Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS).

BACKGROUND: Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone. METHODS: This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis. DISCUSSION: The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts. TRIALS REGISTRATION: ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study.

Intensity modulated arc therapy in bilaterally irradiated head and neck cancer: a comparative and prospective multicenter planning study.

A dosimetric comparison was made of Helical Tomotherapy (HT) and Rapid'Arc(®) (RA) in 115 patients with head and neck carcinoma included in a prospective and multicentric study. HT and RA provided highly conformal plans that easily complied with dose volume constraints for organs at risk. HT reduced high doses to the planning target volumes (PTVs) compared to RA and provided a more homogeneous dose distribution but with an increased Non Tumoral Integral Dose (NTID) than RA. However, the clinical consequences of these dosimetric advantages and disadvantages need further investigation.

Professional ethics in the French medical physicist community: Survey results and implications.

INTRODUCTION: Since 2017, in France, medical physicists (MP) are finally defined by law as health professionals and as such, the roles and responsibilities of an MP lean on those medical professional ethics but MPs lack initial or continuing training in this subject. In order to find out how our colleagues feel about this subject, the following survey was conducted. METHODS: French Society of Medical Physics (SFPM) designed a web survey addressed to its members and non-members concerning ethics based on the 2013 AAPM work; experience and training were highlighted as particularly important within the survey structure. RESULTS: 249 answers were collected and showed a pronounced concern at the lack of initial and continuous training in this subject. Professional experience of non-ethical behaviour was attributed to the lack of training, resources or competences and hostile work environments. CONCLUSION: To address the shortcomings highlighted in the survey, SFPM has created a dedicated voluntary working group aimed at producing a professional code of ethics for MP and training modules to be applied at entry level or as continuing professional development for education.

The role of medical physicists in clinical trials across Europe.

INTRODUCTION: The roles and responsibilities of medical physicists (MPs) are growing together with the evolving science and technology. The complexity of today's clinical trials requires the skills and knowledge of MPs for their safe and efficient implementation. However, it is unclear to what extent the skillsets offered by MPs are being exploited in clinical trials across Europe. METHODS: The EFOMP Working Group on the role of Medical Physics Experts in Clinical Trials has designed a survey that targeted all 36 current National Member Organisations, receiving a response from 31 countries. The survey included both quantitative and qualitative queries regarding the involvement of MPs in trial design, setup, and coordination, either as trial team members or principal investigators. RESULTS: The extent of MPs involvement in clinical trials greatly varies across European countries. The results showed disparities between the roles played by MPs in trial design, conduct or data processing. Similarly, differences among the 31 European countries that responded to the survey were found regarding the existence of national bodies responsible for trials or the available training offered to MPs. The role of principal investigator or co-investigator was reported by 12 countries (39%), a sign of efficient collaboration with medical doctors in designing and implementing clinical studies. CONCLUSION: Organisation of specific training courses and guideline development for clinical trial design and conduct would encourage the involvement of a larger number of MPs in all stages of trials across Europe, leading to a better standardisation of clinical practice.

Highly hypofractionated schedules for localized prostate cancer: Recommendations of the GETUG radiation oncology group.

Stereotactic body radiotherapy (SBRT) has become treatment option for localized prostate cancer but the evidence base remains incomplete. Several clinical studies, both prospective and retrospective, have been published. However, treatment techniques, target volumes and dose constraints lack consistency between studies. Based on the current available literature, the French Genito-Urinary Group (GETUG) suggests that.

The 3rd ESTRO-EFOMP core curriculum for medical physics experts in radiotherapy.

PURPOSE: To update the 2011 ESTRO-EFOMP core curriculum (CC) for education and training of medical physics experts (MPE)s working in radiotherapy (RT), in line with recent EU guidelines, and to provide a framework for European countries to develop their own curriculum. MATERIAL AND METHODS: Since September 2019, 27 European MPEs representing ESTRO, EFOMP and National Societies, with expertise covering all subfields of RT physics, have revised the CC for recent advances in RT. The ESTRO and EFOMP Education Councils, all European National Societies and international stakeholders have been involved in the revision process. RESULTS: A 4-year training period has been proposed, with a total of 240 ECTS (European Credit Transfer and Accumulation System). Training entrance levels have been defined ensuring the necessary physics and mathematics background. The concept of competency-based education has been reinforced by introducing the CanMEDS role framework. The updated CC includes (ablative) stereotactic-, MR-guided- and adaptive RT, particle therapy, advanced automation, complex quantitative data analysis (big data/artificial intelligence), use of biological images, and personalized treatments. Due to the continuously increasing RT complexity, more emphasis has been given to quality management. Clear requirements for a research project ensure a proper preparation of MPE residents for their central role in science and innovation in RT. CONCLUSION: This updated, 3rd edition of the CC provides an MPE training framework for safe and effective practice of modern RT, while acknowledging the significant efforts needed in some countries to reach this level. The CC can contribute to further harmonization of MPE training in Europe.

Two-year clinical experience with tomotherapy: the French national cancer institute project on implementing new technology.

The pooled 2-year clinical experience using three tomotherapy units installed in France in 2007 is presented. Treatment indications and protocols were devised for each disease site and were the result of a consensus. A total of 642 patients were treated for central nervous system, head and neck, thoracic, abdominal, and pelvic tumors. Overall, grade 3, 4, and 5 acute toxicity was 10.7%, 0.3%, and 0.2%, respectively. Grade 3 chronic toxicity was 1.2%. There was no grade 4 or 5 chronic toxicity. The use of tomotherapy in a broad clinical practice is safe, and acute and chronic toxicity both are acceptable for all anatomical locations.

Towards an updated ESTRO-EFOMP core curriculum for education and training of medical physics experts in radiotherapy - A survey of current education and training practice in Europe.

PURPOSE: ESTRO-EFOMP intend to update the core curriculum (CC) for education and training of medical physicists in radiotherapy in line with the European Commission (EC) guidelines on Medical Physics Experts (MPE), the CanMEDS methodology and recent developments in radiotherapy. As input, a survey of the current structure of radiotherapy MPE national training schemes (NTS) in Europe was carried out. METHODS: A 35-question survey was sent to all European medical physics national societies (NS) with a focus on existence of an NTS, its format and duration, required entry-level education, and financial support for trainees. RESULTS: Twenty-six of 36 NS responded. Twenty had an NTS. Minimum required pre-training education varied from BSc in physics or related sciences (5/2) to MSc in medical physics, physics or related sciences (6/5/2) with 50-210 ECTS in fundamental physics and mathematics. The training period varied from 1 to 5 years (median 3 years with 50% dedicated to radiotherapy). The ratio of time spent on university lectures versus hospital training was most commonly 25%/75%. In 14 of 20 countries with an NTS, a research project was mandatory. Residents were paid in 17 of 20 countries. The recognition was mostly obtained by examination. Medical physics is recognised as a healthcare profession in 19 of 26 countries. CONCLUSIONS: The NTS entrance level, duration and curriculum showed significant variations. This survey serves to inform the design of the updated CC to define a realistic minimum training level for safe and effective practice aiming at further harmonization in line with EC guidelines.

Feasibility of Dose Escalation in Patients With Intracranial Pediatric Ependymoma.

Background and purpose: Pediatric ependymoma carries a dismal prognosis, mainly owing to local relapse within RT fields. The current prospective European approach is to increase the radiation dose with a sequential hypofractionated stereotactic boost. In this study, we assessed the possibility of using a simultaneous integrated boost (SIB), comparing VMAT vs. IMPT dose delivery. Material and methods: The cohort included 101 patients. The dose to planning target volume (PTV59.4) was 59.4/1.8 Gy, and the dose to SIB volume (PTV67.6) was 67.6/2.05 Gy. Gross tumor volume (GTV) was defined as the tumor bed plus residual tumor, clinical target volume (CTV59.4) was GTV + 5 mm, and PTV59.4 was CTV59.4 + 3 mm. PTV67.6 was GTV+ 3 mm. After treatment plan optimization, quality indices and doses to target volume and organs at risk (OARs) were extracted and compared with the standard radiation doses that were actually delivered (median = 59.4 Gy [50.4 59.4]). Results: In most cases, the proton treatment resulted in higher quality indices (p < 0.001). Compared with the doses that were initially delivered, mean, and maximum doses to some OARs were no higher with SIB VMAT, and significantly lower with protons (p < 0.001). In the case of posterior fossa tumor, there was a lower dose to the brainstem with protons, in terms of V59 Gy, mean, and near-maximum (D2%) doses. Conclusion: Dose escalation with intensity-modulated proton or photon SIB is feasible in some patients. This approach could be considered for children with unresectable residue or post-operative FLAIR abnormalities, particularly if they have supratentorial tumors. It should not be considered for infratentorial tumors encasing the brainstem or extending to the medulla.

Implementing dosimetry in GATE: dose-point kernel validation with GEANT4 4.8.1.

GATE is a recent Monte Carlo code, based on GEANT4, and used in nuclear medicine mainly for imaging and detector design. Our goal was to implement dosimetry within GATE (i.e., combining the excellent potential of Gate for image modeling with GEANT4 dosimetric capabilities. The latest release of GEANT4 (4.8.1) completely revised the electron multiple scattering propagation algorithm. In this work, we calculated dose point kernels (DPK) for 0.01, 0.05, 0.1, 1, and 3 MeV monoenergetic electrons. We then compared our results with data obtained with another Monte Carlo code (MCNPX) or from the reference publication from Berger and Seltzer. To facilitate comparison, all calculated dose distributions were scaled to the corresponding R(CSDA), as given by the ESTAR NIST web database. Some GEANT4 parameters (i.e., Stepmax), or the shell thickness, had to be adjusted in order to achieve good agreement for energies below 1 MeV. For all energies except 10 keV, calculated DPKs do not differ significantly from the reference, as assessed by a Kolmogorov-Smirnov test. This preliminary step allowed us to consider the integration of GEANT4 dosimetric capabilities within the Gate framework.

Implementation of a microdosimetric model for radioimmunotherapeutic alpha emitters.

A microdosimetric model for alpha-particle-emitting radiolabeled antibodies, based on an analytic method, was developed to be used for in vitro studies. The model took into consideration cell radii distributions or distributions of activity bound to cells, and calculated the single- and multihit distributions of specific energy within the target. The mean absorbed dose could then be derived from the specific energy spectra. The mean number of hits, the probability that no particle crossed the target, and the average lineal energy transfer at which the energy is deposited were also calculated. Many in vitro geometric configurations of cells (single cell, cellular monolayer, and cellular clusters) and many different distributions of radioactive sources observed in experiments (distribution on the cell surface or within the extracellular volume) could be modeled. To verify the implementation of our algorithm, a comparison was carried out for different sources and target configurations between our model and a general Monte Carlo code (MCNPX). A positive agreement was observed between the two approaches. By using the proposed model, computation speed was greatly improved, as compared with the Monte-Carlo approach. An example of the impact of some parameters (cell radii and activity distributions) on the dosimetric results is also given in this paper.

Helical tomotherapy of spinal chordomas: French Multicentric, retrospective study of a cohort of 30 cases.

PURPOSE: To evaluate the efficacy and toxicity of helical tomotherapy (HT) in the management of spine chordomas when proton therapy is unavailable or non-feasible. METHODS AND MATERIALS: Between 2007 and 2013, 30 patients with biopsy-proven chordomas were treated by HT in five French institutions. Information regarding local control (LC), overall survival (OS), progression-free survival (PFS) and metastasis-free survival (MFS) was collected. Clinical efficacy, toxicity and treatment quality were evaluated. RESULTS: Two-year actuarial LC, OS, PFS and MFS were 69.9%, 96.7%, 61.2% and 76.4%, respectively. HT treatments were well tolerated and no Grade 4-5 toxicities were observed. HT permitted the delivery of a mean dose of 68 Gy while respecting organ at risk (OAR) dose constraints, in particular in the spinal cord and cauda equina. CONCLUSIONS: This multicentric, retrospective study demonstrated the feasibility of HT in the treatment of spine chordomas, in the absence of hadron therapy.

Prospective comparison of 3 gamma-probes for sentinel lymph node detection in 200 breast cancer patients.

UNLABELLED: Previous reports have shown that axillary sentinel lymph node (ASLN) radiodetection allows accurate axillary staging for patients with early breast cancer. Radioguided surgery implies the use of a gamma-probe to count the emitted radioactivity of marked ASLNs. Several gamma-probes are commercially available, each with its own properties. The clinical impact of the type of gamma-probe used for ASLN radiodetection remains to be evaluated. METHODS: Three commercially available gamma-probes were evaluated: a scintillator with a bismuth germanate crystal (probe A), a semiconductor with a cadmium telluride crystal (probe B), and a semiconductor with a cadmium zinc telluride crystal (probe C). Two hundred patients with early breast cancer were prospectively enrolled to undergo ASLN radiodetection and axillary lymphadenectomy. ASLN mapping consisted of injecting (99m)Tc-sulfur-colloid around the tumor. For each patient, sentinel lymph nodes were counted successively with the 3 probes and the sensitivity of each gamma-probe was determined from ASLN residual activity. The results of detection rates and false-negative rates for each probe were compared. RESULTS: Mean residual ASLN activity was 52 kBq (range, 0.07-189 kBq). Sensitivity was compared among the 3 probes and found to be best for probe A. The detection rate of probe A was significantly better than that of probe B (93% vs. 86%, P = 0.05) but not different from that of probe C (93% vs. 90%). No differences in false-negative rates were observed among the 3 probes. CONCLUSION: ASLN detection rate depends on the type of gamma-probe used. Because failure to detect the ASLN leads to complete axillary lymphadenectomy, involving local morbidity and other sequelae, the type of gamma-probe must be considered important for sentinel lymph node radiodetection.

Monte Carlo modeling of gamma cameras for I-131 imaging in targeted radiotherapy.

INTRODUCTION: Dosimetric studies for targeted radiotherapy require the quantification of activity from scintigraphic images. Quantitative imaging is difficult to achieve because of several effects that can lead to errors in activity estimates, some of which are more apparent when I-131 is considered as a source. An evaluation of these phenomena was performed by modeling the gamma camera and its behavior using Monte Carlo simulations. Two gamma cameras were modeled: DST-XLi and Millennium VG Hawk-Eye (GEMS), and two Monte Carlo codes were used: MCNP (LANL) and GATE (openGate collaboration). GATE is a dedicated single photon emission computed tomography/positron emission tomography (SPECT)/(PET) software based on Geant4 (CERN, Geneve). MATERIALS AND METHODS: Gamma-camera modeling was performed in 2 steps: first without a collimator, then with a high-energy, all-purpose (HEAP) collimator according to the specifications given by the manufacturer (the simulation took the hexagonal shape of collimator holes into account). Simulated and measured energy spectra from point sources in air were compared (with or without a collimator). Spatial resolution was obtained from line sources in air at various distances from the detector heads. The photons detected in the 20% energy window from a point source were analyzed in order to determine the amount of primary photons, scattered photons (in the collimator), and septal photons (i.e., photons that crossed the collimator septa without interacting). RESULTS: Both codes agree well with experimental measurements for the two gamma cameras considered in this study. This allowed us to validate gamma-camera modeling and also served as a benchmark of GATE (new code) versus MCNP (reference code). As shown previously by Dewaraja et al., septal penetration is an important source of image degradation when HEAP collimators are used for I-131 imaging. With the DST-XLi, and for a point source in air, our simulations have shown that 53% of scattered (30%) and septal penetration (23%) photons are detected in the 20% window. CONCLUSION: The modeling of two gamma cameras (DST-XLi and Millennium VG Hawk-Eye) has been performed with two Monte Carlo codes (MCNP and Gate). Results obtained with the two Monte Carlo codes agree well with experimental results. As already indicated by several authors, septal penetration and scattered photons in the collimator have a major impact on I-131 scintigraphic imaging.

Monte Carlo evaluation of the effect of inhomogeneities on dose calculation for low energy photons intra-operative radiation therapy in pelvic area.

The aim of this study was to evaluate the effect of inhomogeneities on dose calculation for low energy photons intra-operative radiation therapy (IORT) in pelvic area. A GATE Monte Carlo model of the INTRABEAM® was adapted for the study. Simulations were performed in the CT scan of a cadaver considering a homogeneous segmentation (water) and an inhomogeneous segmentation (5 tissues from ICRU44). Measurements were performed in the cadaver using EBT3 Gafchromic® films. Impact of inhomogeneities on dose calculation in cadaver was 6% for soft tissues and greater than 300% for bone tissues. EBT3 measurements showed a better agreement with calculation for inhomogeneous media. However, dose discrepancy in soft tissues led to a sub-millimeter (0.65 mm) shift in the effective point dose in depth. Except for bone tissues, the effect of inhomogeneities on dose calculation for low energy photons intra-operative radiation therapy in pelvic area was not significant for the studied anatomy.

Postoperative interstitial brachytherapy for resectable squamous cell carcinoma of the tongue.

PURPOSE: To evaluate the efficiency and toxicity of postoperative brachytherapy (POBT) in the treatment of resectable mobile tongue squamous cell carcinoma. PATIENTS AND METHODS: This was a retrospective single-center study of patients with SSC of the mobile tongue who were treated between August 1992 and June 2013 by glossectomy and neck dissection followed by (192)Ir interstitial brachytherapy of the tumor bed. Endpoints were local control, cancer-specific survival (CSS), overall survival (OS), and morbidity. Independent prognostic factors were analyzed in a Cox regression model. RESULTS: A total of 112 patients were identified (median age, 55 years [range, 15-84]; 76% male). Patient and tumor characteristics were: T1T2N0 (85%), pN+ (13%), positive surgical margins (14%), negative margins <5 mm (29%), dysplasic margins (14%), lymphatic vessel invasion (5%), and perineural spread (5%). Median followup was 6.7 years (1.5 months to 17.7 years). Local control, CSS, and OS rates at 2 years were 79%, 81%, and 72%, respectively. The corresponding 5-year rates were 76%, 67%, and 56%, respectively. After POBT, 22% of patients presented grade ≥2 necrosis and 8% experienced chronic pain. Independent prognostic factors were positive surgical margins for poor local control and tumor recurrence and lymphatic vessel invasion for poor OS. CONCLUSION: POBT provided good local control and better CSS and OS than reported for surgery alone. Morbidity was higher than that reported for brachytherapy alone but may be considered acceptable in a well-selected patient population at high risk of local recurrence.

Dosimetric impact of correcting count losses due to deadtime in clinical radioimmunotherapy trials involving iodine-131 scintigraphy.

This study describes the use of a new method for correcting count losses due to deadtime in the context of quantitative imaging of patients undergoing scintigraphy after a 4 GBq therapeutic injection of iodine-131. This method, based on measuring the count rate observed throughout the spectrum detected (50-750 keV), had been validated in a previous study and was applied here to 10 patients. Imaging was performed 3, 6, 8 and 10 days after injection. Whole-body images were acquired in six steps in energy-indexed list mode. Before reconstruction of the whole-body image, each step was processed to obtain an appropriate correction. Three days after injection, corrective factors ranged between 1.01 (feet) and 1.20 (liver), and the increase in whole-body activity was estimated at around 10%. The difference between whole-body activities calculated from images corrected for deadtime and those estimated by urine collection was around 1% when urine collection was complete. Correction for count losses led to an 11% increase in whole-body cumulated activity. These results indicate that it is possible to integrate this correction into dosimetric studies in order to allow count rate variations to be taken into account as a function of the regions imaged. Although the complexity of acquisitions in energy-indexed list mode limits the systematic use of this method, it can be simplified if corrections are made only for those steps in which the correction factor exceeds a threshold value. However, this implies a selection of the regions to be corrected. Another possibility consists in acquiring spectrometric images in several windows, which also allows correction for count losses.

Impact of scatter and attenuation corrections for iodine-131 two-dimensional quantitative imaging in patients.

This study assessed the impact of scatter and attenuation corrections on the estimated activity delivered to whole body and liver in five patients included in a radioimmunotherapy clinical trial. Before injection of the radiopharmaceutical, transmission images were acquired with the Transmission Attenuation Correction - Whole-body (SMVi-GEMS) prototype. Emission images were obtained in energy-indexed list mode at least four times after injection. 20% window and scatter-corrected images (Dual Energy Window-DEW and Triple Energy Window-TEW) were generated. Whole-body activity was calculated 1-h after injection (and compared with injected activity). Cumulated activities in whole body and liver were determined according to the geometric mean approach. The mean relative error made in estimations of whole-body activity at 1-h was 6.9+/-10.3% without corrections. Taking scatter into account led to underestimation, but reduced the influence of patient morphotype (-40.0+/-7.6% and -43.3+/-6.2% for DEW and TEW). Attenuation correction led to a large overestimation, whether used alone (155.2+/-39.0%) or associated with scatter correction (39.6+/-10.4% and 35.9+/-10.2% for DEW and TEW). Compared to the geometric mean alone, scatter correction led to a reduction of cumulated activities of around 45% for whole body and less than 30% for liver. Attenuation correction had a more marked impact, particularly for liver where estimated cumulated activity increased from 150 to 300%. Preliminary scatter correction limited the increase to 100% for DEW and 150% for TEW in liver and to 25% for both DEW and TEW in whole body. Although this would probably be different at the organ level, the calculation of whole-body activity without scatter and attenuation correction gave the lowest biases. But from a scientific point of view, this cannot be a satisfactory method. Attenuation correction has a greater impact than scatter correction. The association of both corrections is not sufficient to obtain accurate absolute quantification. Other factors limit planar quantification with iodine-131, notably auto-absorption of sources, septal penetration of high-energy photons through the collimator and superimposition of sources.

Voxeldoes: a computer program for 3-D dose calculation in therapeutic nuclear medicine.

A computer program, VoxelDose, was developed to calculate patient specific 3-D-dose maps at the voxel level. The 3-D dose map is derived in three steps: (i) The SPECT acquisitions are reconstructed using a filtered back projection method, with correction for attenuation and scatter; (ii) the 3-D cumulated activity map is generated by integrating the SPECT data; and (iii) a 3-D dose map is computed by convolution (using the Fourier Transform) of the cumulated activity map and corresponding MIRD voxel S values. To validate the VoxelDose software, a Liqui-Phil abdominal phantom with four simulated organ inserts and one spherical tumor (radius 4.2 cm) was filled with known activity concentrations of 111In. Four cylindrical calibration tubes (from 3.7 to 102 kBq/mL) were placed on the phantom. Thermoluminescent mini-dosimeters (mini-TLDs) were positioned on the surface of the organ inserts. Percent differences between the known and measured activity concentrations were determined to be 12.1 (tumor), 1.8 (spleen), 1.4, 8.1 (right and left kidneys), and 38.2% (liver), leading to percent differences between the calculated and TLD measured doses of 41, 16, 3, 5, and 62%. Large differences between the measured and calculated dose in the tumor and the liver may be attributed to several reasons, such as the difficulty in precisely associating the position of the TLD to a voxel and limits of the quantification method (mainly the scatter correction and partial volume effect). Further investigations should be performed to better understand the impact of each effect on the results and to improve absolute quantification. For all other organs, activity concentration measurements and dose calculations agree well with the known activity concentrations.