Impact of a vaginal dose constraint on the reduction of vaginal shortening after vaginal-cuff brachytherapy in postoperative endometrial cancer
[eng] The present thesis project hypothesizes that "In postoperative endometrial cancer treated with VBT ± EBRT, Grade 2 late vaginal complications can be reduced by applying a dose restriction of < 68 Gy EQD2 (α/β=3) to 2 cm³ from the most exposed part of the dose in the vagina." For t...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/225363 |
| Acceso en línea: | https://hdl.handle.net/2445/225363 http://hdl.handle.net/10803/696299 |
| Access Level: | acceso abierto |
| Palabra clave: | Oncologia Càncer d'endometri Braquiteràpia Malalties de la vagina Oncology Endometrial cancer Radioisotope brachytherapy Vagina diseases |
| Sumario: | [eng] The present thesis project hypothesizes that "In postoperative endometrial cancer treated with VBT ± EBRT, Grade 2 late vaginal complications can be reduced by applying a dose restriction of < 68 Gy EQD2 (α/β=3) to 2 cm³ from the most exposed part of the dose in the vagina." For this reason, its primary objective is "Analysis of the possible factors responsible for grade ≥ 2 vaginal complications, including body mass index, age, use of chemotherapy, vaginal cylinder diameter, brachytherapy dose, use of vaginal dilators, and irradiated vagina volume"; and the secondary one is "Impact of the application of a dose restriction of 68 Gy EQD2 (α/β=3) to the most exposed 2 cm³ of the vagina on the reduction of grade 2 late vaginal shortening", and the third is "To determine whether the prescription of the CTV dose against 5 mm of the applicator surface allows the dose to be reduced to the most exposed 2 cm³ of the vagina". To achieve the above, 4 studies have been published that are summarized below in each objective. Specific objective 1: Analysis of risk factors for grade ≥ G2 vaginal complications. Purpose: This retrospective study analyzed potential risk factors for late grade ≥2 vaginal complications (G2-CVL) in 126 postoperative endometrial cancer patients. Materials and methods: Prognostic factors of CVL were evaluated, including body mass index (BMI), age, use of chemotherapy, diameter of the vaginal cylinder, total dose at the 2 cm³ most exposed to dose of the vagina, use of vaginal dilators (RV) and clinical target volume (CTV). Patients treated with vaginal cylinder brachytherapy (VCB) with or without external radiotherapy (EBRT) between December 2013 and December 2018 were included. Late vaginal complications were assessed using the objective LENT-SOMA criteria. Late rectal, bladder, and small intestine toxicity were classified according to the RTOG criteria. Statistics: A descriptive analysis was applied, the Chi-square test, the Fisher test and the Student's t test. Univariate and multivariate analyses were performed using the exact Baptista-Pike method and multiple logistic regression was also performed. Results: With a mean follow-up of 66 months (8-104): o Higher volumes of CTV (≥9 cm³) were associated with a lower incidence of G2-CVL. o Keeping the equivalent dose restrictions in fractions of 2 Gy (EQD2) below 68 Gy for a coefficient (alpha/beta=3) reduced G2-LVC complications. o Cylinder diameters less than 3 cm did not show a significant association with G2-LVC in this study, although previous research highlighted potential risks due to non-uniform dose distributions. o A total EQD2 (α/β=3) at the most exposed vaginal 2 cm³ less than 68 Gy was associated with a lower rate of G2-LVC. o No significant correlations were observed between chemotherapy use, BMI >35 or age >55 years with G2-LVC. Lack of consistent DV use (<9 months) was the only independent predictor of G2-LVC in the multivariate analysis. Conclusion: The consistent use of vaginal dilators >9 months is a key factor in reducing late grade ≥ G2 vaginal complications in postoperative endometrial cancer brachytherapy. Specific Objective 2: Evaluation of dose restrictions of 68 Gy EQD2(α/β=3) to reduce G2 vaginal foreclosure and other late complications. Purpose: To evaluate whether applying a prospective EQD2(α/β=3) restriction of 68 Gy to the most exposed 2 cm³ of the vagina reduces the risk of grade G2 vaginal shortening and other late complications. Materials and methods: Two studies were conducted: 1. Study 1: Evaluation of EQD2(α/β=3) restrictions of 68 Gy at the most exposed 2 cm³ of the vagina in exclusive treatments with VCB. Materials and methods: Comparison between two groups where complications were prospectively assessed and collected retrospectively: 1. Group-1: 44 patients treated with 6 Gy × 3 fractions. 2. Group-2: 66 patients treated with 7.5 Gy × 2 fractions. The total dose of radiation administered was assessed at 90% of the CTV (D90), the volume of the CTV receiving 100% of the prescribed dose (V100), and the EQD2(α/β=3) received in the 2 cm³ most exposed to the dose within the CTV. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and LENT-SOMA objective criteria for late vaginal toxicity (LVT). Statistics: Descriptive analysis, Chi-square tests, Student's t-tests and the Kaplan-Meier method were performed. Results: With a mean follow-up of 60 months (15-60): o No recurrences were observed in the vaginal fundus or dome or late toxicities in the bladder or rectum. o Late vaginal toxicity (LVT) ≥ G1 appeared in 26 of 44 patients (59.1%) in Group 1 and in 25 of 66 (37.9%) in Group 2. o The mean EQD2(α/β=3) received by the 2 cm³ most exposed in the CTV was 63.7 Gy ± 10.0 in Group 1 and 60.5 Gy ± 3.8 in Group 2 (p = 0.063). o No differences were observed in adherence to the use of the vaginal dilator for ≥9 months, nor in the overall values of D90 and V100. Conclusion: Since no vaginal recurrences have been recorded and late vaginal toxicity (LVT) has remained similar over time, the 7.5 Gy × 2 fractions regimen appears to be more efficient in terms of patient comfort, workload, and cost. Due to the D2cc in the vagina was less than 68Gy EQD2 (alpha/beta=3) in the vast majority of patients, no impact was found when making this dose reduction. 2. Study 2: Evaluation of EQD2(α/β=3) restrictions of 68 Gy at the most exposed 2 cm³ of the vagina in EBRT+VCB treatments. Materials and methods: Comparison between two groups where complications were prospectively assessed and collected retrospectively: 1. Group-1: 65 patients treated with EBRT+VCB, receiving 1 fraction of 7 Gy without EQD2 restrictions (α/β=3) of 68 Gy at the most exposed 2 cm³ of the vagina. 2. Group-2: 66 patients treated with EBRT+VCB, receiving 1 fraction of 5.5-7 Gy with an EQD2(α/β=3) restriction < 68 Gy at the most exposed 2 cm³ of vaginal CTV. Recurrence in the vaginal dome, late toxicity, clinical target volume, use of vaginal dilators, D90 and EQD2 (α/β=3) were evaluated in the most exposed 2 cm³ of the clinical target volume. Statistics: A descriptive analysis was performed, the chi-square test, the Student's t-test, and the proportional Cox models and the Kaplan-Meier model for statistical analysis. Results: With a mean follow-up of 60 months (15-60): o The rate of recurrence in the vaginal dome was 1/131 (0.8%). o Late vaginal complications appeared in 36 of 65 patients (55.4%) in Group 1 and in 17 of 66 (25.8%) in Group 2 (p = 0.003). o The multivariate analysis showed that belonging to Group 1 and the use of the vaginal dilator for <9 months were independent prognostic factors of late vaginal complications, with hazard ratios of 1.99 (p = 0.021) and 3.07 (p = 0.010), respectively. Conclusion: Dose restrictions of 68 Gy EQD2 significantly reduced the risk of G2 vaginal shortening in EBRT+VCB treatments. Long-term outcomes were also correlated with the use of post-treatment vaginal dilators. Conclusion of the two studies: Applying EQD2(α/β=3) restrictions of 68 Gy to the most exposed 2 cm³ of the vagina is effective in reducing late complications and G2 vaginal shortening in patients receiving TEN+BT. Specific objective 3: Prescription to CTV against 5 mm from the surface of the applicator and reduction of the minimum dose to the most irradiated 2 cm³ of the volume of the vagina. Purpose: To determine whether prescribing the dose to clinical volume (CTV) instead of 5 mm from the applicator surface reduces the minimum dose to the most exposed 2 cm³ of the vagina (D2cc). 3 dosimetric analyses were performed on these patients: 5mm prescription of the cylinders considered as CTV, graphic optimization of the CTV and prescription of the volume of the CTV. Materials and methods: D90, EQD2 (α/β=3), the Coverage Index (CI), the Conformity Index (COIN) of three planning methods were analyzed in 217 cases: 1. Group T1: Normalized dose at points located 5 mm from the surface of the applicator. 2. Group T2: Normalized and optimized dose in CTV using 700 randomly generated points according to CTV. 3. Group T3: Manual graphic optimization to cover CTV with the D90 isodose. Statistics: Descriptive analysis, Chi-square test, Student's t-test, GEE model and linear regression model. Results: Group T1 has the best IQ with 0.99 (0.04). Group T2 shows the best COIN with 0.53 (0.11) and achieves a greater balance between CI and COIN. Group T3 reduces the dose in the rectum and bladder, with a D2cc of 5.02 (0.95) in the rectum and 4.96 (0.96) in the bladder. The total EQD2 (α/β=3) in D2cc of the vagina was 66.11 (7.31), 64.36 (8.49) and 61.69 (14.84) in T1, T2 and T3, respectively (p <0.001). The T3 Group reduces the D90 to the CTV with a 7.27 Gy (0.78). Conclusions: Prescription by volume (T2) provides less dose to CTV compared to prescription at 5 mm (T1).Although point-based optimization of the external surface of the CTV can be considered the most balanced method, offering excellent coverage and dose compliance, graphic optimization represents a viable alternative adapted to each case and faster, for clinical practice, especially in contexts where minimizing the dose to the organs at risk (OAR) and simplifying the planning process are priorities. When it is not feasible to cover the CTV with the T1 and T3 schedules, the T2 is the most appropriate. Final recommendations: 1. EQD2(α/β=3) restrictions of 68 Gy at the most exposed 2 cm³ of the vagina in VCB treatments should be implemented in the EBRT+VCB combination when the VCB dose is ≥7Gy above 45 Gy of RTE, with the aim of reducing late G2 complications. 2. Planning can be optimized with CTV prescription-based methods (T2 Group) to achieve a balance between CTV dose coverage and SRO protection. 3. Prioritize the use of vaginal dilators as an essential measure to mitigate late complications. 4. Large-scale prospective studies with appropriate follow-up periods will validate the clinical and dosimetric results presented. |
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