Survival prediction in patients with gynecological cancer irradiated for brain metastases.

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.

Dose painting by numbers in a standard treatment planning system using inverted dose prescription maps.

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.

Quality assurance in radiotherapy on a national level; experience from Norway: the KVIST initiative.

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.

Radiation-induced long-term dysphagia in survivors of head and neck cancer and association with dose-volume parameters.

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.

Chronic fatigue in long-term survivors of head and neck cancer treated with radiotherapy.

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.

Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden.

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).

Surface-guided positioning eliminates the need for skin markers in radiotherapy of right sided breast cancer: A single center randomized crossover trial.

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 (Æ©) 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.

A Prospective Study of High Dose-Rate Brachytherapy or Stereotactic Body Radiotherapy of Intra-Prostatic Recurrence: Toxicity and Long Term Clinical Outcome.

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/ß = 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.

GEC-ESTRO/ACROP recommendations for quality assurance of ultrasound imaging in brachytherapy.

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.

Image registration, contour propagation and dose accumulation of external beam and brachytherapy in gynecological radiotherapy.

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.

Dose planning variations related to delineation variations in MRI-guided brachytherapy for locally advanced cervical cancer.

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 D90, D98 and D2cm3 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 D90 EQD210 variability (SD) was observed for the CTVHR and 1.2-3.6 Gy D2cm3 EQD23 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.

Ring Versus Ovoids and Intracavitary Versus Intracavitary-Interstitial Applicators in Cervical Cancer Brachytherapy: Results From the EMBRACE I Study.

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 EQD210, CTVHR D90% (EQD210), and bladder, rectum, sigmoid, and vaginal 5-mm lateral-point doses (EQD23) were evaluated among center groups. Differences between T&O and T&R were tested with multivariable analysis. RESULTS: For similar point A doses, mean CTVHR D90% 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 (D2cm3 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 D2cm3 and bladder ICRU-point by 3.5 to 5.0 Gy for ovoids centers; and similar OAR doses for ring centers. CTVHR D90% was 2.8 Gy higher, bladder D2cm3 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.

Importance of Technique, Target Selection, Contouring, Dose Prescription, and Dose-Planning in External Beam Radiation Therapy for Cervical Cancer: Evolution of Practice From EMBRACE-I to II.

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.

Consequences of random and systematic reconstruction uncertainties in 3D image based brachytherapy in cervical cancer.

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.

Isodose surface volumes in cervix cancer brachytherapy: Change of practice from standard (Point A) to individualized image guided adaptive (EMBRACE I) brachytherapy.

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/ß 10 Gy and 3 Gy. RESULTS: Median V85 Gy, V75 Gy and V60 Gy EQD210 were 72 cm3, 100 cm3 and 233 cm3, respectively. Median V85 Gy EQD210 was 23% smaller than in standard 85 Gy prescription to Point A. For small (<25 cm3), intermediate (25-35 cm3) and large (>35 cm3) CTVHR volumes, the V85 Gy was 57 cm3, 70 cm3 and 89 cm3, 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 CTVHR volume which demonstrates that dose adaptation was performed per individual tumour size and response during EBRT.

Accuracy of volume and DVH parameters determined with different brachytherapy treatment planning systems.

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.

Reconstruction of a ring applicator using CT imaging: impact of the reconstruction method and applicator orientation.

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.

Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage-a modelling study.

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.

Target volume delineation of anal cancer based on magnetic resonance imaging or positron emission tomography.

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 (GTVT). 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 cm3 for PET and MRI, respectively, while it was 6 and 11 cm3 for GTVT. Both GTV and GTVT 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 (GTVPET) with the GTVs based on MRI and CT (GTVMRI). The median Dice coefficient was 0.56 when comparing the visible tumor volume evaluated by PET (GTVT_PET) with the same volume evaluated by MRI (GTVT_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 GTVT, which may impact future tumor boost strategies.

Dose optimisation in single plane interstitial 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.