Abstract Objectives To determine if readily obtainable markers of frailty predict disease-free survival (DFS) in elderly women with endometrial cancer treated with curative intent. Methods 88 ...consecutive women ≥ age 60 treated with surgery, chemotherapy and radiation for stage I–IV endometrial cancer were included. We considered the following health deficits as markers of “frailty”: albumin < 3.5 mg/dL, hemoglobin < 10 mg/dL, BMI < 20 kg/m,2 unintentional weight loss, ECOG performance status ≥ 2, history of osteopenia or osteoporosis and Charlson comorbidity score. Kaplan–Meier estimates and Cox proportional hazards models of DFS were calculated. Results The median age was 68.5 (range 60–88 years). The majority of women (65/88) had at least one frailty factor at baseline and 23/88 had two or more. All women received radiation and chemotherapy. Treatment was delayed, modified or truncated in 46% (40/88) of women due to treatment-related toxicity. Age (< 70 vs. ≥ 70 y) did not independently predict toxicity or recurrence risk. Women with at least one baseline frailty factor had twice the risk of disease recurrence (HR = 2.21;95% CI:1.02–4.80) when adjusted for age, stage, grade and Charlson score. The 3-year DFS was 77% in those with no frailty markers and 48% in those with at least one ( p = 0.02). The presence of a frailty marker also predicted shortened overall survival (HR = 2.34;95% CI:1.08–5.03) irrespective of treatment administered and stage of disease. Conclusions A combined frailty measure was a more robust predictor of DFS and OS than patient age, tumor characteristics and comorbidities in this cohort of older women with very good functional status.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Worldwide, stage III-IVA carcinomas of the uterine cervix comprise a significant proportion of cases at presentation, and have a higher rate of recurrence and worse overall survival. This review will ...discuss the epidemiology, prevention strategies, clinical presentation, and treatment recommendations for stage III-IVA cervical cancer. The focus will be on the role of radiation therapy, concurrent chemoradiotherapy, and brachytherapy, including the potential benefits and anticipated toxicities. The unique challenges and considerations of fistula formation and approaches to management will be highlighted, and follow-up care and future directions discussed. As low and middle income countries bear the highest burden of advanced stage carcinoma of the uterine cervix, this review will address the unique needs of global communities.
To compare the contours and dose-volume histograms (DVH) of the tumor and organs at risk (OAR) with computed tomography (CT) vs. magnetic resonance imaging (MRI) in cervical cancer brachytherapy.
Ten ...patients underwent both MRI and CT after applicator insertion. The dose received by at least 90% of the volume (D(90)), the minimal target dose (D(100)), the volume treated to the prescription dose or greater for tumor for the high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) and the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were evaluated. A standardized approach to contouring on CT (CT(Std)) was developed, implemented (HR- and IR-CTV(CTStd)), and compared with the MRI contours.
Tumor height, thickness, and total volume measurements, as determined by either CT or CT(Std) were not significantly different compared with the MRI volumes. In contrast, the width measurements differed in HR-CTV(CTStd) (p = 0.05) and IR-CTV(CTStd) (p = 0.01). For the HR-CTV(CTStd), this resulted in statistically significant differences in the volume treated to the prescription dose or greater (MRI, 96% vs. CT(Std), 86%, p = 0.01), D(100) (MRI, 5.4 vs. CT(Std), 3.4, p <0.01), and D(90) (MRI, 8.7 vs. CT(Std), 6.7, p <0.01). Correspondingly, the IR-CTV DVH values on MRI vs. CT(Std), differed in the D(100) (MRI, 3.0 vs. CT(Std), 2.2, p = 0.01) and D(90) (MRI, 5.6 vs. CT(Std), 4.6, p = 0.02). The MRI and CT DVH values of the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were similar.
Computed tomography-based or MRI-based scans at brachytherapy are adequate for OAR DVH analysis. However, CT tumor contours can significantly overestimate the tumor width, resulting in significant differences in the D(90), D(100), and volume treated to the prescription dose or greater for the HR-CTV compared with that using MRI. MRI remains the standard for CTV definition.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Lower brachytherapy utilization for cervical cancer patients is associated with decreased survival. This study examines more recent trends in brachytherapy utilization from 2004 to 2020 to assess any ...trend reversal after awareness increased regarding the importance of brachytherapy.
This study analyzed data from the National Cancer Database of patients with Federation of Gynecology and Obstetrics (FIGO) IB to IVA cervical cancer treated with radiation therapy between 2004 and 2020. To compare brachytherapy utilization over time, 2- to 3-year categories were created to account for potential variation seen in individual years. A multivariate log binomial regression with robust variance was used to estimate the incidence rate ratio (IRR) of brachytherapy utilization in each year category in reference to the 2004-2006 category. Additionally, risk factors for brachytherapy utilization were identified.
Overall brachytherapy utilization for cervical cancer increased from 54.9% in 2004 to 75.7% in 2020. Compared with 2004 to 2006 when rates of utilization totaled 55.2%, brachytherapy utilization significantly increased to 63.4% in 2011 to 2014 (IRR, 1.15; 95% CI, 1.11-1.19), 66.0% in 2015 to 2017 (1.20 1.16-1.23), and 76.0% in 2018 to 2020 (1.38 1.34-1.42). Sociodemographic factors associated with lower brachytherapy utilization included Black race (0.94 0.92-0.97), Hispanic ethnicity (0.92 0.90-0.95), and age >59 years (age ≥60-69: 0.96 0.94-0.98; age ≥70-79: 0.89 0.87-0.92; age ≥80: 0.73 0.69-0.77). Positive predictors of brachytherapy utilization included having insurance (IRR, 1.11; 95% CI, 1.07-1.14).
In patients with FIGO IB-IVA cervical cancer treated with radiation therapy from 2004 to 2020, brachytherapy utilization has increased during the past decade. These results are encouraging given the known benefit to cause-specific survival and overall survival provided by brachytherapy treatment and indicate a reversal in the trend of declining brachytherapy noted previously. Concerns related to disparities by race, ethnicity, and insurance status require further interventions.
Purpose
Brachytherapy combined with external beam radiotherapy (EBRT) is the standard treatment for cervical cancer and has been shown to improve overall survival rates compared to EBRT only. ...Magnetic resonance (MR) imaging is used for radiotherapy (RT) planning and image guidance due to its excellent soft tissue image contrast. Rapid and accurate segmentation of organs at risk (OAR) is a crucial step in MR image‐guided RT. In this paper, we propose a fully automated two‐step convolutional neural network (CNN) approach to delineate multiple OARs from T2‐weighted (T2W) MR images.
Methods
We employ a coarse‐to‐fine segmentation strategy. The coarse segmentation step first identifies the approximate boundary of each organ of interest and crops the MR volume around the centroid of organ‐specific region of interest (ROI). The cropped ROI volumes are then fed to organ‐specific fine segmentation networks to produce detailed segmentation of each organ. A three‐dimensional (3‐D) U‐Net is trained to perform the coarse segmentation. For the fine segmentation, a 3‐D Dense U‐Net is employed in which a modified 3‐D dense block is incorporated into the 3‐D U‐Net‐like network to acquire inter and intra‐slice features and improve information flow while reducing computational complexity. Two sets of T2W MR images (221 cases for MR1 and 62 for MR2) were taken with slightly different imaging parameters and used for our network training and test. The network was first trained on MR1 which was a larger sample set. The trained model was then transferred to the MR2 domain via a fine‐tuning approach. Active learning strategy was utilized for selecting the most valuable data from MR2 to be included in the adaptation via transfer learning.
Results
The proposed method was tested on 20 MR1 and 32 MR2 test sets. Mean ± SD dice similarity coefficients are 0.93 ± 0.04, 0.87 ± 0.03, and 0.80 ± 0.10 on MR1 and 0.94 ± 0.05, 0.88 ± 0.04, and 0.80 ± 0.05 on MR2 for bladder, rectum, and sigmoid, respectively. Hausdorff distances (95th percentile) are 4.18 ± 0.52, 2.54 ± 0.41, and 5.03 ± 1.31 mm on MR1 and 2.89 ± 0.33, 2.24 ± 0.40, and 3.28 ± 1.08 mm on MR2, respectively. The performance of our method is superior to other state‐of‐the‐art segmentation methods.
Conclusions
We proposed a two‐step CNN approach for fully automated segmentation of female pelvic MR bladder, rectum, and sigmoid from T2W MR volume. Our experimental results demonstrate that the developed method is accurate, fast, and reproducible, and outperforms alternative state‐of‐the‐art methods for OAR segmentation significantly (p < 0.05).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer ...treated with radiation therapy (RT) or concurrent chemoradiation therapy (CRT).
Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS) and disease-free survival (DFS) rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed.
The median age at diagnosis was 61 years (range, 18-92 years) and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p = 0.037; 3-yr DFS = 43% vs. 73%, log-rank p = 0.011). Twenty-three patients (45%) in the RT group had a relapse at any site compared to 3 (15%) in the CRT group (p = 0.027). With regard to the sites of first relapse, 10 patients (14%) had local only, 4 (6%) had local and regional, 9 (13%) had regional only, 1 (1%) had regional and distant, and 2 (3%) had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10-0.97; p = 0.04)).
Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The application of magnetic resonance image (MRI)–guided brachytherapy has demonstrated significant growth during the past 2 decades. Clinical improvements in cervix cancer outcomes have been linked ...to the application of repeated MRI for identification of residual tumor volumes during radiotherapy. This has changed clinical practice in the direction of individualized dose administration, and resulted in mounting evidence of improved clinical outcome regarding local control, overall survival as well as morbidity. MRI-guided prostate high-dose-rate and low-dose-rate brachytherapies have improved the accuracy of target and organs-at-risk delineation, and the potential exists for improved dose prescription and reporting for the prostate gland and organs at risk. Furthermore, MRI-guided prostate brachytherapy has significant potential to identify prostate subvolumes and dominant lesions to allow for dose administration reflecting the differential risk of recurrence. MRI-guided brachytherapy involves advanced imaging, target concepts, and dose planning. The key issue for safe dissemination and implementation of high-quality MRI-guided brachytherapy is establishment of qualified multidisciplinary teams and strategies for training and education.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Several decades of observational data have accumulated to implicate a potential role for melatonin in cancer prevention. Experimental studies suggest that the antineoplastic action of ...melatonin arises through many different mechanisms, including melatonin’s antioxidant, antimitotic, and antiangiogenic activity, as well as its ability to modulate the immune system and alter fat metabolism. Melatonin interacts with membrane and nuclear receptors, and may be linked to the regulation of tumor growth. Of particular relevance to breast cancer risk, melatonin may also block the estrogen receptor ERα and impact the enzyme aromatase, which produces estradiol. A growing number of epidemiologic studies have evaluated the relationship between night shift work as well as how varying duration of sleep affects peak melatonin secretion at night. While the studies demonstrate lower nightly melatonin levels in night workers, the evidence for an association between sleep duration and melatonin production is less clear. Similarly, both case-control and prospective cohort studies have consistently linked night shift work with breast cancer risk and, more recently, endometrial cancer – another tumor highly sensitive to estrogens. While, to date, the evidence for an association between sleep duration and breast cancer risk is less convincing, overall, there is increasing support for a potentially important link between melatonin and breast cancer risk and perhaps the risk of other tumors. As evidence increases, modifiable factors that have been shown to affect melatonin production, such as night shift work, are likely to gain increasing recognition as potential public health hazards. Additional studies are needed to delineate further the potential of melatonin in cancer prevention.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose
To present a novel, MRI‐compatible dynamicshield intensity modulated brachytherapy (IMBT) applicator and delivery system using 192Ir, 75Se, and 169Yb radioisotopes for the treatment of ...locally advanced cervical cancer. Needle‐free IMBT is a promising technique for improving target coverage and organs at risk (OAR) sparing.
Methods and materials
The IMBT delivery system dynamically controls the rotation of a novel tungsten shield placed inside an MRI‐compatible, 6‐mm wide intrauterine tandem. Using 36 cervical cancer cases, conventional intracavitary brachytherapy (IC‐BT) and intracavitary/interstitial brachytherapy (IC/IS‐BT) (10Ci 192Ir) plans were compared to IMBT (10Ci 192Ir; 11.5Ci 75Se; 44Ci 169Yb). All plans were generated using the Geant4‐based Monte Carlo dose calculation engine, RapidBrachyMC. Treatment plans were optimized then normalized to the same high‐risk clinical target volume (HR‐CTV) D90 and the D2cc for bladder, rectum, and sigmoid in the research brachytherapy planning system, RapidBrachyMCTPS. Plans were renormalized until either of the three OAR reached dose limits to calculate the maximum achievable HR‐CTV D90 and D98.
Results
Compared to IC‐BT, IMBT with either of the three radionuclides significantly improves the HR‐CTV D90 and D98 by up to 5.2% ± 0.3% (P < 0.001) and 6.7% ± 0.5% (P < 0.001), respectively, with the largest dosimetric enhancement when using 169Yb followed by 75Se and then 192Ir. Similarly, D2cc for all OAR improved with IMBT by up to 7.7% ± 0.6% (P < 0.001). For IC/IS‐BT cases, needle‐free IMBT achieved clinically acceptable plans with 169Yb‐based IMBT further improving HR‐CTV D98 by 1.5% ± 0.2% (P = 0.034) and decreasing sigmoid D2cc by 1.9% ± 0.4% (P = 0.048). Delivery times for IMBT are increased by a factor of 1.7, 3.3, and 2.3 for 192Ir, 75Se, and 169Yb, respectively, relative to conventional 192Ir BT.
Conclusions
Dynamic shield IMBT provides a promising alternative to conventional IC‐ and IC/IS‐BT techniques with significant dosimetric enhancements and even greater improvements with intermediate energy radionuclides. The ability to deliver a highly conformal, OAR‐sparing dose without IS needles provides a simplified method for improving the therapeutic ratio less invasively and in a less resource intensive manner.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials.
One male pelvis computed tomography (CT) data set and one female pelvis CT data ...set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified.
The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed.
Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
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