). Two patients (11%) had a local relapse. The overall survival rate was 100% at 24 months. FDG PET CT after CIRT showed uptake decreasing compared with the baseline exam in all but one patient. CONCLUSIONS: The histological presence of necrosis and of fibrosclerosis after CIRT at the histological analysis supports the previous clinical evidence on the efficacy of CIRT. Volumetric stability of the residual mass should be considered as a success of treatment. In cases of a volumetric increase of the mass, a CT needle biopsy should always be performed. In our series, during the follow-up, the FDG-PET was able to promptly detect an increased uptake in the case which later was histologically defined as dedifferentiated chordoma.

Aggressive hemangioma starting from l5 body, treated with mass embolization and radiation therapy with protons: a case report.

A hemangioma is a benign tumor of endothelial cells, multiplying into the medullary spaces of the cancellous bone. This tumor is in most cases not symptomatic, and in this case, they do not require any specific treatment. Pain and neurological symptoms derived from hemangiomas as shown in 2-11% of the cases. The 55% of these cases presents low back pain, while the 45% presents neurological deficit from compression of the spinal cord, peripheral nerves or both. We present a clinical case report of a young woman, affected by aggressive L5 hemangioma causing a spinal canal stenosis with associated sciatalgic symptoms. We performed a review of the current literature on the treatment options, giving the rationale of our treatment choice (mass embolization and radiation therapy with protons).

Dosimetric characterization of carbon fiber stabilization devices for post-operative particle therapy.

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.

Cervical 10 kHz spinal cord stimulation in the management of chronic, medically refractory migraine: A prospective, open-label, exploratory study.

BACKGROUND: A significant minority of chronic migraine (CM) subjects fail conventional medical treatment (rCM), becoming highly disabled. Implantation of an occipital nerve stimulator is a therapeutic option for these subjects. Paresthesia-free cervical 10 kHz spinal cord stimulation (HF10 SCS) may provide an alternative. We report the results of a prospective, open-label, exploratory study assessing the long-term safety, tolerability and efficacy of cervical HF10 SCS in cohort of rCM subjects. METHODS: Included subjects were diagnosed with CM by an experienced headache specialist with the aid of an hourly headache diary. They were refractory to conventional medical treatments including onabotulinumtoxin-A injections. Medication overuse headache was not an exclusion criteria. Enrolled subjects underwent a 2- to 4-week tunnelled cervical HF10 SCS trial followed by a permanent system implant if a significant, subjective reduction in headache intensity/episodes was reported during the trial. Subjects were evaluated at baseline and 6 months after implantation with the aid of monthly diaries and headache-specific questionnaires. RESULTS: Seventeen subjects underwent a trial of cervical HF10 SCS; 14 were still implanted at 6 months (one trial failure, one trial infection, one implant site infection). Seven of the 14 subjects had >30% reduction in headache days. The average reduction in headache days was 6.9 for the overall population and 12.9 among the responders. Three subjects reported tenderness over the IPG/connection site, and one had a lead migration that required surgical revision. CONCLUSION: Paresthesia-free cervical HF10 SCS may be a safe and effective therapeutic option for chronic migraineurs refractory to conventional treatments.

Early effects comparison of X-rays delivered at high-dose-rate pulses by a plasma focus device and at low dose rate on human tumour cells.

A comparative study has been performed on the effects of high-dose-rate (DR) X-ray beams produced by a plasma focus device (PFMA-3), to exploit its potential medical applications (e.g. radiotherapy), and low-DR X-ray beams produced by a conventional source (XRT). Experiments have been performed at 0.5 and 2 Gy doses on a human glioblastoma cell line (T98G). Cell proliferation rate and potassium outward currents (IK) have been investigated by time lapse imaging and patch clamp recordings. The results showed that PFMA-3 irradiation has a greater capability to reduce the proliferation rate activity with respect to XRT, while it does not affect IK of T98G cells at any of the dose levels tested. XRT irradiation significantly reduces the mean IK amplitude of T98G cells only at 0.5 Gy. This work confirms that the DR, and therefore the source of radiation, is crucial for the planning and optimisation of radiotherapy applications.

Initial clinical experience with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO).

We report the initial toxicity data with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO). In September 2011, CNAO commenced patient treatment with scanned proton beams within two prospective Phase II protocols approved by the Italian Health Ministry. Patients with chondrosarcoma or chordoma of the skull base or spine were eligible. By October 2012, 21 patients had completed treatment. Immobilization was performed using rigid non-perforated thermoplastic-masks and customized headrests or body-pillows as indicated. Non-contrast CT scans with immobilization devices in place and MRI scans in supine position were performed for treatment-planning. For chordoma, the prescribed doses were 74 cobalt grey equivalent (CGE) and 54 CGE to planning target volume 1 (PTV1) and PTV2, respectively. For chondrosarcoma, the prescribed doses were 70 CGE and 54 CGE to PTV1 and PTV2, respectively. Treatment was delivered five days a week in 35-37 fractions. Prior to treatment, the patients' positions were verified using an optical tracking system and orthogonal X-ray images. Proton beams were delivered using fixed-horizontal portals on a robotic couch. Weekly MRI incorporating diffusion-weighted-imaging was performed during the course of proton therapy. Patients were reviewed once weekly and acute toxicities were graded with the Common Terminology Criteria for Adverse Events (CTCAE). Median age of patients = 50 years (range, 21-74). All 21 patients completed the proton therapy without major toxicities and without treatment interruption. Median dose delivered was 74 CGE (range, 70-74). The maximum toxicity recorded was CTCAE Grade 2 in four patients. Our preliminary data demonstrates the clinical feasibility of scanned proton beams in Italy.

Quality of life in patients with chordomas/chondrosarcomas during treatment with proton beam therapy.

INTRODUCTION: Health-related quality of life (HQL) parameters have never been tested in patients having chondromas/chondrosarcomas who are being treated with protons. The aim of this study was to document changes in HQL of chordoma/chondrosarcoma patients treated with proton beam radiotherapy. Treatments commenced in September 2011 at CNAO, and HQL studies were initiated in January 2012 for all patients undergoing treatment. METHODS: The validated Italian translation of the EORTC QLQ-C30 version 3.0 was used for HQL evaluation. The HQL assessments were made prior to starting radiation and at completion of treatment. Scoring was as per the EORTC manual. As per standard norms, a difference of >10 points in the mean scores was taken to be clinically meaningful. RESULTS: Between January and September 2012, 17 patients diagnosed with chordoma or chondrosarcoma, with a mean ± SD age of 49.5 ± 16.4 years, had completed treatment. The involved sites were skull base (n = 12) and sacral/paraspinal (n = 5). The prescribed dose was 70-74 GyE at 2 GyE per fraction, 5 days/week. When comparing pre- and post-treatment scores, neither a clinically meaningful nor a statistically significant change was documented. CONCLUSIONS: During treatment, HQL is not adversely affected by protons, allowing normal life despite the long course of treatment. This is an ongoing study and more long-term assessment will help evaluate the actual impact of proton therapy on HQL for these slow-responding tumours.