3D-printed boluses for radiotherapy: influence of geometrical and printing parameters on dosimetric characterization and air gap evaluation.

The work investigates the implementation of personalized radiotherapy boluses by means of additive manufacturing technologies. Boluses materials that are currently used need an excessive amount of human intervention which leads to reduced repeatability in terms of dosimetry. Additive manufacturing can solve this problem by eliminating the human factor in the process of fabrication. Planar boluses with fixed geometry and personalized boluses printed starting from a computed tomography scan of a radiotherapy phantom were produced. First, a dosimetric characterization study on planar bolus designs to quantify the effects of print parameters such as infill density and geometry on the radiation beam was made. Secondly, a volumetric quantification of air gap between the bolus and the skin of the patient as well as dosimetric analyses were performed. The optimization process according to the obtained dosimetric and airgap results allowed us to find a combination of parameters to have the 3D-printed bolus performing similarly to that in conventional use. These preliminary results confirm those in the relevant literature, with 3D-printed boluses showing a dosimetric performance similar to conventional boluses with the additional advantage of being perfectly conformed to the patient geometry.

Hypofractionated proton therapy for benign tumors of the central nervous system: A systematic review of the literature.

AIMS: Aim of the present analysis was to report results of a systematic review of the literature in the setting of patients treated with hypoF PT for benign lesions of the central nervous system (CNS). METHODS: The methodology complied with the PRISMA recommendations. PubMed, EMBASE and Scopus databases were interrogated in September 2022. RESULTS: Twelve papers have been selected including patients treated for base of the skull meningiomas (6 papers), vestibular schwannoma (3 papers) and pituitary adenomas (3 papers). Clinical outcomes were evaluated with both radiologic images and clinical parameters. Long-term toxicity was reported in all but one series with an incidence ranging from 2 % to 7 % in patients treated for base of skull meningioma and 1-9 % for schwannoma. CONCLUSIONS: HypoF PT is a safe and effective treatment in selected benign tumors of the CNS. Further dosimetric and clinical comparisons are required to better refine the patients' selection criteria.

Ultrahypofractionated radiotherapy for localized prostate cancer with simultaneous boost to the dominant intraprostatic lesion: a plan comparison.

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.

Finding safe dose-volume constraints for re-irradiation with SBRT of patients with prostate cancer relapse: The IEO experience.

AIM: The primary aim of this study is to provide preliminary indications for safe constraints of rectum and bladder in patients re-irradiated with stereotactic body RT (SBRT). METHODS: Data from patients treated for prostate cancer (PCa) and intraprostatic relapse, from 1998 to 2016, were retrospectively collected. First RT course was delivered with 3D conformal RT techniques, SBRT or volumetric modulated arc therapy (VMAT). All patients underwent re-irradiation with SBRT with heavy hypofractionated schedules. Cumulative dose-volume values to organs at risk (OARs) were computed and possible correlation with developed toxicities was investigated. RESULTS: Twenty-six patients were included. Median age at re-irradiation was 75 years, mean interval between the two RT courses was 5.6 years and the median follow-up was 47.7 months (13.4-114.3 months). After re-irradiation, acute and late G ≥ 2 GU toxicity events were reported in 3 (12%) and 10 (38%) patients, respectively, while late G ≥ 2 GI events were reported in 4 (15%) patients. No acute G ≥ 2 GI side effects were registered. Patients receiving an equivalent uniform dose of the two RT treatments < 131 Gy appeared to be at higher risk of progression (4-yr b-PFS: 19% vs 33%, p = 0.145). Cumulative re-irradiation constraints that appear to be safe are D30% < 57.9 Gy for bladder and D30% < 66.0 Gy, D60% < 38.0 Gy and V122.1 Gy < 5% for rectum. CONCLUSION: Preliminary re-irradiation constraints for bladder and rectum have been reported. Our preliminary investigation may serve to clear some grey areas of PCa re-irradiation.

Stereotactic Body Radiation Therapy for Oligometastatic Ovarian Cancer: A Step Toward a Drug Holiday.

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

Short-term high precision radiotherapy for early prostate cancer with concomitant boost to the dominant lesion: ad interim analysis and preliminary results of Phase II trial AIRC-IG-13218.

OBJECTIVE: To report preliminary results of a cutting edge extreme hypofractionated treatment with concomitant boost to the dominant lesion for patients with early stage prostate cancer (PCa). METHODS: AIRC-IG-13218 is a prospective Phase II trial started in June 2015. Patients with low and intermediate risk PCa who met the inclusion criteria underwent extreme hypofractionated radiotherapy to the prostate (36.25 Gy in 5 fractions) and a simultaneous integrated boost to the dominant intraprostatic lesion (DIL) to 37.5 Gy. The DIL was identified by a multiparamentric MRI (mpMRI) co-registered with planning CT. Toxicity was assessed according to CTCAE v4.0 and RTOG/EORTC criteria. The preliminary evaluation of the first 13 patients was required to confirm the feasibility of the treatment before completing the enrollment of 65 patients. RESULTS: The first 13 patients completed the treatment between June 2015 and February 2016. With a median clinical follow-up of 17 months (range 11-26), no Grade 3 or 4 early toxicity was reported. CONCLUSIONS: Our preliminary data about early toxicity of an extreme hypofractionated schedule with concomitant boost on the DIL are encouraging. The higher number of patients expected for the trial and a longer follow-up are needed to confirm these results. Advances in knowledge: The use of mpMRI to identify and boost the DIL is an innovative and interesting approach to PCa. Our preliminary findings suggest that dose escalation using DIL boost and extremely hypofractionated radiotherapy regimens might be a safe approach, allowing for short and effective treatment of organ-confined PCa.

Dosimetric characterization of 3D printed bolus at different infill percentage for external photon beam radiotherapy.

BACKGROUND AND PURPOSE: 3D printing is rapidly evolving and further assessment of materials and technique is required for clinical applications. We evaluated 3D printed boluses with acrylonitrile butadiene styrene (ABS) and polylactide (PLA) at different infill percentage. MATERIAL AND METHODS: A low-cost 3D printer was used. The influence of the air inclusion within the 3D printed boluses was assessed thoroughly both with treatment planning system (TPS) and with physical measurements. For each bolus, two treatment plans were calculated with Monte Carlo algorithm, considering the computed tomography (CT) scan of the 3D printed bolus or modelling the 3D printed bolus as a virtual bolus structure with a homogeneous density. Depth dose measurements were performed with Gafchromic films. RESULTS: High infill percentage corresponds to high density and high homogeneity within bolus material. The approximation of the bolus in the TPS as a homogeneous material is satisfying for infill percentages greater than 20%. Measurements performed with PLA boluses are more comparable to the TPS calculated profiles. For boluses printed at 40% and 60% infill, the discrepancies between calculated and measured dose distribution are within 5%. CONCLUSIONS: 3D printing technology allows modulating the shift of the build-up region by tuning the infill percentage of the 3D printed bolus in order to improve superficial target coverage.

High-Risk Prostate Cancer and Radiotherapy: The Past and the Future. A Benchmark for a New Mixed Beam Radiotherapy Approach.

BACKGROUND: The prognosis for patients with high-risk prostate cancer is poor. No consensus exists on the most effective treatment. The aim of this retrospective study was to identify the biochemical progression-free survival and the toxicity profile of patients with localized high-risk prostate cancer treated with external beam radiation therapy. These results will constitute a benchmark for a prospective "mixed beam" trial: a boost with carbon ions followed by a pelvic photon intensity-modulated radiotherapy (NCT02672449 [clinicaltrials.gov]). PATIENTS AND METHODS: We retrospectively reviewed the data of 76 patients treated in our institution with photon radiation therapy according to the inclusion criteria of the future "mixed beam" trial: cT3a and/or serum prostate-specific antigen > 20 ng/mL and/or Gleason score of 8 to 10, cN0 cM0. Toxicity, and biochemical and clinical progression-free survival were assessed. RESULTS: Seventy-six patients fulfilled our criteria. The median follow-up was 30.2 months (range, 7.2-61.1). Biochemical progression was observed in 22 patients (28.9%) after a median time of 20.2 months (range, 5-58.1) from the end of radiotherapy. Sixteen patients had clinical progression, in all the cases preceded by biochemical progression. Fifty-seven patients (75%) are alive with no evidence of disease, 13 (17.1%) are alive with clinically evident disease, 6 died (3 of prostate disease 3.9%). CONCLUSION: Our results suggest that a more aggressive treatment is necessary. Local treatment intensification based on the "mixed beam" approach combining carbon ions (with its known radiobiological advantages) and photons might represent a promising strategy in high-risk prostate cancer and it will be investigated with our prospective clinical trial.

Intra-fraction respiratory motion and baseline drift during breast Helical Tomotherapy.

BACKGROUND AND PURPOSE: To investigate the intra-fraction breast motion during long-lasting treatments of breast cancer with Helical Tomotherapy by means of an optical tracking system. MATERIALS AND METHODS: A set of seven radio-transparent passive markers was placed on the thoraco-abdominal surface of twenty breast cancer patients and tracked by an infrared tracking system. A continuous non-invasive monitoring of intra-fraction motion from patient setup verification and correction to the end of radiation delivery was thus obtained. The measured displacements were analysed in terms of cyclic respiratory motion and slow baseline drift. RESULTS: The average monitoring time per patient was 15.57min. The breathing amplitude of the chest was less than 2mm, on average, along all anatomical directions. The baseline drift of the body led to more significant setup uncertainties than the respiratory motion. The main intra-fraction baseline drifts were in posterior and inferior directions and occurred within the first eight minutes of monitoring. Considering the intra-fraction motion only, the resultant clinical-to-planning target volume safety margins are highly patient-specific and largely anisotropic. CONCLUSION: The non-respiratory motion occurring during prolonged treatments induces notable uncertainties. Non-invasive continuous monitoring of patient setup variations including baseline drifts is recommended in order to minimize dosimetric deviations, which might jeopardize the therapeutic ratio between target coverage and the sparing of organs at risk.

3D-printed applicators for high dose rate brachytherapy: Dosimetric assessment at different infill percentage.

PURPOSE: Dosimetric assessment of high dose rate (HDR) brachytherapy applicators, printed in 3D with acrylonitrile butadiene styrene (ABS) at different infill percentage. MATERIALS AND METHODS: A low-cost, desktop, 3D printer (Hamlet 3DX100, Hamlet, Dublin, IE) was used for manufacturing simple HDR applicators, reproducing typical geometries in brachytherapy: cylindrical (common in vaginal treatment) and flat configurations (generally used to treat superficial lesions). Printer accuracy was investigated through physical measurements. The dosimetric consequences of varying the applicator's density by tuning the printing infill percentage were analysed experimentally by measuring depth dose profiles and superficial dose distribution with Gafchromic EBT3 films (International Specialty Products, Wayne, NJ). Dose distributions were compared to those obtained with a commercial superficial applicator. RESULTS: Measured printing accuracy was within 0.5mm. Dose attenuation was not sensitive to the density of the material. Surface dose distribution comparison of the 3D printed flat applicators with respect to the commercial superficial applicator showed an overall passing rate greater than 94% for gamma analysis with 3% dose difference criteria, 3mm distance-to-agreement criteria and 10% dose threshold. CONCLUSION: Low-cost 3D printers are a promising solution for the customization of the HDR brachytherapy applicators. However, further assessment of 3D printing techniques and regulatory materials approval are required for clinical application.

Rationale and protocol of AIRC IG-13218, short-term radiotherapy for early prostate cancer with concomitant boost to the dominant lesion.

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.

Translational and rotational localization errors in cone-beam CT based image-guided lung stereotactic radiotherapy.

PURPOSE: Accurate localization is crucial in delivering safe and effective stereotactic body radiation therapy (SBRT). The aim of this study was to analyse the accuracy of image-guidance using the cone-beam computed tomography (CBCT) of the VERO system in 57 patients treated for lung SBRT and to calculate the treatment margins. MATERIALS AND METHODS: The internal target volume (ITV) was obtained by contouring the tumor on maximum and mean intensity projection CT images reconstructed from a respiration correlated 4D-CT. Translational and rotational tumor localization errors were identified by comparing the manual registration of the ITV to the motion-blurred tumor on the CBCT and they were corrected by means of the robotic couch and the ring rotation. A verification CBCT was acquired after correction in order to evaluate residual errors. RESULTS: The mean 3D vector at initial set-up was 6.6±2.3mm, which was significantly reduced to 1.6±0.8mm after 6D automatic correction. 94% of the rotational errors were within 3°. The PTV margins used to compensate for residual tumor localization errors were 3.1, 3.5 and 3.3mm in the LR, SI and AP directions, respectively. CONCLUSIONS: On-line image guidance with the ITV-CBCT matching technique and automatic 6D correction of the VERO system allowed a very accurate tumor localization in lung SBRT.

Geometric and dosimetric accuracy and imaging dose of the real-time tumour tracking system of a gimbal mounted linac.

PURPOSE: To suggest a comprehensive testing scheme to evaluate the geometric and dosimetric accuracy and the imaging dose of the VERO dynamic tumour tracking (DTT) for its clinical implementation. METHODS: Geometric accuracy was evaluated for gantry 0° and 90° in terms of prediction (EP), mechanical (EM) and tracking (ET) errors for sinusoidal patterns with 10 and 20 mm amplitudes, 2-6 s periods and phase shift up to 1 s and for 3 patient patterns. The automatic 4D model update was investigated simulating changes in the breathing pattern during treatment. Dosimetric accuracy was evaluated with gafchromic films irradiated in static and moving phantom with and without DTT. The entrance skin dose (ESD) was assessed using a solid state detector and gafchromic films. RESULTS: The RMS of EP, EM, and ET were up to 0.8, 0.5 and 0.9 mm for all non phased-shifted motion patterns while for the phased-shifted ones, EP and ET increased to 2.2 and 2.6 mm. Up to 4 updates are necessary to restore a good correlation model, according to type of change. For 100 kVp and 1 mA s X-ray beam, the ESD per portal due to 20 s fluoroscopy was 16.6 mGy, while treatment verification at a frequency of 1 Hz contributed with 4.2 mGy/min. CONCLUSIONS: The proposed testing scheme highlighted that the VERO DTT system tracks a moving target with high accuracy. The automatic update of the 4D model is a powerful tool to guarantee the accuracy of tracking without increasing the imaging dose.