To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer.
Records ...were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method.
At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy).
Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure adequate tumor coverage while minimizing the D2cc to the rectum.
Abstract Objective To summarize the literature on quality of life for patients treated with definitive radiation for gynecologic cancers, with a specific focus on patient reported outcomes. Methods A ...literature review was performed to summarize studies about patient-reported outcomes and quality of life in women with gynecologic malignancies who were treated with definitive radiation therapy. Summaries are by disease site, including endometrial, cervical and vulvar cancers. Results Over 20 different survey instruments have been used to describe patient-reported outcomes for women treated with radiation for gynecologic cancer. Regardless of disease site, all patients describe a degree of compromise in physical and social functioning, as well as sexual dysfunction. Specific symptoms which are most bothersome for patients vary by disease site, such as bowel concerns predominating for endometrial cancer patients, while body image is more concerning for cervical cancer patients. Conclusions Several quality of life concerns exist for women treated with radiation therapy for gynecologic malignancies. Significant overlap exists in the QOL issues affecting these patients. Whether to combine or separate surveys by diagnosis, treatment type, age, or time point should be explored further. Assessing patients' psychological, emotional, and physical concerns helps to understand long-term adjustment, enabling incorporation of these domains into future trials that will ultimately improve patient well-being.
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.
To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy.
Twenty-three ...experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case.
For all 3 cases, the mean tumor volume was smaller on MR than on CT (P<.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR.
In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx.
The global cervical cancer burden falls disproportionately upon women in low and middle-income countries. Insufficient infrastructure, lack of access to preventive HPV vaccines, screening, and ...treatment, as well as limited trained personnel and training opportunities, continue to impede efforts to reduce incidence and mortality in these nations. These hurdles have been substantial challenges to radiation delivery in particular, preventing treatment for a disease in which radiation is a cornerstone of curative therapy. In this review, we discuss the breadth of these barriers, while illustrating the need for adaptive approaches by proposing the use of brachytherapy alone in the absence of available external beam radiotherapy. Such modifications to current guidelines are essential to maximize radiation treatment for cervical cancer in limited resource settings.
•Challenges to radiation delivery for cervical cancer in LMIC are discussed.•The efficacy of treatment with brachytherapy alone is presented.•Limited resource settings require adaptive approaches to treatment guidelines.
Management of Nodal Disease in Advanced Cervical Cancer Jürgenliemk-Schulz, Ina-Maria; Beriwal, Sushil; de Leeuw, Astrid A.C. ...
Seminars in radiation oncology,
April 2019, 2019-04-00, 20190401, Letnik:
29, Številka:
2
Journal Article
Recenzirano
During the last decade the adoption of image-guided adaptive brachytherapy has dramatically improved local control in patients with locally advanced cervical cancer (LACC) treated with radiotherapy ...and concomitant chemotherapy; however, nodal failure remains an obstacle. Metastatic lymph nodes can be detected by surgical and imaging approaches with different sensitivities and specificities, that improve the definition of relevant targets for macroscopic and microscopic nodal disease, and that influence our understanding of dose levels of external beam radiotherapy. Systematic use of modern radiotherapy techniques including intensity modulated radiotherapy and simultaneously integrated nodal boosts in combination with daily position verification is emerging as increasingly important for obtaining nodal control in LACC. This review summarizes published and ongoing efforts for optimizing nodal disease treatment in LACC, elaborates the state of the art approach for nodal disease detection, radiotherapy planning and delivery, and discusses future investigational efforts needed for precise optimization.
Abstract Objective HPV status is an important prognostic factor for patients with oropharyngeal, anal and cervical cancers treated with radiotherapy. This study evaluates the association between HPV ...and p16 status and outcome in a radiation-treated cohort with vulvar squamous cell carcinoma (SCC). Methods Patients with vulvar SCC who received radiotherapy with or without surgical resection between 1985 and 2011 were identified retrospectively. Immunostaining for p16 and multiplex PCR for HPV genotyping were performed using archival tumor tissue from 57 patients. Actuarial estimates of PFS, OS and in-field recurrence were calculated using the Kaplan-Meier method. Cox proportional hazards models were used for multivariable analysis. Median follow-up was 58 months among the 57 patients with an available tumor specimen. Results HPV prevalence was implied in 37% by (diffuse linear) p16 immunostaining and confirmed in 27% by HPV PCR with good agreement (κ = 0.7). HPV-16 was identified in 80% of HPV-positive tumors. Women with p16-positive tumors had significantly higher 5-year PFS (65% vs. 16%, p < 0.01) and OS (65% vs. 22%, p = 0.01) rates, as well as lower in-field relapse rates (19% vs. 75%, p < 0.01) compared to those with p16-negative disease. On multivariable analysis adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.4, 95% CI 0.2–0.9) and lower rates of in-field relapse (HR 0.2, 95% CI 0.06–0.6). Results were similar when analyzed by HPV DNA status. Conclusion In this study, the presence of HPV or its surrogate of p16 immunostaining was an independent prognostic factor for in-field relapse and survival in women with vulvar SCC treated with radiotherapy. This finding warrants validation in larger cohorts or the prospective setting.
Abstract Purpose To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal ...brachytherapy (VB) alone using a novel low dose regimen. Methods We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan–Meier method. Results All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5–76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient. Conclusion Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity.
There is a clinical need to develop anatomic phantoms for simulation-based learning in gynecological brachytherapy. Here, we provide a step-by-step approach to build a life-sized gynecological ...training phantom based on magnetic resonance imaging (MRI) of an individual patient. Our hypothesis is that this phantom can generate convincing ultrasound (US) images that are similar to patient scans.
Organs-at-risk were manually segmented using patient scans (MRI). The gynecological phantom was constructed using positive molds from 3D printing and polyvinyl chloride (PVC) plastisol. Tissue texture/acoustic properties were simulated using different plastic softener/hardener ratios and microbead densities. Nine readers (residents) were asked to evaluate 10 cases (1 ultrasound image per case) and categorize each as a "patient" or "phantom" image. To evaluate whether the phantom and patient images were equivalent, we used a multireader, multicase equivalence study design with two composite null hypotheses with proportion (p
) at H
: p
≤ 0.35 and H
: p
≥ 0.65. Readers were also asked to review US videos and identify the insertion of an interstitial needle into the pelvic phantom. Computed Tomography (CT) and magnetic resonance (MR) images of the phantom were acquired for a feasibility study.
Readers correctly classified "patient" and "phantom" scans at p
= 53.3% ± 6.2% (p values 0.013 for H
and 0.054 for H
, df = 5.96). Readers reviewed US videos and identified the interstitial needle 100% of the time in transabdominal view, and 78% in transrectal view. The phantom was CT and MR safe.
We have outlined a manufacturing process to create a life-sized, gynecological phantom that is compatible with multi-modality imaging and can be used to simulate clinical scenarios in image-guided brachytherapy procedures.
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