Intermediate-risk Clinical Target Volume Research Articles

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes

ObjectiveVaginal carcinoma is a rare malignancy accounting for 1–2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy–chemotherapy followed by interventional radiotherapy is considered a valid alternative....

High-dose-rate brachytherapy in uterine cervix carcinoma: a comparison of dosimetry and clinical outcomes among three fractionation schedules.

To assess the differences among three dose-fractionation schedules of image-guided adaptive brachytherapy (IGABT) in cervical squamous cell carcinoma (CSCC) by comparing the dosimetry and clinical outcomes. Forty-five patients with CSCC who underwent chemoradiotherapy and IGABT were retrospectively enrolled and divided into three groups based on their dose-fractionation schedules of brachytherapy as: Group-5.5 (5.5 Gy × 6 fractions), Group-6.0 (6.0 Gy × 5 fractions), and Group-7.0 (7.0 Gy × 4 fractions). The analyzed dose-volume histogram parameters included D90% and D98% of the high-risk clinical target volume (HR-CTV), D90% and D98% of intermediate-risk clinical target volume (IR-CTV), and D0.1cc and D2cc of the organs-at-risk (OARs, namely the bladder, rectum, sigmoid and small intestine). Furthermore, the therapeutic efficacy and late toxicities were also compared among the three groups. The doses of HR-CTV and IR-CTV in Group-5.5 were found to be the highest among the three groups, followed by those in Group-6.0. Significant differences were found for the doses of HR-CTV between Group-5.5 and the other groups. There were no significant differences in the bladder, sigmoid and small intestine dose among the three groups. However, Group-6.0 yielded the lowest rectum received doses, with a significant difference in D0.1cc being detected between Group-6.0 and Group-5.5. The median follow-up time was 30.08 months [range, 6.57-46.3]. The numbers of patients with complete response in Group-5.5, Group-6.0 and Group-7.0 were 13, 14 and 14, respectively (P > 0.05). In regard to the toxicitiy, the incidence of radiation cystitis and proctitis in Group-6.0 was lower than that in Group-5.5 and Group-7.0 (P > 0.05). The dose-fractionation schedule of 6.0 Gy × 5 fractions provided the most beneficial effects with relatively low OARs doses, suggesting that this dose-fractionation schedule should be prioritized in the clinical application of brachytherapy in cervical cancer.

Are active dwell positions always necessary in the ring/ovoids channel of the cervical applicator in the intracavitary-interstitial brachytherapy of cervical cancer?

To compare dosimetric parameters of brachytherapy (BT) treatment plans made with or without active source positions of the ring/ovoid (R/O) applicator in locally advanced cervical cancer patients. Sixty patients with cervical cancer without vaginal involvement were selected for the study, who received intra-cavitary/interstitial BT. For each patient, two plans with and without active source dwell positions in R/O were created, using the same dose-volume constraints. EQD2 total doses from external beam and BT of target volumes and organs at risk (OARs) between the competing plans were compared. There was no significant difference in the dose of high-risk clinical target volume (HR-CTV) and gross tumor volume (GTV) between the plans with inactive vs. active R/O. The mean D98 of intermediate-risk clinical target volume (IR-CTV) was significantly lower with inactive R/O; however, the GEC-ESTRO (EMBRACE II study) and ABS criteria were fulfilled in 96% in both plans. There was no difference in dose homogeneity, but conformity of the plans with inactive R/O was higher. Doses to all OARs were significantly lower in plans without R/O activation. While all the plans without R/O activation fulfilled the recommended dose criteria for OARs, it was less achievable with R/O activation. Inactivation of R/O applicator results in similar dose coverage of the target volumes with lower doses to all OARs, as activation of R/O in cervix cancer patients when HR-CTV does not extend to R/O applicator. The use of active source positions in R/O shows worse performance regarding the fulfilment of the recommended criteria for OARs.

Inter-observer variation of target volume delineation for CT-guided cervical cancer brachytherapy.

Delineation is a critical and challenging step in radiotherapy planning. Differences in delineation among observers are common, despite the presence of contouring guidelines. This study aimed to identify the inter-observer variability in the target volume delineation of computed tomography (CT)-guided brachytherapy for cervical cancer. Four radiation oncologists (ROs) with different expertise levels delineated high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) according to GYN GEC-ESTRO recommendations, in a blinded manner on every CT set of ten locally advanced cervical cancer cases. The most experienced RO's contours were determined as the index and used for comparison. Dice similarity coefficient (DSC) and pairwise Hausdorff distance (HD) metrics were applied to compare the overlap and gross deviations of all contours. Median DSC for HR-CTV and IR-CTV were 0.73 and 0.76, respectively, and a good concordance was achieved for both in majority of contours. While there was no difference in DSC measurements for HR-CTV among the three ROs, RO-3 provided improved DSC values for IR-CTV (p = 0.01). Median HD95 was 5.02 mm and 6.83 mm, and median HDave was 1.69 mm and 2.21 mm for HR-CTV and IR-CTV, respectively. There was no significant difference among ROs in HR-CTV for HD95 or HDave; however, IR-CTV value was significantly improved according to RO-3 (p = 0.01). Case-by-case HD analysis showed no significant inter-observer variations, except for two cases. The inter-observer agreement is generally high for target volumes in CT-guided brachytherapy for cervical cancer. The agreement is lower for IR-CTV than HR-CTV. The individual characteristics of each case and different expertise levels of the ROs may have caused the differences. Despite the good concordance for delineation, dosimetric consequences can still be clinically significant.

PHSOR08 Presentation Time: 1:05 PM: Retrospective Comparison of TG43 vs. AcurosBV Model-Based Dose Calculation Algorithm (MBDCA) in Cervical Cancer Patients Treated with HDR Brachytherapy Boost

<h3>Purpose</h3> To evaluate dosimetric impact of heterogeneity from applicators and patient tissue between plans treated with tandem and ovoid applicators with interstitial needles calculated with the TG43 formalism and Acuros®BV MBDCA (Varian Medical Systems (VMS), Inc). <h3>Materials Methods</h3> For this retrospective analysis, HDR plans prescribing 5.5 Gy to high-risk clinical target volume (CTV) D_90% for locally advanced cervical cancer patients were selected. The implants consisted of tandem and ovoid (T&O) with or without interstitial needles, treated using a GammaMedPlus™ iX afterloader with a ¹⁹²Ir source. Implants were stabilized by Alatus vaginal balloons (Angiodynamics) filled with a 5% IsoVue to 95% saline ratio. Imaging for applicator digitization and planning was done using either Acuity CBCT (VMS, Inc), or AIRO CT (BrainLab AG). For standard TG43 clinical dose calculation, all applicators were manually digitized on the CT or CBCT images. Solid renderings of Fletcher-Suit Delclos applicators included in BrachyVision (VMS, Inc) were matched to those used clinically. The composition of the applicators was assigned from the applicator library. Titanium needles were left unchanged, as there is no solid applicator model available. The dose was recalculated using Varian's Acuros®BV 13.5 and dose-to-medium-in-medium (D_m,m) was reported. Equivalent dose in 2 Gy per fraction (EQD2) values for targets and organs at risk (OARs) were compared between TG43 formalism and the Acuros®BV plans. D_90% and D_98% values were reported for the high and intermediate-risk CTVs, and D_2cm3 values were reported for OARs including bladder, rectum, sigmoid, bowel, and vagina. In a separate analysis, we compared dosimetric endpoint differences between TG43 and Acuros®BV plans imaged with CT versus CBCT, and also between plans with T&O applicators with and without needles. Linear regression and Bland Altman Analysis (BAA) were performed between the two plans to show the correlation and dosimetric differences between both methods. <h3>Results</h3> Thirty-two patients with a total of 156 fractions were included in this study, 70 planned on CBCT, and 86 planned on AIRO CT. Consistently, Acuros®BV plans showed lower dosimetric values for all plans compared to TG43. The average ± standard deviation of dosimetric reduction in D_90% was 4.33 ± 0.09% (0.41 ± 0.13 Gy) for CTV_HR and 4.12 ± 0.09% (0.21 ± 0.07Gy) for CTV_IR . Fig.1 shows an example BAA plot for differences between TG43 and Acuros®BV D_90% for the targets. The reduction to OARs D_2cm3 was: 4.99 ± 0.15% (0.34 ± 0.17 Gy) for bladder, 7.87 ± 0.16% (0.20 ± 0.09 Gy) for rectum, 5.79 ± 0.17% (0.21 ± 0.09 Gy) for sigmoid, 6.91 ± 0.14% (0.25 ± 0.13 Gy) for bowel, and 4.55 ± 0.14% (0.46 ± 0.27 Gy) for vagina. There was no statistically significant difference between TG43 and Acuros®BV plans calculated on CBCT versus CT images (p value = 0.24). A set of 5 patients with a total of 24 fractions planed with T&O applicators without needles was used for comparison with plans with interstitial needles, and no statistically significant difference between TG43 and Acuros®BV plans was observed (p value = 0.35). <h3>Conclusion</h3> This large patient cohort study confirms that plans calculated using Acuros®BV MBDCA show a reduction in dose to all structures when compared to the standard TG43 formalism. This is expected mainly due to more photon attenuation by high-density material of the applicators, as well as tissue heterogeneities. Clinical implementation of Acuros®BV can be challenging due to increased calculation time, alteration of the clinical flow, and increased planning complexity. These factors must be evaluated, and further investigation should be conducted in order to understand the effects of its utilization as a primary dose calculation method.

GEC-ESTRO (ACROP)–ABS–CBG Consensus Brachytherapy Target Definition Guidelines for Recurrent Endometrial and Cervical Tumors in the Vagina

Representatives from the Gynecologic Groupe European de Curietherapie-European Society for Radiation Therapy and Oncology (GYN GEC-ESTRO), the American Brachytherapy Society (ABS), and the Canadian Brachytherapy Group (CBG) met to develop international consensus recommendations for target definitions for image-guided adaptive brachytherapy for vaginal recurrences of endometrial or cervical cancer. Seventeen radiation oncologists and 2 medical physicists participated. Before an in-person meeting each participant anonymously contoured 3 recurrent endometrial/cervical cancer cases. Participants contoured the residual gross primary tumor volume (GTV-Tres), a high-risk clinical target volume (CTV-THR), and an intermediate-risk clinical target volume (CTV-TIR), on T2-weighted magnetic resonance images (MRIs). All contours were drawn using Falcon EduCase. Contours were reviewed at an in-person meeting during which a consensus document was created defining agreed-upon target definitions (Trial 1). After establishing these definitions, the group was sent one of the cases again (recurrent cervical cancer vaginal recurrence) and asked to contour the targets again (Trial 2). The Computerized Environment for Radiation Research (CERR) software (The Mathworks, Natwick, MA) was used to analyze the contours. Kappa statistics were generated to assess level of agreement between contours. A conformity index (CI), defined as the ratio between the intersection and union volume of a given pair of contours, was calculated. A simultaneous truth and performance level estimation (STAPLE) contour was created for the CTV-THR and CTV-TIR for the postmeeting case. Consensus definitions for GTV-Tres, CTV-THR, and CTV-TIR were established. Kappa statistics (Trial 1/Trial 2) for GTV-Tres, CTV-THR, and CTV-TIR were 0.536/0.583, 0.575/0.743 and 0.522/0.707. Kappa statistics for Trial 2 for the CTV-THR and CTV-TIR showed "substantial" agreement while the GTV-Tres remained at moderate agreement. This consensus provides recommendations to facilitate future collaborations for MRI-guided adaptive brachytherapy target definitions in endometrial/cervical vaginal recurrences.

Dose-effect relationship between dose-volume parameters of residual gross tumor volume and clinical prognosis in MRI-guided adaptive brachytherapy for locally advanced cervical cancer: asingle-center retrospective study.

To investigate the dose-effect relationship between the dose-volume parameters of residual gross tumor volume (GTVres) and clinical prognosis in MRI image-guided adaptive brachytherapy (IGABT) of patients with locally advanced cervical cancer in our center. The clinical data of 93patients with locally advanced cervical squamous cell cancer who received external beam radiotherapy (EBRT) combined with IGABT ± chemotherapy in our center were retrospectively analyzed. The disease stage, overall treatment time (OTT), chemotherapy, and the dose-volume parameters D90, D98, and D100 of GTVres, the intermediate-risk clinical target volume (CTVIR), and the high-risk clinical target volume (CTVHR) of the patients were statistically analyzed. Kaplan-Meier and uni- and multivariable Cox regression analyses were used to analyze 2‑year overall survival (OS), progression-free survival (PFS), and local control rate (LC). Aprobit model was employed to assess the dose-effect relationship between the volume and dose-volume parameters of GTVres and 2‑year OS, PFS, and LC. The median follow-up time was 19.6months and 2‑year OS, PFS, and LC were 79.6%, 68.8%, and 94.6%, respectively. CTVHR D90 was an independent influencing factor for 2‑year PFS (P = 0.041); GTVresBT1 volume was an independent factor for 2‑year OS, PFS, and LC (P < 0.001). The probit model showed that at GTVresBT1 volume < 32.86 cm3, the expected 2‑year LC was > 90%; at GTVres D98 > 129.12 GyEQD2, the expected 2‑year OS was > 90%. Both the volume and dose-volume parameters of GTVres are promising predictors in assessment of IGABT prognosis of cervical cancer.

Quantitative Comparisons of Deep-learning-based and Atlas-based Auto- segmentation of the Intermediate Risk Clinical Target Volume for Nasopharyngeal Carcinoma.

Manual segment target volumes were time-consuming and inter-observer variability couldn't be avoided. With the development of computer science, auto-segmentation had the potential to solve this problem. To evaluate the accuracy and stability of Atlas-based and deep-learning-based auto-segmentation of the intermediate risk clinical target volume, composed of CTV2 and CTVnd, for nasopharyngeal carcinoma quantitatively. A cascade-deep-residual neural network was constructed to automatically segment CTV2 and CTVnd by deep learning method. Meanwhile, a commercially available software was used to automatically segment the same regions by Atlas-based method. The datasets included contrast computed tomography scans from 102 patients. For each patient, the two regions were manually delineated by one experienced physician. The similarity between the two auto-segmentation methods was quantitatively evaluated by Dice similarity coefficient, the 95th Hausdorff distance, volume overlap error and relative volume difference, respectively. Statistical analyses were performed using the ranked Wilcoxon test. The average Dice similarity coefficient (±standard deviation) given by the deep-learning- based and Atlas-based auto-segmentation were 0.84 (±0.03) and 0.74 (±0.04) for CTV2, 0.79 (±0.02) and 0.68 (±0.03) for CTVnd, respectively. For the 95th Hausdorff distance, the corresponding values were 6.30±3.55 mm and 9.34±3.39 mm for CTV2, 7.09±2.27 mm and 14.33±3.98 mm for CTVnd. Besides, volume overlap error and relative volume difference could also predict the same situations. Statistical analyses showed significant difference between the two auto-segmentation methods (p<0.01). Compared with the Atlas-based segmentation approach, the deep-learning-based segmentation method performed better both in accuracy and stability for meaningful anatomical areas other than organs at risk.

Automatic segmentation of magnetic resonance images for high-dose-rate cervical cancer brachytherapy using deep learning.

Magnetic resonance (MR) imaging is the gold standard in image-guided brachytherapy (IGBT) due to its superior soft-tissue contrast for target and organs-at-risk (OARs) delineation. Accurate and fast segmentation of MR images are very important for high-quality IGBT treatment planning. The purpose of this work is to implement and evaluate deep learning (DL) models for the automatic segmentation of targets and OARs in MR image-based high-dose-rate (HDR) brachytherapy for cervical cancer. A 2D DL model using residual neural network architecture (ResNet50) was developed to contour the targets (gross tumor volume (GTV), high-risk clinical target volume (HR CTV), and intermediate-risk clinical target volume (IR CTV)) and OARs (bladder, rectum, sigmoid, and small intestine) automatically on axial MR slices of HDR brachytherapy patients. Furthermore, two additional 2D DL models using sagittal and coronal images were also developed. A 2.5D model was generated by combining the outputs from axial, sagittal, and coronal DL models. Similarly, a 2D and 2.5D DL models were also generated for the inception residual neural network (InceptionResNetv2 (InRN)) architecture. The geometric (Dice similarity coefficient (DSCs) and 95th percentile of Hausdorff distance (HD)) and dosimetric accuracy of 2D (axial only) and 2.5D (axial+sagittal+coronal) DL model generated contours were calculated and compared. The mean (range) DSCs of ResNet50 across all contours were 0.674 (0.05-0.96) and 0.715 (0.26-0.96) for the 2D and 2.5D models, respectively. For InRN, these were 0.676 (0.11-0.96) and 0.723 (0.35-0.97) for the 2D and 2.5D models, respectively. The mean HD of ResNet50 across all contours was 15.6mm (1.8-69mm) and 12.1mm (1.7-44mm) for the 2D and 2.5D models, respectively. The similar results for InRN were 15.4mm (2-68mm) and 10.3mm (2.7-39mm) for the 2D and 2.5D models, respectively. The dosimetric parameters (D90) of GTV and HR CTV for manually contoured plans matched better with the 2.5D model (p>0.6) and the results from the 2D model were slightly lower (p<0.08). On the other hand, the IR CTV doses (D90) for all of the models were slightly lower (2D: -1.3 to -1.5Gy and 2.5D: -0.5 to -0.6Gy) and the differences were statistically significant for the 2D model (2D: p<0.000002 and 2.5D: p>0.06). In case of OARs, the 2.5D model segmentations resulted in closer dosimetry than 2D models (2D: p=0.07-0.91 and 2.5D: p=0.16-1.0). The 2.5D DL models outperformed their respective 2D models for the automatic contouring of targets and OARs in MR image-based HDR brachytherapy for cervical cancer. The InceptionResNetv2 model performed slightly better than ResNet50.

Effect of applicator removal from target volume for cervical cancer patients treated with Venezia high-dose-rate brachytherapy applicator.

PurposeThe volume of Venezia applicator with vaginal caps can be relatively large compared to target volumes. This study investigated the dosimetric and radiobiological effects of applicator volume removal for cervical cancer patients treated with Venezia (VZ) and tandem and split-ring (TSR) applicators used in the clinic.Material and methodsA total of 40 patients (101 plans) with stage IIA-IIIC cervical cancer were retrospectively reviewed. Thirty patients were treated with VZ and ten patients were treated with TSR. Applicators were contoured on planning CTs where target contours were involved. Applicator contours were subtracted from the target contours. External beam radiation therapy (EBRT) and brachytherapy doses were calculated in biologically equivalent doses in 2 Gy fractions (EQD2) and combined using full parameter addition for dose-volume histogram (DVH) parameters of composited dose. D90%, D50%, V100%, V150%, V200%, and tumor control probability (TCP) were evaluated and compared for targets after applicator exclusion.ResultsThe average volume changes in gross tumor volume (GTV), high-risk clinical target volume (HR-CTV), and intermediate-risk clinical target volume (IR-CTV) after VZ applicator exclusion were 1.4 ±1.5 cm3, 15.7 ±6.6 cm3, and 33.8 ±15.1 cm3, respectively. VZ exclusion resulted in significant changes (p < 0.05) in small volume parameters (D50%) and high-dose parameters (V150% and V200%) for HR-CTV and IR-CTV. Dosimetric impact of TSR exclusion on targets was not significant. There was no significant change in TCP after applicator exclusion.ConclusionsVenezia applicator with vaginal caps has significant impact on small volume and high-dose DVH parameters of the target. Applicator contour exclusion is recommended for dosimetric evaluation when Venezia applicator is used.

Comparative dosimetry of brachytherapy treatment planning between a volume-based plan by CT and a point-based plan by TAUS in CT datasets for brachytherapy

Abstract Aim: To evaluate comparative dosimetry of brachytherapy treatment planning between a volume-based plan by computed tomography (CT) and a point-based plan by transabdominal ultrasound (TAUS) in CT datasets for brachytherapy. Materials and methods: From 2019 to 2021, 59 different datasets of CT images were collected from 38 patients treated by intracavitary brachytherapy with tandem ovoid or tandem ring applicators. At that time, TAUS was performed to prevent uterine perforation and to evaluate topography of the cervix during application. In volume-based planning by CT, the target dose was used to keep the dose at 90% of high-risk clinical target volume (HR-CTV), to give a dose of at least 7Gy, while in the point-based plan by TAUS, the target dose was used to keep the minimum dose to eight cervix reference points (measured by TAUS), to give a dose of at least 7Gy. The doses to targets and organs at risk were evaluated and compared between volume-based planning by CT and the point-based plan by TAUS. Results: Of 59 fractions, a tandem ovoid applicator was used in 48 fractions (81·3%). In the volume-based plan by CT, the mean doses to HR-CTV(D90), intermediate-risk clinical target volume (IR-CTV)(D90), bladder(D2cc), rectum(D2cc) and sigmoid colon(D2cc) were 7·0, 3·9, 4·9, 2·9 and 3·3 Gy, respectively, while in the point-based plan by TAUS, the mean doses to HR-CTV(D90), IR-CTV(D90), bladder(D2cc), rectum(D2cc) and sigmoid colon(D2cc) were 8·2, 4·6, 5·9, 3·4 and 3·9 Gy, respectively. The percentages of mean dose differences between TAUS and CT of HR-CTV(D90), IR-CTV(D90), bladder(D2cc), rectum(D2cc) and sigmoid colon(D2cc) were 17·7, 19·5, 20·5, 19·5, 21·3 and 19·8%, respectively. With the target dose to the point-based plan by TAUS (7 Gy to the cervix reference points), this was close to D98 of HR-CTV with a mean percentage of difference of 0·6%. Findings: The point-based plan by TAUS showed higher values to targets and organs at risk than the volume-based plan by CT. With the point-based plan by TAUS, it was close to D98 of HR-CTV.

Feasibility of Evaluating Result of Auto-segmentation of Target Volumes in Radiotherapy with Medical Consideration Index

To explore the feasibility of using the bidirectional local distance based medical similarity index (MSI) to evaluate automatic segmentation on medical images. Taking the intermediate risk clinical target volume for nasopharyngeal carcinoma manually segmented by an experience radiation oncologist as region of interest, using Atlas-based and deep-learning-based methods to obtain automatic segmentation respectively, and calculated multiple MSI and Dice similarity coefficient (DSC) between manual segmentation and automatic segmentation. Then the difference between MSI and DSC was comparatively analyzed. DSC values for Atlas-based and deep-learning-based automatic segmentation were 0.73 and 0.84 respectively. MSI values for them varied between 0.29~0.78 and 0.44~0.91 under different inside-outside-level. It is feasible to use MSI to evaluate the results of automatic segmentation. By setting the penalty coefficient, it can reflect phenomena such as under-delineation and over-delineation, and improve the sensitivity of medical image contour similarity evaluation.

Morbidity following image-guided brachytherapy for cervical cancer: Patient and treatment related factors

PurposeThis retrospective study aims to assess factors associated with the occurrence of toxicity after brachytherapy (BT), as boost after external beam radiotherapy (EBRT) for treatment of invasive cervix carcinoma. METHODS AND MATERIALSAll consecutive patients diagnosed with cervical carcinoma, and treated with concurrent radiochemotherapy from August 2017 to January 2020 were retrospectively included. An isodose conformation index (ICI) was developed to assess the percentage of the prescription isodose contained within the intermediate risk clinical target volume (IR-CTV). ResultsEighty-one patients with invasive cervix carcinoma from stage IB to stage IVa were included. Thirty-two (40%) and 49 (60%) patients were treated with Pulsed Dose Rate (PDR) and High Dose Rate (HDR) BT, respectively. Median follow-up was 19.6 months (5.6–41.2). The main factors associated with development of gastrointestinal toxicity were: the median volume of the prescription isodose (67.9cm[3] [37.6–92.9] vs. 49.1cm[3] [34.5–53.5], p = 0.05), the value of ICI (59% [51%-83%] vs. 86% [65%-96%], p = 0.01), the median equivalent dose delivered to the sigmoid (D2cc= 58.4 GyEQD2 [53.9–61.1] vs. 55.2 GyEQD2 [52.8–57.5], p = 0.06) and the median equivalent dose delivered to the IR-CTV (D90= 63.9 GyEQD2 [60.6–66.4] vs. 61.2 GyEQD2 [59.4–64.5], p = 0.03). The proportion of patients who received EBRT lymph node boost was higher in patients who developed urinary toxicity than in patients who did not (57.1% vs. 28.6%, p = 0.08). Anticoagulant (p = 0.02) and antiaggregant therapy (p = 0.01) were associated with occurrence of both urinary and gastrointestinal toxicity. ConclusionSOur study confirms the predictive value of irradiated volume in the occurrence of gastrointestinal toxicity, as well as the need for a better conformation to the target volume. Precautions should be considered in patients with vascular comorbidities.

The Relationship Between Late Morbidity and Dose-Volume Parameter of Rectum in Combined Intracavitary/Interstitial Cervix Cancer Brachytherapy: A Mono-Institutional Experience.

PurposeTo establish a dose volume–effect relationship for predicting late rectal complication (LRC) in locally advanced cervical cancer patients treated with external beam radiotherapy (EBRT) followed by combined intracavitary/interstitial brachytherapy (IC/IS-BT).Materials and MethodsA retrospective analysis was performed in 110 patients with locally advanced cervical cancer who underwent definitive radiotherapy combined with IC/IS-BT from July 2010 to September 2018. We report the 90% of the target volume receiving the minimum dose for high risk clinical target volume (HR-CTV D90) and intermediate risk clinical target volume (IR-CTV D90), and the minimum doses to the most exposed 0.1, 1, and 2 cm³ doses at the International Commission on Radiation Units and Measurements (DICRU) for organs at risk (OARs). The total dose of EBRT plus brachytherapy was transformed to the biologically equivalent dose in 2 Gy fractions (EQD2) with α/β value of 10 Gy for target, 3 Gy for organs at risk using the linear quadratic model. The morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria. The Probit model was used to establish a prediction model on rectum between the organs at risk for dose and LRC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of dose volume parameters for LRC.ResultsThe median follow-up time was 72.3 months. The mean ( ± standard deviation) , and DICRU values of rectum were 64.72 ± 7.47 GyEQD2, 70.18 ± 5.92 GyEQD2, 79.32 ± 7.86 GyEQD2, and 67.22 ± 7.87 GyEQD2, respectively. The Probit model showed significant relationships between , and the probability of grade1–4, grade 2–4 rectal events at 1 year, and between and the probability of grade2–4 rectal events at 3 and 5 years. The dose values for 10% complication rates (ED10) of were 74.18 (70.42–76.71) GyEQD2, 67.80 (59.91, 71.08) GyEQD2, 66.37 (52.00, 70.27) GyEQD2 for grade 2–4 with rectal morbidity at 1, 3, and 5 years, respectively.ConclusionOur study proved that were considered as useful dosimetric parameters for predicting the risk of grade1–4 and grade2–4 LRC at 1-year, and might be an indicator for predicting grade2-4 LRC at 3/5years. The patients with rectal >66.37–74.18 GyEQD2 should be closely observed for grade2–4 LRC.

Quantitative and qualitative application of clinical drawings for image-guided brachytherapy in cervical cancer patients.

PurposeClinical drawings are integral part of image-guided adaptive brachytherapy (IGABT) of cervical cancer. It was used in EMBRACE study protocol as a useful tool. In our study clinical drawings from EMBRACE study were modified to include scales in all the dimensions for more accurate representation of various tumor related volumes. The aim of the present study was to understand patterns of tumor regression and relationship between gross tumor at diagnosis (GTVD) and high-risk clinical target volume (CTV-THR)/intermediate-risk clinical target volume (CTV-TIR) in brachytherapy (BRT), using modified clinical drawings.Material and methods42 cervical cancer patients, staged as FIGO IIB-IIIB according to EMBRACE study, were enrolled. Advanced schematic 3D mapping diagram (3D-MD) in axial, coronal, and sagittal orientations, with a measurement scale (grid with 10 mm distance) for precise assessment and documentation was applied (through MRI at diagnosis and during brachytherapy). Dimensions, including height, width, and thickness as well as volumes (GTVD, CTV-THR and CTV-TIR) were compared both qualitatively and quantitatively.Results and conclusionsWe found qualitative and quantitative correlation of the dimensions of final CTV-THR with initial GTVD. Meticulous mapping of tumor volumes can provide useful insights to CTV-THR volume during brachytherapy.

Toxicity of Simultaneous Integrated Boost Intensity Modulated Radiation Therapy in Post-Operative Oral Cavity Cancer

To assess the acute toxicity of Simultaneous integrated boost intensity modulated radiation therapy (SIB-IMRT) in postoperative oral cavity cancers with intermediate risk features was the primary objective of this study. The secondary objectives were to assess late toxicity and efficacy. This was a prospective, interventional study conducted at a single center. Patient accrual was done from November 2017 to August 2018 and data was analyzed in November 2019. Patients of oral cavity carcinoma who underwent surgery and had at least one risk factor on histopathological evaluation i.e., T3/T4 stage, node positive without extra capsular extension, lymphovascular invasion (LVI), perineural invasion (PNI), close margin (<5 mm), depth of invasion ≥3 mm for tongue and ≥7 mm for buccal mucosa were included. All patients had indication for adjuvant RT alone without concurrent chemotherapy. Post-operative RT was delivered with SIB-IMRT technique using 6 MV X-rays on a Linear accelerator. A dose of 63.6 Gray (Gy) in 30 fractions was delivered to high risk clinical target volume (CTV), 54 Gy in 30 fractions to intermediate risk CTV and 51 Gy in 30 fractions to low risk CTV. Dose constraints for the spinal cord was Dmax ≤ 42Gy, PRV cord Dmax ≤ 48Gy, brainstem Dmax ≤50.4 Gy, each parotid Dmean ≤ 26 Gy. Weekly assessment was done during RT and acute radiation toxicities were recorded as per Radiation Therapy Oncology Group (RTOG) acute toxicity criteria in terms of oral mucositis (OM), skin toxicity and dysphagia. Subsequent visits were monthly for the first 3 months, 2 monthly for the next 6 months and 3 monthly thereafter. Clinical examination with an assessment of the late toxicity was done as per RTOG late morbidity scoring schema. Radiological imaging (CECT or MRI) was done at 3 months post RT. Statistical analysis was performed using statistical package for sciences (SPSS version 20.0). Survival analysis was done by Kaplan-Meier method with log rank test. A total of 30 patients were included in the study with a median age of 48.5 years (range 33-75 year). The frequency N (%) of primary site involved was tongue 13(43.33), buccal mucosa 12(40), alveolus 4 (13.33) and retromolar trigone 1 (3.33). All patients completed RT and the median duration of RT was 42 days [mean days 42.3±0.93]. Maximum acute grade ≤2 vs grade 3 oral mucositis was 46.67% vs 53.33%, skin toxicity was 86.67% vs 13.33 %, dysphagia was 66.67% vs 33.33% respectively. No patients had grade 4 or 5 acute toxicity. At a median follow up of 11 months [range 6-18 month], grade 1 late toxicities were 53.33% (subcutaneous toxicity) and 33.33% (xerostomia). Loco regional control was 96.67%. IMRT-SIB is safe in terms of acute toxicity however the short follow up duration limits assessment of late toxicity and locoregional control rates in post-operative oral cavity cancers with intermediate risk.Abstract 3966; TableRisk factor for adjuvant RTN (%)>pT316(53.33)p N+9(30)PNI+11(36.67)LVI+5(16.67)Close margin1(3.33)DOI20(66.67) Open table in a new tab

Assessing cumulative dose distributions in combined external beam radiotherapy and intracavitary brachytherapy for cervical cancer by treatment planning based on deformable image registration.

BackgroundThis study aimed to validate the feasibility of deformable image registration (DIR) in assessing the cumulative dose distributions in combined external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) for cervical cancer.MethodsThis retrospective study included 23 patients with stage IIB disease treated with combined EBRT to the whole pelvis (50.4 Gy in 28 fractions) using an intensity-modulated radiotherapy technique with 6-MV X-ray, followed by three-dimensional (3D) ICBT (28 Gy in 4 fractions). Tumor gross target volume at diagnosis (GTV-Tinit), tumor gross target volume before brachytherapy, high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), and parametrium and organs at risk were recontoured on computed tomography images of EBRT and ICBT, respectively. The dose-volume parameters were also determined. The DIR results were reviewed using MIM Maestro (Reg Review) and modified by function (Reg Refine). To evaluate the accuracy of DIR, DIR-based cumulative dose-volume histogram (DVH) parameters and simple DVH parameter addition were compared using Wilcoxon rank-sum tests.ResultsThe cumulative dose distributions of EBRT and four ICBT sessions were successfully illustrated using DIR. The mean tumor diameters were 68.35 cm3 at diagnosis and 29.63 cm3 at ICBT initiation. The mean tumor regression was 56.6%. The median minimum dose covering 90% (D90) of HR-CTV, GTV-Tinit, IR-CTV, and parametrium were 69.58±4.94, 68.81±7.98, 59.28±3.78, and 60.97±1.1 Gyα/β=10, respectively, for DIR and 69.11±5.68, 68.49±8.62, 58.89±3.59, and 61±1.49 Gyα/β=10, respectively, with conventional simple DVH parameter addition.No statistically significant differences in dosimetric parameters were observed between the two methods.ConclusionsAlthough there were limitations in the DIR accuracy, DIR-based dose accumulation was significantly beneficial in visually showing the cumulative dose distribution in the target area to clinicians in combined radiotherapy for cervical cancer in routine clinical practice.

Dose–effect response in image-guided adaptive brachytherapy for cervical cancer: A systematic review and meta-regression analysis

PurposeThis study aimed to integrate and update the dose–effect relationship between volumetric dose and local control for cervical cancer brachytherapy. Methods and MaterialsWe identified studies that reported high-risk clinical target volume (HR-CTV) D90 and local control probability by searching PubMed, Web of Science, and the Cochrane Library databases through Oct 27, 2019. The regression analyses were performed using a probit model between HR-CTV D90, D100, intermediate-risk clinical target volume (IR-CTV) D90, and dose to Point A vs. local control probability. Subgroup analyses were performed according to stratification: time of local control, income level of the country or region, stage of cancer, pathology, mean volume of HR-CTV, dose rate, image modality, concurrent chemoradiotherapy proportion, interstitial proportion, and mean overall treatment time. ResultsThirty-three studies encompassing 2893 patients were included. The probit model showed a significant relationship between the HR-CTV D90 value and the local control probability, p < 0.0001. The D90 corresponding to a probability of 90% local control was 83.7 GyEQD2,10 (80.6–87.8 GyEQD2,10). Of the 33 studies included in our analysis, eight studies, including 1172 patients, reported the IR-CTV D90 value, ranging from 59.1 GyEQD2,10 to 72.3 GyEQD2,10. The probit model also showed a significant relationship between the IR-CTV D90 value and the local control probability, p = 0.0464. The 60 GyEQD2,10 for IR-CTV D90 corresponded to an 86.1% local control probability (82.0%–89.8%). ConclusionsA significant dependence of local control on HR-CTV D90 and IR-CTV D90 was found. A tumor control probability of >90% can be expected at doses >84 GyEQD2,10 and 69 GyEQD2,10, respectively, based on an updated meta-regression analysis.

Analysis of dose-effect relationship between DVH parameters and clinical prognosis of definitive radio(chemo)therapy combined with intracavitary/interstitial brachytherapy in patients with locally advanced cervical cancer: A single-center retrospective study

PurposeThe purpose of the study was to explore the dose-effect relationship between dose-volume histogram parameters and clinical prognosis of definitive radio(chemo)therapy followed by intracavitary/interstitial brachytherapy in locally advanced cervical cancer. Methods and MaterialsA retrospective analysis was performed on 110 patients with locally advanced cervical cancer who underwent external beam radiotherapy combined with intracavitary/interstitial brachytherapy with or without chemotherapy from July 2010 to September 2018. We reported D100, D98, and D90 for high-risk clinical target volume (HR-CTV) and intermediate-risk clinical target volume, D2cm³ for organs at risk. Multivariate Cox regression was used to screen independent factors. Dose-volume parameters screened by the Cox regression were incorporated into the probit model for investigating its relationship with survival. ResultsThe median followup time was 72.33 months. Multivariate Cox regression analysis showed that HR-CTV D100, HR-CTV D98, and HR-CTV D90 were independent factors, affecting the 5-year overall survival (OS), cancer-specific survival (CSS), and local control (LC) rates. The probit model showed that HR-CTV D98 had predictive values for the 5-year OS, CSS, and LC, and HR-CTV D100 had predictive values for the 5-year OS, CSS, whereas HR-CTV D90 had a predictive value only for the 5-year OS. The HR-CTV D98 corresponding to OS ED90, CSS ED90, and LC ED90 was 86.8, 85.6, and 78.6 Gy, respectively. ConclusionsA significant dependence of OS, CSS, and LC on D98 for HR-CTV was found. When the long-term OS, CSS, and LC rate of the patient was >90%, HR-CTV D98 > 86.8 Gy EQD2, 85.6 Gy EQD2, and 78.6 Gy EQD2 were required.

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

PurposeOnly 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 MaterialsThree-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. ResultsAs 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. ConclusionBoth 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.