Dose-response relationships of intestinal organs and excessive mucus discharge after gynaecological radiotherapy.

BACKGROUND: The study aims to determine possible dose-volume response relationships between the rectum, sigmoid colon and small intestine and the 'excessive mucus discharge' syndrome after pelvic radiotherapy for gynaecological cancer. METHODS AND MATERIALS: From a larger cohort, 98 gynaecological cancer survivors were included in this study. These survivors, who were followed for 2 to 14 years, received external beam radiation therapy but not brachytherapy and not did not have stoma. Thirteen of the 98 developed excessive mucus discharge syndrome. Three self-assessed symptoms were weighted together to produce a score interpreted as 'excessive mucus discharge' syndrome based on the factor loadings from factor analysis. The dose-volume histograms (DVHs) for rectum, sigmoid colon, small intestine for each survivor were exported from the treatment planning systems. The dose-volume response relationships for excessive mucus discharge and each organ at risk were estimated by fitting the data to the Probit, RS, LKB and gEUD models. RESULTS: The small intestine was found to have steep dose-response curves, having estimated dose-response parameters: γ50: 1.28, 1.23, 1.32, D50: 61.6, 63.1, 60.2 for Probit, RS and LKB respectively. The sigmoid colon (AUC: 0.68) and the small intestine (AUC: 0.65) had the highest AUC values. For the small intestine, the DVHs for survivors with and without excessive mucus discharge were well separated for low to intermediate doses; this was not true for the sigmoid colon. Based on all results, we interpret the results for the small intestine to reflect a relevant link. CONCLUSION: An association was found between the mean dose to the small intestine and the occurrence of 'excessive mucus discharge'. When trying to reduce and even eliminate the incidence of 'excessive mucus discharge', it would be useful and important to separately delineate the small intestine and implement the dose-response estimations reported in the study.

RapidBrachyDL: Rapid Radiation Dose Calculations in Brachytherapy Via Deep Learning.

PURPOSE: Detailed and accurate absorbed dose calculations from radiation interactions with the human body can be obtained with the Monte Carlo (MC) method. However, the MC method can be slow for use in the time-sensitive clinical workflow. The aim of this study was to provide a solution to the accuracy-time trade-off for 192Ir-based high-dose-rate brachytherapy by using deep learning. METHODS AND MATERIALS: RapidBrachyDL, a 3-dimensional deep convolutional neural network (CNN) model, is proposed to predict dose distributions calculated with the MC method given a patient's computed tomography images, contours of clinical target volume (CTV) and organs at risk, and treatment plan. Sixty-one patients with prostate cancer and 10 patients with cervical cancer were included in this study, with data from 47 patients with prostate cancer being used to train the model. RESULTS: Compared with ground truth MC simulations, the predicted dose distributions by RapidBrachyDL showed a consistent shape in the dose-volume histograms (DVHs); comparable DVH dosimetric indices including 0.73% difference for prostate CTV D90, 1.1% for rectum D2cc, 1.45% for urethra D0.1cc, and 1.05% for bladder D2cc; and substantially smaller prediction time, acceleration by a factor of 300. RapidBrachyDL also demonstrated good generalization to cervical data with 1.73%, 2.46%, 1.68%, and 1.74% difference for CTV D90, rectum D2cc, sigmoid D2cc, and bladder D2cc, respectively, which was unseen during the training. CONCLUSION: Deep CNN-based dose estimation is a promising method for patient-specific brachytherapy dosimetry. Desired radiation quantities can be obtained with accuracies arbitrarily close to those of the source MC algorithm, but with much faster computation times. The idea behind deep CNN-based dose estimation can be safely extended to other radiation sources and tumor sites by following a similar training process.

Modeling Complex Deformations of the Sigmoid Colon Between External Beam Radiation Therapy and Brachytherapy Images of Cervical Cancer.

PURPOSE: In this study, we investigated registration methods for estimating the large interfractional sigmoid deformations that occur between external beam radiation therapy (EBRT) and brachytherapy (BT) for cervical cancer. METHODS AND MATERIALS: Sixty-three patients were retrospectively analyzed. The sigmoid colon was delineated on 2 computed tomography images acquired during EBRT (without applicator) and BT (with applicator) for each patient. Five registration approaches were compared to propagate the contour of the sigmoid from BT to EBRT anatomies: rigid registration, commercial hybrid (ANAtomically CONstrained Deformation Algorithm), controlling ROI surface projection of RayStation, and the classical and constrained symmetrical thin-plate spline robust point matching (sTPS-RPM) methods. Deformation of the sigmoid due to insertion of the BT applicator was reported. Registration performance was compared by using the Dice similarity coefficient (DSC), distance to agreement, and Hausdorff distance. The 2 sTPS-RPM methods were compared by using surface triangle quality criteria between deformed surfaces. Using the deformable approaches, the BT dose of the sigmoid was deformed toward the EBRT anatomy. The displacement and discrepancy between the deformable methods to propagate the planned D1cm3 and D2cm3 of the sigmoid from BT to EBRT anatomies were reported for 55 patients. RESULTS: Large and complex deformations of the sigmoid were observed for each patient. Rigid registration resulted in poor sigmoid alignment with a mean DSC of 0.26. Using the contour to drive the deformation, ANAtomically CONstrained Deformation Algorithm was able to slightly improve the alignment of the sigmoid with a mean DSC of 0.57. Using only the sigmoid surface as controlling ROI, the mean DSC was improved to 0.79. The classical and constrained sTPS-RPM methods provided mean DSCs of 0.95 and 0.96, respectively, with an average inverse consistency error <1 mm. The constrained sTPS-RPM provided more realistic deformations and better surface topology of the deformed sigmoids. The planned mean (range) D1cm3 and D2cm3 of the sigmoid were 13.4 Gy (1-24.1) and 12.2 Gy (1-21.5) on the BT anatomy, respectively. Using the constrained sTPS-RPM to deform the sigmoid from BT to EBRT anatomies, these hotspots had a mean (range) displacement of 27.1 mm (6.8-81). CONCLUSIONS: Large deformations of the sigmoid were observed between the EBRT and BT anatomies, suggesting that the D1cm3 and D2cm3 of the sigmoid would unlikely to be at the same position throughout treatment. The proposed constrained sTPS-RPM seems to be the preferred approach to manage the large deformation due to BT applicator insertion. Such an approach could be used to map the EBRT dose to the BT anatomy for personalized BT planning optimization.

Clinical Anastomotic Leakage After Rectal Cancer Resection Can Be Predicted by Pelvic Anatomic Features on Preoperative MRI Scans: A Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: We demonstrated previously that radiation proctitis induced by preoperative radiotherapy is a predisposing factor for clinical anastomotic leakage in patients undergoing rectal cancer resection. Quantitative measurement of radiation proctitis is needed. OBJECTIVE: This study aimed to quantitate the changes of anatomic features caused by preoperative radiotherapy for rectal cancer and evaluate its ability to predict leakage. DESIGN: It was a secondary analysis of a randomized controlled trial (NCT01211210). MRI variables were retrospectively assessed. SETTINGS: The study was conducted in the leading center of the trial, which is a tertiary GI hospital. PATIENTS: Patients undergoing preoperative chemoradiation with sphincter-preserving surgery were included. MAIN OUTCOME MEASURES: Anatomic features were measured by preradiotherapy and postradiotherapy MRI. Univariate analyses were used to identify prognostic factors. Receiver operating characteristic curves were constructed to determine the cutoff value of the changes of MRI variables in predicting leakage. RESULTS: Eighteen (14.4%) of the 125 included patients developed clinical anastomotic leakage. Baseline characteristics were comparable between leakage group and nonleakage group. Relative increments of width of presacral space, thickness of rectal wall, and distal end of sigmoid colon discriminate between the 2 groups better than random chance. Relative increments of width of presacral space was the best performing predictor, with area under the curve of 0.722, sensitivity of 66.7%, specificity of 72.0%, and positive and negative predictive value of 28.6% and 92.8%. LIMITATIONS: The study was limited by its small sample size and retrospective design. CONCLUSIONS: Increments of the width of the presacral space, thickness of rectal wall, and distal part of the sigmoid colon helps to identify individuals not at risk for clinical anastomotic leakage after rectal cancer resection. The first variable is the strongest predictor. Changes of these variables should be taken into consideration when evaluating the application of defunctioning stoma. See Video Abstract at http://links.lww.com/DCR/B23. CLINICAL TRIALS IDENTIFIER: NCT1211210. LAS FUGAS ANASTOMÓTICAS CLÍNICAS DESPUÉS DE LA RESECCIÓN DEL CÁNCER DEL RECTO PUEDEN PREDECIRSE POR LAS CARACTERÍSTICAS ANATÓMICAS PÉLVICAS EN LAS IMAGENES DE RESONANCIA MAGNÉTICA PREOPERATORIA: UN ANÁLISIS SECUNDARIO DE UN ESTUDIO CONTROLADO ALEATORIZADO:: Anteriormente demostramos que la proctitis inducida por la radiación de radioterapia preoperatoria es un factor predisponente para la fuga anastomótica clínica en pacientes sometidos a resección de cáncer rectal. Es necesaria la medición cuantitativa de la proctitis por radiación.Este estudio tuvo como objetivo cuantificar los cambios en las características anatómicas causados por la radioterapia preoperatoria para el cáncer de recto y evaluar su capacidad para predecir las fugas anastomoticas.Fue un análisis secundario de un estudio controlado aleatorio (NCT01211210). Los variables de imagines de resonancia magnetica se evaluaron retrospectivamente.Se llevó a cabo en el centro principal del estudio, que es un hospital gastrointestinal terciario.Se incluyeron pacientes sometidos a quimiorradiación preoperatoria con cirugía conservadora del esfínter.Las características anatómicas se midieron mediante imagines de resonancia magnetica previa y posterior a la radioterapia. Se utilizaron análisis univariados para identificar los factores pronósticos. Las curvas de características operativas del receptor se construyeron para determinar el valor de corte de los cambios de los variables de resonancia magnetica en la predicción de fugas.Dieciocho (14.4%) de los 125 pacientes incluidos desarrollaron fugas anastomóticas clínicas. Las características basales fueron comparables entre el grupo de fugas y el grupo de no fugas. Los incrementos relativos del ancho del espacio presacro, el grosor de la pared rectal y distal del colon sigmoide discriminan entre los dos grupos mejor que la posibilidad aleatoria. Los incrementos relativos del ancho del espacio presacro fueron el mejor pronóstico con un AUC de 0.722, sensibilidad del 66.7%, especificidad del 72.0%, valor predictivo positivo y negativo del 28.6% y 92.8%.Estaba limitado por el tamaño de muestra pequeño y el diseño retrospectivo.Los incrementos en el ancho del espacio presacro, el grosor de la pared rectal y la parte distal del colon sigmoide ayudan a identificar a las personas que no tienen riesgo de fuga anastomótica clínica después de la resección del cáncer rectal. La primera variable es el predictor más fuerte. Los cambios de estos variables deben tenerse en cuenta al evaluar la aplicación del estoma para desvio. Vea el Resumen del Video en http://links.lww.com/DCR/B23.

Late side effects of 3T MRI-guided 3D high-dose rate brachytherapy of cervical cancer : Institutional experiences.

PURPOSE: This article reports experiences with 3T magnetic resonance imaging(MRI)-guided brachytherapy (BT) for cervical cancer focusing on late side effects. METHODS: Between June 2012 and March 2017 a total of 257 uterovaginal BT administrations were performed in 61 consecutive patients with inoperable cervical cancer. All patients were treated with BT combined with external beam radiotherapy. RESULTS: The mean HR-CTV (high risk-clinical target volume) D90 was 87 ± 5.1 Gy equivalent dose corresponding to the conventional fractionation using 2 Gy per fraction (EQD2, range 70.7-97.9 Gy). The mean doses in OAR (organs at risk), namely rectum, sigmoid and bladder were D2 cm3rectum = 62.6 ± 6.9 Gy EQD2 (range 38.2-77.2 Gy), D2 cm3sigmoid = 66.2 ± 6.8 Gy EQD2 (43.2-78.6 Gy) and D2 cm3bladder = 75.1 ± 8.3 Gy EQD2 (58.2-92.6 Gy). There were no signs of late gastrointestinal (GI) toxicity in 49 patients, grade 3 toxicity was seen in 2 patients and grade 4 toxicity in 3 patients. There were no signs of late genitourinary (GU) toxicity in 41 patients, grade 3 toxicity was seen in 4 patients and no signs of grade 4 toxicity were seen. After the treatment, 60 patients (98.4%) achieved locoregional remission. In 54 patients (88.5%) the remission was complete, whereas in 6 patients (9.8%) remission was partial. CONCLUSION: The use of 3T MRI-guided BT leads to achievement of high rates of local control with limited late morbidity as demonstrated in this series of patients.

Hypovolemic shock after pelvic radiotherapy. A rare combination leading to a devastating complication.

BACKGROUND: Radiotherapy currently plays a key role in pelvic malignancies' management. Excellent outcomes have been reported on its association with chemotherapy for the treatment of the anal carcinoma. Despite that, the combined use of chemo- and radiotherapy and the high doses administered seem to be strongly associated with early and late onset side effects. METHODS: We reported a case of a 72 years old woman, affected by anal squamous cell carcinoma. She underwent chemotherapy, and then radiotherapy, with good results. RESULTS: During a regular MR control, the patient developed anaphylactic reaction to Gadolinium, and after that a rectosigmoid ischemia with total necrosis of the posterior rectal wall was diagnosed and surgically treated with Hartmann procedure. CONCLUSION: In our case we faced with the rapid and severe degeneration of pelvic anatomy determined by the sum of vascular alterations following hypovolemic shock and pelvic tissues alteration after radiotherapy. It seems essential not to underestimate the exponential outcome of a similar unusual combination of events. KEY WORDS: Anal carcinoma, Hypovolemic shock, Pelvic radiotherapy, Rectal necrosis.

Radiobiological optimization comparison between pulse-dose-rate and high-dose-rate brachytherapy in patients with locally advanced cervical cancer.

PURPOSE: Only scarce data are available on the possibility to include radiobiological optimization as part of the dosimetric process in cervical cancer treated with brachytherapy (BT). We compared dosimetric outcomes of pulse-dose-rate (PDR) and high-dose-rate (HDR)-BT, according to linear-quadratic model. METHODS AND MATERIALS: Three-dimensional dosimetric data of 10 consecutive patients with cervical cancer undergoing intracavitary image-guided adaptive PDR-BT after external beam radiation therapy were examined. A new HDR plan was generated for each patient using the same method as for the PDR plan. The procedure was intended to achieve the same D90 high-risk clinical target volume with HDR as with PDR planning after conversion into dose equivalent per 2 Gy fractions (EQD2) following linear-quadratic model. Plans were compared for dosimetric variables. RESULTS: As per study's methodology, the D90 high-risk clinical target volume was strictly identical between PDR and HDR plans: 91.0 Gy (interquartile: 86.0-94.6 Gy). The median D98 intermediate-risk clinical target volume was 62.9 GyEQD2 with HDR vs. 65.0 GyEQD2 with PDR (p < 0.001). The median bladder D2cc was 65.6 GyEQD2 with HDR, vs. 62 GyEQD2 with PDR (p = 0.004). Doses to the rectum, sigmoid, and small bowel were higher with HDR plans with a median D2cc of 55.6 GyEQD2 (vs. 55.1 GyEQD2, p = 0.027), 67.2 GyEQD2 (vs. S 64.7 GyEQD2, p = 0.002), and 69.4 GyEQD2 (vs. 66.8 GyEQD2, p = 0.014), respectively. For organs at risk (OARs), the effect of radiobiological weighting depended on the dose delivered. When OARs BT contribution to D2cc doses was <20 GyEQD2, both BT modalities were equivalent. OARs EQD2 doses were all higher with HDR when BT contribution to D2cc was ≥20 GyEQD2. CONCLUSION: Both BT modalities provided satisfactory target volume coverage with a slightly higher value with the HDR technique for OARs D2cc while intermediate-risk clinical target volume received higher dose in the PDR plan. The radiobiological benefit of PDR over HDR was predominant when BT contribution dose to OARs was >20 Gy.

Simulated dosimetric impact of online replanning for stereotactic body radiation therapy of lymph node oligometastases on the 1.5T MR-linac.

PURPOSE: Online 1.5T MR imaging on the MR-linac gives better target visualization compared to CBCT and facilitates online adaptive treatment strategies including daily replanning. In this simulation study, the dosimetric impact of online replanning was investigated for SBRT of lymph node oligometastases as a method for correcting for inter-fraction anatomical changes. METHODS: Pre-treatment plans were created for 17 pelvic and para-aortic lymph nodes, with 3 and 8 mm PTV margins reflecting our clinical practice for lymph nodes with good and poor visibility on CBCT. The dose-volume parameters of the pre-treatment plans were evaluated on daily anatomy as visible on the repeated MRIs and compared to online replanning. RESULTS: With online MRI-based replanning significant dosimetric improvements are obtained for the rectum, bladder, bowel and sigmoid without compromising the target dose. The amount of unintended violations of the dose constraints for target and surrounding organs could be reduced by 75% for 8 mm and 66% for 3 mm PTV margins. CONCLUSION: The use of online replanning based on the actual anatomy as seen on repeated MRI compared to online position correction for lymph node oligometastases SBRT gives beneficial dosimetric outcomes and reduces the amount of unplanned violations of dose constraints.

Evaluation of offline adaptive planning techniques in image-guided brachytherapy of cervical cancer.

Modern three-dimensional image-guided intracavitary high dose rate (HDR) brachytherapy is often used in combination with external beam radiotherapy (EBRT) to manage cervical cancer. Intrafraction motion of critical organs relative to the HDR applicator in the time between the planning CT and treatment delivery can cause marked deviations between the planned and delivered doses. This study examines offline adaptive planning techniques that may reduce intrafraction uncertainties by shortening the time between the planning CT and treatment delivery. Eight patients who received EBRT followed by HDR boosts were retrospectively reviewed. A CT scan was obtained for each insertion. Four strategies were simulated: (A) plans based on the current treatment day CT; (B) plans based on the first fraction CT; (C) plans based on the CT from the immediately preceding fraction; (D) plans based on the closest anatomically matched previous CT, using all prior plans as a library. Strategies B, C, and D allow plans to be created prior to the treatment day insertion, and then rapidly compared with the new CT. Equivalent doses in 2 Gy for combined EBRT and HDR were compared with online adaptive plans (strategy A) at D90 and D98 for the high-risk CTV (HR-CTV), and D2 cc for the bladder, rectum, sigmoid, and bowel. Compared to strategy A, D90 deviations for the HR-CTV were -0.5 ± 2.8 Gy, -0.9 ± 1.0 Gy, and -0.7 ± 1.0 Gy for Strategies B, C, and D, respectively. D2 cc changes for rectum were 2.7 ± 5.6 Gy, 0.6 ± 1.7 Gy, and 1.1 ± 2.4 Gy for Strategies B, C, and D. With the exception of one patient using strategy B, no notable variations for bladder, sigmoid, and bowel were found. Offline adaptive planning techniques can shorten time between CT and treatment delivery from hours to minutes, with minimal loss of dosimetric accuracy, greatly reducing the chance of intrafraction motion.

Dose-response relationships of the sigmoid for urgency syndrome after gynecological radiotherapy.

PURPOSE: To find out what organs and doses are most relevant for 'radiation-induced urgency syndrome' in order to derive the corresponding dose-response relationships as an aid for avoiding the syndrome in the future. MATERIAL AND METHODS: From a larger group of gynecological cancer survivors followed-up 2-14 years, we identified 98 whom had undergone external beam radiation therapy but not brachytherapy and not having a stoma. Of those survivors, 24 developed urgency syndrome. Based on the loading factor from a factor analysis, and symptom frequency, 15 symptoms were weighted together to a score interpreted as the intensity of radiation-induced urgency symptom. On reactivated dose plans, we contoured the small intestine, sigmoid colon and the rectum (separate from the anal-sphincter region) and we exported the dose-volume histograms for each survivor. Dose-response relationships from respective risk organ and urgency syndrome were estimated by fitting the data to the Probit, RS, LKB and gEUD models. RESULTS: The rectum and sigmoid colon have steep dose-response relationships for urgency syndrome for Probit, RS and LKB. The dose-response parameters for the rectum were D50: 51.3, 51.4, and 51.3 Gy, γ50 = 1.19 for all models, s was 7.0e-09 for RS and n was 9.9 × 107 for LKB. For Sigmoid colon, D50 were 51.6, 51.6, and 51.5 Gy, γ50 were 1.20, 1.25, and 1.27, s was 2.8 for RS and n was 0.079 for LKB. CONCLUSIONS: Primarily the dose to sigmoid colon as well as the rectum is related to urgency syndrome among gynecological cancer survivors. Separate delineation of the rectum and sigmoid colon in order to incorporate the dose-response results may aid in reduction of the incidence of the urgency syndrome.

Deformable image registration-based contour propagation yields clinically acceptable plans for MRI-based cervical cancer brachytherapy planning.

PURPOSE: To study the dosimetric impact of deformable image registration-based contour propagation on MRI-based cervical cancer brachytherapy planning. METHODS AND MATERIALS: High-risk clinical target volume (HRCTV) and organ-at-risk (OAR) contours were delineated on MR images of 10 patients who underwent ring and tandem brachytherapy. A second set of contours were propagated using a commercially available deformable registration algorithm. "Manual-contour" and "propagated-contour" plans were optimized to achieve a maximum dose to the most minimally exposed 90% of the volume (D90) (%) of 6 Gy/fraction, respecting minimum dose to the most exposed 2cc of the volume (D2cc) OAR constraints of 5.25 Gy and 4.2 Gy/fraction for bladder and rectum/sigmoid (86.5 and 73.4 Gy equivalent dose in 2 Gy fractions [EQD2] for external beam radiotherapy [EBRT] + brachytherapy, respectively). Plans were compared using geometric and dosimetric (total dose [EQD2] EBRT + brachytherapy) parameters. RESULTS: The differences between the manual- and propagated-contour plans with respect to the HRCTV D90 and bladder, rectum, and sigmoid D2cc were not statistically significant (per-fraction basis). For the EBRT + brachytherapy course, the D2cc delivered to the manually contoured OARs by the propagated-contour plans ranging 98-107%, 95-105%, and 92-108% of the dose delivered by the manual-contour plans (max 90.4, 70.3, and 75.4 Gy for the bladder, rectum, and sigmoid, respectively). The HRCTV dose in the propagated-contour plans was 97-103% of the dose in the manual-contour plans (maximum difference 2.92 Gy). Increased bladder filling resulted in increased bladder dose in manual- and propagated-contour plans. CONCLUSIONS: When deformable image registration-propagated contours are used for cervical brachytherapy planning, the HRCTV dose is similar to the dose delivered by manual-contour plans and the doses delivered to the OARs are clinically acceptable, suggesting that our algorithm can replace manual contouring for appropriately selected cases that lack major interfractional anatomical changes.

Clinical outcomes with MRI-guided image-based brachytherapy in cervical cancer: An institutional experience.

PURPOSE: To evaluate the long-term disease control and toxicity to the organs at risk after dose-escalated image-based adaptive brachytherapy (BT) in cervical cancer. METHODS AND MATERIALS: Sixty patients of cervical cancer were treated with external radiotherapy 46 Gy in 23 fractions with weekly cisplatin and MRI-guided BT 7 Gy × 4 fractions with a minimum dose of 85.7 Gy (EQD2) to the high-risk clinical target volume (HRCTV). The BT dose was initially prescribed to point A and plans were optimized to ensure coverage of both point A and HRCTV while maintaining doses to the organs at risk within the recommended constraints. Patients were followed up clinically every three months for the first two years and six months thereafter. Toxicity scoring for urinary and bowel symptoms was done using CTCAE version 3.0. RESULTS: The mean doses to the point A and D90 HRCTV were 85.5 (±2.75) Gy and 98.4 (±9.6) Gy EQD2 respectively. The mean 2 cc EQD2, the bladder, rectum, and sigmoid were 90.6 Gy, 70.2 Gy, and 74.2 Gy respectively. The overall survival at a median followup of 49.8 months was 91.66%. Six (10%) patients developed grade 3 gastrointestinal toxicity. One patient developed grade 3 bladder toxicity. The incidence of bladder, rectal, and sigmoid toxicity increased significantly with doses >85 Gy, 66 Gy, and >71 Gy EQD2 respectively. CONCLUSIONS: While the incidence of grade 3-4 toxicity was low (8.3% for gastrointestinal toxicity and 1.6% for bladder), the threshold for development of grade 1-2 bladder and rectal toxicity was lower than the doses recommended by the GEC-ESTRO group. By adhering to volume-based prescriptions, there is scope of further reduction in toxicity to organs at risk.

Sigmoid colon perforation after postoperative hypofractionated intensity-modulated radiation therapy in a cervical cancer patient.

BACKGROUND: Radiation-induced complication occurs in two phases: acute and chronic toxicities. Bowel perforation is regarded as a chronic toxicity associated with injury to vascular and connective tissue. It is usually noted a few months to several years after radiation treatment (RT). CASE: Herein, we present a case of sigmoid colon perforation relatively early after completion of RT. A 70-year-old woman was treated with laparoscopic radical hysterectomy and postoperative hypofractionated intensity-modulated RT for clinical stage IB1 cervical cancer. RT was delivered with a total dose 4000 cGy in 16 fractions to whole pelvis once a day. Sigmoid colon perforation was found 40 days after completion of RT without any typical signs of perforated viscera. Emergency exploratory laparotomy was performed. Pathology revealed chronic inflammation with mucosal ulceration and submucosal fibrosis, a typical radiation effect. CONCLUSION: Although the cause of perforation remains unclear, early-onset sigmoid colon perforation as an effect of irradiation can occur. We should keep in mind the possibility of perforation in the care of radiated patients who present abdominal pain with atypical presentation regardless of satisfaction of dose constraint for radiotherapy.

Evaluation of interfractional variation of organs and displacement of catheters during high-dose-rate interstitial brachytherapy for gynecologic malignancies.

PURPOSE: To investigate the dosimetric effects due to interfractional changes in catheter position and variation in patient's anatomy during the course of interstitial high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A total of 15 patients with either cervical or vaginal cancer underwent interstitial HDR brachytherapy. Interstitial catheters and fiducials were placed under fluoroscopy and intraoperative 3T MRI to confirm the desired catheter placement for adequate target volume coverage. Single plan was generated from first-fraction CT fused with the MRI and used for all fractions of treatment. CT image was acquired before each treatment and registered to the first-fraction CT. Displacement of fiducials and catheters was calculated for each fraction and its effects on dosimetric parameters such as dose covering 90% for high-risk clinical target volume and intermediate-risk clinical target volume and dose to the 2 cm3 of the volume for bladder, rectum, sigmoid, and bowel were studied. RESULTS: Average movements of fiducials and catheters were 1.6 mm (range: 0.1-7.1 mm) and 1.7 mm (range: 0.1-4.5 mm), respectively. Overall, deviation of the delivered dose to the target in each fraction was insignificant for all patients (p-value: 0.66 for high-risk clinical target volume and 0.87 for intermediate-risk clinical target volume). The mean dose to organs at risk showed maximum difference up to 0.9, 2.7, 1.6, and 2.1 Gy for bladder, rectum, sigmoid, and bowel, respectively (p-value: 0.88, 0.34, 0.68, and 0.85 for bladder, rectum, sigmoid, and bowel, respectively). CONCLUSIONS: The interfractional dosimetric variation for both target and organs at risk was within clinically acceptable limit throughout the entire course of interstitial HDR-Syed brachytherapy. Only 6% of cases performed replanning, which could be readily identified using CT imaging.

Dosimetric analysis and preliminary clinical result of image-guided brachytherapy with or without hybrid technique for cervical cancer using VariSource titanium ring applicator with "Siriraj Ring Cap".

PURPOSE: Titanium ring cap applicator (VariSource) was applied in treating cervical cancer patients by using image-guided brachytherapy (IGBT). However, its sizes appeared to be relatively large for most of our patients. Thus, we have developed a specific applicator "Siriraj Ring Cap," which is slightly smaller and more suitable for our patients. This study was to evaluate effectiveness of this equipment. METHODS AND MATERIALS: Locally advanced cervical cancer patients were treated with external beam radiation therapy with or without concomitant chemotherapy. Siriraj Ring Cap was applied in all of the patients for at least one fraction. Dosimetric analysis was performed in each fraction of IGBT. Clinical outcomes of these patients were evaluated. RESULTS: Twenty-nine patients with 117 dosimetric planning were evaluated between January and December of 2014. Siriraj Ring Cap was fit to all patients in this study. By using this applicator, radiation doses to the targets (D90 high-risk clinical target volume and D90 intermediate-risk clinical target volume) were higher in each fraction. There were no statistically differences of radiation doses to the bladder, rectum, sigmoid colon, and small bowel. Within 2-year followup, 3 patients (10.3%) developed locoregional recurrence. Two-year disease-free survival and overall survival were 75.9% and 89.7%, respectively. According to RTOG/EORTC complication criteria, Grade 1, 2, and 3 gastrointestinal complications were developed in 2 (6.9%), 4 (13.8%), and 1 (3.4%) patients, respectively. For genitourinary complications, 3 patients (10.3%) and 1 patient (3.4%) had Grades 1 and 2, respectively. CONCLUSIONS: Siriraj Ring Cap is feasible for IGBT in cervical cancer patients with narrow vagina. Dosimetry and clinical outcomes were satisfactory by using our specific applicator.

Effect of bladder distension on doses to organs at risk in Pulsed-Dose-Rate 3D image-guided adaptive brachytherapy for locally advanced cervical cancer.

PURPOSE: To evaluate the impact of bladder distension on doses to organs at risk in patients treated with 3D image-guided adaptive pulsed-dose-rate (PDR) brachytherapy (BT) for locally advanced cervical cancer. METHODS AND MATERIALS: Twenty-two patients who had previously been treated by external beam radiation therapy (EBRT), underwent BT treatment planning to a pelvic MRI (or a CT scan in case of contraindication) after their bladder was filled with 100 cc of physiological saline (full bladder). This was immediately followed by a CT scan after emptying of the bladder. A fusion of these two examinations was conducted, and the dosimetry was duplicated for the study with an empty bladder. Equieffective doses of 2 Gy per fraction from EBRT and BT of bladder/rectum/sigmoid colon/small bowel were compared. RESULTS: A full bladder condition was found to be non-inferior in terms of the bladder D2cc (a difference of -0.9 Gy; 97.5% CI [-∞; 2.6]), and it resulted in a reduction in the bladder D0.1cc (p = 0.038). Bladder expansion resulted in a significant reduction of maximum doses received by the small bowel, both in terms of the D0.1cc (51.2 Gy vs. 63.4 Gy, p < 0.001) and the D2cc (48.5 Gy vs. 53.6 Gy, p < 0.001). A negative correlation was seen between the difference in the small bowel D2cc and the body mass index; (r = -0.55; p = 0.008). No differences were noted in regard to doses to the rectum and sigmoid colon. CONCLUSIONS: Bladder distension with 100 cc of physiological saline can reduce maximum doses received by the small bowel without the alteration of the doses received by the other organs at risk during a 3D image-guided adaptive PDR BT for locally advanced cervical cancer. However, the maintenance of a predefined bladder volume is difficult to achieve with PDR BT, whereas it could be easily managed before each session in case of high-dose-rate BT.

Rectum and bladder spacing in cervical cancer brachytherapy using a novel injectable hydrogel compound.

PURPOSE: The aim of this study was to evaluate injection of a novel hydrogel (TraceIT; Augmenix, Waltham, MA) between the cervix, rectum, and bladder in female cadavers compared with, and in addition to, the current standard of gauze packing, for organ-at-risk sparing in cervical cancer brachytherapy planning. METHODS AND MATERIALS: This brachytherapy cadaver study used T2-weighted MRI and CT imaging to compare three scenarios: (1) gauze packing alone, (2) hydrogel injection placed in the cervical fornices and rectovaginal septum, and (3) gauze packing in conjunction with hydrogel injection. Hydrogel distribution was evaluated. Doses to 2 cm3 volumes (D2cc) for the rectum, bladder, and sigmoid were collected. Statistical significance (p < 0.05) was evaluated using a two-tailed paired t test. RESULTS: Hydrogel was successfully injected to space the bladder and rectum from the cervix in all five cadavers. The spacer was easily identifiable on both CT and MRI. The use of hydrogel in addition to packing resulted in a 22% decrease in rectum D2cc dose (p = 0.02), a 10% decrease in bladder D2cc (p = 0.27), and no change in sigmoid D2cc dose. No difference was observed between hydrogel only vs. gauze packing only. CONCLUSIONS: Our results revealed a significant clinically meaningful decrease in rectal D2cc associated with the use of hydrogel in addition to gauze packing-TraceIT hydrogel holds promise as a spacer in cervical cancer therapy.

Point A vs. HR-CTV D90 in MRI-based cervical brachytherapy of small and large lesions.

PURPOSE: To evaluate the dosimetric benefits of MRI-based brachytherapy in small and large high-risk clinical target volume (HR-CTV) in cervical cancer. METHODS AND MATERIALS: Twenty-eight fractions obtained from sixteen cervical cancer patients treated with MRI-based high-dose-rate brachytherapy with standard tandem and ovoid applicators were used; original fractions were optimized to HR-CTV D90. Fractions were separated based on the median volume into small and large (HR-CTV <25 cm3 or >25 cm3) lesion groups. Retrospective plans prescribed to Point A were created for each fraction. D0.1 cc, D2 cc, and International Commission of Radiation Unit and Measurements (ICRU) points were used to compare Point A vs. HR-CTV D90 plans for bladder, rectum, and sigmoid. RESULTS: In the small lesion group, Point A plans vs. HR-CTV D90 plans had significantly higher D0.1 cc, D2 cc, and ICRU points for bladder, rectum, and sigmoid (p < 0.05). In the large lesion group, there was no significant difference between Point A and HR-CTV D90 plans for D0.1 cc, D2 cc, and ICRU points to the organs at risk (OARs). CONCLUSIONS: The dosimetric advantages to OARs offered by MRI-based brachytherapy with prescription to HR-CTV D90 compared to Point A is most distinct for patients with smaller HR-CTV (<25 cm3). This study demonstrates sufficient tumor coverage with lower doses to OARs in HR-CTV D90 vs. Point A plans in the small lesion group. These improvements were not seen in the large lesion group, indicating a lesser dosimetric advantage of HR-CTV D90 compared to Point A planning when the cervical lesion is >25 cm3. Incorporation of interstitial needles for patients with larger HR-CTV is likely the best method to decrease dose to OARs and improve tumor coverage.

Long term experience with 3D image guided brachytherapy and clinical outcome in cervical cancer patients.

BACKGROUND AND PURPOSE: To report our 10years' experience and learning curve of the treatment of cervical cancer patients with chemo radiotherapy and MRI (or CT in 9 selected patients) guided brachytherapy using pulsed dose rate (PDR) brachytherapy (BT). METHODS AND MATERIALS: Hundred and seventy consecutive patients with cervical cancer FIGO stage IB-IVB (without metastases beyond the para-aortic nodal region) were treated in our institute between 2002 and 2012. Patients received external beam radiotherapy (nodal boost to the lymph nodes positive at diagnosis)±chemotherapy followed by a pulsed or low dose rate brachytherapy boost. MRI (or CT) images were taken with the applicator in situ. The first 16 patients were treated according to X-ray-based plans, optimized on MRI. High-risk CTV, intermediate-risk CTV, bladder, rectum and sigmoid were retrospectively contoured according to the GEC-ESTRO recommendations. In all other patients, treatment plans were optimized after delineation of the target volumes and organs at risk at MRI (or CT). Doses were converted to the equivalent dose in 2Gy (EQD2) by applying the linear quadratic model. The median age of the patients was 55years (range 16-88). 41% had stage III or IV disease. Of the 170 patients, 91 patients had on imaging metastatic lymph nodes at diagnosis (62 patients pelvic lymph node involvement and 29 para-aortic). In 27 (16%) patients the intracavitary technique was combined with interstitial brachytherapy. RESULTS: The mean D90 and D100 for the high-risk CTV were 84.8±8.36Gy and 67.5±6.29Gy for the entire patient group. Mean D90 and D100 values for the IR CTV were 68.7±5.5Gy and 56.5±6.25Gy. There was an important learning curve between both patient groups, with an increase in mean D90 of 75.8Gy for the first 16 patients compared to 85.8Gy for the second group. At the same time, the mean dose to 2cm3 of bladder and sigmoid decreased from 86.1Gy to 82.7Gy and from 70Gy to 61.7Gy, respectively. At a median follow-up of 37months (range 2-136months), local control rate for all patients was 96%, the regional control (pelvic and para-aortic) rate 81% and crude disease free survival rate 55%. The overall survival at 5years is 65%. The higher dose to the target volume resulted in an increase in local control from 88% in the first 16 patients compared to 97% in the second patient group. Regarding late toxicity, 21 patients (12%) presented grade 3-4 late morbidity. Rectal, urinary, sigmoid and vaginal morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006). CONCLUSION: Although the majority of the patients presented with locally advanced carcinoma, excellent local and regional control rates were achieved. Rectal, urinary, sigmoid and vaginal grade 3-4 morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006).