Abstract Purpose Image guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This ...is the first comprehensive report on clinical outcome in a large multi-institutional cohort. Patients and methods From twelve centres 731 patients, treated with definitive EBRT ± concurrent chemotherapy followed by IGBT, were analysed. Kaplan–Meier estimates at 3/5 years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3–4 late toxicity (CTCAEv3.0) was reported. Results Median follow up was 43 months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA–IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46 ± 2.5 Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87 ± 15 Gy (EQD210 ), mean D2cc was: bladder 81 ± 22 Gy, rectum 64 ± 9 Gy, sigmoid 66 ± 10 Gy and bowel 64 ± 9 Gy (all EQD23 ). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5 years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5 years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3–G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina. Conclusion IGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity.
Abstract Background and purpose Currently, there is no consensus on dose prescription in image guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. The purpose of this study was ...to provide evidence based recommendations for tumor dose prescription based on results from a multi-center patient series (retroEMBRACE). Materials and methods This study analyzed 488 locally advanced cervical cancer patients treated with external beam radiotherapy ± chemotherapy combined with IGABT. Brachytherapy contouring and reporting was according to ICRU/GEC-ESTRO recommendations. The Cox Proportional Hazards model was applied to analyze the effect on local control of dose-volume metrics as well as overall treatment time (OTT), dose rate, chemotherapy, and tumor histology. Results With a median follow up of 46 months, 43 local failures were observed. Dose (D90) to the High Risk Clinical Target Volume (CTVHR ) ( p = 0.022, HR = 0.967 per Gy) was significant for local control, whereas increasing CTVHR volume ( p = 0.004, HR = 1.017 per cm3 ), and longer OTT ( p = 0.004, HR = 1.023 per day) were associated with worse local control. Histology ( p = 0.084), chemotherapy ( p = 0.49) and dose rate ( p = 1.00) did not have significant impact on local control. Separate analyses according to stage of disease showed that dose to CTVHR , residual gross tumor volume (GTVres ), and Intermediate Risk CTV (CTVIR ) has significant impact on local control. Conclusion CTVHR dose of ⩾85 Gy (D90) delivered in 7 weeks provides 3-year local control rates of >94% in limited size CTVHR (20 cm3 ), >93% in intermediate size (30 cm3 ) and >86% in large size (70 cm3 ) CTVHR . CTVIR and GTVres dose of ⩾60 Gy and ⩾95 Gy (D98) leads to similar local control. A dose of 5 Gy (CTVHR ) is required to compensate an increase of OTT by one week. Increased CTVHR volume by 10 cm3 requires additional 5 Gy for equivalent local control.
Abstract
Background. The first Nordic protocol for three-dimensional (3D) planned radiotherapy in locally advanced cervical cancer was the prospective NOCECA study (1994-2000). NOCECA consisted of ...computed tomography (CT)-based 3D conformal external beam radiotherapy (EBRT) with a simultaneous integrated boost (SIB) to the primary tumour combined with brachytherapy (BT) based on x-ray imaging. In NOCECA the planning aim was to achieve 80 Gy at point A from EBRT and BT combined. However, the balance of dose between EBRT and BT was determined by tumour size at diagnosis with more EBRT dose given to point A and less by BT in more advanced stages. In 2005 image-guided adaptive brachytherapy (IGABT) based on magnetic resonance imaging (MRI) and optimisation of the BT dose distribution to the remaining tumour and cervix at time of BT (HR CTV) was introduced in Aarhus. EBRT remained like in NOCECA until 2008 when the SIB to the primary tumour was abandoned and IMRT was introduced as routine technique. In this study, we report outcome of our first five-year experience with IGABT using our NOCECA cohort as reference. Material and methods. The NOCECA cohort comprising 99 patients was compared with 140 consecutive patients treated by IGABT. Patients with para-aortic nodes were excluded in NOCECA but were present in 9% of the patients treated with IGABT. No patient in NOCECA received chemotherapy whereas concomitant cisplatin was given to 79% of the IGABT patients. Results. With IGABT actuarial local control was 91% at three years. When comparing NOCECA with IGABT overall survival was significantly improved from 63% to 79% (p = 0.005). In parallel, both moderate and severe late morbidity were reduced by about 50% (p = 0.02). Conclusion. Introduction of IGABT reduced morbidity and generated a very high rate of local control, which likely has improved survival by at least as much as concomitant chemotherapy.
•CT Based Contouring recommendations in IGABT for cervical cancer is a collaborative effort of 13 experts from Indian Brachytherapy Society (IBS), GEC-ESTRO and American Brachytherapy Society ...(ABS).•The recommendations are comprehensive, providing a pragmatic solution to contour target on CT Imaging at BT in different prevailing clinic-radiological environments which have not been comprehensively addressed.•We expect each institution with no access to MRI at BT to review their working environment and utilize appropriate definitions for defining the target to implement CT based IGABT for cervical cancers.
MR Imaging is regarded asthe gold standardfor Image Gudied Adaptive Brachytherapy (IGABT) for cervical cancer. However, its wide applicability is limited by its availability, logistics and financial implications. Use of alternative imaging like CTand Ultrasound (US) for IGABT has been attempted. In order to arrive at a systematic, uniform and international approach for CT based definition and contouring of target structures, GEC ESTRO, IBS and ABS agreed to jointly develop such recommendations based on the concepts and terms as published in the ICRU Report 89.
The minimum requirements are clinical examination & documentation, CT or MR imaging at diagnosis and at a minimum, CT imaging with the applicator in place. The recommendations are based on (i) assessment of the GTV at diagnosis and at brachytherapy, (ii) categorizing the response to external radiation into different clinical remission patterns, (iii) defining various clinico-radiological environments and (iv) definition & delineation of a target on CT imaging at the time of brachytherapy with the applicator in situ. CT based target contouring recommendations based on 4 remission categories within 8 defined environments, aim at improving the contouring accuracy for IGABT using CT, US and MRI as available. For each clinico-radiological environment, there is an attempt to minimize the specific uncertainties in order to arrive at the best possible contouring accuracy.
Evaluating feasibility & reproducibility, to achieve a benchmark towards a gold standard MR IGABT and further clinical research including outcomes with CT Based IGABT will become the next steps.
To investigate the incidence of and risk factors for pelvic insufficiency fracture (PIF) after definitive chemoradiation therapy for locally advanced cervical cancer (LACC).
We analyzed 101 patients ...with LACC treated from 2008-2014. Patients received weekly cisplatin and underwent external beam radiation therapy with 45 Gy in 25 fractions (node-negative patients) or 50 Gy in 25 fractions with a simultaneous integrated boost of 60 Gy in 30 fractions (node-positive patients). Pulsed dose rate magnetic resonance imaging guided adaptive brachytherapy was given in addition. Follow-up magnetic resonance imaging was performed routinely at 3 and 12 months after the end of treatment or based on clinical indication. PIF was defined as a fracture line with or without sclerotic changes in the pelvic bones. D
and V
were calculated for the os sacrum and jointly for the os ileum and pubis. Patient- and treatment-related factors including dose were analyzed for correlation with PIF.
The median follow-up period was 25 months. The median age was 50 years. In 20 patients (20%), a median of 2 PIFs (range, 1-3 PIFs) were diagnosed; half were asymptomatic. The majority of the fractures were located in the sacrum (77%). Age was a significant risk factor (P<.001), and the incidence of PIF was 4% and 37% in patients aged ≤50 years and patients aged >50 years, respectively. Sacrum D
was a significant risk factor in patients aged >50 years (P=.04), whereas V
of the sacrum and V
of the pelvic bones were insignificant (P=.33 and P=.18, respectively). A dose-effect curve for sacrum D
in patients aged >50 years showed that reduction of sacrum D
from 40 Gy
to 35 Gy
reduces PIF risk from 45% to 22%.
PIF is common after treatment of LACC and is mainly seen in patients aged >50 years. Our data indicate that PIFs are not related to lymph node boosts but rather to dose and volume associated with irradiation of the elective pelvic target. Reducing the prescribed elective dose from 50 to 45 Gy may reduce the risk of PIF considerably.
In vivo dosimetry in brachytherapy Tanderup, Kari; Beddar, Sam; Andersen, Claus E. ...
Medical physics (Lancaster),
July 2013, Letnik:
40, Številka:
7
Journal Article
Recenzirano
Odprti dostop
In vivo dosimetry (IVD) has been used in brachytherapy (BT) for decades with a number of different detectors and measurement technologies. However, IVD in BT has been subject to certain difficulties ...and complexities, in particular due to challenges of the high-gradient BT dose distribution and the large range of dose and dose rate. Due to these challenges, the sensitivity and specificity toward error detection has been limited, and IVD has mainly been restricted to detection of gross errors. Given these factors, routine use of IVD is currently limited in many departments. Although the impact of potential errors may be detrimental since treatments are typically administered in large fractions and with high-gradient-dose-distributions, BT is usually delivered without independent verification of the treatment delivery. This Vision 20/20 paper encourages improvements within BT safety by developments of IVD into an effective method of independent treatment verification.
To compare dose-volume histogram parameters of standard Point A and magnetic resonance imaging-based three-dimensional optimized dose plans in 21 consecutive patients who underwent pulsed-dose-rate ...brachytherapy (PDR-BT) for locally advanced cervical cancer.
All patients received external beam radiotherapy (elective target dose, 45 Gy in 25-30 fractions; tumor target dose, 50-60 Gy in 25-30 fractions). PDR-BT was applied with a tandem-ring applicator. Additional ring-guided titanium needles were used in 4 patients and a multichannel vaginal cylinder in 2 patients. Dose planning was done using 1.5 Tesla T(1)-weighted and T(2)-weighted paratransversal magnetic resonance imaging scans. T(1)-weighted visible oil-containing tubes were used for applicator reconstruction. The prescribed standard dose for PDR-BT was 10 Gy (1 Gy/pulse, 1 pulse/h) for two to three fractions to reach a physical dose of 80 Gy to Point A. The total dose (external beam radiotherapy plus brachytherapy) was normalized to an equivalent dose in 2-Gy fractions using alpha/beta = 10 Gy for tumor, alpha/beta = 3 Gy for normal tissue, and a repair half-time of 1.5 h. The goal of optimization was dose received by 90% of the target volume (D(90)) of > or =85 Gy(alpha/beta10) in the high-risk clinical target volume (cervix and remaining tumor at brachytherapy), but keeping the minimal dose to 2 cm(3) of the bladder and rectum/sigmoid at <90 and <75 Gy(alpha/beta3), respectively.
Using three-dimensional optimization, all dose-volume histogram constraints were met in 16 of 21 patients compared with 3 of 21 patients with two-dimensional library plans (p < 0.001). Optimization increased the minimal target dose (D(100)) of the high-risk clinical target volume (p < 0.007) and decreased the minimal dose to 2 cm(3) for the sigmoid significantly (p = 0.03). For the high-risk clinical target volume, D(90) was 91 +/- 8 Gy(alpha/beta10) and D(100) was 76 +/- 5 Gy(alpha/beta10). The minimal dose to 2 cm(3) for the bladder, rectum, and sigmoid was 73 +/- 6, 67 +/- 6, and 69 +/- 6 Gy(alpha/beta3), respectively.
The results of our study have shown that magnetic resonance imaging-guided optimization of PDR-BT for locally advanced cervical cancer significantly improved the dose-volume histogram parameters.
•Rigid registration on applicator good for contour mapping and applicator reconstruction.•Current DIR algorithms are not yet robust enough to handle complexities.•Wide range of uncertainties when ...using deformable dose accumulation.•Direct addition of doses provides reasonable estimate for target, bladder and rectum.•Substantial uncertainties if EBRT dose gradients in the region of the BT boost.
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.
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