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A survey regarding utilisation of brachytherapy was distributed to European brachytherapy professionals. Eighty replies from 26 countries were received, two of which were outside Europe. The replies showed that brachytherapy is still widely used. The main indications for brachytherapy are gynaecological and prostate cancer, with >80 % of the responding countries performing brachytherapy for these indications. There is on average one brachytherapy centre per 0.8 million inhabitants, ranging from 0.4 per million to 2.3 per million inhabitants. The organisation of brachytherapy on national levels also varies from country to country, with less than half of the countries having a central brachytherapy registry. All in all, the survey shows that brachytherapy still plays a role on modern radiotherapy, but the field could benefit from a stronger collaboration both nationally and internationally., (© 2024 The Authors.)

Background: There is lack of evidence on chronic fatigue (CF) following radiotherapy (RT) in survivors of head and neck cancer (HNC). We aimed to compare CF in HNC survivors > 5 years post-RT with a reference population and investigate factors associated with CF and the possible impact of CF on health-related quality of life (HRQoL)., Material and Methods: In this cross-sectional study we included HNC survivors treated in 2007-2013. Participants filled in patient-reported outcome measures and attended a one-day examination. CF was measured with the Fatigue Questionnaire and compared with a matched reference population using t-tests and Cohen's effect size. Associations between CF, clinical and RT-related factors were investigated using logistic regression. HRQoL was measured with the EORTC Quality of Life core questionnaire., Results: The median age of the 227 HNC survivors was 65 years and median time to follow-up was 8.5 years post-RT. CF was twice more prevalent in HNC survivors compared to a reference population. In multivariable analyses, female sex (OR 3.39, 95 % CI 1.82-6.31), comorbidity (OR 2.17, 95 % CI 1.20-3.94) and treatment with intensity-modulated RT (OR 2.13, 95 % CI 1.16-3.91) were associated with CF, while RT dose parameters were not. Survivors with CF compared to those without, had significantly worse HRQoL., Conclusions: CF in HNC survivors is particularly important for female patients, while specific factors associated with RT appear not to play a role. The high CF prevalence in long-term HNC survivors associated with impaired HRQoL is important information beneficial for clinicians and patients to improve patient follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Improvements in treatment outcome for patients with locally advanced cervical cancer (LACC) require a better classification of patients according to their risk of recurrence. We investigated whether an imaging-based approach, combining pretreatment hypoxia and tumor response during therapy, could improve risk classification., Material and Methods: Ninety-three LACC patients with T2-weigthed (T2W)-, dynamic contrast enhanced (DCE)- and diffusion weighted (DW)-magnetic resonance (MR) images acquired before treatment, and T2W- and, for 64 patients, DW-MR images, acquired at brachytherapy, were collected. Pretreatment hypoxic fraction (HF pre ) was determined from DCE- and DW-MR images using the consumption and supply-based hypoxia (CSH)-imaging method. Volume regression at brachytherapy was assessed from T2W-MR images and combined with HF pre . In 17 patients with adequate DW-MR images at brachytherapy, the apparent diffusion coefficient (ADC), reflecting tumor cell density, was calculated. Change in ADC during therapy was combined with volume regression yielding functional regression as explorative response measure. Endpoint was disease free survival (DFS)., Results: HF pre was the strongest predictor of DFS, but a significant correlation with outcome was found also for volume regression. The combination of HF pre and volume regression showed a stronger association with DFS than HF pre alone. Patients with disease recurrence were selected to either the intermediate- or high-risk group with a 100 % accuracy. Functional regression showed a stronger correlation to HF pre than volume regression., Conclusion: The combination of pretreatment hypoxia and volume regression at brachytherapy improved patient risk classification. Integration of ADC with volume regression showed promise as a new tumor response parameter., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG-267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments., (© 2024 American Association of Physicists in Medicine.)

Background: Patients treated for lung cancer (LC) often experience locoregional failure after initial treatment. Due to technological advances, thoracic reirradiation (re-RT) has become a viable treatment option. We sought to investigate the use of thoracic re-RT in LC patients over a time period characterized by technological advances in a large, multi-center cohort., Methods and Materials: LC patients treated with thoracic re-RT in two University Hospitals from 2010-2020 were identified. Clinical variables and RT data were extracted from the medical records and treatment planning systems. Overall survival (OS) was calculated from the last day of re-RT until death or last follow up., Results: 296 patients (small cell LC n=30, non-small cell LC n=266) were included. Three-dimensional conformal radiation therapy was the RT technique used most frequently (63%), and 86% of all patients were referred for re-RT with palliative treatment intent. During the second half of the study period, the use of thoracic re-RT increased in general, more patients received curative re-RT, and there was an increased use of stereotactic body radiation therapy (SBRT). Median time between initial RT and re-RT was 18 months (range 1-213 months). Only 83/296 patients had combined treatment plans that allowed for registration of combined doses to organs at risk (OAR). Most of the combined doses to OAR were below recommendations from guidelines. Multivariate analysis showed superior OS (p<0.05) in patients treated with curative intent, SBRT or intensity modulated radiation therapy or had excellent performance status prior to re-RT., Conclusions: The use of re-RT increased in the second half of the study period, although 2020 did not follow the trend. The use of SBRT and IMRT became more frequent over the years, yet the majority received palliative re-RT. Combined dose plans were only created for one third of the patients., (Copyright © 2024. Published by Elsevier Inc.)

Background and Purpose: This large population-based, retrospective, single-center study aimed to identify prognostic factors in patients with brain metastases (BM) from gynecological cancers., Material and Methods: One hundred and forty four patients with BM from gynecological cancer treated with radiotherapy (RT) were identified. Primary cancer diagnosis, age, performance status, number of BM, presence of extracranial disease, and type of BM treatment were assessed. Overall survival (OS) was calculated using the Kaplan-Meier method and the Cox proportional hazards regression model was used for multivariable analysis. A prognostic index (PI) was developed based on scores from independent predictors of OS., Results: Median OS for the entire study population was 6.2 months. Forty per cent of patients died within 3 months after start of RT. Primary cancer with the origin in cervix or vulva (p = 0.001),  Eastern Cooperative Oncology Group (ECOG) 3-4 (p < 0.001), and the presence of extracranial disease (p = 0.001) were associated with significantly shorter OS. The developed PI based on these factors, categorized patients into three risk groups with a median OS of 13.5, 4.0, and 2.4 months for the good, intermediate, and poor prognosis group, respectively., Interpretation: Patients with BM from gynecological cancers carry a poor prognosis. We identified prognostic factors and developed a scoring tool to select patients with better or worse prognosis. Patients in the high-risk group have a particular poor prognosis, and omission of RT could be considered.

Background: Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models., Methods: This cross-sectional study conducted in 2018-2020, included HNC survivors treated in 2007-2013. Participants attended a one-day examination in hospital and filled in patient questionnaires. Dysphagia was measured with the EORTC QLQ-H&N35 swallowing scale. Toxicity was scored with CTCAE v.4. We contoured swallowing organs at risk (SWOAR) on RT plans, calculated dose-volume histograms (DVHs), performed logistic regression analyses and tested our data in established NTCP models., Results: Of the 239 participants, 75 (31%) reported dysphagia. Compared to survivors without dysphagia, this group had reduced HRQoL and the DVHs for infrahyoid SWOAR were significantly shifted to the right. Long-term dysphagia was associated with age (OR 1.07, 95% CI 1.03-1.10), female sex (OR 2.75, 95% CI 1.45-5.21), and mean dose to middle pharyngeal constrictor muscle (MD-MPCM) (OR 1.06, 95% CI 1.03-1.09). NTCP models overall underestimated the risk of long-term dysphagia., Conclusions: Long-term dysphagia was associated with higher age, being female, and high MD-MPCM. Doses to distally located SWOAR seemed to be risk factors. Existing NTCP models do not sufficiently predict long-term dysphagia. Further efforts are needed to reduce the prevalence and consequences of this late effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Head and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects., Methods: In a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H&N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls., Results: Median time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58%, 31%, and 33%, respectively, with a preponderance of females. We found no significant associations between IL-6, IL-8, IP-10, TARC, TNF, or ENA-78 and the three late effects. The odds of having elevated levels of IL-6 and IP-10 were significantly higher in the survivors compared to the controls., Conclusions: More than one-third of long-term HNC survivors experienced xerostomia, dysphagia, and CF. Persistent inflammation, with elevated systemic cytokines, was not associated with these late effects, although HNC survivors had higher levels of some cytokines than the controls., Implications for Cancer Survivors: This study provides new knowledge on late effects that can serve as grounds for informing patients with HNC about risk of late effects more than 5 years after RT., (© 2022. The Author(s).)

Introduction: The use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase ( IDH )-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life., Methods and Analysis: PRO-GLIO (PROton versus photon therapy in IDH -mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH -mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints., Ethics and Dissemination: To implement proton therapy as part of standard of care for patients with IDH -mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums., Trial Registration Number: ClinicalTrials.gov Registry (NCT05190172)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: To prospectively investigate whether surface guided setup of right sided breast cancer patients can increase efficiency and accuracy compared to traditional skin marker/tattoo based setup., Material and Methods: Twenty-five patients were included in this study. Each patient was positioned using skin marks and tattoos (procedure A) for half of the fractions and surface guidance using AlignRT (procedure B) for the other half of the fractions. The order of the two procedures was randomized. Pretreatment CBCT was acquired at every fraction for both setup procedures. A total of ten time points were recorded during every treatment session. Applied couch shifts after CBCT match were recorded and used for potential error calculations if no CBCT had been used., Results: In the vertical direction procedure B showed significant smaller population based systematic (Ʃ) and random (σ) errors. However, a significant larger systematic error on the individual patient level (M) was also shown. This was found to be due to patient relaxation between setup and CBCT matching. Procedure B also showed a significant smaller random error in the lateral direction, while no significant differences were seen in the longitudinal direction. No significant difference in setup time was found between the two procedures., Conclusion: Setup of right sided breast cancer patients using surface guidance yields higher accuracy than setup using skin marks/tattoos and lasers with the same setup time. Patient alignment for this patient group can safely be done without the use of permanent tattoos and skin marks when utilizing surface-guided patient positioning. However, CBCT should still be used as final setup verification., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Up to half of patients with localized prostate cancer experience biochemical relapse within 10 years after definitive radiotherapy. The aim of this prospective study was to investigate the toxicity, dose to the organs at risk (OARs), and efficacy of dose-intensified focal salvage radiotherapy., Methods and Material: Thirty-three patients (median age 68.8 years) with histologically confirmed relapse after primary definitive radiotherapy were enrolled between 2012 and 2019. No patients had metastases at imaging or in bone marrow aspiration. Twenty-three patients were treated with high dose-rate brachytherapy to the recurrent tumor, defined at multiparametric MRI, with 3 fractions of 10 Gy with two weeks interval, and 10 patients by stereotactic body radiotherapy with 35 Gy to the local recurrence and 25 Gy to the whole prostate in 5 fractions. We used the RTOG-scoring system to grade genitourinary (GU) and gastrointestinal toxicity (GI) at three months (acute), and at 12, 24, and 36 months (late). Dose-volume histogram parameters to the local recurrence and the OARs were obtained and 2 Gy equivalent (EQD2) total dose was calculated using the linear-quadratic model with α/β = 3 Gy. Efficacy was assessed by the progression-free interval and overall survival., Results: Median follow-up time was 81 months (range 21-115). The cumulative moderate to severe GI and GU toxicities were 3.0% (1/33) and 15.2% (5/33). Six patients had grade 1 acute GI toxicity, none had grade 2 or 3. One patient had grade 3 acute GU toxicity, two had grade 2, and fourteen had grade 1. One patient had late GI toxicity grade 2 and eight had grade 1. Four patients had late GU toxicity grade 2 and eight had grade 1. No patients had grade 3 late toxicity. The mean total D90 to the recurrent tumor was 77.7 ± 17.0 Gy. The mean total rectum D2cc was 17.0 ± 7.9 Gy and the mean total urethra D0.1cc was 29.1 ± 8.2 Gy. Twenty-eight patients had re-irradiation without androgen deprivation therapy (ADT). Nine of these are still relapse-free and 10 had a recurrence-free interval longer than 2 years., Conclusion: The toxicity of salvage radiotherapy was mild to moderate. One-third of the patients achieved long-term stable disease without ADT and one-third had a recurrence-free interval longer than 2 years. Some patients progressed rapidly and probably did not benefit from re-irradiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ryg, Seierstad, Nilsen, Hellebust, Djupvik, Gustafson, Hydal, Kishan, Hole and Lilleby.)

Background and Purpose: To evaluate dose-effect relationships between vaginal dose points and vaginal stenosis in patients treated for locally advanced cervical cancer with radio(chemo)therapy and image-guided adaptive brachytherapy., Material and Methods: Patients from six centres participating in the EMBRACE-I study were included. Information on doses to different vaginal dose points, including the Posterior-Inferior Border of Symphysis (PIBS) points and recto-vaginal reference (RV-RP) point, were retrieved from the treatment planning system. In addition, the vaginal reference length (VRL) was evaluated. Vaginal stenosis was prospectively assessed according to the CTCAEv3.0 system at baseline and follow-up. Primary endpoint was grade 2 or higher (G ≥ 2) vaginal stenosis. Impact of dose to the vaginal dose points, and impact of VRL, age, vaginal involvement and applicator on vaginal stenosis G ≥ 2 was evaluated with a Cox proportional-hazard regression model., Results: 301 patients were included. Median follow-up was 49 months. During follow-up, the incidence of G0, G1, G2, and G3 vaginal stenosis was 25% (76), 52% (158), 20% (59) and 3% (8), respectively. Median total doses to PIBS+2 cm, PIBS, PIBS-2 cm and the RV-RP were 52.9 (IQR 49.3-64.7), 41.0 (IQR 15.4-49.0), 4.1 (IQR 2.9-7.0) and 64.6 (IQR 60.0-70.6) Gy EQD2 3 , respectively. Higher doses to the PIBS, PIBS + 2 cm and RV-RP points were significantly associated with increased risk for vaginal stenosis G ≥ 2. Other risk factors for vaginal stenosis were: vaginal involvement at diagnosis, higher age, shorter VRL and use of a tandem-ovoid applicator., Conclusion: Higher doses to the PIBS+2 cm, PIBS and RV-RP dose points are associated with vaginal stenosis G ≥ 2., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Brain metastases (BM) occur in about 30% of all patients with non-small cell lung cancer (NSCLC). BM treatment guidelines recommend more frequent use of stereotactic radiotherapy (SRT). Overall, studies report no difference in overall survival (OS) comparing SRT to whole-brain radiotherapy (WBRT). We examined survival after radiotherapy for BM in a population-based sample from the South-Eastern Norway Regional Health Authority treated 2006-2018., Methods: We reviewed electronic medical records of 2140 NSCLC patients treated with SRT or WBRT for BM from 2006-2018. Overall survival (OS) was compared to predicted survival according to the prognostic systems DS-GPA and Lung-molGPA., Results: Use of SRT increased during the period, from 19% (2006-2014) to 45% (2015-2018). Median OS for all patients was 3.0 months, increasing from 2.0 (2006) to 4.0 (2018). Median OS after SRT was 7.0 months ( n  = 435) and 3.0 months after WBRT ( n  = 1705). Twenty-seven percent of SRT patients and 50% of WBRT patients died within 90 days after start of RT. Age ≥70, male sex, KPS ≤70, non-adenocarcinoma histology, ECM present, multiple BM, and WBRT were associated with shorter survival ( p  < .001). Actual mOS corresponded best with predicted mOS by DS-GPA and Lung-molGPA for the SRT group., Conclusion: Overall survival after radiotherapy (RT) for BM improved during the study period, but only for patients treated with SRT. Survival after WBRT remains poor; its use should be questioned. DS-GPA and Lung-molGPA seem most useful in predicting prognosis considered for SRT.

The beneficial effects of protons are primarily based on reduction of low to intermediate radiation dose bath to normal tissue surrounding the radiotherapy target volume. Despite promise for reduced long-term toxicity, the percentage of cancer patients treated with proton therapy remains low. This is probably caused by technical improvements in planning and delivery of photon therapy, and by high cost, low availability and lack of high-level evidence on proton therapy. A number of proton treatment facilities are under construction or have recently opened; there are now two operational Scandinavian proton centres and two more are under construction, thereby eliminating the availability hurdle. Even with the advantageous physical properties of protons, there is still substantial ambiguity and no established criteria related to which patients should receive proton therapy. This topic was discussed in a session at the Nordic Collaborative Workshop on Particle Therapy, held in Uppsala 14-15 November 2019. This paper resumes the Nordic-Baltic perspective on proton therapy indications and discusses strategies to identify patients for proton therapy. As for indications, neoplastic entities, target volume localisation, size, internal motion, age, second cancer predisposition, dose escalation and treatment plan comparison based on the as low as reasonably achievable (ALARA) principle or normal tissue complication probability (NTCP) models were discussed. Importantly, the patient selection process should be integrated into the radiotherapy community and emphasis on collaboration across medical specialties, involvement of key decision makers and knowledge dissemination in general are important factors. An active Nordic-Baltic proton therapy organisation would also serve this purpose.

Ultrasound (US) is an important imaging modality in brachytherapy (BT). In particular for low-dose-rate (LDR) and high-dose-rate (HDR) prostate implants transrectal ultrasound (TRUS) is widespread. Besides the common use of US for prostate implants, US can also be applied in gynecological and anal cancer therapies as examples amongst others. The BRAPHYQS (BRAchytherapy PHYsics Quality assurance System) and UroGEC (urology) working groups of GEC-ESTRO (GEC: Groupe Européen de Curiethérapie, committee of ESTRO: European SocieTy for Radiotherapy & Oncology) elaborated upon guidelines describing quality assurance (QA) methods for US in BT. The total quality management (QM) for the unit includes acceptance testing, commissioning and periodic image testing. In 2008, the AAPM (American Association of Physicists in Medicine) published the TG (Task group) 128 report. Whereas the TG 128 focuses on US systems and prostate BT, the current recommendations also cover tests for stepping devices and include other interstitial or intracavitary treatment sites in BT, such as anal implants and gynecological BT. The recommendations presented herein do not replace regular maintenance for the US devices performed by the vendor. They are the QA of US in BT but are not sufficient for the whole maintenance of medical US devices. Moreover, national regulations and recommendations should also be followed. For the tests presented in this report tolerances or action limits are given. These recommendations explain practical test procedures of US devices in BT. They will help the clinics to perform a high level of quality in the use of US for BT in Europe., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A thorax phantom was used to assess radiotherapy dose deviations induced by respiratory motion of the target volume. Both intensity modulated and static, non-modulated treatment plans were planned on CT scans of the phantom. The plans were optimized using various CT reconstructions, to investigate whether they had an impact on robustness to target motion during delivery. During irradiation, the target was programmed to simulate respiration-induced motion of a lung tumor, using both patient-specific and sinusoidal motion patterns in three dimensions. Dose was measured in the center of the target using an ion chamber. Differences between reference measurements with a stationary target and dynamic measurements were assessed. Possible correlations between plan complexity metrics and measured dose deviations were investigated. The maximum observed motion-induced dose differences were 7.8% and 4.5% for single 2 Gy and 15 Gy fractions, respectively. The measurements performed with the largest target motion amplitude in the superior-inferior direction yielded the largest dosimetric deviations. For 2 Gy fractionation schemes, the summed dose deviation after 33 fractions is likely to be less than 2%. Measured motion-induced dose deviations were significantly larger for one CT reconstruction compared to all the others. Static, non-modulated plans showed superior robustness to target motion during delivery. Moderate correlations between the modulation complexity score applied to VMAT (MCSv) and measured dose deviations were found for 15 Gy SBRT treatment plans. Correlations between other plan complexity metrics and measured dose deviations were not found., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: The aim of this study was to investigate the influence of brachytherapy technique and applicator type on target dose, isodose surface volumes, and organ-at-risk (OAR) dose., Methods and Materials: Nine hundred two patients treated with tandem/ovoids (T&O) (n = 299) and tandem/ring (T&R) (n = 603) applicators from 16 EMBRACE centers were analyzed. Patients received external beam radiation therapy and magnetic resonance imaging guided brachytherapy with dose prescription according to departmental practice. Centers were divided into 4 groups, according to applicator/technique: Ovoids and ring centers treating mainly with the intracavitary (IC) technique and ovoids and ring centers treating routinely with the intracavitary/interstitial (IC/IS) technique. V85Gy EQD2 10 , CTV HR D 90% (EQD2 10 ), and bladder, rectum, sigmoid, and vaginal 5-mm lateral-point doses (EQD2 3 ) were evaluated among center groups. Differences between T&O and T&R were tested with multivariable analysis., Results: For similar point A doses, mean CTV HR D 90% was 3.3 Gy higher and V85Gy was 23% lower for ring-IC compared with ovoids-IC centers (at median target volumes). Mean bladder/rectum doses (D 2cm3 and ICRU-point) were 3.2 to 7.7 Gy smaller and vaginal 5-mm lateral-point was 19.6 Gy higher for ring-IC centers. Routine use of IC/IS technique resulted in increased target dose, whereas V85Gy was stable (T&R) or decreased (T&O); reduced bladder and rectum D 2cm3 and bladder ICRU-point by 3.5 to 5.0 Gy for ovoids centers; and similar OAR doses for ring centers. CTV HR D 90% was 2.8 Gy higher, bladder D 2cm3 4.3 Gy lower, rectovaginal ICRU-point 4.8 Gy lower, and vagina 5-mm lateral-point 22.4 Gy higher for ring-IC/IS versus ovoids-IC/IS centers. The P values were <.002 for all comparisons. Equivalently, significant differences were derived from the multivariable analysis., Conclusions: T&R-IC applicators have better target dose and dose conformity than T&O-IC in this representative patient cohort. IC applicators fail to cover large target volumes, whereas routine application of IC/IS improves target and OAR dose considerably. Patients treated with T&R show a more favorable therapeutic ratio when evaluating target, bladder/rectum doses, and V85Gy. A comprehensive view on technique/applicators should furthermore include practical considerations and clinical outcome., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To examine the variability in prescribed dose due to contouring variations in intracavitary image-guided adaptive brachytherapy for cervical cancer. To identify correlations between dosimetric outcomes and delineation uncertainty metrics., Methods and Materials: A data set from an EMBRACE sub-study on contouring uncertainties was used, consisting of magnetic resonance images of six patients with cervical cancer delineated by 10 experienced observers (target volumes and organs at risk). Two gold standard contours were generated, an expert consensus and the simultaneous truth and performance level estimation. Plans were individually optimised to all of the contour sets (12 in total). Plans were applied to the gold standard contour sets, and dose volume histogram parameters including D 90 , D 98 and D 2cm 3 were determined. The variability between plans was assessed. Dose volume histogram parameters and delineation uncertainty metrics were correlated using the Spearman's non-parametric rank correlation., Results: There is a dosimetric variability between observers, patients and the gold standard contour used for analysis. Approximately 3 Gy D 90 EQD2 10 variability (SD) was observed for the CTVHR and 1.2-3.6 Gy D 2cm 3 EQD2 3 for the organs at risk. The maximum geometric dimensions of the delineations are most commonly correlated with dosimetry changes. Although the correlations are similar across gold standards, the direction of these correlations differs, indicating that the dosimetric outcomes are dependent on the contour that the plan is optimised to., Conclusion: This study highlights the dosimetric differences interobserver uncertainty in contouring can have for cervical cancer brachytherapy. The importance of carefully choosing a gold standard from which to benchmark is reiterated., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

This review provides an overview of the current status of image registration for image guided gynaecological brachytherapy including combination with external beam radiotherapy. Contour propagation between individual fractions and dose accumulation can be useful for cervix cancer radiotherapy. Contour mapping and applicator reconstruction with rigid registration based on the applicator geometry provide good accuracy. However, deformable image registration is particularly challenging in the pelvic region, due to the large and complex deformations caused by tumor shrinkage, bladder and rectum filling, insertion of a brachytherapy applicator and presence of packing material. This causes substantial limitations and uncertainties when using it in the clinical workflow so that the current generation of deformable image registration algorithms is not yet robust enough to handle complexities involving the dose accumulation of external beam and brachytherapy. The direct addition of doses provides a reasonable estimate of the total absorbed dose. However, in case of significant dose gradients from external beam boosts or midline-shielding adding dose contributions from the different radiotherapy modalities and fractions remains subject to large uncertainties., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To describe the evolution of external beam radiation therapy (EBRT) from EMBRACE-I (general guidelines for EBRT) to the initial phase of the EMBRACE-II study (detailed protocol for EBRT)., Methods and Materials: EMBRACE-I enrolled 1416 locally advanced cervical cancer patients treated with chemoradiation including image-guided adaptive brachytherapy during 2008 to 2015. From March 2016 until March 2018, 153 patients were enrolled in the ongoing EMBRACE-II study, which involves a comprehensive detailed strategy and accreditation procedure for EBRT target contouring, treatment planning, and image guidance. EBRT planning target volumes (PTVs), treated volumes (V43 Gy), and conformity index (CI; V43 Gy/PTV) were evaluated in both studies and compared., Results: For EMBRACE-I, conformal radiation therapy (60% of patients) or intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT; 40%) was applied with 45 to 50 Gy over 25 to 30 fractions to the elective clinical target volume (CTV). For pelvic CTVs (82%), median PTV and V43 Gy volumes were 1549 and 2390 mL, respectively, and CI was 1.54. For pelvic plus paraortic nodal (PAN) CTVs (15%), median PTV and V43 Gy volumes were 1921 and 2895 mL, and CI was 1.51. For pelvic CTVs treated with 45 to 46 Gy, the use of conformal radiation therapy was associated with a median V43 Gy volume that was 546 mL larger than with IMRT/VMAT. For pelvic CTVs treated with IMRT, the use of a dose prescription ≥48 Gy was associated with a median V43 Gy volumes that was 428 mL larger than with a dose prescription of 45 to 46 Gy. For EMBRACE-II, all patients were treated with: IMRT/VMAT, daily IGRT, 45 Gy over 25 fractions for the elective CTV, and simultaneously integrated boost for pathologic lymph nodes. For pelvic CTVs (61%), median PTV and V43 Gy volumes were 1388 and 1418 mL, and CI was 1.02. For pelvic plus PAN CTVs (32%), median PTV and V43 Gy volumes were 1720 and 1765 mL, and CI was 1.03. From EMBRACE-I to initial II, median V43 Gy was decreased by 972 mL (41%) and 1130 mL (39%), and median CI decreased from 1.54 to 1.02 and 1.51 to 1.03 for pelvic and pelvic plus PAN irradiation, respectively., Conclusions: Application of IMRT/VMAT, IGRT, and a 45-Gy dose provides the potential of higher conformality inducing significant reduction of treated volume. Adherence to a detailed protocol including comprehensive accreditation, as in EMBRACE-II, reduces considerably V43 Gy and V50 Gy and improves conformality and interinstitutional consistency., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The survival benefit of dose-escalation with High-Dose-Rate brachytherapy (HDR-BT) boost combined with External Beam Radiotherapy (EBRT) for the treatment of high-risk prostate cancer (PCa) remains debatable. We investigated 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in high-risk patients treated with HDR-BT/EBRT (calculated EQD2 = 102 Gy) compared to EBRT alone (70 Gy)., Methods: HDR-BT boosts (10 Gy × 2) were given 2 weeks apart followed by 50 Gy conformal EBRT (2 Gy × 25) to the prostate and seminal vesicles. The HDR-BT/EBRT group (N:325) received Androgen Deprivation Therapy for a median duration of 2 years. The historical control group (N:296), received a median dose of 70 Gy (2 Gy × 35) to the prostate and seminal vesicles with lifelong Anti-Androgen Treatment. For each treatment group PCSM and OM were established by competing-risk analyses and Kaplan-Meier analyses respectively. Differences were evaluated by the logrank test. Independent associations were established by Cox regression analyses. Significance level set to p < 0.05., Results: Median follow-up was 104 and 120 months for the HDR-BT/EBRT and the EBRT group respectively. A 3.6-fold decreased risk of PCSM (p < 0.01) and a 1.6-fold decreased risk of OM (p = 0.02) in the HDR-BT/EBRT cohort compared to the EBRT-only group were revealed. Ten-year OM and PCSM rates were 16% and 2.5% in the HDR-BT/EBRT group versus 23% and 8.2% in the EBRT-only group respectively. Both treatment modality (HR = 3.59, 95%CI 1.50-8.59) and Gleason score (HR = 2.48, 95%CI 1.18-5.21) were associated with PCSM. Only treatment modality (HR = 1.63, 95%CI = 1.08-2.44) was significantly associated with OM., Conclusions: Men with high-risk PCa have a significantly reduced PCSM and OM rates when treated with dose-escalated radiotherapy achieved by HDR-BT/EBRT compared to EBRT alone (70 Gy). A Gleason score of 8-10 was independently associated with increased risk of PCSM. Randomized studies are warranted., Summary: Observational study of 10-year survival in high-risk Prostate Cancer (PCa) after High-Dose-Rate brachytherapy combined with External Beam Radiation Therapy (HDR-BT/EBRT) compared to EBRT alone. The combined HDR-BT/EBRT treatment was found to give a 3.6-fold decrease in Prostate Cancer Specific Mortality (PCSM) and a 1.6-fold decrease in Overall Mortality (OM). Gleason score and type of treatment strongly influenced PCSM whereas only treatment modality was associated with OM. The observed benefits of dose-escalation warrant future randomized trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To investigate the isodose surface volumes (ISVs) for 85, 75 and 60 Gy EQD2 for locally advanced cervix cancer patients., Materials and Methods: 1201 patients accrued in the EMBRACE I study were analysed. External beam radiotherapy (EBRT) with concomitant chemotherapy was followed by MR based image-guided adaptive brachytherapy (MR-IGABT). ISVs were calculated using a predictive model based on Total Reference Air Kerma and compared to Point A-standard loading systems. Influence of fractionation schemes and dose rates was evaluated through comparison of ISVs for α/β 10 Gy and 3 Gy., Results: Median V85 Gy , V75 Gy and V60 Gy EQD2 10 were 72 cm 3 , 100 cm 3 and 233 cm 3 , respectively. Median V85 Gy EQD2 10 was 23% smaller than in standard 85 Gy prescription to Point A. For small (<25 cm 3 ), intermediate (25-35 cm 3 ) and large (>35 cm 3 ) CTV HR volumes, the V85 Gy was 57 cm 3 , 70 cm 3 and 89 cm 3 , respectively. In 38% of EMBRACE patients the V85 Gy was similar to standard plans with 75-85 Gy to Point A. 41% of patients had V85 Gy smaller than standard plans receiving 75 Gy at Point A, while 21% of patients had V85 Gy larger than standard plans receiving 85 Gy at Point A., Conclusions: MR-IGABT and individualized dose prescription during EMBRACE I resulted in improved target dose coverage and decreased ISVs compared to standard plans used with classical Point A based brachytherapy. The ISVs depended strongly on CTV HR volume which demonstrates that dose adaptation was performed per individual tumour size and response during EBRT., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Imaging has probably been the most important driving force for the development of brachytherapy treatments the last 20 years. Due to implementation of three-dimensional imaging, brachytherapy is nowadays a highly accurate and reliable treatment option for many cancer patients. To be able to optimize the dose distribution in brachytherapy the anatomy and the applicator(s) or sources should be correctly localised in the images. For computed tomography (CT) the later criteria is easily fulfilled for most brachytherapy sites. However, for many sites, like cervix and prostate, CT is not optimal for delineation since soft tissue is not adequately visualized and the tumor is not well discriminated. For cervical cancer treatment planning based on magnetic resonance imaging (MRI) is recommended. Some centres also use MRI for postimplant dosimetry of permanent prostate seed implant and high dose rate prostate brachytherapy. Moreover, in so called focal brachytherapy where only a part of the prostate is treated, multiparametric MRI is an excellent tool that can assist in defining the target volume. Applicator or source localization is challenging using MRI, but tolls exist to assist this process. Also, geometrical distortions should be corrected or accounted for. Transrectal ultrasound is considered to be the gold standard for high dose rate prostate brachytherapy and transrectal ultrasound -based brachytherapy procedure offers a method for interactive treatment planning. Reconstruction of the needles is sometimes challenging, especially to identify the needle tip. The accuracy of the reconstruction could be improved by measuring the residuals needle length and by using a bi-planar transducer. The last decade several groups worldwide have explored the use of transrectal and transabdominal ultrasound for cervical cancer brachytherapy. Since ultrasonography is widely available, offers fast image acquisition and is a rather inexpensive modality such development is interesting. However, more work is needed to establish this as an adequate alternative for all phases of the treatment planning process. Studies using positron emission tomography imaging in combination with brachytherapy treatment planning are limited. However, development of new tracers may offer new treatment approaches for brachytherapy in the future. Combination of several image modalities will be the optimal solution in many situations, either during the same session or for different fractions. When several image modalities are combined so called image registration procedures are used and it is important to understand the principles and limitations of such procedures., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To compare target volume delineation of anal cancer using positron emission tomography (PET) and magnetic resonance imaging (MRI) with respect to inter-observer and inter-modality variability., Methods: Nineteen patients with anal cancer undergoing chemoradiotherapy were prospectively included. Planning computed tomography (CT) images were co-registered with 18F-fluorodexocyglucose (FDG) PET/CT images and T2 and diffusion weighted (DW) MR images. Three oncologists delineated the Gross Tumor Volume (GTV) according to national guidelines and the visible tumor tissue (GTV T ). MRI and PET based delineations were evaluated by absolute volumes and Dice similarity coefficients., Results: The median volume of the GTVs was 27 and 31 cm 3 for PET and MRI, respectively, while it was 6 and 11 cm 3 for GTV T . Both GTV and GTV T volumes were highly correlated between delineators (r = 0.90 and r = 0.96, respectively). The median Dice similarity coefficient was 0.75 when comparing the GTVs based on PET/CT (GTV PET ) with the GTVs based on MRI and CT (GTV MRI ). The median Dice coefficient was 0.56 when comparing the visible tumor volume evaluated by PET (GTV T&#95;PET ) with the same volume evaluated by MRI (GTV T&#95;MRI ). Margins of 1-2 mm in the axial plane and 7-8 mm in superoinferior direction were required for coverage of the individual observer's GTVs., Conclusions: The rather good agreement between PET- and MRI-based GTVs indicates that either modality may be used for standard target delineation of anal cancer. However, larger deviations were found for GTV T , which may impact future tumor boost strategies.

Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

Background: Patients with large, locally advanced cervical cancers (LACC) are challenging to treat. The purpose of this work is to use 18F-FDG PET as planning basis for a short-course simultaneous integrated boost (SIB) in external beam radiotherapy of LACC in order to increase tumour shrinkage and likelihood of local control., Methods: Ten previously treated patients with LACC were included, all with pre-treatment FDG PET/CT images available. The FDG avid tumour volume, MTV50, was dose escalated in silico by intensity modulated radiotherapy from the standard 1.8 Gy to 2.8 Gy per fraction for the 10 first fractions; a short-course SIB. For the 18 remaining external fractions, standard pelvic treatment followed to total PTV and MTV50 doses of 50.4 Gy and 60.4 Gy, respectively. Photon and proton treatment were considered using volumetric modulated arc treatment (VMAT) and intensity-modulated proton therapy (IMPT), respectively. All treatment plans were generated using the Eclipse Treatment Planning System (TPS). The impact of tumour shrinkage on doses to organs at risk (OARs) was simulated in the TPS for the SIB plans., Results: Dose escalation could be implemented using both VMAT and IMPT, with a D98 ≥ 95 % for MTV50 being achieved in all cases. The sum of the 10 fraction short-course SIB and subsequent 18 standard fractions was compared to the standard non-SIB approach by dose volume histogram (DVH) analysis. Only marginal increase of dose to OARs was found for both modalities and a small further increase estimated from tumour shrinkage. Most DVH parameters showed a mean difference below 2 %. IMPT had, compared to VMAT, reduced OAR doses in the low to intermediate dose range, but showed no additional advantage in dose escalation., Conclusions: Planning of dose escalation based on a FDG avid boost volume was here demonstrated feasible. The concept may allow time for enhanced tumour shrinkage before brachytherapy. Thus, this strategy may prove clinically valuable, in particular for patients with large tumours.

Background: Dose painting by numbers (DPBN) is a method to deliver an inhomogeneous tumor dose voxel-by-voxel with a prescription based on biological medical images. However, planning of DPBN is not supported by commercial treatment planning systems (TPS) today. Here, a straightforward method for DPBN with a standard TPS is presented., Material and Methods: DPBN tumor dose prescription maps were generated from (18)F-FDG-PET images applying a linear relationship between image voxel value and dose. An inverted DPBN prescription map was created and imported into a standard TPS where it was defined as a mock pre-treated dose. Using inverse optimization for the summed dose, a planned DPBN dose distribution was created. The procedure was tested in standard TPS for three different tumor cases; cervix, lung and head and neck. The treatment plans were compared to the prescribed DPBN dose distribution by three-dimensional (3D) gamma analysis and quality factors (QFs). Delivery of the DPBN plans was assessed with portal dosimetry (PD)., Results: Maximum tumor doses of 149%, 140% and 151% relative to the minimum tumor dose were prescribed for the cervix, lung and head and neck case, respectively. DPBN distributions were well achieved within the tumor whilst normal tissue doses were within constraints. Generally, high gamma pass rates (> 89% at 2%/2 mm) and low QFs (< 2.6%) were found. PD showed that all DPBN plans could be successfully delivered., Conclusions: The presented methodology enables the use of currently available TPSs for DPBN planning and delivery and may therefore pave the way for clinical implementation.

Background and Purpose: This study aims to analyze subsections of the target volume that are sensitive to delineation uncertainties with respect to underdosage (spatial dosimetric uncertainty) in MRI-based brachytherapy of cervical cancer., Material and Methods: A methodology was developed to simulate delineation uncertainties by shifting an angular segment of the contour perpendicular to the original HR-CTV. For shifts of 3, 6 and 9mm resulting D90 and D98 were calculated for the modified contour. The sensitivity of the dose plan to the locally introduced error was estimated by linear regression of D90 or D98 against the magnitude of the shift. The methodology was employed on 20 patients treated with tandem ring brachytherapy., Results: Topographic maps resulting from the dosimetric sensitivity analysis showed both large spatial variations and substantial inter-patient variations. For all plans included the spatial sensitivity in D90 ranged from 0.0 to -1.6%/mm, correspondingly sensitivity in D98 ranged from 0 to -4.6%/mm. A significantly increased dosimetric sensitivity was found in anterior direction and the cranial part of the tumor (p<0.05)., Conclusions: The developed methodology identifies specific tumor regions and patients with increased risk of underdosage from delineation uncertainties in brachytherapy of cervical cancer., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: According to the American Association of Physicists in Medicine Task Group No. 43 (TG-43) formalism used for dose calculation in brachytherapy treatment planning systems, the absolute level of absorbed dose is determined through coupling with the measurable quantity air-kerma strength or the numerically equal reference air-kerma rate (RAKR). Traceability to established standards is important for accurate dosimetry in laying the ground for reliable comparisons of results and safety in adoption of new treatment protocols. The purpose of this work was to compare the source strength for a high-dose rate (HDR) (192)Ir source as measured using equipment traceable to different standard laboratories in Europe and the United States., Methods and Materials: Source strength was determined for one HDR (192)Ir source using four independent systems, all with traceability to different primary or interim standards in the United States and Europe., Results: The measured HDR (192)Ir source strengths varied by 0.8% and differed on average from the vendor value by 0.3%. Measurements with the well chambers were 0.5% ± 0.1% higher than the vendor-provided source strength. Measurements with the Farmer chamber were 0.7% lower than the average well chamber results and 0.2% lower than the vendor-provided source strength. All of these results were less than the reported source calibration uncertainties (k=2) of each measurement system., Conclusions: In view of the uncertainties in ion chamber calibration factors, the maximum difference in source strength found in this study is small and confirms the consistency between calibration standards in use for HDR (192)Ir brachytherapy., (Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: In radiotherapy (RT), there are high requirements for quality assurance (QA) in all the steps of the process. Development of QA systems are demanding in terms of financial and human resources. A national QA programme (KVIST) has been established in Norway to facilitate implementation of QA activity on hospital level., Method: The KVIST organisation comprises the KVIST team, the reference group (RG) and the working groups (WGs). The KVIST team is multidisciplinary and are employed in permanent positions. The RG acts as an advisory body for the KVIST team in defining and ranking the priority of projects. Relevant national QA projects are identified in collaboration with the RG, and WGs are established to carry out the various projects., Result: Several national consensus documents have been prepared by the various WGs. Systems for incident handling and activity reporting have been established and clinical audits have been implemented in Norwegian RT. Guidelines for RT of various diagnoses have also been prepared in collaboration with National Cancer groups., Conclusion: The KVIST programme has been very well acknowledged in the Norwegian RT community. It has succeeded in creating a positive attitude towards QA and improved the communication between centres and the various professions.

Background and Purpose: A substantial reduction of uncertainties in clinical brachytherapy should result in improved outcome in terms of increased local control and reduced side effects. Types of uncertainties have to be identified, grouped, and quantified., Methods: A detailed literature review was performed to identify uncertainty components and their relative importance to the combined overall uncertainty., Results: Very few components (e.g., source strength and afterloader timer) are independent of clinical disease site and location of administered dose. While the influence of medium on dose calculation can be substantial for low energy sources or non-deeply seated implants, the influence of medium is of minor importance for high-energy sources in the pelvic region. The level of uncertainties due to target, organ, applicator, and/or source movement in relation to the geometry assumed for treatment planning is highly dependent on fractionation and the level of image guided adaptive treatment. Most studies to date report the results in a manner that allows no direct reproduction and further comparison with other studies. Often, no distinction is made between variations, uncertainties, and errors or mistakes. The literature review facilitated the drafting of recommendations for uniform uncertainty reporting in clinical BT, which are also provided. The recommended comprehensive uncertainty investigations are key to obtain a general impression of uncertainties, and may help to identify elements of the brachytherapy treatment process that need improvement in terms of diminishing their dosimetric uncertainties. It is recommended to present data on the analyzed parameters (distance shifts, volume changes, source or applicator position, etc.), and also their influence on absorbed dose for clinically-relevant dose parameters (e.g., target parameters such as D90 or OAR doses). Publications on brachytherapy should include a statement of total dose uncertainty for the entire treatment course, taking into account the fractionation schedule and level of image guidance for adaptation., Conclusions: This report on brachytherapy clinical uncertainties represents a working project developed by the Brachytherapy Physics Quality Assurances System (BRAPHYQS) subcommittee to the Physics Committee within GEC-ESTRO. Further, this report has been reviewed and approved by the American Association of Physicists in Medicine., (Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Purpose: This follow-up of a randomized study was conducted to assess the long-term effects of external beam radiation therapy (EBRT) in the adjuvant treatment of early-stage endometrial cancer., Patients and Methods: Between 1968 and 1974, 568 patients with stage I endometrial cancer were included. After primary surgery, patients were randomly assigned to either vaginal radium brachytherapy followed by EBRT (n = 288) or brachytherapy alone (n = 280). Overall survival was analyzed by using the Kaplan-Meier method. A Cox proportional hazards model was used to estimate hazard ratios (HRs) with 95% CIs. We also conducted analyses stratified by age groups., Results: After median 20.5 years (range, 0 to 43.4 years) of follow-up, no statistically significant difference was revealed in overall survival (P = .186) between treatment groups. However, women younger than age 60 years had significantly higher mortality rates after EBRT (HR, 1.36; 95% CI, 1.06 to 1.76) than the control group. The risk of secondary cancer increased after EBRT, especially in women younger than age 60 years (HR, 2.02; 95% CI, 1.30 to 3.15)., Conclusion: We observed no survival benefit of external pelvic radiation in early-stage endometrial carcinoma. In women younger than age 60 years, pelvic radiation decreased survival and increased the risk of secondary cancer. Adjuvant EBRT should be used with caution, especially in women with a long life expectancy.

Background and Purpose: To compare the dosimetric impact of organ and target variations relative to the applicator for intracavitary brachytherapy by a multicentre analysis with different application techniques and fractionation schemes., Material and Methods: DVH data from 363 image/contour sets (120 patients, 6 institutions) were included for 1-6 fractions per patient, with imaging intervals ranging from several hours to ∼20 days. Variations between images acquired within one (intra-application) or between consecutive applicator insertions (inter-application) were evaluated. Dose plans based on a reference MR or CT image series were superimposed onto subsequent image sets and D(2cm(3)) for the bladder, rectum and sigmoid and D(90) for HR CTV were recorded., Results: For the whole sample, the systematic dosimetric variations for all organs at risk, i.e. mean variations of D(2cm(3)), were found to be minor (<5%), while random variations, i.e. standard deviations were found to be high due to large variations in individual cases. The D(2cm(3)) variations (mean±1SD) were 0.6±19.5%, 4.1±21.7% and 1.6±26.8%, for the bladder, rectum and sigmoid. For HR CTV, the variations of D90 were found to be -1.1±13.1% for the whole sample. Grouping of the results by intra- and inter-application variations showed that random uncertainties for bladder and sigmoid were 3-7% larger when re-implanting the applicator for individual fractions. No statistically significant differences between the two groups were detected in dosimetric variations for the HR CTV. Using 20% uncertainty of physical dose for OAR and 10% for HR CTV, the effects on total treatment dose for a 4 fraction HDR schedule at clinically relevant dose levels were found to be 4-8 Gy EQD2 for OAR and 3 Gy EQD2 for HR CTV., Conclusions: Substantial variations occur in fractionated cervix cancer BT with higher impact close to clinical threshold levels. The treatment approach has to balance uncertainties for individual cases against the use of repetitive imaging, adaptive planning and dose delivery., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background and Aim: We aimed to quantify target volume delineation uncertainties in cervix cancer image guided adaptive brachytherapy (IGABT)., Materials and Methods: Ten radiation oncologists delineated gross tumour volume (GTV), high- and intermediate-risk clinical target volume (HR CTV, IR CTV) in six patients. Their contours were compared with two reference delineations (STAPLE-Simultaneous Truth and Performance Level Estimation and EC- expert consensus) by calculating volumetric and planar conformity index (VCI and PCI) and inter-delineation distances (IDD)., Results: VCISTAPLE and VCIEC were 0.76 and 0.72 for HR CTV, 0.77 and 0.68 for IR CTV and 0.59 and 0.58 for GTV. Variation was most prominent caudally and cranially in all target volumes and posterolaterally in IR CTV. IDDSTAPLE and IDDEC for HR CTV (3.6±3.5 and 3.8±3.4 mm) were significantly lower than for GTV (4.8±4.2 and 4.2±3.5 mm) and IR CTV (4.7±5.2 and 5.2±5.6 mm) (p<0.05)., Conclusions: Due to lower delineation uncertainties when compared to GTV and IR CTV, HR CTV may be considered most robust volume for dose prescription and optimization in cervix cancer IGABT. Adequate imaging, training and use of contouring recommendations are main strategies to minimize delineation uncertainties., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose and Background: To study the dosimetric impact of interobserver delineation variability (IODV) in MRI-based cervical cancer brachytherapy., Materials and Methods: MR images of six patients were distributed to 10 experienced observers worldwide. They were asked to delineate the target volumes and the organs at risk (OARs) for each patient. Two types of reference contours were created (Expert Consensus - EC and Simultaneous Truth and Performance Level Estimation - STAPLE). Optimised plans based on both EC- and STAPLE-contours were prepared. These plans were transferred to each of the observer contour sets and the resulting DVH parameters (D(90) and D(2cc)) were calculated. For each patient the standard deviation (SD) for the 10 observers was calculated., Results: A mean relative SD of 8-10% was found for GTV and High Risk CTV (HR-CTV) D(90) analysing one single fraction. For rectum and bladder the mean relative SD for D(2cc) was 5-8% while sigmoid was at 11%. For the whole treatment the IODV in HR-CTV caused an uncertainty of ±5 Gy(α/β=10) (1SD). The corresponding figure for OARs was ±2-3 Gy(α/β=3). The results were not sensitive as to which structure set was used for the optimisation., Conclusions: For the target volumes the dosimetric impact of IODV was smallest for the GTV and HR-CTV, while IODV had an even smaller impact on the bladder and rectum., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: This descriptive survey evaluated brachytherapy (BT) practices and resources in the European area. This was a follow-up study to the original patterns of care for brachytherapy in Europe (PCBE)., Materials and Methods: A total of 1121 radiotherapy (RT) centres from 41 countries were asked to complete an online questionnaire on BT practices and resources. Countries with fewer than 50% of centres responding were excluded. Participating countries were divided into three groups based on gross domestic product (GDP); group I contained the countries with the highest GDP., Results: The response rate was 56% (633/1121 centres) with 30/41 countries (73%) meeting the inclusion criteria. Sixty percent of reporting centres provided brachytherapy. Responding centres treated an average of 138 (±10, 1 SD) patients with BT; in group I, the mean was 110/centre, an increase of 18% from 2002. CT-dosimetry increased to 61% of centres vs. 33% in 2002. HDR (high-dose rate) BT was the most commonly reported technique (65% of centres). Most BT interventions were for gynaecological tumors (59% of all cases), followed by prostate (17%), breast (9%), lung/bronchus (3%), and esophagus tumors(2%)., Conclusion: Gynaecological BT remains the most common application, although both prostate and breast BT have increased. CT-based dosimetry has become increasingly common since 2002. The use of HDR and PDR (pulsed-dose rate) techniques has increased markedly, while both LDR and MDR (medium-dose rate) have declined., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Image-guided brachytherapy in cervical cancer is increasingly replacing X-ray based dose planning. In image-guided brachytherapy the geometry of the applicator is extracted from the patient 3D images and introduced into the treatment planning system; a process referred to as applicator reconstruction. Due to the steep brachytherapy dose gradients, reconstruction errors can lead to major dose deviations in target and organs at risk. Appropriate applicator commissioning and reconstruction methods must be implemented in order to minimise uncertainties and to avoid accidental errors. Applicator commissioning verifies the location of source positions in relation to the applicator by using auto-radiography and imaging. Sectional imaging can be utilised in the process, with CT imaging being the optimal modality. The results from the commissioning process can be stored as library applicators. The importance of proper commissioning is underlined by the fact that errors in library files result in systematic errors for clinical treatment plans. While the source channel is well visualised in CT images, applicator reconstruction is more challenging when using MR images. Availability of commercial dummy sources for MRI is limited, and image artifacts may occur with titanium applicators. The choice of MR sequence is essential for optimal visualisation of the applicator. Para-transverse imaging (oriented according to the applicator) with small slice thickness (< or =5 mm) is recommended or alternatively 3D MR sequences with isotropic voxel sizes. Preferably, contouring and reconstruction should be performed in the same image series in order to avoid fusion uncertainties. Clear and correct strategies for the applicator reconstruction will ensure that reconstruction uncertainties have limited impact on the delivered dose. Under well-controlled circumstances the reconstruction uncertainties are in general smaller than other brachytherapy uncertainties such as contouring and organ movement., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To compare the severe late effects (Grade 3 or greater) for two groups of cervical cancer patients treated with the same external beam radiotherapy and two high-dose-rate intracavitary brachytherapy regimens and to investigate the influence of the dose delivered each week., Methods and Materials: For 120 patients, intracavitary brachytherapy was delivered with 33.6 Gy in eight fractions to Point A (HD group), and for 119, intracavitary brachytherapy was delivered with 29.4 Gy in seven fractions to Point A (LD group). The cumulative incidence of severe gastrointestinal and genitourinary late effects were calculated for both dose groups using Kaplan-Meier survival analysis. This method was also used to explore whether the number of weeks with different dose levels could predict the cumulative incidence of late effects., Results: The actuarial rate of developing severe gastrointestinal morbidity at 7 years was 10.7% and 8.3% for HD and LD groups, respectively. The rate for genitourinary morbidity was 6.6% for the HD group and 5.0% for the LD group, respectively. No significant difference was found between the two groups. The analyses showed that a marginally significant increase occurred in severe gastrointestinal complications as the number of weeks with a physical dose >20 Gy increased in the HD group (p = .047)., Conclusion: To establish dose-response relationships for late complications, three-dimensional imaging and dose-volume histogram parameters are needed. We found some indications that 20 Gy/wk is an upper tolerance level when the dose to the International Commission on Radiation Units and Measurements rectum point is 81 Gy(alpha/beta=3) (isoeffective [equivalent] dose of 2-Gy fractions). However, additional investigations using three-dimensional data are needed., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background and Purpose: The purpose of this study was to evaluate the impact of random and systematic applicator reconstruction uncertainties on DVH parameters in brachytherapy for cervical cancer., Material and Methods: Dose plans were analysed for 20 cervical cancer patients with MRI based brachytherapy. Uncertainty of applicator reconstruction was modelled by translating and rotating the applicator. Changes in DVH parameters per mm of applicator displacement were evaluated for GTV, CTV, bladder, rectum, and sigmoid. These data were used to derive patient population based estimates of delivered dose relative to expected dose., Results: Deviations of DVH parameters depend on direction of reconstruction uncertainty. The most sensitive organs are rectum and bladder where mean DVH parameter shifts are 5-6% per mm applicator displacement in ant-post direction. For other directions and other DVH parameters, mean shifts are below 4% per mm. By avoiding systematic reconstruction errors, uncertainties on DVH parameters can be kept below 10% in 90% of a patient population. Systematic errors of a few millimetres can lead to significant deviations., Conclusion: Comprehensive quality control of afterloader, applicators and imaging procedures should be applied to prevent systematic errors in applicator reconstruction. Random errors should be minimised by using small slice thickness. With careful reconstruction procedures, reliable DVH parameters for target and OAR's can be obtained.

Purpose: To determine the uncertainties in dose volume histogram (DVH) analysis used in modern brachytherapy treatment planning systems (TPSs)., Materials and Methods: A phantom with three different volumes was scanned with CT and MRI. An inter-observer analysis was based on contouring performed by 5 persons. The volume of a standard contour set was calculated using seven different TPSs. For five systems a typical brachytherapy dose distribution was used to compare DVH determination., Results: The inter-observer variability (1SD) was 13% for a small cylindrical volume, 5% for a large cylinder and 3% for a conical shape. A standardized volume for a 4mm CT scan contoured on seven different TPS varied by 7%, 2%, and 5% (1SD). Use of smaller slice thickness reduced the variations. A treatment plan with the sources between the large cylindrical shape and the cone showed variations for D(2cc) of 1% and 5% (1SD), respectively. Deviations larger than 10% were observed for a smaller source to cylinder surface distance of 5mm., Conclusions: Modern TPSs minimize the volumetric and dosimetric calculation uncertainties. These are comparable to inter-observer contouring variations. However, differences in volume result from the methods of calculation in the first and last slice of a contoured structure. For this situation and in case of high dose gradients inside analyzed volumes, high uncertainties were observed. The use of DVH parameters in clinical practice should take into account the method of calculation and the possible uncertainties.

The purpose of this study is to investigate whether the method of applicator reconstruction and/or the applicator orientation influence the dose calculation to points around the applicator for brachytherapy of cervical cancer with CT-based treatment planning. A phantom, containing a fixed ring applicator set and six lead pellets representing dose points, was used. The phantom was CT scanned with the ring applicator at four different angles related to the image plane. In each scan the applicator was reconstructed by three methods: (1) direct reconstruction in each image (DR), (2) reconstruction in multiplanar reconstructed images (MPR) and (3) library plans, using pre-defined applicator geometry (LIB). The doses to the lead pellets were calculated. The relative standard deviation (SD) for all reconstruction methods was less than 3.7% in the dose points. The relative SD for the LIB method was significantly lower (p < 0.05) than for the DR and MPR methods for all but two points. All applicator orientations had similar dose calculation reproducibility. Using library plans for applicator reconstruction gives the most reproducible dose calculation. However, with restrictive guidelines for applicator reconstruction the uncertainties for all methods are low compared to other factors influencing the accuracy of brachytherapy.

Background and Purpose: Brachytherapy dose distributions can be optimised by modulation of source dwell times. In this study dose optimisation in single planar interstitial implants was evaluated in order to quantify the potential benefit in patients., Material and Methods: In 14 patients, treated for recurrent rectal and cervical cancer, flexible catheters were sutured intra-operatively to the tumour bed in areas with compromised surgical margin. Both non-optimised, geometrically and graphically optimised CT -based dose plans were made. The overdose index (OI), homogeneity index (HI), conformal index (COIN), minimum target dose, and high dose volumes were evaluated. The dependence of OI, HI, and COIN on target volume and implant regularity was evaluated. In addition, 12 theoretical implant configurations were analyzed., Results: Geometrical and graphical optimisation improved the dose plans significantly with graphical optimisation being superior. Graphically optimised dose plans showed a significant decrease of 18%+/-9% in high dose volume (p<0.001). HI, COIN, and OI were significantly improved from 0.50+/-0.05 to 0.60+/-0.05, from 0.65+/-0.04 to 0.71+/-0.04, and from 0.19+/-0.03 to 0.15+/-0.03, respectively (p<0.001 for all). Moreover, minimum target dose increased significantly from 71%+/-5% to 80%+/-5% (p<0.001). The improvement in OI and HI obtained by optimisation depended on the regularity of the implant, such that the benefit of optimisation was larger for irregular implants. OI and HI correlated strongly with target volume limiting the usability of these parameters for comparison of dose plans between patients., Conclusions: Dwell time optimisation significantly improved the dose distribution regarding homogeneity, conformity, minimum target dose, and size of high dose volumes. Graphical optimisation is fast, reproducible and superior to geometric optimisation.

In radiotherapy planning systems, delineation of hollow normal tissue organs, such as the bladder, is time-consuming. Automated delineation may presuppose two assumptions: (1) the bladder resembles a spherical shell and (2) the volume of bladder tissue is preserved regardless of the volume of urine (luminal volume) inside. The purpose of the present study was to test these assumptions. 22 CT scans from 7 patients were studied retrospectively. Transverse cross-sectional areas enclosed by the outer contour (A(out)) and inner contour of the bladder (A(in)) were recorded from the images. Hence, the transverse cross-sectional area of the wall, A(wall)=A(out)-A(in), and the volume of bladder tissue at various luminal volumes, could be calculated. To quantify the method uncertainty, the same procedure was applied on three spherical plastic phantoms. The results were also compared with data from the Visible Human Project's photographs of cadaver cryo-sections. Assumption no. 1 stated above, implies that A(wall) is constant regardless of the level of intersection of the sphere. The data from cryo-sections revealed a positive correlation for A(wall) and A(out), in contradiction to assumption no. 1 (p<0.001). The corresponding association derived from the repetitive CT scans of patients was also statistically significant (p<0.001) although linear regression revealed a less steep slope. A relationship was found between the volume of bladder tissue and luminal volume, hence contradicting assumption no. 2 (p<0.001). In conclusion the cross-sectional wall areas of the bladder, measured from patient CT scans, increase slightly with luminal cross-sectional areas in contradiction to expected values derived from a simplistic spherical shell model. In addition, the volume of bladder tissue is related to the luminal volume. Our results may be of practical value when developing automated delineation tools in radiotherapy planning systems.

Background and Purpose: Brachytherapy (BT) plays a crucial role in the management of invasive cervix cancer from stage I to IV. Intracavitary techniques are based on afterloading devices, with different types of applicators. CT and/or MRI compatible applicators allow a sectional image based approach with a better assessment of gross tumour volume (GTV) and definition and delineation of target volume (CTV) compared to traditional approaches. Accurate and reproducible delineation of GTV, CTV and PTV, as well as of critical organs has a direct impact on BT treatment planning, especially if it is possible to adapt the pear-shape isodose by optimisation using DVH analysis. When introducing a 3D image based approach for GTV and CTV assessment, there is a need for a common language to describe the concepts and to define the terms which are to be used., Methods: In 2000, GEC-ESTRO decided to support 3D imaging based 3D treatment planning approach in cervix cancer BT with the creation of a Working Group. The task was to describe basic concepts and terms and to work out a terminology enabling various groups working in this advanced field to use a common language. The recommendations described in this report were proposed based on clinical experience and dosimetric concepts of different institutions (IGR, Leuven, Vienna) and were stepwise validated against the background of different clinical experience., Conclusions: As GTV and CTV for BT change significantly during treatment, time frame for assessment of GTV and CTV for BT is specified in this report: at time of diagnosis GTV(D), CTV(D) and at time of BT GTV(B), CTV(B). Furthermore, CTV for BT is defined related to risk for recurrence: high risk CTV and intermediate risk CTV. Beside verbal descriptions detailed examples are given, partly in form of schematic drawings.

Optimization of radiotherapy treatment plans based on dose-volume histograms relies on accurate organ delineation. Hollow organs, such as the rectum, are difficult and time-consuming to delineate owing to unclear visualization of the border between wall tissue and filling. Automated hollow organ delineation would be a valuable tool, but its development depends upon improved understanding of the dynamics of the rectum in response to filling. Two reasonable assumptions proposed in the literature are that (1) the rectal wall tissue along a constant length of the rectal cylinder is preserved over time and (2) the rectal wall tissue is distributed homogeneously along the cylinder. Therefore, variations in wall thickness can be explained by variable rectal filling. To investigate these assumptions, transversal cross-sectional areas enclosed by the outer contour (A(out)) and inner contour (A(in)) of the rectum were recorded from digital photographs of cadaver cryo-sections from the U.S. National Library of Medicine's Visible Human Project. In addition, A(out) and A(in) were recorded from 19 CT scans of 5 of our own patients. The transversal cross-sectional area of the wall of the rectum, A(wall)=A(out)-A(in), was calculated. The data derived both from cryo-sections and repetitive CT scans of patients, revealed that there was a significant correlation between A(wall) and A(out), in contradiction to assumption (1) stated above (male cryo-sections: p<0.001, female cryo-sections: p=0.03, repetitive CT scans p<0.001). Moreover, the mean A(wall) calculated from one CT scan differed significantly from the mean A(wall) from other CT scans and was correlated with the mean A(out), i.e. rectal filling (p<0.001). This finding was confirmed by careful analysis of another study (p=0.001) and opposes assumption (2). Hence, the amount of wall tissue within a constant length of rectum is not preserved over time, but increases with increased filling. This implies that the longitudinal length of the rectum decreases in response to distension of the organ.

Purpose: To analyze the significance of volume effects in experimental brachytherapy, based on modeling normal tissue complication probability., Methods and Materials: Experimental brachytherapy in the rat rectum was based on an eight-step 2.5-mm step size source configuration for 192Ir, afterloaded into an unshielded polystyrene applicator. Volume effects were studied using a half-circumferential lead-shielded applicator and a shorter (two-step) source configuration. The main end point was rectal stenosis., Results: Rectal stenosis was always caused by a radiation ulcer. With the shielded configuration, single-dose ED50 (50% incidence of rectal stenosis) increased from 23 Gy to 36.5 Gy. Single-dose ED50 for the short configuration was 77.9 Gy. The data showed a reasonable fit to a three-parameter version of the biophysical model described by Jackson et al. (1995). This model assumes that organs consist of a large number of radiobiologically independent subunits and that radiation causes a complication if the fraction of the organ damaged is greater than its functional reserve. The fraction of the organ damaged is calculated summing over fractions of the organ damaged at each dose level. The calculated mean functional reserve (nu50) of the rat rectum, assuming a cumulative functional reserve distribution in the group of experimental rats, was 0.53., Conclusions: The volume effect observed within small brachytherapy volumes agreed well with clinical experience of large tolerance doses in contact X-ray therapy. However, the nu50 value was comparable to the high functional reserve value reported for liver. Experimental volume effects probably reflect repair processes originating in the areas adjacent to small radiation fields of brachytherapy more than the radiobiologic characteristics of the cells in the irradiated volume.

Purpose: To evaluate variation of dose to organs at risk for patients receiving fractionated high dose rate gynaecological brachytherapy by using CT-based 3D treatment planning and dose-volume histograms (DVH)., Materials and Methods: Fourteen patients with cancer of the uterine cervix underwent three to six CT examinations (mean 4.9) during their course of high-dose-rate brachytherapy using radiographically compatible applicators. The rectal and bladder walls were delineated and DVHs were calculated., Results: Inter fraction variation of the bladder volume (CV(mean)=44.1%) was significantly larger than the inter fraction variation of the mean dose (CV(mean)=19.9%, P=0.005) and the maximum dose (CV(mean)=17.5%, P=0.003) of the bladder wall. The same trend was seen for rectum, although the figures were not significantly different. Performing CT examinations at four of seven brachytherapy fractions reduced the uncertainty to 4 and 7% for the bladder and rectal doses, respectively. A linear regression analysis showed a significant, negative relationship between time after treatment start and the whole bladder volume (P=0.018), whereas no correlation was found for the rectum. For both rectum and bladder a linear regression analysis revealed a significant, negative relationship between the whole volume and median dose (P<0.05)., Conclusion: Preferably a CT examination should be provided at every fraction. However, this is logistically unfeasible in most institutions. To obtain reliable DVHs the patients will in the future undergo 3-4 CT examinations during the course of brachytherapy at our institution. Since this study showed an association between large bladder volumes and dose reductions, the patients will be treated with a standardized bladder volume.

Purpose: To calculate the normal tissue complication probability (NTCP) of late radiation effects on the rectum and bladder from repetitive CT scans during fractionated high-dose-rate brachytherapy (HDRB) and external beam radiotherapy (EBRT) of the uterine cervix and compare the NTCP with the clinical frequency of late effects., Methods and Materials: Fourteen patients with cancer of the uterine cervix (Stage IIb-IVa) underwent 3-6 (mean, 4.9) CT scans in treatment position during their course of HDRB using a ring applicator with an Iridium stepping source. The rectal and bladder walls were delineated on the treatment-planning system, such that a constant wall volume independent of organ filling was achieved. Dose-volume histograms (DVH) of the rectal and bladder walls were acquired. A method of summing multiple DVHs accounting for variable dose per fraction were applied to the DVHs of HDRB and EBRT together with the Lyman-Kutcher NTCP model fitted to clinical dose-volume tolerance data from recent studies., Results: The D(mean) of the DVH from EBRT was close to the D(max) for both the rectum and bladder, confirming that the DVH from EBRT corresponded with homogeneous whole-organ irradiation. The NTCP of the rectum was 19.7% (13.5%, 25. 9%) (mean and 95% confidence interval), whereas the clinical frequency of late rectal sequelae (Grade 3-4, RTOG/EORTC) was 13% based on material from 200 patients. For the bladder the NTCP was 61. 9% (46.8%, 76.9%) as compared to the clinical frequency of Grade 3-4 late effects of 14%. If only 1 CT scan from HDRB was assumed available, the relative uncertainty (standard deviation or SD) of the NTCP value for an arbitrary patient was 20-30%, whereas 4 CT scans provided an uncertainty of 12-13%., Conclusion: The NTCP for the rectum was almost consistent with the clinical frequency of late effects, whereas the NTCP for bladder was too high. To obtain reliable (SD of 12-13%) NTCP values, 3-4 CT scans are needed during 5-7 fractions of HDRB treatments.

Background and Purpose: MRI ferrous sulphate gel dosimetry has proven to be a valuable method for assessment of dose delivered in teletherapy. The intention of this study was to investigate ferrous sulphate gel as a possible dosimeter for intracavitary brachytherapy applications., Materials and Methods: A plastic duplicate of a cervix ring applicator set was submerged in Fe2(+)-infused gelatin gel. The gel was subsequently irradiated by a stepwise moving 192Ir source, using automatic afterloading equipment (Microselectron, Nucletron-Oldelft International BV, Veenendaal, The Netherlands). A 3D dose distribution was reconstructed from MR images of the gel., Results: The gel dose measurements were found to be of the same accuracy as TLD measurements. Isodose curves based on gel dosimetry and isodose curves computed by a dose planning system were generally less than 2 mm apart. MR images showing the position of the applicator set in a patient during treatment were used to obtain images describing patient anatomy in the sagittal and ring planes of the applicator set. Isodose curves computed from the gel measurements were then superimposed on these images, illustrating one possible way of linking dosimetrical and anatomical data., Conclusions: Our study shows that MRI ferrous sulphate gel dosimetry is a useful tool for studies of dose distributions in brachytherapy and their relation to critical organs. Possible improvements of the gel dosimeter lie in reducing the diffusion of ferric ions and increasing the radiation sensitivity of the gel.