Nanotechnology in radiation oncology: The need for implantable nano dosimeters for in-vivo real time measurements

International audienceRapidly advancing technology provides successive generations of irradiation techniques and modalities of cancer treatment in radiation oncology. Most of these techniques are able to deliver higher doses per fraction than the standard 2 Gy per day. The complexity of these new techniques involves hundreds of parameters for the delivery of each beam making quality assurance increasingly demanding. A direct assessment of the "final product", namely the absorbed dose, would be extremely useful if easy to obtain. Thus, a real need exists for dosimeters able to provide direct and real time measurements within the target volume. Nanotechnology is a relatively new field, and in some ways raises new technological aspirations, especially in the field of medical applications for cancer treatment. In this paper we argue the need for an implantable " nano-dosimeter " based on nanotechnology to monitor the delivered dose, combining all the ideal features such a future tool should have for quality assurance in radiation oncology

Statistical evaluation of dosimetric differences changes between the Modified Batho's density correction method and the Anisotropic Analytical Algorithm for clinical practice

Purpose: The aim of this work was to assess and to quantify, for clinical practice, the differences in computed doses using two types of dose calculation algorithm for the heterogeneity correction including target volumes and organs at risk (OARs).Methods: 35 patients having lung, breast, spine, head & neck, brain and pelvic tumors, were studied. For each patient, 2 treatment plans were generated. In plan 1, the dose was calculated using the Modified Batho's (MB) density correction method integrated in the Pencil Beam Convolution algorithm. In plan 2, the dose was calculated using the Anisotropic Analytical Algorithm (AAA). To compare the two plans a dosimetric analysis was carried out including cumulative and differential dose volume histograms (DVH), coverage index, and conformity index. Wilcoxon signed rank and Spearman’s tests were used to calculate p-values and correlation coefficients (r), respectively. Bootstrap simulation with 1000 random samplings was used to calculate the 95% confidence interval (95% CI).Results: The analysis of DVH showed that the AAA method calculated significantly higher doses for OARs for all cancer sites and lower doses for target volumes, especially for targets located in lung, with p < 0.05. The data demonstrated a strong correlation between MB and AAA for all cancer sites with r > 0.9.Conclusion: This study confirms that using the AAA integrated into Eclipse® TPS, the calculated dose will be increased to OARs, and reduced to target volumes. Thus, when changing from the MB algorithm to AAA, attention should be paid to avoid any bias of over/under estimating the dose given by AAA and to hold discussions between physicists and oncologists regarding any necessary modification in the prescription method

Irradiation de métastases cérébrales en conditions stéréotaxiques par rayonnement synchrotron (évaluation dosimétrique d une technique innovante)

CONTEXTE: Ces dernières années, des techniques d irradiation innovantes sont apparues avec la RC3D, la STEREO et la RCMI. L ESRF dispose d une source de rayons X permettant de délivrer des irradiations d intérêt médical, la SSRT. OBJECTIFS: Effectuer une comparaison dosimétrique entre ces techniques et la SSRT en absence puis en présence de produit de contraste iodé pour l irradiation stéréotaxique d une métastase cérébrale. Effectuer une comparaison dosimétrique entre la STEREO et la SSRT/PdCI pour 5 patientes atteintes de métastases cérébrales et évaluer l impact des variations liées aux lésions. PATIENTS ET MÉTHODE: Cette étude repose sur 5 patientes âgées de 34 à 70 ans. La prescription d une dose de 23,1 Gy s est effectuée sur l isodose 70% avec une dose à l isocentre de 33 Gy. La comparaison s est portée sur la conformation de la dose et sur l évaluation des doses reçues par les organes à risque. RÉSULTATS: Le traitement le plus optimal pour l irradiation stéréotaxique d une métastase cérébrale unique semble être la STEREO. La SSRT/PdCI est très proche de la STEREO avec une couverture des volumes cibles et une préservation des OAR adaptées. Les différences de dose observées sont corrélées à l hétérogénéité de la prise de contraste tumorale. L inconvénient de la SSRT reste la surdose délivrée à l os. CONCLUSION: La STEREO doit rester la référence du traitement des métastases cérébrales uniques. La SSRT en présence d éléments lourds apparaît être une technique prometteuse pour le traitement de lésions de petite taille, présentant un rehaussement homogène, une localisation intra-parenchymateuse centrale, à distance des structures osseuses et des gros vaisseaux.BACKGROUND: In recent years, innovative radiation techniques have emerged with RC3D, STEREO and IMRT. ESRF has an X-ray source for delivering medical radiation of interest, the SSRT. OBJECTIVES: Perform a dosimetric comparison between these techniques and the SSRT in the absence and in the presence of iodinated contrast agent for stereotactic irradiation of brain metastasis. Perform a dosimetric comparison between STEREO and SSRT / PdCl for 5 patients with brain metastases and evaluate the impact of changes related injuries. PATIENTS AND METHODS: This study is based on five patients aged 34 to 70 years. Prescribing a dose of 23.1 Gy was performed on the 70% isodose with a dose of 33 Gy to the isocenter. The comparison is focused on the shape of the dose and the evaluation of doses to organs at risk. RESULTS: The most optimal treatment for stereotactic irradiation of a single brain metastasis appears to be STEREO. The SSRT / PdCI is very close to the STEREO with coverage of target volumes and preservation of SRO adapted. The observed differences in dose are correlated with the heterogeneity of the tumor contrast enhancement. The disadvantage of the SSRT remains overdose delivered to the bone. CONCLUSION: STEREO must remain the main treatment for single brain metastases. The SSRT in the presence of heavy elements appears to be a promising technique for the treatment of small lesions, with a homogeneous enhancement, a intra-parenchymal central location, away from the bone structures and great vessels.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Les enjeux de l’hadronthérapie par ions carbone

National audienceL’ambition de doter la France d’un centre de traitement des tumeurs par faisceaux d’ions carbone est née, à la fin des années 1990, de la rencontre à l’Université Claude Bernard Lyon 1 de quelques médecins et physiciens, convaincus que la France avait toutes les capacités médicales et scientifiques pour initier un tel programme. Ce projet de « carbonethérapie » prit le nom de projet ETOILE (Espace de Traitement Oncologique par Ions Légers en Europe) au début des années 2000. Pour comprendre pourquoi il n’a pas été réalisé et évaluer les chances pour qu’il le soit un jour, il faut analyser les enjeux, les difficultés et les avantages de la carbonethérapie, comparée à la protonthérapie et aux formes les plus avancées de la radiothérapie

Statistical methods to evaluate the correlation between measured and calculated dose using quality assurance method in IMRT

Purpose: the objective of this study is to validate a procedure based on a statistical method to assess the agreement and the correlation between measured and calculated dose in the process of quality assurance (QA) for Intensity-Modulated Radiation Therapy (IMRT).Patients and methods: 10 patients including 56 fields for head and neck cancer treatment were analyzed. For each patient, one treatment plan was generated using Eclipse TPS®. To compare the calculated dose with measured dose a CT-scan of solid water slabs (30 × 30 × 15 cm3) was used. The measurements were done for absolute dose by a pinpoint ionization chamber and 2D dose distributions using electronic portal imaging device dosimetry. Six criteria levels were applied for each case (3%, 3 mm), (4%, 3 mm), (5%, 3 mm), (4%, 4 mm), (5%, 4 mm) and (5%, 5 mm). The normality of the data and the variance homogeneity were tested using Shapiro-Wilks test and Levene’s test, respectively. Wilcoxon signed-rank paired test was used to calculate p-value. Bland-Altman method was used to calculate the limit of agreement between calculated and measured doses and to draw a scatter plot. The correlation between calculated and measured doses was assessed using Spearman’s rank test.Results: The statistical tests indicate that the data do not fulfill normal distribution, p < 0.001 and had a homogenous variance, p = 0.85. The upper and lower limit of agreements for absolute dose measurements were 6.44% and -6.40%, respectively. Wilcoxon test indicated a significance difference between calculated and measured dose with ionization chamber, p = 0.01. Spearman’s test indicated a strong correlation between calculated and absolute measured dose, ρ = 0.99. Therefore, there is a lack of correlation between dose difference for absolute dose measurements and gamma passing rates for 2D dose measurements.Conclusion: the statistical tests showed that the common acceptance criteria’s using gamma evaluation are not able to predict the dose difference for a global treatment plan or per beam. The current QA method is limited to protect the patient. The described method provides an overall analysis for dosimetric data issued from calculation and measurement and it can be quickly integrated in QA system for IMRT

Nanotechnology in radiation oncology: The need for implantable nano dosimeters for in-vivo real time measurements

Rapidly advancing technology provides successive generations of irradiation techniques and modalities of cancer treatment in radiation oncology. Most of these techniques are able to deliver higher doses per fraction than the standard 2 Gy per day. The complexity of these new techniques involves hundreds of parameters for the delivery of each beam making quality assurance increasingly demanding. A direct assessment of the "final product", namely the absorbed dose, would be extremely useful if easy to obtain. Thus, a real need exists for dosimeters able to provide direct and real time measurements within the target volume. Nanotechnology is a relatively new field, and in some ways raises new technological aspirations, especially in the field of medical applications for cancer treatment. In this paper we argue the need for an implantable “nano-dosimeter” based on nanotechnology to monitor the delivered dose, combining all the ideal features such a future tool should have for quality assurance in radiation oncology.

What should we know about photon dose calculation algorithms used for radiotherapy? Their impact on dose distribution and medical decisions based on TCP/NTCP

The dose calculation algorithms, integrated in a radiotherapy treatment planning system, use different approximations to swiftly compute the dose distributions. Any biological effect is somehow related to the dose delivered to the tissues. Thus, the optimization of treatment planning in radiation oncology requires, as a basis, the most accurate dose calculation to carry out the best possible prediction of the Normal Tissue Complication Probability (NTCP), as well as Tumor Control Probability (TCP). Presently, a number of bio-mathematical models exist to estimate TCP and NTCP from a physical calculated dose using the differential dose volume histogram (dDVH). The purpose of this review is to highlight the link between any change of algorithms and possible significant changes of DVH metrics, TCP, NTCP and even more of estimated Quality-adjusted life years (QALY) based on predicted NTCP. The former algorithms, such as pencil beam convolution (PBC) algorithm with 1D or 3D density correction methods, overestimated the TCP while underestimating NTCP for lung cancer. The magnitude of error depends on the algorithms, the radiobiological models and their assumed radiobiological parameters setting. The over/under estimation of radiotherapy outcomes can reach up to 50% relatively. Presently, the anisotropic analytical algorithm (AAA), collapsed cone convolution algorithm (CCC), Acuros-XB or Monte Carlo are the most recommended algorithms to consistently estimate the TCP/ NTCP outcomes and QALY score, to rank and compare radiotherapy plans, to make a useful medical decision regarding the best plan. This paper points out also that the values of the NTCP radiobiological parameters should be adjusted to each dose calculation algorithm to provide the most accurate estimates.

Monitoring methods for skin dose in interventional radiology

Interventional radiology makes an increasing use of X-ray for diagnostic and therapeutic procedures. The dose received by the patient sometime exceeds the threshold value of deterministic effects, and this requires monitoring of the dose delivered to the patients. Delivered dose could be assessed through either direct or indirect methods. The direct methods use dosimeters that are placed on the skin during the procedure, whereas, the indirect methods are based on measured quantities derived from the equipment itself. Each method has its own limitations; however, the main concern is the ability to measure the dose more accurately due to complexity of the anatomical structures of the patient and the variable course of each procedure. This review article summarizes the principle and main advantages and disadvantages of each method. A comparison of the performances of each method for interventional fluoroscopy and radiography in its ability to monitor the patient’s skin dose is provided. </p

Monitoring methods for skin dose in interventional radiology

Interventional radiology makes an increasing use of X-ray for diagnostic and therapeutic procedures. The dose received by the patient sometime exceeds the threshold value of deterministic effects, and this requires monitoring of the dose delivered to the patients. Delivered dose could be assessed through either direct or indirect methods. The direct methods use dosimeters that are placed on the skin during the procedure, whereas, the indirect methods are based on measured quantities derived from the equipment itself. Each method has its own limitations; however, the main concern is the ability to measure the dose more accurately due to complexity of the anatomical structures of the patient and the variable course of each procedure. This review article summarizes the principle and main advantages and disadvantages of each method. A comparison of the performances of each method for interventional fluoroscopy and radiography in its ability to monitor the patient’s skin dose is provided.

The choice of statistical methods for comparisons of dosimetric data in radiotherapy

Purpose: Novel irradiation techniques are continuously introduced in radiotherapy to optimize the accuracy, the security and the clinical outcome of treatments. These changes could raise the question of discontinuity in dosimetric presentation and the subsequent need for practice adjustments in case of significant modifications. This study proposes a comprehensive approach to compare different techniques and tests whether their respective dose calculation algorithms give rise to statistically significant differences in the treatment doses for the patient. Methods: Statistical investigation principles are presented in the framework of a clinical example based on 62 fields of radiotherapy for lung cancer. The delivered doses in monitor units were calculated using three different dose calculation methods: the reference method accounts the dose without tissues density corrections using Pencil Beam Convolution (PBC) algorithm, whereas new methods calculate the dose with tissues density correction for 1D and 3D using Modified Batho (MB) method and Equivalent Tissue air ratio (ETAR) method, respectively. The normality of the data and the homogeneity of variance between groups were tested using Shapiro-Wilks and Levene test, respectively, then non-parametric statistical tests were performed. Specifically, the dose means estimated by the different calculation methods were compared using Friedman’s test and Wilcoxon signed-rank test. In addition, the correlation between the doses calculated by the three methods was assessed using Spearman’s rank and Kendall’s rank tests Results: The Friedman’s test showed a significant effect on the calculation method for the delivered dose of lung cancer patients (p 0.001). The density correction methods yielded to lower doses as compared to PBC by on average (−5 ± 4.4 SD) for MB and (−4.7 ± 5 SD) for ETAR. Post-hoc Wilcoxon signed-rank test of paired comparisons indicated that the delivered dose was significantly reduced using density-corrected methods as compared to the reference method. Spearman’s and Kendall’s rank tests indicated a positive correlation between the doses calculated with the different methods. Conclusion: This paper illustrates and justifies the use of statistical tests and graphical representations for dosimetric comparisons in radiotherapy. The statistical analysis shows the significance of dose differences resulting from two or more techniques in radiotherapy