Brachytherapy Fractions Research Articles

In vitro α/β ratio Variations in Cervical Cancer, with Consequent Effects on Equivalent Dose in 2 Gy Fraction in High Dose Rate Brachytherapy

In vitro α/β ratio Variations in Cervical Cancer, with Consequent Effects on Equivalent Dose in 2 Gy Fraction in High Dose Rate Brachytherapy

Dosimetric evaluation of adaptive planning for five-fraction gynecologic template-based interstitial brachytherapy

Purpose: The purpose of this work was to evaluate whether inter-fraction imaging and replanning enhance treatment delivery adherence to clinical planning objectives in the context of a 5-fraction template-based interstitial brachytherapy (TISB) approach for gynecologic cancer treatment. Methods and Materials: This retrospective study analyzed nineteen patients who underwent five fractions of interstitial brachytherapy over three days using the Syed-Neblett template. A verification CT scan was acquired for applicator assessment and reviewed by a radiation oncologist and medical physicist before each fraction. Eleven patients required replanning at least once during the treatment course. Replanning on the verification CT scan consisted of generating new target and organ-at-risk contours, digitizing catheter positions, and optimizing source dwell times to meet planning objectives. Dwell times and positions from the initial treatment plan were evaluated on the new contours to assess the dose that would have been delivered without replanning (non-adapted). Significance of non-adapted versus adapted dose differences were evaluated using a two-sided Wilcoxon sum rank test. Results: The average (min, max) change in dose (Gy) between the clinically delivered plans and the non-adapted plans were HR-CTV D90%: -6.5 (-0.6, -15.1), HR-CTV D98%: -6.5 (-0.4, -12.6), Bladder D2cc: -0.5 (0.0, -2.8), Bowel D2cc: -0.8 (0.0, -3.2), Rectum D2cc: -1.1 (0.0, -11.5), Sigmoid D2cc: -1.4 (-0.1, -5.4). Dosimetric changes in HR-CTV coverage were significantly improved with replanning while organ-at-risk differences were nonsignificant (p>0.05). Fraction 3 was the most common fraction indicated for replanning. Conclusions: Replanning template-based interstitial brachytherapy can improve target coverage and adherence to planning goals.

Clinical Outcomes of 3 Versus 4 Fractions of Magnetic Resonance Image-Guided Brachytherapy in Cervical Cancer

PURPOSEMRI-guided brachytherapy (MRgBT) is essential in the management of locally advanced cervical cancer. This study compares disease and toxicity outcomes in cervical cancer patients treated with 24 Gy/3 fractions (Fr) versus the conventional 28 Gy/4 Fr. METHODS AND MATERIALSThis retrospective study included 241 consecutive patients with FIGO 2018 stage IB-IVA cervical cancer treated with definitive chemoradiation between April 2014 - March 2021. Disease-free survival (DFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Cumulative incidence of local failure (LF), distant failure (DF) and G2+ gastrointestinal (GI), urinary (GU) and vaginal toxicity were estimated using the cumulative incidence function with death as a competing risk and compared using the Gray's test. RESULTSOf the 241 patients, 42% received 24 Gy/3 Fr and 58% received 28 Gy/4 Fr. With a median follow up of 3.2 (range 0.2-9.2) years, there were 14 local, 41 regional nodal and 51 distant failures in 63 (26%) patients. No significant differences were found between the 24 Gy/3 Fr vs 28 Gy/4 Fr group in 3-year DFS (77% vs 68%, P = 0.21), 3-year cumulative incidence of LF (5% vs 7%, P = 0.57), DF (22% vs 25%, P = 0.86), G2+ GI toxicity (11% vs 20%, P = 0.13), or G2+ vaginal toxicity (14% vs 17%, P = 0.48), respectively. The 3-year cumulative G2+ urinary toxicity rate was lower in the 24 Gy/3 Fr group (9% vs 23%, P = 0.03). CONCLUSIONCervical cancer patients treated with 24 Gy/3 Fr had similar DFS, LF, DF, GI and vaginal toxicity rates, and a trend towards lower G2+ urinary toxicity rate compared to those treated with 28 Gy/4 Fr. A less resource-intensive brachytherapy fractionation schedule of 24 Gy/3 Fr is a safe alternative to 28 Gy/4 Fr for definitive treatment of cervical cancer.

The care and management of patients with indication for intracavitary 3D brachytherapy

This paper evaluates the differences between two types of normalization of 3D intracavitary brachytherapy (3D-BT) treatment plans for malignant cervical lesions. Immediately after the end of the treatment, intracavitary irradiation was continued, three fractions with 7.5 Gy per session, using High Dose Rate (HDR) brachytherapy and 3D imaging. Tree plans were made, one for the 3 cm diameter vaginal applicator and two for the vaginal applications where 2.6 cm diameter intracavitary applicators were used. Treatment plans were made using the dedicated software Eclipse-BrachyVision version 10.0.42, manufacturer Varian Medical Systems. Dose Calculation Model-Linear source and step size 0.50 cm. The normalization was done in the first phase at the surface of the applicator, at the prescription line. The next normalization was by volume. We present the results of the two normalizations. The data obtained from the 2 normalization methods was entered into an Excel spreadsheet. We took into account the dose prescribed for EBRT, the number of fractions, the dose/fr, the dose prescribed for 3D-BT and the dose absorbed by the OAR in 2 cm. We also took into account the isodose obtained for 90%, 100% and 150% of the volume of interest. In the first optimization, the absorbed dose was between 7.45–8 Gy. We also tracked BED and EQD2 in the spreadsheet. Results: In the second optimization, on the target volume, we obtained for the plan with a cylinder with a diameter of 3 cm (Ф = 3 cm), 90% of the IR volume the dose of 7.5 Gy. For Ф = 2.6 cm, of the IR volume with a dose of 7.5 Gy and for the last plane also with Ф = 2.6 cm, of the IR2 volume with a dose of 7.5 Gy. Calculated data for EQD2 in the three planes with normalization to the line on the applicator surface resulted in higher doses for OARs compared to EQD2 data from volume optimization. The volume of interest according to EQD2 calculations in the first optimization had 77.8 Gy and in the second optimization it had 78.4 Gy. After volume optimization, we achieved 78.4 Gy for all three brachytherapy fractions and the 25 EBRT fractions, the rectum totaling a dose of 67.1 Gy and the bladder 77.5 Gy. With the volume-optimized plans, we obtained a coverage between V90% = D100%.

794: Clinical outcomes of 3 vs 4 Fractions of MRI-guided brachytherapy in cervical cancer

794: Clinical outcomes of 3 vs 4 Fractions of MRI-guided brachytherapy in cervical cancer

Definitive radiation for advanced cervix cancer is not associated with vaginal shortening—a prospective vaginal length and dose correlation

PurposeProspectively measure change in vaginal length after definitive chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD). Materials and MethodsTwenty one female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. An initial measurement was made at the time of the first ICBT procedure and subsequently at 3 month intervals up to 1 year post radiation. The vagina was contoured as a 3-dimensional structure for each brachytherapy plan. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. ResultsThe mean initial VL was 8.7 cm (6.5–12) with median value of 8.5 cm. The mean VL after 6 months was 8.6 cm (6.5–12) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 Gy (99.6–252.2), 96.9 Gy (84.2–114.9), and 89.6 Gy (82.4–102.2), respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. ConclusionDefinitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward.

Comparative Study between Two Fractions of 9Gy & Three Fractions of 7Gy High Dose Rate Brachytherapy Following Concurrent Chemo Radiotherapy in Patients with Locally Advanced Carcinoma of Uterine Cervix

Introduction: Traditionally, a judicious combination of external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) is the widely accepted primary modality of treatment for locally advanced carcinoma of the cervix. Although the recommendation ofAmerican Brachytherapy Society is <7.5 Gyfor individual fraction and four to eight should be the range of fractions; however, literature showed high dose rate (HDR) brachytherapy of two fractions of 9Gyresults in acceptable toxicity without compromising the local control. Methods: This was a Prospective Quasi-Experimental study, conducted in Department of Radiation Oncology, National Institute of Cancer Research and Hospital, Mohakhali, Dhaka from July 2018 to June 2019. Patients with Clinically diagnosed and histopathologically proven squamous cell carcinoma of uterine cervix in locally advanced stage (FIGO stage IIB to IVA) were selected. Total 60 patients were enrolled according to selection criteria and allocated in to group. Both arm was received 50Gy EBRT in 25 fractions with concurrent inj.Cisplatin 40 mg/m2 weekly. Then Arm A was given HDR Brachytherapy 9Gy in each fraction for 2 fractions and Arm B was given HDR Brachytherapy 7Gy in each fraction for 3 fractions. Then treatment responses, locoregional control of disease and acute toxicities were compared between groups. Result:Follow up at 6 months after completion of treatment, complete remission was 90% and 86% respectively for arm A and arm B. The overall complete response was 88%. The common toxicities associated with treatment were bladder and rectal toxicities, skin reaction, small bowel toxicity and haematologic complications which were managed well. During follow up after 6 months, 3 patients in arm A and 2 patients in arm B developed grade II bladder toxicities and only 2 patients in arm A developed rectal grade II toxicities, but there was no rectal toxicity in arm B. Conclusions: Present study showed that a total dose of 18 Gy ICRT in two fractions of 9 Gy over 2 weeks is equally effective in short term local control with acceptable toxicities in comparison with a total dose of 21 Gy in three fractions of 7 Gy ICRT. J Bangladesh Coll Phys Surg 2024; 42: 49-56

Single- versus Multi-computed Tomography Simulation for High-dose-rate Postoperative Gynecological Intracavitary Brachytherapy.

This study aimed to investigate whether there is a dosimetric difference of implementing single instead of multi-computed tomography (CT) simulation treatment planning for high-dose-rate postoperative gynecological intracavitary brachytherapy (BT). Eighty patients were registered in the study. They received three BT fractions of 7 Gy/week (three CTs, three original plans). The organs at risk (OAR), the rectal wall, and the clinical target volume (CTV) were delineated. The delivered doses for the 2cc of OARs (D2cc), 1cc of rectal wall (D1cc), as well as for the 90% and 100% of CTV volume (DCTV90%, DCTV100%) were evaluated. To evaluate the values of the above parameters if the single-CT-simulation method has been chosen, the time of the first treatment plan was corrected for the decay and applied as the second and third CT, retrospectively, creating the next fractions (two revised plans). No statistically significant (P > 0.05) differences were found between the original and revised plans for the OARs and CTV. However, for the single-CT-simulation method, it was noted that the dose constraints for the total rectal dose were exceeded in some cases (36.3%). The fact that rectal dose constraints were exceeded in 1/3 of patients with the single-CT-simulation method is dosimetrically significant.

Dose and fractionation regimen for brachytherapy boost in cervical cancer in the US

PurposeCurative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. MethodsWe retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018–2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. ResultsAmong the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). ConclusionsIn the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes.

Dosimetric Parameters Predictive of Treatment-Related Toxicity in High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer.

High dose-rate (HDR) brachytherapy as monotherapy is an effective treatment for patients with low- and intermediate-risk prostate cancer and is increasingly being offered as a 2-fraction protocol. There is a lack of consensus on the optimal dosimetric planning parameters to use, or whether there is any benefit summating dosimetric parameters from more than one implant. Our goal is to determine planning parameters associated with disease control, toxicity and health-related quality of life (HRQOL). Data were collected on 83 patients with low- and intermediate-risk prostate cancer who received 2 fractions of 13.5 Gy HDR brachytherapy without androgen-deprivation therapy as part of a randomized phase II clinical trial. An in-house deformable, registration algorithm was used to co-register and dose-summate the plans from both implants for each patient. Acute and late GU and GI toxicities were measured using CTCAE 4.0 and HRQOL was measured in urinary, bowel, sexual and hormonal domains using the EPIC scores. Treatment efficacy was assessed through PSA measurement and imaging with or without biopsy where indicated. Covariates included baseline clinical factors, disease characteristics and treatment dosimetric parameters. Cox proportional hazards was performed to evaluate covariates impact on treatment toxicity and efficacy, and logistic regression analysis evaluated covariates impact on HRQOL. Among the 83 patients, median prostate volume was 46.7cm3. Median summated planning target volume receiving 100% prescription dose (PTV V100%) was 97.4%, median PTV V150% 42.4% and median PTV V200% 15.5%. Median highest dose to the 1cm3 rectum (D1cc) was 66.9% of the prescription dose and median rectum V80% was 0.008cm3. Median urethral D1cc was 99.0% of the prescription dose, median urethral Dmax 121.7% and median urethral D10% 116.2%. Grade ≥2 GI toxicity was uncommon (3.7% acute and 8.5% late), but grade ≥2 GU toxicity was reported in 73.2% (acute) and 46.3% (late) patients. Rectum D1cc and V80% were found to be significantly associated with grade 2 or higher acute GI toxicity, while use of a-blocker at baseline was associated with grade ≥2 acute GU toxicity. Similarly, use of a-blocker was associated with late grade ≥2 GU toxicity, but with no dosimetric associations. No other variables were associated with treatment-related toxicities. Only rectum D1cc was significantly associated with changes in bowel EPIC scores. Estimated 5-year biochemical disease-free survival was 93.9% and 5-year cumulative incidence of local failure was 3.8%. HDR monotherapy with 27 Gy delivered in 2 fractions in treatment of prostate cancer is well tolerated with high rates of disease control and minimal toxicity. Dose summation between 2 fractions of HDR brachytherapy is feasible, with rectal dose predicting acute GI toxicity. The lack of association between dose metrics and urinary toxicity raises the potential for further dose escalation.

Impact of Race and Socioeconomic Factors on Clinical Outcomes in Cervical and Endometrial Cancer Patients Treated with Brachytherapy

Racial and socioeconomic disparities impact cancer care and outcomes. This project aimed to evaluate relationship between race and socioeconomic factors and clinical outcomes in patients with cervical and endometrial cancer. All cervical and endometrial cancer patients treated with brachytherapy at our institution from 2007-2017 were identified. Race, insurance status, employment status, disability status, and distance from brachytherapy center were recorded. Clinical characteristics including stage at presentation, number of involved nodes, histology, and brachytherapy technique (cervical cancer only) were recorded. PFS and OS were calculated from date of last brachytherapy fraction, with censorship at date of last follow-up. Correlation was tested between race and socioeconomic factors and PFS and OS using Cox regression models. Association with other outcomes was examined with Wilcoxon rank sum tests, Fisher's exact tests, and Spearman's rank correlation coefficients. A total of 251 cervical and 130 endometrial cancer patients were identified, with median follow-up 5.2 years and 4.8 years, respectively. For cervical cancer, UVA showed significant correlation for PFS and OS with race, insurance status, employment status, and disability status. For endometrial cancer, UVA showed significant correlation for PFS with race, insurance status, and disability status, and for OS with race and insurance status. For cervical cancer, MVA showed significantly improved PFS in patients with insurance (p < 0.001) and patients who were employed (p = 0.002), and significantly improved OS in patients who were white (p = 0.039), patients with insurance (p<0.001), and patients who were employed (p-0.001). For endometrial cancer, MVA showed significantly improved PFS and OS in patients who were white (p = 0.003 and p = 0.005, respectively) and patients with insurance (p = 0.027 and p = 0.002, respectively). For cervical cancer, there was no correlation between insurance or employment status and stage. For endometrial cancer, there was no correlation between race or insurance status and stage. For cervical cancer, insurance and employment status are significant predictors of PFS and OS, and race is additionally a significant predictor of OS. For endometrial cancer, race and insurance status are significant predictors of PFS and OS.

Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) in Early Endometrial Cancer: Primary Endpoint Results of the SAVE Randomized Clinical Trial

Prospective trials in early stage endometrial cancer demonstrate increased locoregional control with adjuvant radiotherapy for patients with high risk features. VCB is widely utilized, yet there is substantial practice variation and limited randomized data examining optimal dose/fractionation. We aimed to study the safety and efficacy of short course VCB compared to commonly used regimens. We conducted a prospective, randomized, multicenter trial examining short course adjuvant VCB (11 Gy x 2 fractions at the surface) compared with other standard regimens (7 Gy x 3 fractions at 0.5 cm depth, 6 Gy x 5 fractions at the surface, or 5-5.5 Gy x 4 fractions at 0.5 cm depth). Eligible patients underwent hysterectomy and had pathologically confirmed endometrioid adenocarcinoma, serous, clear cell, or carcinosarcoma. Patients with stage I and II cancers were included, with lymphovascular invasion (LVI) required for stage IAG1. The primary outcome was Global Health Status measured by the EORTC QLQ-C30 with a pre-specified non-inferiority margin of 15 points. Secondary outcomes included patient-reported outcomes, toxicities as assessed by CTCAEv5, and patterns of recurrence. Data were collected at each brachytherapy fraction and at 1-, 6-, and 12-month follow-up. One hundred eight patients were enrolled, 54 in each study arm. Data completion was 94%, 91%, and 77% at 1 month, 6 months, and 12 months, respectively. 70% of patients had endometrioid adenocarcinoma, 18% serous carcinoma, and 12% other histologies. 23% were FIGO grade 1, 33% grade 2, and 43% grade 3 or high risk histologies. The majority of patients were stage I (56% IA, 38% IB). 22% of patients had LVI. The QLQ-C30 Global Health Status for the experimental arm was within the predefined boundary and thus 2 fractions were non-inferior to standard of care at one month (p = 0.000005) and 12 months (p = 0.0005). Using EORTC EN24 for patient reported vaginal/sexual, urologic, and gastrointestinal symptoms, the change in mean patient reported symptom score from baseline to 1 month and baseline to 12 months were not significantly different between arms. Using CTCAEv5, 51 patients experienced short-term AEs related to study treatment, 20 in the experimental arm and 31 in the control arm (p = 0.053). All study treatment-related AEs were grade 1-2, except for two grade 3-4 AEs, both on the control arm. At median follow-up of 19 months, the isolated vaginal control rate in each arm was 100%. There was no significant difference in the total number of recurrences between study arms, with 3 distant and 3 distant/pelvic/vaginal recurrences in the experimental arm, and 2 distant, 2 pelvic, and 1 pelvic/vaginal recurrence in the control arm. Short course VCB is safe with acceptable acute toxicity and non-inferior patient reported outcomes. Short course VCB improves patient convenience and may improve access to care for rural or underserved populations while providing similar local control.

Prospective Application of an Artificial Intelligence Decision Support Tool for Applicator and Needle Selection in High-Dose-Rate Brachytherapy for Cervical Cancer Patients

To assess the performance of an artificial intelligence (AI)-based decision support tool under differing thresholds to determine optimal applicator selection in a prospective clinical setting. Cervical cancer patients scheduled for high-dose-rate brachytherapy implants with intracavitary tandem and ring (IC) or interstitial tandem and ring (IC/IS) implants in a single tertiary cancer center were eligible for enrollment. Prior to the first brachytherapy implant, a diagnostic MRI was acquired. The clinical target volume and the expected inserted position of the intrauterine tandem and ring were identified and contoured on the T2-MRI. An in-house artificial intelligence-based predicted the need for an IC or IC/IS implant, based on target volume geometric features. For IC/IS implants, an optimal needle arrangement for target coverage was also predicted. Blinded to the AI outcome, a clinical determination was made by the clinician reviewing the MR image. AI algorithm prediction provided a confidence level associated with each decision. The algorithm performance for different confidence thresholds using the IC applicator of 50%, 60%, and 80% was investigated. Performance metrics of the initial clinical determination and the AI prediction were calculated based on the consensus optimal applicator determined from an assessment of planning dosimetry in the first fraction and clinical use for the final brachytherapy implants and fractions. The performance metrics were accuracy, precision, and recall. A total of 10 eligible patients were accrued between December 2020 and October 2022. Table 1 shows the initial clinical determination and consensus applicator AI predictions that were made with different confidence thresholds. The optimal confidence threshold (60%) yielded performance scores of 80%, 83.3%, and 83.3% for the accuracy, precision, and recall, respectively. The performance metrics were equivalent for the optimal confidence threshold and the initial clinical decision. The AI-based decision support tool shows strong predictive results for a clinical brachytherapy application that is important to patient outcome. This prospective study demonstrates that the algorithm's utility is a critical step in using AI-based tools clinically. Further work to determine the optimal brachytherapy applicator, based on treatment planning dosimetry, is required.

Comparison of Two Different Adjuvant High Dose Rate Vaginal Brachytherapy Fractionation Regimens in Early-Stage Endometrial Cancer

Adjuvant vaginal brachytherapy (VBT) as monotherapy is commonly used as treatment for early-stage uterine cancer following hysterectomy. No ABS guidelines existed at the onset of our institution's high dose rate (HDR) brachytherapy program, so a regimen of 30 Gy in six fractions was adopted in this setting. Due to the COVID pandemic in 2020, we implemented the use of 22 Gy in four fractions as our primary regimen to reduce overall treatment duration and healthcare exposure risks. In this analysis, we seek to compare outcomes and toxicities between the two treatment regimens. This is a single institution retrospective review of patients with Stage I-II endometrial cancer who received adjuvant VBT as monotherapy between 1998 and 2022. HDR VBT was delivered via a vaginal cylinder prescribed to a depth of 5 mm, to a dose of 22 or 30 Gy in four or six fractions, respectively. We evaluated maximum acute and chronic toxicities, defined as ≤6 months and ≥ 6 months following treatment completion, respectively. Toxicities were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) criteria. We evaluated clinical outcomes including local recurrence (LR), distant metastasis (DM), cause-specific survival (CSS) and overall survival (OS). P-values <0.05 were considered significant. A total of 270 patients were included in our analysis, with a median follow up of 4.98 years (7.7 and 1.3 years for six-fraction and 4-fraction regimen, respectively, p<0.001). The median age at the time of treatment was 66 (range 31-89). 195 patients (72.2%) were treated with six fractions and 75 (27.8%) were treated with four fractions. There was significantly less chronic vaginal dryness (p = 0.017) and vaginal stenosis (p<0.001) with the four-fraction compared to the 6-fraction regimen. There was no difference in acute toxicity (p = 0.468). There were no grade ≥3 toxicities in either group. The 2-year LR, DM, CSS, and OS rates for four/six fractions were 2.4%/3.7%, 6.8%/3.7%, 95.8%/97.9%, and 95.8%/95.8%, respectively. There were no significant differences in outcomes between the two groups. Our experience supports that VBT in four fractions is well tolerated with minimal acute and chronic toxicities. When comparing to our institution's historical data for a six-fraction regimen, the use of a four-fraction regimen resulted in less chronic vaginal dryness and stenosis, supporting its continued use. The clinical outcomes have been similar thus far. Further analysis with a longer follow-up duration and a match-pair analysis is warranted.

A general framework to develop a radiomic fingerprint for progression-free survival in cervical cancer

PurposeTreatment of locally advanced cervical cancer patients includes chemoradiation followed by brachytherapy. Our aim is to develop a delta radiomics (DRF) model from MRI-based brachytherapy treatment and assess its association with progression free survival (PFS). Materials and MethodsA retrospective analysis of FIGO stage IB- IV cervical cancer patients between 2012 and 2018 who were treated with definitive chemoradiation followed by MRI-based intracavitary brachytherapy was performed. Clinical factors together with 18 radiomic features extracted from different radiomics matrices were analyzed. The delta radiomic features (DRFs) were extracted from MRI on the first and last brachytherapy fractions. Support Vector Machine (SVM) models were fitted to combinations of 2–3 DRFs found significant after Spearman correlation and Wilcoxon rank sum test statistics. Additional models were tested that included clinical factors together with DRFs. ResultsA total of 39 patients were included in the analysis with a median patient age of 52 years. Progression occurred in 20% of patients (8/39). The significant DRFs using two DRF feature combinations was a model using auto correlation (AC) and sum variance (SV). The best performing three feature model combined mean, AC & SV. Additionally, the inclusion of FIGO stages with the 2- and 3 DRF combination model(s) improved performance compared to models with only DRFs. However, all the clinical factor + DRF models were not significantly different from one another (all AUCs were 0.77). ConclusionsOur study shows promising evidence that radiomics metrics are associated with progression free survival in cervical cancer.

Indian data on response of positive pelvic lymph nodes in carcinoma cervix patients treated with simultaneous integrated boost using volumetric modulated arc radiation therapy

Objectives The percentage of pelvic lymph node positivity in cervical cancer patients varies from 19% in early stages to 68% in advanced cases. Thirty three percent of patients will develop recurrence within 2 years following therapy and 5-year relative survival for patients with affected regional lymph nodes is 57%. Hence, pelvic lymph nodes need to be included in the definitive plan of radiation treatment for better disease control and longer survival. With conventional radiation therapy, dose escalation was not possible because of small bowel constraints. With higher conformity of intensity modulated radiotherapy technique (IMRT), doses to pelvic and abdominal organs can be minimized. The added advantage of simultaneous integrated boost (SIB) is that high dose per fraction is delivered to the gross disease and low dose to the microscopic disease, thereby reducing the total treatment time and improving the therapeutic ratio. Material and Methods Forty one patients presenting to the Department of Radiation Oncology, between January 2016 and June 2017, with newly biopsy proven carcinoma cervix Stage IB to IVA were enrolled in the study and all the investigations were performed. The radiation dose was delivered using volumetric modulated arc therapy plan to a dose of 5000 cGy in 25 fractions to the whole pelvis and 5500 cGy in 25 fractions at 220 cGy per fraction to the involved nodes using SIB along with weekly cisplatin at 40 mg/m2. After completion of external beam radiation, all the patients received three fractions of brachytherapy to a total dose of 21 Gy. Acute toxicities were assessed using RTOG criteria. At 3 months after completion of treatment, all the patients had been followed up with DW MRI of abdomen and pelvis to assess the response. Results Of the 41 carcinoma cervix patients with significantly positive lymph nodes treated with SIB VMAT, 9.8% of the patients (4 patients) had residual nodal disease, 87.8% of the patients (36 patients) had complete response, 19.5% (8 patients) had residual disease of primary disease, and 78% (32 patients) had complete response at 3 months after completion of treatment with only Grade – I and Grade – II toxicities. Conclusion Treatment with SIB VMAT in carcinoma cervix patients with significant pelvic lymph nodes shows very good response with acceptable acute toxicities. But longer follow-up period is required to see if this response translates into better DFS and OS.

Simultaneous integrated or sequential boost to clinically involved lymph nodes in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy

ObjectiveThe optimal treatment of metastatic lymph nodes (LNs) in locally-advanced cervical cancer (LACC) is controversial. With the widespread use of modern radiotherapy (RT) techniques, it is become possible to perform dose escalation in clinically involved LNs. This study aimed to evaluate the oncologic outcomes of dose escalation to the involved LNs with the simultaneous-integrated (SIB) or sequential boost (SEB) techniques as a part of definitive chemoradiotherapy (CRT) for patients with LACC. MethodsThe data of 47 patients treated with definitive CRT with either a SIB or SEB technique to the metastatic LNs between 2015 and 2021 were retrospectively analyzed. All patients received 50.4 Gy/28 fractions of external-beam RT and 28 Gy/4 fractions of brachytherapy. ResultsThe number of boosted LNs was 146. The median size of the LNs was 2 cm (range, 1–5 cm). The median cumulative equivalent dose in 2-Gy fractions for the LNs was 64.2 Gy (range, 57.6–71.2 Gy). During the median 30 months of follow-up (range, 14–91 months), no boosted LNs recurred and the local control (LC) rate was 100%. The 2-year overall, disease-free, local recurrence-free, and distant metastasis-free survival rate was 83.1%, 70.5%, 77.5%, and 74.4%, respectively. In multivariate analysis, the non-squamous cell histology was the only negative independent prognostic factor for DFS and DMFS. Treatment was well tolerated without any serious acute toxicity. Serious late toxicity developed in three (6%) patients as ureteral stenosis, rectal bleeding and pelvic fracture in one patient each. ConclusionsRT dose escalation provides excellent LC for the clinically involved LNs, even for bulky ones, with a low toxicity profile. Routine LN dissection may not be necessary. However, randomized trials are needed to determine the optimal treatment approach.

Interfraction variations in doses at OARs during three-dimensional high dose rate brachytherapy planning of cervix cancer.

The American Brachytherapy (BT) Society recommends that BT must be included as a component of the definitive radiation therapy for cervical carcinoma because recurrences and complications are decreased when BT is used in addition to external beam radiotherapy. The aim of this study is to quantify the interfraction dose variations (VARacts) during high dose rate (HDR) BT, the effect of variation in dose in terms of excess "unrecognized" dose to OAR and to conclude the reason of the variation in reference of applicator position/geometry versus deformation of the organ at risk (OAR) concerned. Total 30 patients of carcinoma cervix, biopsy proven, between June 2018 and May 2019, were taken for the study. All patients were treated with external beam radiation therapy to a dose of 50 Gy in 25 fractions over 5 weeks, followed by three fractions of HDR intracavitary brachytherapy (ICBT) (7.5 Gy to point A in each fraction) by two-dimensional (2D) X-ray-based planning. Before treatment in the first and last fraction of BT, computed tomography (CT) scan was done for every patient. Then, a 3D-based planning was performed with CT images on our HDR Plus software with image sequence option. VARact was calculated. Rigid image registration of consecutive fraction images was used for quantification of the hypothetical variation in dose (VARhypo) arising exclusively due to changes in applicator placement and geometry. The mean contoured rectal volumes for the first and third fractions were 41.49 cc and 44.72 cc, respectively, while the respective volumes for bladder were 9.33 cc and 9.35 cc cm. These differences were statistically insignificant (P value: 0.263 and 0.919 for rectum and bladder, respectively). The mean equivalent dose in 2 Gy fraction (EQD2) bladder D2cc was 5.68 Gy and 5.79 Gy in the first and third fraction ICBT, respectively. The mean EQD2 for the rectal D2cc was 11.63 Gy and 12.85 Gy in the first and third fraction ICBT, respectively. None of the patients had an actual cumulative EQD2 more than 90 Gy for bladder, but 36.66% of the patients had a rectal dose exceeding the tolerance (75 Gy). Regression plots showed that VARhypo alone could predict about 42.2% of the VARact in the rectum and 19.2% of the VARact in the bladder. Thus, the remaining variation was due to the organ deformation-related dose variations between the two fractions. There were no statistically significant variations in the volumes or doses of OAR between the two fractions. However, a significant proportion of patients may have a higher dose to the OAR in the third fraction in the absence of individualized planning. This increase is likely to be more detrimental where higher doses per fraction are used. Variations in OAR doses may be caused by organ deformation and/or changes in applicator placement/geometry.

Boost modalities in cervical cancer: dosimetric comparison between intracavitary BT vs. intracavitary + interstitial BT vs. SBRT.

Purpose / objectiveThis study compares the dosimetric plans of three distinct boost modalities in cervical cancer (CC): intracavitary (IC) with tandem/ovoids brachytherapy (BT), IC + interstitial (IS) BT, and Stereotactic-Body-Radiotherapy (SBRT). The aim is to determine the dosimetric impact in terms of target coverage and organ at risk (OAR) doses.Materials and methods24 consecutive IC + IS BT boost treatment plans were retrospectively identified. For each plan included, two additional plans were created: IC-BT and SBRT. Importantly, no planning target volume (PTV) or planning (organ at) risk volume (PRV) margins were generated, therefore all structures were identical for any boost modality. Two different normalizations were performed: (1) Normalization to the target: prescription of 7.1 Gy to the D90% (defined as the minimum dose covering 90%) of the high-risk clinical target volume (HR-CTV); (2) Normalization to the OARs. HR-CTV coverage and OARs sparing were compared. The equivalent doses in 2 Gy fractions (EQD2) of EBRT and BT for CTV-HR and OARs were calculated using the linear-quadratic model with α/β of 10 (EQD210) and 3 (EQD23), respectivelyResultsA total of 72 plans were investigated. In the first normalization, the mean EQD23−D2cc (defined as the minimal dose of the 2 cc) of OAR was significantly higher in the IC-BT plans, and the bladder D2cc hard constraint could not be reached. IC + IS BT leads to a 1 Gy mean absolute decrease of bladder EQD23-D2cc (relative dose: -19%), allowing to reach the hard constraint. SBRT (without PTV) delivers the lowest EQD23-D2cc to the OAR. In the second normalization, IC-BT provides a significantly lower dose to the EQD210-D90% (6.62 Gy) and cannot achieve the coverage goal. SBRT (without PTV) yields the highest dose to the D90% of HR-CTV and a significantly lower EQD210-D50% and D30%.ConclusionThe key dosimetric benefit of BT over SBRT without PTV is a significantly higher D50% and D30% in the HR-CTV, which increases the local and conformal dose to the target. IC + IS BT vs. IC-BT provides significantly better target coverage and a lower dose to the OARs, making it the preferred boost modality in CC.

Deep learning for segmentation of the cervical cancer gross tumor volume on magnetic resonance imaging for brachytherapy

BackgroundSegmentation of the Gross Tumor Volume (GTV) is a crucial step in the brachytherapy (BT) treatment planning workflow. Currently, radiation oncologists segment the GTV manually, which is time-consuming. The time pressure is particularly critical for BT because during the segmentation process the patient waits immobilized in bed with the applicator in place. Automatic segmentation algorithms can potentially reduce both the clinical workload and the patient burden. Although deep learning based automatic segmentation algorithms have been extensively developed for organs at risk, automatic segmentation of the targets is less common. The aim of this study was to automatically segment the cervical cancer GTV on BT MRI images using a state-of-the-art automatic segmentation framework and assess its performance.MethodsA cohort of 195 cervical cancer patients treated between August 2012 and December 2021 was retrospectively collected. A total of 524 separate BT fractions were included and the axial T2-weighted (T2w) MRI sequence was used for this project. The 3D nnU-Net was used as the automatic segmentation framework. The automatic segmentations were compared with the manual segmentations used for clinical practice with Sørensen–Dice coefficient (Dice), 95th Hausdorff distance (95th HD) and mean surface distance (MSD). The dosimetric impact was defined as the difference in D98 (ΔD98) and D90 (ΔD90) between the manual segmentations and the automatic segmentations, evaluated using the clinical dose distribution. The performance of the network was also compared separately depending on FIGO stage and on GTV volume.ResultsThe network achieved a median Dice of 0.73 (interquartile range (IQR) = 0.50–0.80), median 95th HD of 6.8 mm (IQR = 4.2–12.5 mm) and median MSD of 1.4 mm (IQR = 0.90–2.8 mm). The median ΔD90 and ΔD98 were 0.18 Gy (IQR = -1.38–1.19 Gy) and 0.20 Gy (IQR =-1.10–0.95 Gy) respectively. No significant differences in geometric or dosimetric performance were observed between tumors with different FIGO stages, however significantly improved Dice and dosimetric performance was found for larger tumors.ConclusionsThe nnU-Net framework achieved state-of-the-art performance in the segmentation of the cervical cancer GTV on BT MRI images. Reasonable median performance was achieved geometrically and dosimetrically but with high variability among patients.