Vaginal dose of radical radiotherapy for cervical cancer in China: a multicenter study.

BACKGROUND: The posterior-inferior border of symphysis (PIBS) point system is a novel vaginal dose-reporting method and is a simple and reliable method proposed by the Medical University of Vienna proposed for both external-beam radiotherapy (EBRT) and brachytherapy (BT). In this multicenter study, we sought to first evaluate the vaginal radiation dose in Chinese cervical cancer patients according to the PIBS point system and then to analyze the factors influencing the dose distribution. METHODS: We collected data from the medical records of 936 cervical cancer patients who underwent concurrent radiochemotherapy at 13 different institutions in China. Radiation doses at points A, PIBS+ 2 cm, PIBS and PIBS-2 cm, International Commission on Radiation Units (ICRU)-R and ICRU-B were measured. RESULTS: The median total doses in EQD2α/ß = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 82.5 (52.7-392.1) Gy, 56.2 (51.4-82.1) Gy and 2.6 (0.9-7.4) Gy, respectively. The median total doses in EQD2α/ß = 3 at ICRU-R and ICRU-B were 77.5 (54.8-132.4) Gy and 79.9 (60.7-133.7) Gy, respectively. The mean vaginal reference length (VRL) was 4.6 ± 1.0 cm (median, 4.5 cm). In patients with VRL ≤4.5 cm, the mean total doses in EQD2α/ß = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 128.5, 60.7 and 0.8 Gy, respectively. In patients with VRL > 4.5 cm, the mean total doses at these three points were 68.9, 0.5 and 54.5 Gy, respectively. Classification of patients revealed significant differences (P < 0.05) between these two groups. CONCLUSIONS: With the PIBS point system, Chinese patients with a shorter VRL of < 4.5 cm received higher radiation doses at the PIBS+ 2 cm, PIBS and PIBS-2 cm points than European and American patients. Further studies are required to establish the dose-effect relationships with these points as references. The study was registered as a clinical trial (NCT03257475) on August 22, 2017.

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

PURPOSE: Prospectively 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 METHODS: Twenty 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. RESULTS: The 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. CONCLUSION: Definitive 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.

Dose at posterior-inferior border of symphysis point: A predictor for vaginal stricture in cervical cancer.

PURPOSE: To study the effect of various dose-volume parameters on the severity of vaginal stricture (VS) and the correlation of the latter with the posterior-inferior border of symphysis (PIBS) points in locally advanced cervical cancer patients treated with concurrent chemoradiation and brachytherapy. METHODS AND MATERIALS: A prospective study was done on 45 histologically proven locally advanced cervical cancer patients between January 2020 and March 2021. All of them were treated with concurrent chemoradiation with 6 MV photon linear accelerator to a dose of 45 Gy/25 fractions in 5 weeks. Twenty-three patients were treated with intracavitary brachytherapy with a dose of 7 Gy/fraction/week for three fractions. Twenty-two patients were treated with interstitial brachytherapy, with 6 Gy/fraction for four fractions, each fraction 6 h apart. Grading of VS was done as per Common Terminology Criteria for Adverse Events version 5. RESULTS: The median followup was 21.5 months. About 37.8% of patients had VS with a median duration of 8.0 months (4.0-12 months). About 22.2% had Grade 1, 6.7% had Grade 2, and 8.9% had Grade 3 toxicity. Doses at PIBS and PIBS-2 points had no correlation with vaginal toxicity, however, the dose at PIBS+2 was significantly associated with VS (p = 0.004). The treated length of the vagina at the time of brachytherapy (p = 0.001), initial tumor volume (p = 0.009), and vaginal involvement after completion of external beam radiotherapy (EBRT) (p = 0.01) were also statistically significant with the development of VS of Grade 2 or more. CONCLUSIONS: Dose at PIBS + 2, treated length of the vagina with brachytherapy, initial tumor volume, and post-EBRT vaginal involvement are strong predictors for the severity of VS.

Vaginal Dose Reduction by Changing the Ovoid Loading Pattern in Image Guided Intracavitary Brachytherapy of Cervix.

Aim: Locally advanced cervical cancer is frequently treated using a combination of external beam radiotherapy and brachytherapy. Radiotherapy often leads to vaginal morbidity, which poses a significant problem. This study aims to analyze the impact of reducing ovoid loading on dosimetry. Materials and methods: We analyzed forty-five CT-based intracavitary brachytherapy plans from fifteen patients. Three plan sets were created for the 45 applications: a standard loading plan (A), a plan with reduced ovoid loading (B), and a tandem-only loading plan (C). We generated Dose-Volume Histograms and recorded dose volume parameters for the three plan sets. Results: The D90 for the Clinical Target Volume (CTV) did not show significant differences among the three plan sets (p = 0.20). The average D90 values for plans A, B, and C were 8.15 Gy, 8.16 Gy, and 7.4 Gy, respectively. No statistically significant differences were observed in D2cc bladder (p = 0.09) (average values: 6.8 Gy, 6.5 Gy, and 5.9 Gy for plans A, B, and C, respectively) and D2cc sigmoid (p = 0.43) (average values: 2.8 Gy, 2.6 Gy, and 2.4 Gy, respectively) among the three plan sets. However, there was a statistically significant difference in D2cc rectum (p < 0.001) (average values: 4 Gy, 3.3 Gy, and 1.8 Gy, respectively), as well as in vaginal dose points (p < 0.001). Conclusion: Reducing ovoid loading significantly decreased the doses to vaginal dose points and the rectum without compromising the dose to the Clinical Target Volume (CTV). Therefore, in carefully selected cases, the adoption of tandem-only loading or reduced ovoid loading could be considered to minimize vaginal morbidity following high dose rate intracavitary brachytherapy.

Comparison of dose delivered to vagina using two different intracavitary brachytherapy applicators for carcinoma cervix.

PURPOSE: The aim of the study was to compare the dose to vaginal points between two intracavitary applicators used for HDR brachytherapy in Carcinoma Cervix METHODS AND MATERIALS: Patients reporting to our center for Carcinoma cervix intracavitary brachytherapy were randomly allocated to treatment with either Manchester or Fletcher Suit Delclos (FSD) applicator. All patients received an EBRT dose of 50 Gy in 25 fractions along with weekly Cisplatin (40 mg/m2). Brachytherapy was administered using CT based planning. All patients received a dose of 7 Gy to Point A one week apart for a total of three fractions. For vaginal dose reporting, the PIBS points (PIBS, PIBS+1, PIBS+2, PIBS-1, PIBS-2) and dose to vagina at the level of ovoids was compared between the two applicators RESULTS: A total of 30 Carcinoma cervix patients were randomly allocated to receive intracavitary brachytherapy with either Manchester or FSD applicator. The mean vaginal reference length for patients treated with Manchester applicator was 4.3 and for patients treated with FSD applicator was 4.4. On analyzing dose to different vaginal points, patients treated with Manchester applicator received significantly higher mean and median doses to all PIBS points (except PIBS-2 cm) as compared to FSD applicator. On analyzing dose to the upper vagina at the level of the ovoids, the Manchester applicator delivered higher antero-posterior doses as compared to FSD applicator. CONCLUSIONS: Manchester applicator gives higher dose to the vagina as compared to FSD applicator for intracavitary brachytherapy in Carcinoma Cervix. The choice of using a particular applicator depends on the residual disease at the time of brachytherapy and patient anatomy.

Vaginal 11-point and volumetric dose related to late vaginal complications in patients with cervical cancer treated with external beam radiotherapy and image-guided adaptive brachytherapy.

OBJECTIVE: To investigate the vaginal 11-point and volumetric dose-toxicity relationships in definitive cervical cancer radiotherapy. METHODS: A retrospective cohort study of patients with cervical cancer with a complete response of at least 12 months was performed. Additional per vaginal examinations and patient-scoring questionnaires on the date of patient enrolment were assessed for vaginal strictures. Retrospective dosimetric analysis of vaginal 11-point and volumetric doses was performed with descriptive and probit analyses to investigate dose-toxicity relationships. RESULTS: Ninety-seven patients were included in the study, with a 20-month median follow-up. The incidence rate of grade 3 vaginal strictures was 22.7%. A comparison between patients with grade 1-3 vaginal strictures revealed significant differences in age, stage, initial tumour size, and vaginal involvement. PIBS + 2, PIBS, PIBS-2, D + 5, and D2cc were all significantly different among grade 1-3 vaginal strictures and showed significant probit coefficients. The lateral dose points were significantly higher in grade 2 strictures, but negative probit coefficients failed to establish causal inferences. Post-estimation analyses yielded effective doses (ED) for 15% and 20% probability of grade 3 vaginal strictures (ED15 and ED20) for PIBS + 2 at 57.4 and 111 Gy3, respectively. PIBS-2 yielded an ED20 of 7 Gy3. D + 5 yielded positive ED10, ED15, and ED20 values of 52.2, 66.6, and 78 Gy3, respectively. CONCLUSIONS: This study showed a significant relationship between age, tumour size, and lower-third vaginal involvement with the incidence of vaginal toxicity. The goal of a cumulative radiotherapy dose of ≤ 55 Gy3 to PIBS + 2, ≤5 Gy3 to PIBS-2, and ≤ 65 Gy3 to D + 5 points may reduce the risk of grade 3 vaginal stenosis to less than 15-20%.

EQD2 Analyses of Vaginal Complications in Exclusive Brachytherapy for Postoperative Endometrial Carcinoma.

Background: To evaluate whether EQD2(α/ß = 3Gy) at 2 cm3 of the most exposed area of the vagina is related to late vaginal toxicity in postoperative endometrial cancer (PEC) patients (p) treated with exclusive brachytherapy (BT). Methods: From 2014 to 2017, 43p were included in this study. BT was administered: 3-fractions of 6Gy in 37p and 2-fractions of 7.5Gy in 6p. The dose was prescribed at a depth of 5 mm from the applicator surface with dose-point optimization based on distance. The active treatment length was 2.5 cm. CTV-D90 and the dose to the most exposed 2 cm3 of the vagina was calculated for each patient. Late toxicity of the bladder and rectum was assessed using Radiation Therapy Oncology Group (RTOG) criteria, and vaginal toxicity by objective Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) criteria. Statistics: frequency tables, mean, median, range, standard deviation, and box plot. Results: The median follow-up was 51 months (12-68). 20 p (46.5%) and 2 p (4.7%) developed G1 and G2 vaginal complications, respectively. Only 1/2 p-G2 receiving EQD2(α/ß = 3Gy) at 2 cm3 >68Gy presented vaginal shortening and 18/20 p-G1 received doses < 68Gy. Conclusions: PECp receiving exclusive brachytherapy with doses < 68Gy EQD2(α/ß = 3Gy) at 2 cm2 of the vagina presented only G0-G1 vaginal toxicity, except for one with bleeding telangiectasias. Larger prospective studies are necessary to confirm the present results.

Vaginal dose de-escalation in image guided adaptive brachytherapy for locally advanced cervical cancer.

PURPOSE: Vaginal stenosis is a major problem following radiotherapy in cervical cancer. We investigated a new dose planning strategy for vaginal dose de-escalation (VDD). MATERIALS AND METHODS: Fifty consecutive locally advanced cervical cancer patients without lower or middle vaginal involvement at diagnosis from 3 institutions were analysed. External beam radiotherapy was combined with MRI-guided brachytherapy. VDD was obtained by decreasing dwell times in ovoid/ring and increasing dwell times in tandem/needles. The aim was to maintain the target dose (D90 of HR-CTV⩾85Gy EQD2) while reducing the dose to the surface of the vagina to <140% of the physical fractional brachytherapy dose corresponding to a total EQD2 of 85Gy. RESULTS: The mean vaginal loading (ovoid/ring) was reduced from 51% to 33% of the total loading with VDD, which significantly reduced the dose to the vaginal dose points (p<0.001) without compromising the target dose. The dose to the ICRU recto-vaginal point was reduced by a mean of 4±4Gy EQD2 (p<0.001), while doses to bladder and rectum (D2cm3) were reduced by 2±2Gy and 3±2Gy, respectively (p<0.001). CONCLUSIONS: VDD significantly reduces dose to the upper vagina which is expected to result in reduction of vaginal stenosis.