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.

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.

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.

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.

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.

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.

GTV-based prescription in SBRT for lung lesions using advanced dose calculation algorithms.

BACKGROUND: The aim of current study was to investigate the way dose is prescribed to lung lesions during SBRT using advanced dose calculation algorithms that take into account electron transport (type B algorithms). As type A algorithms do not take into account secondary electron transport, they overestimate the dose to lung lesions. Type B algorithms are more accurate but still no consensus is reached regarding dose prescription. The positive clinical results obtained using type A algorithms should be used as a starting point. METHODS: In current work a dose-calculation experiment is performed, presenting different prescription methods. Three cases with three different sizes of peripheral lung lesions were planned using three different treatment platforms. For each individual case 60 Gy to the PTV was prescribed using a type A algorithm and the dose distribution was recalculated using a type B algorithm in order to evaluate the impact of the secondary electron transport. Secondly, for each case a type B algorithm was used to prescribe 48 Gy to the PTV, and the resulting doses to the GTV were analyzed. Finally, prescriptions based on specific GTV dose volumes were evaluated. RESULTS: When using a type A algorithm to prescribe the same dose to the PTV, the differences regarding median GTV doses among platforms and cases were always less than 10% of the prescription dose. The prescription to the PTV based on type B algorithms, leads to a more important variability of the median GTV dose among cases and among platforms, (respectively 24%, and 28%). However, when 54 Gy was prescribed as median GTV dose, using a type B algorithm, the variability observed was minimal. CONCLUSION: Normalizing the prescription dose to the median GTV dose for lung lesions avoids variability among different cases and treatment platforms of SBRT when type B algorithms are used to calculate the dose. The combination of using a type A algorithm to optimize a homogeneous dose in the PTV and using a type B algorithm to prescribe the median GTV dose provides a very robust method for treating lung lesions.

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.

Is IMAT the ultimate evolution of conformal radiotherapy? Dosimetric comparison of helical tomotherapy and volumetric modulated arc therapy for oropharyngeal cancer in a planning study.

BACKGROUND: Intensity Modulated Arc Therapy (IMAT) can be planned and delivered via several techniques. Advanced Radiotherapy (ARTORL) is a prospective study that aims to evaluate the treatment costs and clinical aspects of implementing these IMAT techniques for head and neck cancers. In this context, we evaluated the potential dosimetric gain of Helical Tomotherapy (TomoTherapy, Accuray, HT) versus VMAT (Rapid'Arc(®), Varian Medical System, RA) for oropharyngeal cancer (OC). MATERIAL AND METHODS: Thirty patients were selected from our database in whom bilateral neck irradiation and treatment to the primary were indicated. Each patient was planned twice using both HT and RA planning systems using a simultaneous integrated boost approach. For the planning target volumes (PTV) and organs at risk, ICRU 83 reporting guidelines were followed. RA and HT plans were compared using paired Student's t-test. RESULTS: RA and HT produced plans with a good coverage of PTVs and acceptable sparing of OARs. Although some dosimetric differences were statistically significant, they remained small. However, the near maximal dose to the PRV of spinal cord and brain stem was lower with HT. Regarding normal tissue, HT increased the volume irradiated at doses between 4 and 20 Gy compared to RA. CONCLUSION: In OC, HT and RA showed similar dosimetric results. They represent the maximum gains obtained with photon beams. The medicoeconomic evaluation of our study is ongoing and may reveal differences between these techniques in terms of MU number, fraction time, and clinical evaluation.

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.

Helical tomotherapy for resected malignant pleural mesothelioma: dosimetric evaluation and toxicity.

This study evaluated adjuvant helical tomotherapy after extrapleural pneumonectomy ± neo-adjuvant chemotherapy in 24 patients with malignant pleural mesothelioma. Toxicity was judged acceptable despite 2 cases (8%) of suspected grade 5 pneumonitis. With a mean follow-up of 7 months, 5 patients had distant and 2 local and distant failure.

Mesothelioma at era of helical tomotherapy: results of two institutions in combining chemotherapy, surgery and radiotherapy.

PURPOSE: There is a scarce clinical experience about adjuvant helical tomotherapy (HT) in patients affected by malignant pleural mesothelioma (MPM) even though it appears as a useful technique to treat complex volume as the pleural cavity, and seems to have better dose distribution than the "classic" intensity modulated radiotherapy (IMRT). METHODS AND MATERIALS: Twenty-four patients received adjuvant radiotherapy (RT) by HT from August 1st, 2007 to December 1st, 2009 at Curie Institute (Paris) and René Gauducheau Cancer Center (Nantes). Thirteen patients had neoadjuvant chemotherapy. Extrapleural pleuropneumonectomy (EPP) was done in 23 patients. Median dose to PTV was 50Gy [48.7-55.9Gy] (2Gy/fraction). Acute and long term toxicities, disease free survival (DFS), overall survival (OS) and relapses are presented. RESULTS: Average follow up after RT was 7 months. The disease was staged mostly as T2-T3, N1-N2. Nineteen patients had epithelial type histology. Most patients tolerated radiotherapy with grade 1-2 side effects: redness of the skin, light cough or dyspnea, fatigue, nausea and odynophagia, mild increase of the post-operative thoracic pain. Grade 3 pneumonitis was suspected in 2 patients. Two grade 5 pneumonitis were also suspected. Eleven patients had a follow up of more than 6 months and no long term side effects related with HT were noted. At 24 months, 51.8% of patients were free of disease. Thirty percent of patients relapsed, with 2 patients presenting local relapses. Two patients died from recurrence. CONCLUSION: With limited follow up, HT has comparable toxicity to those observed with traditional IMRT. Higher radiation dose and good coverage results in excellent local control.

No impairment of quality of life 18 months after high-dose intensity-modulated radiotherapy for localized prostate cancer: a prospective study.

PURPOSE: To determine prospectively intermediate-term toxicity and quality of life (QoL) of prostate cancer patients after intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS: Fifty-five patients with localized prostate adenocarcinoma were treated by IMRT (76 Gy). Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events version 3.0. Patients assessed general and prostate-specific QoL before IMRT (baseline) and at 2, 6, and 18 months using European Organization for Research and Treatment of Cancer questionnaires QLQ-C30(+3) and QLQ-PR25. RESULTS: Median age was 73 years (range, 54-80 years). Risk categories were 18% low risk, 60% intermediate risk, and 22% high risk; 45% of patients received hormonal therapy (median duration, 6 months). The incidence of urinary and bowel toxicity immediately after IMRT was, respectively, 38% and 13% (Grade 2) and 2% and none (Grade 3); at 18 months it was 15% and 11% (Grade 2) and none (Grade 3). Significant worsening of QoL was reported at 2 months with regard to fatigue (+11.31, p = 1.10(-7)), urinary symptoms (+9.07, p = 3.10(-11)), dyspnea (+7.27, p = 0.008), and emotional (-7.02, p = 0.002), social (-6.36, p = 0.003), cognitive (-4.85, p = 0.004), and physical (-3.39, p = 0.007) functioning. Only fatigue (+5.86, p = 0.003) and urinary symptoms (+5.86, p = 0.0004) had not improved by 6 months. By 18 months all QoL scores except those for dyspnea (+8.02, p = 0.01) and treatment-related symptoms (+4.24, p = 0.01) had returned to baseline. These adverse effects were exacerbated by hormonal therapy. CONCLUSION: High-dose IMRT with accurate positioning induces only a temporary worsening of QoL.

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.

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.