Adaptive Brachytherapy For Cervical Cancer Research Articles

Direction modulated brachytherapy (DMBT) tandem applicator for cervical cancer treatment: Choosing the optimal shielding material.

To investigate the dose modulation capability of a novel MRI-compatible direction modulated brachytherapy (DMBT) tandem applicator design with various high-density shielding materials for brachytherapy treatment of cervical cancer. The shield materials that have been evaluated are tantalum (Ta), pure tungsten (W), gold (Au), rhenium (Re), osmium (Os), platinum (Pt), iridium (Ir), and W' tungsten alloy (95%W, 3.5%Ni, 1.5%Cu). The recently proposed six-channel DMBT tandem is composed of nonmagnetic tungsten alloy (W') rod with diameter of 5.4mm and coated with 0.3-mm thick bio-safe plastic sheath. The tandem shielding material can, however, be individually replaced with various other shields to create directional radiation. Monte Carlo N-Particle (MCNP) code was used to calculate the three-dimensional (3D) dose distributions in a water phantom for an HDR 192 Ir (mHDR-v2) source inside each DMBT tandem with various shields and a plastic conventional tandem (Con.T). Then, the 3D dose distributions were imported into an in-house-coded inverse planning optimization algorithm to obtain optimal plans for 12 clinical cases chosen at random from the international RetroEMBRACE dataset involving conventional tandem and ring (Con.T&R) applicators. All plans generated by the DMBT tandem and ring (DMBT&R) with the tungsten alloy [DMBT(W')&R] were compared with the corresponding Con.T&R plans, to generate benchmark results. These benchmark results were then considered as reference plans for other shields performances. Plans were normalized to receive the same high-risk clinical target volume (CTVHR ) D90 . The D100 , D10 , and V100 for CTVHR , and D2cm3 for organs at risk (OARs) of bladder, sigmoid, and rectum were calculated and compared. Transmission factor (TF), that is, the dose in the backside of the DMBT shield over that in the front opening, at a 5cm distance, were 36.6%, 34.8%, 31.9%, 28.9%, 27.9%, 26.2%, 26.2%, and 25.5%, for Ta, W', W, Re, Au, Os, Pt, and Ir shields, respectively. On average, the CTVHR values for D100 , V100 , D10 were not significantly different across all DMBT&R shields and the Con.T&R plans (P>0.219). For the D2cm3 , the benchmark results showed significant reductions (P<0.03), that is, on average, -8.3% for bladder, -10.7% for rectum, and -10.1% for sigmoid, compared to the Con.T&R plans. However, the various shields showed little improvement from the tungsten alloy (W'), where on average, rectum (bladder) [sigmoid] D2cm3 were reduced by -1.32% (-0.85%) [-1.01%], -1.25% (-0.78%) [-0.91%], -1.22% (-0.75%) [-0.86%], -0.94% (-0.60%) [-0.70%], -0.84% (-0.51%) [-0.59%], and -0.38% (-0.24%) [-0.23%] for Ir, Pt, Os, Au, Re, and W shields, relative to the benchmark W' DMBT plans, respectively. These corresponding values for Ta increased by +0.28% (+0.08%) [+0.25%], respectively. The Ir, Pt, Os, Au, Re, and W shielding materials, respectively, in descending order, lead to better OAR sparing than the DMBT(W')&R plans. However, the amount of improvement is limited and clinically insignificant. This finding suggests that the initial W' shield remains a suitable choice given the proven MR compatibility, for use in MR-guided adaptive brachytherapy of cervical cancer.

A Prospective Comparison of Computed Tomography with Transrectal Ultrasonography Assistance and Magnetic Resonance Imaging–Based Target-Volume Definition During Image Guided Adaptive Brachytherapy for Cervical Cancers

Although magnetic resonance imaging (MRI) represents the gold standard for image guided adaptive brachytherapy (IGABT) for cervical cancer, the majority of brachytherapy (BT) continues to be guided by computed tomography (CT). However, CT seems to overestimate the target-volume definition, and the potential of transrectal ultrasonography (TRUS) needs further evaluation. This prospective, comparative study aimed to evaluate CT-based target contouring with the incorporation of TRUS during BT. Patients with locally advanced cervical cancer undergoing magnetic resonance IGABT between January 2013 and March 2014 were included. During the BT procedure, TRUS imaging with central tandem in situ was acquired at 3 representative levels. Reference points/dimensions (D1-D4) of the hypoechoic region on TRUS images with respect to the central tandem were recorded. CT and magnetic resonance BT planning imaging was performed after BT application. The high-risk clinical target volume (HR-CTV) was contoured on CT scans with incorporation of clinical and TRUS imaging findings and was compared with the gold standard MRI-based target approach. The image sets of 25 patients (International Federation of Gynecology and Obstetrics clinical stage IIB [11; 44%] and IIIB [14; 56%]) were evaluable. The mean (±standard deviation) volumes of HR-CTV on CT and MRI imaging were 39.1 (±20) cm³ and 39 (±19) cm³, respectively (r = 0.92; P < .001). A significant correlation was found between the HR-CTV dimensions (width and thickness) of CT and MRI scans at various levels (r = 0.70-0.80; P < .001). In addition, the absolute differences in target dimensions between CT and MRI were <0.5 cm. A strong correlation was seen between CT and MRI for patients with medial and lateral parametrial invasion (P < .05) compared with no parametrial disease at BT. Furthermore, the mean differences in HR-CTV width between CT and MRI contours at various levels, irrespective of parametrial involvement, was only 0.1 to 0.4 cm. This study suggests that a CT-based target and organ-at-risk delineation using MRI at diagnosis and real-time TRUS information during BT seems comparable with the gold standard MRI-based approach in IGABT for cervical cancer.

Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study

Background/PurposeThis study describes late bowel morbidity prospectively assessed in the multi-institutional EMBRACE study on MRI-guided adaptive brachytherapy in locally advanced cervical cancer (LACC). Materials/MethodsA total of 1176 patients were analyzed. Physician reported morbidity (CTCAE v.3.0) and patient reported outcome (PRO) (EORTC QLQ C30/CX24) were assessed at baseline and at regular follow-up. ResultsAt 3/5 years the actuarial incidence of bowel morbidity grade 3–4 was 5.0%/5.9%, including incidence of stenosis/stricture/fistula of 2.0%/2.6%. Grade 1–2 morbidity was pronounced with prevalence rates of 28–33% during follow-up. Diarrhea and flatulence were most frequently reported, significantly increased after 3 months and remained elevated during follow-up. Incontinence gradually worsened with time. PRO revealed high prevalence rates. Diarrhea ≥“a little” increased from 26% to 37% at baseline to 3 months and remained elevated, difficulty in controlling bowel increased from 11% to 26% at baseline to 3 months gradually worsening with time. Constipation and abdominal cramps improved after treatment. ConclusionBowel morbidity reported in this large cohort of LACC patients was limited regarding severe/life-threatening events. Mild-moderate diarrhea, flatulence and incontinence were prevalent after treatment with PROs indicating a considerable and clinically relevant burden. Critical knowledge based on the extent and manifestation pattern of treatment-related morbidity will serve future patient management.

OC-0365: Dose contribution to pelvic nodes of image-guided adaptive brachytherapy in cervical cancer

OC-0365: Dose contribution to pelvic nodes of image-guided adaptive brachytherapy in cervical cancer

Combining transrectal ultrasound and CT for image-guided adaptive brachytherapy of cervical cancer: Proof of concept

PurposeTo investigate the feasibility of a treatment planning workflow for three-dimensional image-guided cervix cancer brachytherapy, combining volumetric transrectal ultrasound (TRUS) for target definition with CT for dose optimization to organs at risk (OARs), for settings with no access to MRI. Methods and MaterialsA workflow for TRUS/CT-based volumetric treatment planning was developed, based on a customized system including ultrasound probe, stepper unit, and software for image volume acquisition. A full TRUS/CT-based workflow was simulated in a clinical case and compared with MR- or CT-only delineation. High-risk clinical target volume was delineated on TRUS, and OARs were delineated on CT. Manually defined tandem/ring applicator positions on TRUS and CT were used as a reference for rigid registration of the image volumes. Treatment plan optimization for TRUS target and CT organ volumes was performed and compared to MRI and CT target contours. ResultsTRUS/CT-based contouring, applicator reconstruction, image fusion, and treatment planning were feasible, and the full workflow could be successfully demonstrated. The TRUS/CT plan fulfilled all clinical planning aims. Dose-volume histogram evaluation of the TRUS/CT-optimized plan (high-risk clinical target volume D90, OARs D2cm³ for) on different image modalities showed good agreement between dose values reported for TRUS/CT and MRI-only reference contours and large deviations for CT-only target parameters. ConclusionsA TRUS/CT-based workflow for full three-dimensional image-guided cervix brachytherapy treatment planning seems feasible and may be clinically comparable to MRI-based treatment planning. Further development to solve challenges with applicator definition in the TRUS volume is required before systematic applicability of this workflow.

Tumor dose–volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis

PurposeImage-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose–volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. Methods and MaterialsEligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie–European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2–3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. ResultsAn exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3–83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8–96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose–volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2–86.0%) local control probability. ConclusionBased on published data from a high number of patients, significant dose–volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria.

Direction Modulated Brachytherapy for Treatment of Cervical Cancer. II: Comparative Planning Study With Intracavitary and Intracavitary–Interstitial Techniques

To perform a comprehensive comparative planning study evaluating the utility of the proposed direction modulated brachytherapy (DMBT) tandem applicator against standard applicators, in the setting of image guided adaptive brachytherapy of cervical cancer. A detailed conceptual article was published in 2014. The proposed DMBT tandem applicator has 6 peripheral grooves of 1.3-mm width, along a 5.4-mm-thick nonmagnetic tungsten alloy rod of density 18.0g/cm(3), capable of generating directional dose profiles. We performed a comparative planning study with 45 cervical cancer patients enrolled consecutively in the prospective observational EMBRACE study. In all patients, MRI-based planning was performed while utilizing various tandem-ring (27 patients) and tandem-ring-needles (18 patients) applicators, in accordance with the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology recommendations. For unbiased comparisons, all cases were replanned with an in-house-developed inverse optimization code while enforcing a uniform set of constraints that are reflective of the clinical practice. All plans were normalized to the same high-risk clinical target volume D90 values achieved in the original clinical plans. In general, if the standard tandem was replaced with the DMBT tandem while maintaining all other planning conditions the same, there was consistent improvement in the plan quality. For example, among the 18 tandem-ring-needles cases, the average D2cm(3) reductions achieved were -2.48%±11.03%, -4.45%±5.24%, and -5.66%±6.43% for the bladder, rectum, and sigmoid, respectively. An opportunity may also exist in avoiding use of needles altogether for when the total number of needles required is small (approximately 2 to 3 needles or less), if DMBT tandem is used. Integrating the novel DMBT tandem onto both intracavitary and intracavitary-interstitial applicator assembly enabled consistent improvement in the sparing of the OARs, over a standard "single-channel" tandem, though individual variations in benefit were considerable. Although at an early stage of development, the DMBT concept design is demonstrated to be useful and pragmatic for potential clinical translation.

Image-guided adaptive brachytherapy in cervical cancer: Patterns of relapse by brachytherapy planning parameters

PurposeCervical cancer patients with a bulky high-risk clinical target volume (HR-CTV) get the largest benefit of dose escalation in terms of local control. However, the expected survival benefit could be lessened by a higher metastatic risk. We examined the patterns of relapse according to major prognostic factors: the HR-CTV volume and to the D90 HR-CTV. Methods and MaterialsThe clinical records of patients treated with pulsed-dose-rate image-guided adaptive brachytherapy after concurrent pelvic chemoradiation were reviewed. All patients had an optimal workup before treatment comprising a 18-fluorodeoxyglucose positron emission tomography/computed tomography and a para-aortic lymph node dissection. Patients with initial extrapelvic disease were excluded. ResultsA total of 109 patients fulfilled inclusion criteria. Median followup was 39 months. An HR-CTV volume ≥40 cm3 was associated with a poorer local failure-free survival. There was a strong inverse correlation between the HR-CTV volume and the D90 of the HR-CTV (correlation coefficient r = −0.696; p < 0.001) with increasing HR-CTV volume being associated with a decreasing D90 HR-CTV. A D90 HR-CTV <85 Gy and an HR-CTV volume ≥40 cm3 were significant univariate factors for experiencing nonlocal failure (p = 0.002 and 0.035, respectively), even after exclusion of local relapses. ConclusionA lower ability to reach the target D90 HR-CTV planning and an HR-CTV volume ≥ 40 cm3 correlated with a high propensity of relapsing at distance, these factors being interrelated. Next step of treatment personalization should design strategies integrating this risk, which is now the main cause of failure.

A Dosimetric Analysis of MRI-Guided Combined Intracavitary and Interstitial Dynamic Adaptive Brachytherapy for Cervical Cancer with a Novel Split Ring Applicator

A Dosimetric Analysis of MRI-Guided Combined Intracavitary and Interstitial Dynamic Adaptive Brachytherapy for Cervical Cancer with a Novel Split Ring Applicator

Use of Two Different Types of Applicator in the Same Patient for Fractionated MRI-Based Adaptive Brachytherapy for Cervical Cancer - A Dosimetric Study

Use of Two Different Types of Applicator in the Same Patient for Fractionated MRI-Based Adaptive Brachytherapy for Cervical Cancer - A Dosimetric Study

More Needles Is Better: A Planning Study Aiming at Optimizing MRI Guided Adaptive Brachytherapy for Cervical Cancer

More Needles Is Better: A Planning Study Aiming at Optimizing MRI Guided Adaptive Brachytherapy for Cervical Cancer

Image-Guided Adaptive Brachytherapy in Cervical Cancer: The Inability to Achieve the Planning Aims Is Linked to a Poorer Distant Control

Image-Guided Adaptive Brachytherapy in Cervical Cancer: The Inability to Achieve the Planning Aims Is Linked to a Poorer Distant Control

Quality assurance in MR image guided adaptive brachytherapy for cervical cancer: Final results of the EMBRACE study dummy run

PurposeUpfront quality assurance (QA) is considered essential when starting a multicenter clinical trial in radiotherapy. Despite the long experience gained for external beam radiotherapy (EBRT) trials, there are only limited audit QA methods for brachytherapy (BT) and none include the specific aspects of image guided adaptive brachytherapy (IGABT). Methods and materialsEMBRACE is a prospective multicenter trial aiming to assess the impact of (MRI)-based IGABT in locally advanced cervical cancer. An EMBRACE dummy run was designed to identify sources and magnitude of uncertainties and errors considered important for the evaluation of clinical, and dosimetric parameters and their relation to outcome. Contouring, treatment planning and dose reporting was evaluated and scored with a categorical scale of 1–10. Active feedback to centers was provided to improve protocol compliance and reporting. A second dummy run was required in case of major deviations (score <7) for any item. ResultsOverall 27/30 centers passed the dummy run. 16 centers had to repeat the dummy run in order to clarify major inconsistencies to the protocol. The most pronounced variations were related to contouring for both EBRT and BT. Centers with experience in IGABT (>30 cases) had better performance as compared to centers with limited experience. ConclusionThe comprehensive dummy run designed for the EMBRACE trial has been a feasible tool for QA in IGABT of cervix cancer. It should be considered for future IGABT trials and could serve as the basis for continuous quality checks for brachytherapy centers.

Pulsed-dose rate image-guided adaptive brachytherapy in cervical cancer: Dose–volume effect relationships for the rectum and bladder

PurposeTo establish dose–volume effect correlations for late bladder and rectum side effects in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate image-guided adaptive brachytherapy. Material and methodsThe dosimetric data, converted in 2Gy equivalent, from 217 patients were confronted to late morbidity defined as any event lasting or occurring 90days after treatment initiation. Toxicity was assessed using the CTC-AE 3.0. Probit analyses and Log rank tests were performed to assess relationships. ResultsOne hundred and sixty-one urinary and 58 rectal events were reported, affecting 98 (45.1%) and 51 (23.5%) patients, respectively. Cumulative incidences for grade 2–4 bladder and rectal morbidity were 24.3% and 9.6% at 3years, respectively. Significant relationships were observed between grade 2–4 and 3–4 events and D0.1cm3 and D2cm3 for the bladder and between grade 1–4 and 2–4 event probability and rectal D2cm3. The effective doses for 10% grade 2–4 morbidity were 65.3Gy (59.8–81.3), and 55.4Gy (15.7–63.6), respectively, for the rectum and bladder. Without considering urinary and rectal incontinence, for which the pertinence of correlating them with D2cm3 is questionable, ED10 were 68.5Gy (62.9–110.6) and 65.5Gy (51.4–71.6Gy). When sorting patients according to D2cm3 levels, patients with high D2cm3 had significantly lower morbidity free survival rates for grade 1–4 and 2–4 urinary and rectal morbidity. ConclusionSignificant dose–volume effect relationships were demonstrated between the modern dosimetric parameters and the occurrence of late rectal and urinary morbidity in patients treated with pulsed-dose-rate brachytherapy. Further studies are required to refine these relationships according to clinical cofactors, such as comorbidities.

OC-0130: Dose effect relationships for rectal bleeding after MRI-guided adaptive brachytherapy for cervical cancer

OC-0130: Dose effect relationships for rectal bleeding after MRI-guided adaptive brachytherapy for cervical cancer

OC-0129: Image-guided adaptive brachytherapy in cervical cancer: towards a personalization of planning aims

OC-0129: Image-guided adaptive brachytherapy in cervical cancer: towards a personalization of planning aims

PO-1015: High Dose Rate image guided adaptive brachytherapy for cervical cancer - a single centre experience

PO-1015: High Dose Rate image guided adaptive brachytherapy for cervical cancer - a single centre experience

OC-0276: Comparison of MRI, TRUS and CT for target definition in image-guided adaptive brachytherapy of cervical cancer

OC-0276: Comparison of MRI, TRUS and CT for target definition in image-guided adaptive brachytherapy of cervical cancer

D2cm³/DICRU ratio as a surrogate of bladder hotspots localizations during image-guided adaptive brachytherapy for cervical cancer: assessment and implications in late urinary morbidity analysis.

To evaluate the efficiency and potential implications of the lowest dose evaluated in the maximally exposed 2cm(3) of the bladder/dose evaluated at the International Commission for Radiation Units and Measurements (ICRU) bladder point (D2cm(3)/DICRU) ratio as surrogate to locate the D2cm(3) in patients treated with MRI-guided adaptive brachytherapy for cervical cancer. The D2cm(3) area of the bladder was located in 69 patients, using the Digital Imaging and Communications in Medicine coordinates of its barycenter, with respect to the ICRU bladder point. The D2cm(3)/DICRU ratio was correlated with the longitudinal coordinate of the D2cm(3). Afterward, the ratio was used in a retrospective cohort of 216 patients to evaluate its impact in dose-effect analyses for late urinary incontinence. The mean position of the D2cm(3) was 1.73±0.98 cm cranially, 0.59±0.65 cm backwardly, and 0.02±0.89 cm to the right of the ICRU point. It was located above the ICRU point in 95.7% of the patients. Its position was lower in patients with vaginal involvement at diagnosis (p=0.03). The D2cm(3)/DICRU ratio was correlated with the position of the D2cm(3) (R²=0.716, p<10(-6)). In speculating that a ratio greater than one would predict a D2cm(3) located above the ICRU point, the sensibility, specificity, positive, and negative predictive values were 95.2%, 100%, 100%, and 66.8%, respectively. Among the retrospective cohort, 85 patients had a ratio lower than 1.1, reflecting a D2cm(3) located in the lower bladder. In these patients, analyses showed significant dose relationship with Grade 2-4 incontinence (p=0.017), whereas no correlation was demonstrated in the remaining patients. The D2cm(3)/DICRU ratio is a relevant surrogate to estimate the localization of the D2cm(3). Significant dose-effect correlations for incontinence were established in patients with low values for this ratio.

SP-0479: Adaptive brachytherapy in cervical cancer

SP-0479: Adaptive brachytherapy in cervical cancer