This guideline reviews the evidence and provides recommendations for the indications and appropriate techniques of radiation therapy (RT) in the treatment of nonmetastatic cervical cancer.
The ...American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT in definitive and postoperative management of cervical cancer. These questions included the indications for postoperative and definitive RT, the use of chemotherapy in sequence or concurrent with RT, the use of intensity modulated radiation therapy (IMRT), and the indications and techniques of brachytherapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.
The guideline recommends postoperative RT for those with intermediate risk factors, and chemoradiation for those with high-risk factors. In the definitive setting, chemoradiation is recommended for stages IB3-IVA, and RT or chemoradiation is conditionally recommended for stages IA1-IB2 if medically inoperable. IMRT is recommended for postoperative RT and conditionally recommended for definitive RT, for the purposes of reducing acute and late toxicity. Brachytherapy is strongly recommended for all women receiving definitive RT, and several recommendations are made for target dose and fractionation, the use of intraoperative imaging, volume-based planning, and recommendations for doses limits for organs at risk.
There is strong evidence supporting the use of RT with or without chemotherapy in both definitive and postoperative settings. Brachytherapy is an essential part of definitive management and volumetric planning is recommended. IMRT may be used for the reduction of acute and late toxicity. The use of radiation remains an essential component for women with cervical cancer to achieve cure.
Purpose
The purpose of this study was to evaluate the impact of dose reporting schemes and tissue/applicator heterogeneities for 192Ir‐, 75Se‐, and 169Yb‐based MRI‐guided conventional and ...intensity‐modulated brachytherapy.
Methods and Materials
Treatment plans using a variety of dose reporting and tissue/applicator segmentation schemes were generated for a cohort (n = 10) of cervical cancer patients treated with 192Ir‐based Venezia brachytherapy. Dose calculations were performed using RapidBrachyMCTPS, a Geant4‐based research Monte Carlo treatment planning system. Ultimately, five dose calculation scenarios were evaluated: (a) dose to water in water (Dw,w); (b) Dw,w taking the applicator material into consideration (Dw,wApp); (c) dose to water in medium (Dw,m); (d and e) dose to medium in medium with mass densities assigned either nominally per structure (Dm,m (Nom)) or voxel‐by‐voxel (Dm,m).
Results
Ignoring the plastic Venezia applicator (Dw,wApp) overestimates Dm,m by up to 1% (average) with high energy source (192Ir and 75Se) and up to 2% with 169Yb. Scoring dose to water (Dw,wApp or Dw,m) generally overestimates dose and this effect increases with decreasing photon energy. Reporting dose other than Dm,m (or Dm,m Nom) for 169Yb‐based conventional and intensity‐modulated brachytherapy leads to a simultaneous overestimation (up to 4%) of CTVHR D90 and underestimation (up to 2%) of bladder D2cc due to a significant dip in the mass‐energy absorption ratios at the depths of nearby targets and OARs. Using a nominal mass‐density assignment per structure, rather than a CT‐derived voxel‐by‐voxel assignment for MRI‐guided brachytherapy, amounts to a dose error up to 1% for all radionuclides considered.
Conclusions
The effects of the considered dose reporting schemes trend correspondingly between conventional and intensity‐modulated brachytherapy. In the absence of CT‐derived mass densities, MRI‐only‐based dosimetry can adequately approximate Dm,m by assigning nominal mass densities to structures. Tissue and applicator heterogeneities do not significantly impact dosimetry for 192Ir and 75Se, but do for 169Yb; dose reporting must be explicitly defined since Dw,m and Dw,w may overstate the dosimetric benefits.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), ...Australia/New Zealand (ANZ), Europe (E), and North America (NAm).
A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey.
A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation SD 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4.96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05; p = 0.02 for Asia vs. other regions).The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002).
Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Vaginal necrosis is a late radiation tissue injury with serious morbidity complications. It is rare, and its incidence is not well assessed in prospective trials. Patient comorbidities and radiation ...dose can significantly increase the risk. As treatment of gynecologic malignancies often involve a multidisciplinary approach, timely diagnosis and appropriate management by physicians of the team are crucial. Untreated vaginal necrosis can lead to infection, hemorrhage, necrosis-related fistulation to the bladder or rectum, perforation, and death. In this review, we describe the pathophysiology of vaginal necrosis, its clinical course, and management options.
•Vaginal necrosis occurs after a high dose of radiation.•Conservative treatment includes antibiotics, hydrogen peroxide douching.•When clinically refractory, hyperbaric oxygen, debridement or pelvic exenteration may be required.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Melatonin has several oncostatic properties, including possible anti-estrogenic and anti-aromatase activity, and seems to be linked with fat metabolism. Night workers have lower levels of melatonin, ...which may predispose them to develop cancer. Endometrial cancer risk is influenced significantly by hormonal and metabolic factors; therefore, we hypothesize that night workers may have an increased risk of endometrial cancer. Of the 121,701 women enrolled in a prospective cohort study, 53,487 women provided data on rotating night shift work in 1988 and were followed through on June 1, 2004. A total of 515 women developed medical record-confirmed invasive endometrial cancer. We used Cox regression models to calculate multivariate relative risks (MVRRs), controlling for endometrial cancer risk factors. Women who worked 20+ years of rotating night shifts had a significantly increased risk of endometrial cancer MVRR, 1.47; 95% confidence interval (95% CI), 1.03-1.14. In stratified analyses, obese women working rotating night shifts doubled their baseline risk of endometrial cancer (MVRR, 2.09; 95% CI, 1.24-3.52) compared with obese women who did no night work, whereas a nonsignificant increase was seen among non-obese women (MVRR, 1.07; 95% CI, 0.60-1.92). Women working rotating night shifts for a long duration have a significantly increased risk of endometrial cancer, particularly if they are obese. We speculate that this increased risk is attributable to the effects of melatonin on hormonal and metabolic factors. Our results add to growing literature that suggests women who work at night may benefit from cancer prevention strategies.
This report presents an update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer.
Members of the ABS with expertise in ...cervical cancer formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder, or interstitial applicators for locally advanced cervical cancer. These guidelines were written based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy.
The ABS affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion before treatment delivery. Applicator placement, dose specification, and dose fractionation must be documented, quality assurance measures must be performed, and followup information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2-Gray (Gy) per fraction radiobiologic equivalence (normalized therapy dose) is 80-90Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed.
These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011.
Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains ...variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group.
A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants.
Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate.
This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Purpose
Contouring clinical target volume (CTV) from medical images is an essential step for radiotherapy (RT) planning. Magnetic resonance imaging (MRI) is used as a standard imaging modality for ...CTV segmentation in cervical cancer due to its superior soft‐tissue contrast. However, the delineation of CTV is challenging as CTV contains microscopic extensions that are not clearly visible even in MR images, resulting in significant contour variability among radiation oncologists depending on their knowledge and experience. In this study, we propose a fully automated deep learning–based method to segment CTV from MR images.
Methods
Our method begins with the bladder segmentation, from which the CTV position is estimated in the axial view. The superior–inferior CTV span is then detected using an Attention U‐Net. A CTV‐specific region of interest (ROI) is determined, and three‐dimensional (3‐D) blocks are extracted from the ROI volume. Finally, a CTV segmentation map is computed using a 3‐D U‐Net from the extracted 3‐D blocks.
Results
We developed and evaluated our method using 213 MRI scans obtained from 125 patients (183 for training, 30 for test). Our method achieved (mean ± SD) Dice similarity coefficient of 0.85 ± 0.03 and the 95th percentile Hausdorff distance of 3.70 ± 0.35 mm on test cases, outperforming other state‐of‐the‐art methods significantly (p‐value < 0.05). Our method also produces an uncertainty map along with the CTV segmentation by employing the Monte Carlo dropout technique to draw physician's attention to the regions with high uncertainty, where careful review and manual correction may be needed.
Conclusions
Experimental results show that the developed method is accurate, fast, and reproducible for contouring CTV from MRI, demonstrating its potential to assist radiation oncologists in alleviating the burden of tedious contouring for RT planning in cervical cancer.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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