[Why is brachytherapy still essential in 2017?] / Pourquoi la curiethérapie reste-t-elle indispensable en 2017 ?

These recent years, brachytherapy has benefited from imaging modalities advances. A more systematic use of tomodensitometric, ultrasonographic and MRI images during brachytherapy procedures has allowed an improvement in target and organs at risk assessment as well as their relationship with the applicators. New concepts integrating tumor regression during treatment have been defined and have been clinically validated. New applicators have been developed and are commercially available. Optimization processes have been developed, integrating hypofractionation modalities leading to tumor control improvement. All these opportunities led to further development of brachytherapy, with indisputable ballistic advantages, especially compared to external irradiation.

[New calculation algorithms in brachytherapy for iridium 192 treatments]. / Nouveaux algorithmes de calcul en curiethérapie pour les traitements par iridium 192.

Since 1995, the brachytherapy dosimetry protocols follow the methodology recommended by the Task Group 43. This methodology, which has the advantage of being fast, is based on several approximations that are not always valid in clinical conditions. Model-based dose calculation algorithms have recently emerged in treatment planning stations and are considered as a major evolution by allowing for consideration of the patient's finite dimensions, tissue heterogeneities and the presence of high atomic number materials in applicators. In 2012, a report from the American Association of Physicists in Medicine Radiation Therapy Task Group 186 reviews these models and makes recommendations for their clinical implementation. This review focuses on the use of model-based dose calculation algorithms in the context of iridium 192 treatments. After a description of these algorithms and their clinical implementation, a summary of the main questions raised by these new methods is performed. Considerations regarding the choice of the medium used for the dose specification and the recommended methodology for assigning materials characteristics are especially described. In the last part, recent concrete examples from the literature illustrate the capabilities of these new algorithms on clinical cases.

45 or 50 Gy, Which is the Optimal Radiotherapy Pelvic Dose in Locally Advanced Cervical Cancer in the Perspective of Reaching Magnetic Resonance Image-guided Adaptive Brachytherapy Planning Aims?

AIMS: In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions. MATERIALS AND METHODS: The optimised plans of 120 patients treated with pelvic chemoradiation followed by magnetic resonance image-guided intracavitary brachytherapy were reviewed. The doses per pulse were calculated, and the number of pulses required to reach the planning aims, or a limiting dose constraint to organs at risk, was calculated. All doses were converted to 2-Gy equivalents. Three scenarios were applied consisting of different sets of planning aims: 85 and 60 Gy for the HR-CTV and the intermediate-risk CTV (IR-CTV) D90 (minimal dose received by 90% of the volume) in scenario 1, 90 and 60 Gy, respectively, for scenarios 2 and 3. For organs at risk, dose constraints were 90, 75 and 75 Gy to the bladder, rectum and sigmoid D2cm(3), respectively, in scenarios 1 and 2, and 80, 65 and 70 Gy in scenario 3. RESULTS: A similar HR-CTV D90 could have been reached in scenarios 1 and 2 according to both pelvic doses. In scenario 3, a higher mean HR-CTV could have been reached in the 45 Gy arm (83.5 ± 8.0 versus 82.4 ± 8.0, P < 0.0001). The mean D2cm(3) of organs at risk was systematically and significantly increased after a delivery of 50.4 Gy to the pelvis, from 0.9 to 2.89 Gy. The proportions of plans reaching planning aims were 85.8, 72.5 and 42.5% after 45 Gy and 85.5, 67.5 and 33.3% after 50.4 Gy according to scenarios 1, 2 and 3, respectively. According to scenario 3, 50.4 Gy, the reachable HR-CTV D90 was higher in 30% of the cases, by 2 Gy in two cases. Those cases were unpredictable and due to unfavourable organs at risk topography and poor response to external beam radiotherapy. CONCLUSION: The delivery of 45 Gy in 25 fractions to the pelvis before brachytherapy warrants a higher probability to reach brachytherapy planning aims, in comparison with 50.4 Gy in 28 fractions.

What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer.

PURPOSE: Concomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders. METHODS: Among the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities. RESULTS: Fifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3-4 toxicities were reported in 10.4% and urinary grades 3-4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (>55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P=0.021 and P=0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P=0.046, odds ratio=7.0). CONCLUSIONS: Although immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.

Clinical Experience with Pulse Dose Rate Brachytherapy for Conservative Treatment of Penile Carcinoma and Comparison with Historical Data of Low Dose Rate Brachytherapy.

AIMS: To assess the efficacy of pulse dose rate (PDR) interstitial brachytherapy in the treatment of carcinoma of the penis and to compare with historical data of low dose rate (LDR) brachytherapy. MATERIALS AND METHODS: We reviewed the clinical records of 27 consecutive patients treated in our institution with exclusive PDR brachytherapy for a squamous cell carcinoma of the penis. The median tumour greatest diameter was 20 mm (range: 10-50 mm). Twenty-three patients (85%) had tumours limited to the glans and/or prepuce and four patients (15%) also had inguinal lymph node metastases. Implantations were carried out according to the Paris system and treatments were delivered with PDR brachytherapy. RESULTS: The median brachytherapy dose was 60 Gy (range: 60-70 Gy). The median treated volume was 28 cm(3) (range: 8-62 cm(3)). The median reference isodose rate was 0.4 Gy/pulse/h (range: 0.4-0.5 Gy/pulse/h). The median number of pulses was 150 (range: 120-175 pulses). With a median follow-up of 33 months (range: 6-64 months), tumour relapses in the penis were reported in four patients (15%). All patients with only local relapse (n = 3) were successfully salvaged with partial amputation. The estimated overall survival rate at 3 years was 95% (95% confidence interval: 83-100%). No grade 3 or more acute reaction was observed. Delayed ulcerations and stenoses requiring at least one meatal dilatation were reported in two (9%) and five (22%) patients without local relapse. The treated volume was significantly correlated to the risk of clinically relevant delayed toxicity. CONCLUSIONS: The efficacy/toxicity results of PDR brachytherapy for the treatment of penile carcinoma are comparable with those obtained with LDR brachytherapy in historical cohorts.

Interstitial pulsed-dose-rate brachytherapy for the treatment of squamous cell anal carcinoma: A retrospective single institution analysis.

OBJECTIVE: To examine the outcome of patients receiving interstitial pulsed-dose-rate brachytherapy (PDR-BT) after pelvic radiation therapy for treatment of an anal squamous cell carcinoma. METHODS AND MATERIALS: Twenty-one patients were identified: 13, six, and two with stages I, II, and III tumors, respectively. After receiving received pelvic irradiation +/- concurrent chemotherapy, patients were delivered a PDR-BT boost to the residual tumor, with intention to deliver a minimal total dose of 60 Gy. The greatest dimension of residual tumor at the time of brachytherapy procedure was 12.5 mm (range: 0-20 mm). Brachytherapy implantation was performed according to the Paris system, only one plane implant being used. RESULTS: Median dose delivered through BT was 20 Gy (range: 10-30 Gy). Median number of pulses was 48 (range: 20-80 pulses). Median treated volume was 9 cm(3) (range: 5-16 cm(3)). Median dose per pulse was 40 cGy (range: 37.5-50 cGy). No Grade 3 or more acute toxicity was reported. No Grade 3 or more delayed toxicity was seen among 18 patients with more than 6 months follow-up. Median followup was 47 months (range: 6-73 months). Twenty patients (95%) were alive at last follow-up. Tumor relapses were experienced in four patients (19%), including local relapse in three patients (14%). CONCLUSION: With almost 4 years median followup, this study confirms previous data suggesting that PDR-BT is effective and safe in this indication. Local control rate and toxicity were in the range of what was seen with continuous low-dose-rate BT.

Configuration and validation of an analytical model predicting secondary neutron radiation in proton therapy using Monte Carlo simulations and experimental measurements.

PURPOSE: This study focuses on the configuration and validation of an analytical model predicting leakage neutron doses in proton therapy. METHODS: Using Monte Carlo (MC) calculations, a facility-specific analytical model was built to reproduce out-of-field neutron doses while separately accounting for the contribution of intra-nuclear cascade, evaporation, epithermal and thermal neutrons. This model was first trained to reproduce in-water neutron absorbed doses and in-air neutron ambient dose equivalents, H*(10), calculated using MCNPX. Its capacity in predicting out-of-field doses at any position not involved in the training phase was also checked. The model was next expanded to enable a full 3D mapping of H*(10) inside the treatment room, tested in a clinically relevant configuration and finally consolidated with experimental measurements. RESULTS: Following the literature approach, the work first proved that it is possible to build a facility-specific analytical model that efficiently reproduces in-water neutron doses and in-air H*(10) values with a maximum difference less than 25%. In addition, the analytical model succeeded in predicting out-of-field neutron doses in the lateral and vertical direction. Testing the analytical model in clinical configurations proved the need to separate the contribution of internal and external neutrons. The impact of modulation width on stray neutrons was found to be easily adjustable while beam collimation remains a challenging issue. Finally, the model performance agreed with experimental measurements with satisfactory results considering measurement and simulation uncertainties. CONCLUSION: Analytical models represent a promising solution that substitutes for time-consuming MC calculations when assessing doses to healthy organs.

[Pulsed-dose rate brachytherapy in cervical cancers: why, how?]. / Curiethérapie de débit de dose pulsé dans les cancers du col utérin : pourquoi, comment ?

The end of the production of 192 iridium wires terminates low dose rate brachytherapy and requires to move towards pulsed-dose rate or high-dose rate brachytherapy. In the case of gynecological cancers, technical alternatives exist, and many teams have already taken the step of pulsed-dose rate for scientific reasons. Using a projector source is indeed a prerequisite for 3D brachytherapy, which gradually installs as a standard treatment in the treatment of cervical cancers. For other centers, this change implies beyond investments in equipment and training, organizational consequences to ensure quality.

Monte Carlo modeling of proton therapy installations: a global experimental method to validate secondary neutron dose calculations.

Monte Carlo calculations are increasingly used to assess stray radiation dose to healthy organs of proton therapy patients and estimate the risk of secondary cancer. Among the secondary particles, neutrons are of primary concern due to their high relative biological effectiveness. The validation of Monte Carlo simulations for out-of-field neutron doses remains however a major challenge to the community. Therefore this work focused on developing a global experimental approach to test the reliability of the MCNPX models of two proton therapy installations operating at 75 and 178 MeV for ocular and intracranial tumor treatments, respectively. The method consists of comparing Monte Carlo calculations against experimental measurements of: (a) neutron spectrometry inside the treatment room, (b) neutron ambient dose equivalent at several points within the treatment room, (c) secondary organ-specific neutron doses inside the Rando-Alderson anthropomorphic phantom. Results have proven that Monte Carlo models correctly reproduce secondary neutrons within the two proton therapy treatment rooms. Sensitive differences between experimental measurements and simulations were nonetheless observed especially with the highest beam energy. The study demonstrated the need for improved measurement tools, especially at the high neutron energy range, and more accurate physical models and cross sections within the Monte Carlo code to correctly assess secondary neutron doses in proton therapy applications.

Comparison between the ICRU rectal point and modern volumetric parameters in brachytherapy for locally advanced cervical cancer.

PURPOSE: The implementation of image-guided brachytherapy in cervical cancer raises the problem of adapting the experience acquired with 2D brachytherapy to this technique. The GEC-ESTRO (Groupe européen de curiethérapie - European Society for Radiotherapy and Oncology) has recommended reporting the dose delivered to the rectum in the maximally exposed 2 cm(3) volume, but so far, the recommended dose constraints still rely on 2D data. The aim of this study was to evaluate the relationship between the doses evaluated at the ICRU rectal point and modern dosimetric parameters. MATERIAL AND METHODS: For each patient, dosimetric parameters were generated prospectively at the time of dosimetry and were reported. For analysis, they were converted in 2 Gy equivalent doses using an α/ß ratio of 3 with a half-time of repair of 1.5 hours. RESULTS: The dosimetric data from 229 consecutive patients treated for locally advanced cervical cancer was analyzed. The mean dose calculated at ICRU point (DICRU) was 55.75 Gy ± 4.15, while it was 59.27 Gy ± 6.16 in the maximally exposed 2 cm(3) of the rectum (P=0.0003). The D2 cm(3) was higher than the DICRU in 78% of the cases. The mean difference between D2 cm(3) and DICRU was 3.53 Gy ± 4.91. This difference represented 5.41% ± 7.40 of the total dose delivered to the rectum (EBRT and BT), and 15.49% ± 24.30 of the dose delivered when considering brachytherapy alone. The two parameters were significantly correlated (P=0.000001), and related by the equation: D2 cm(3)=0.902 × DICRU + 0.984. The r(2) coefficient was 0.369. CONCLUSION: In this large cohort of patients, the DICRU significantly underestimates the D2 cm(3). This difference probably results from the optimization process itself, which consists in increasing dwell times above the ICRU point in the cervix. Considering these findings, caution must be taken while implementing image-guided brachytherapy and dose escalation.

Secondary neutron doses in proton therapy treatments of ocular melanoma and craniopharyngioma.

Monte Carlo simulations were used to assess secondary neutron doses received by patients treated with proton therapy for ocular melanoma and craniopharyngioma. MCNPX calculations of out-of-field doses were done for ∼20 different organs considering realistic treatment plans and using computational phantoms representative of an adult male individual. Simulations showed higher secondary neutron doses for intracranial treatments, ∼14 mGy to the salivary glands, when compared with ocular treatments, ∼0.6 mGy to the non-treated eye. This secondary dose increase is mainly due to the higher proton beam energy (178 vs. 75 MeV) as well as to the impact of the different beam parameters (modulation, collimation, field size etc.). Moreover, when compared with published data, the assessed secondary neutron doses showed similar trends, but sometimes with sensitive differences. This confirms secondary neutrons to be directly dependent on beam energy, modulation technique, treatment configuration and methodology.

Volumetric evaluation of an alternative bladder point in brachytherapy for locally advanced cervical cancer.

PURPOSE: To evaluate an alternative dose point, so-called ALG (for Alain Gerbaulet), for the bladder in comparison to the International Commission on Radiation Units and Measurements (ICRU) point and D2cm(3) (minimal dose to maximally exposed 2 cm(3)) in a large cohort of patients with locally advanced cervical cancer treated with external beam radiotherapy followed by image-guided pulsed dose rate brachytherapy. METHODS AND MATERIALS: For each patient, the ALG point was constructed 1.5 cm above the ICRU bladder, parallel to the tandem (coronal and sagittal planes). The dosimetric data from 162 patients were reviewed. RESULTS: Average doses to ALG and bladder points were 19.40 Gy ± 7.93 and 17.14 ± 8.70, respectively (p=0.01). The 2 cm(3) bladder dose averaged 24.40 ± 6.77 Gy. Ratios between D2cm(3) and dose points were 1.37 ± 0.46 and 1.68 ± 0.74 (p<0.001) for ALG and ICRU points, respectively. Both dose points appeared correlated with D2cm(3) (p<0.001) with coefficients of determination (R(2)) of 0.331 and 0.399 respectively. The estimated dose to the ICRU point of the rectum was 12.77 ± 4.21 and 15.76 ± 5.94 for D2cm(3) (p<0.0001). Both values were significantly correlated (p<0.0001, R(2) = 0.485). CONCLUSION: The ALG point underestimates the D2cm(3), but its mean on a large cohort is closer to D2cm(3) than the dose to ICRU point. However, it shows great variability between cases and the weak strength of its correlation to D2cm(3) indicates that it is not a good surrogate for individual volumetric evaluation of the dose D2cm(3).

[Contribution of 3D imaging in brachytherapy: which kind of imaging for which localization?]. / Apport de l'imagerie 3D en curiethérapie : quel type d'imagerie pour quelle localisation ?

The use of image-guided brachytherapy has led to a significant change in application techniques and improvements in treatment planning. Today, 3D imaging has replaced orthogonal radiographs for a large number of treatments, providing a possibility of an optimization adapted to the anatomy of each patient. When properly selected and implemented, this imaging provides accurate 3D information of volumes and brachytherapy device, allowing moving from a dose to points assessment to a dose/volume evaluation. This article describes the contribution of different imaging modalities for the different brachytherapy techniques: gynecological brachytherapy, interstitial brachytherapy (breast, penis, etc.) and prostate brachytherapy. It reminds recommendations for the establishment of protocols of images acquisition and 3D reconstruction of brachytherapy devices (applicators, plastic tubes, needles, etc.).

[Involved-node radiotherapy combined with deep-inspiration breath-hold technique in patients with Hodgkin lymphoma]. / Optimisation de la radiothérapie involved-node grâce à l'inspiration profonde bloquée dans la maladie de Hodgkin.

PURPOSE: To assess the clinical outcome of the involved-node radiotherapy (INRT) concept with the use of deep-inspiration breath-hold (DIBH) technique in patients with localized supra-diaphragmatic Hodgkin lymphoma. PATIENTS AND METHODS: All were patients with stage I-II Hodgkin lymphoma and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy concept according to the European Organization for Research and Treatment of Cancer Guidelines and a spirometer dedicated to DIBH radiotherapy was used for every patient. RESULTS: Twenty-seven patients with Hodgkin lymphoma (26 patients with primary Hodgkin lymphoma, one with refractory disease), treated from November 2004 to October 2010, were retrospectively analysed. The median age was 27 years (range 16 to 54). Seventeen (63%) patients had stage I-IIA and 10 (37%) had stage I-IIB disease. All patients received two to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine. The median radiation dose to patients was 30,6 Gy (range: 19,8-40). Protection of various organs at risk was satisfactory. Median follow-up, 3-year progression-free and 3-year overall survival were 38 months (range: 7-70), 96% (95%CI: 79-99%) and 95% (95%CI: 75-99%), respectively. Recurrence occurred in one patient (mediastinal in-field relapse). There was one grade 3 acute toxicity (transient pneumonitis). CONCLUSIONS: Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using deep-inspiration breath technique and the involved-node radiotherapy concept. Longer follow-up is needed to assess late toxicity, especially for the heart and the coronary arteries.