High-dose-rate brachytherapy boost in prostate cancer: clinical outcomes, late rectal toxicity and uncertainties in organ at risk delineation
- Autores: Rodolfo Augusto Chicas Sett
- Directores de la Tesis: José María Benlloch Baviera (dir. tes.), José Pérez Calatayud (dir. tes.)
- Lectura: En la Universidad Católica de Valencia San Vicente Mártir ( España ) en 2018
- Idioma: español
- Tribunal Calificador de la Tesis: Facundo Ballester (presid.), José Luis Guinot Rodríguez (secret.), César David Vera Donoso (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencias de la Salud por la Universidad Católica de Valencia San Vicente Mártir
- Materias:
- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
HIGH-DOSE-RATE BRACHYTHERAPY BOOST IN PROSTATE CANCER: CLINICAL OUTCOMES, LATE RECTAL TOXICITY AND UNCERTAINTIES IN ORGAN AT RISK DELINEATION ABSTRACT High-dose-rate brachytherapy (HDRBT) is a brachytherapy technique, and when combined with external beam radiotherapy (EBRT), it allows for dose escalation, administration of the complete dose to the target (the prostate), and minimisation of the dose received by the surrounding normal tissues. It has been assessed by both retrospective and prospective studies showing excellent treatment outcomes with acceptable toxicity and high grade of local control. However, there are no specific recommendations about the best dose fractionation scheme for HDRBT boost. Several studies have reported various treatment schemes, which has made it difficult to compare the results of acute and late toxicity. The aim of this thesis was to evaluate the clinical outcomes of a cohort of patients diagnosed with prostate cancer and treated with singlefraction HDRBT boost in combination with EBRT, including the occurrence of late rectal toxicity (LRT) and its relation to dose-volume parameters.
In Paper I, we evaluated the efficacy of single-fraction HDRBT boost and EBRT combination in prostate cancer. In addition, we determined the significance of dosevolume histogram (DVH) parameters for predicting LRT in this cohort of patients.
Three hundred patients with intermediate- or high-risk prostate cancer were included between August 2010 and March 2015. Treatment comprised a single-fraction HDRBT boost of 15.0 Gy plus EBRT (46.0 Gy delivered in 23 fractions) or an HDRBT boost of 9.5 Gy plus EBRT (60.0 Gy delivered in 30 fractions) if the seminal vesicles were infiltrated using real-time transrectal ultrasound-based planning. LRT was evaluated every 3 months after the end of the combined treatment using the Common Terminology Criteria for Adverse Events, version 4.0. The minimum dose received by the most exposed 0.1 and 2.0 cm3 volume of the rectum (D0.1 cc/D2cc) was analyzed by estimating the biologically equivalent rectal dose according to the recommendations of the Groupe Européen de Curiethérapie (GEC)/European Society for Radiotherapy and Oncology (ESTRO). The clinical results showed an estimated 5-year bDFS rate of 90% and OS of 87% with a median follow-up of 33 (2 – 68) months. Twenty patients (6.7%) developed grade 2 and 3 patients (1%) developed grade 3 LRT. A significant association was observed between D2cc and the probability of developing grade1-3 LRT (p = 0.04). As concluded from de study, the use of HDRBT boost for prostate cancer is feasible. D2cc is associated with the occurrence of LRT in this group of patients.
Paper II, is a pilot study to evaluate D2cc for rectal contouring via interobserver variability. This was motivated by GEC and ESTRO recommendation, who proposed using a rectal dose constraint of the most exposed 2-cc volume (D2cc of ≤ 75 Gy EQD2α/β = 3) during EBRT plus HDRBT in localized prostate cancer patients.
Four blinded observers contoured rectums of 5 patients.
Rectal contouring anatomical limits were determined through previous consensus.
DVH dosimetric parameters (D0.1cc, D1cc, and D2cc) were analysed according to GEC/ESTRO recommendations and subjected to intra-‐ and interobserver comparisons.
Latter comparisons involved coefficients of variation.
For each parameter, the mean, standard deviation (SD), and range were evaluated.
The effect of interobserver variation on total dose was analysed by estimating the biologically equivalent rectal dose (EQD2α/β = 3).
Interobserver coefficients of variation for D0.1cc, D1cc, and D2cc were 5.7%, 4.5%, and 4%, respectively.
The highest interobserver rectal delineation variation yielded a rectal dose difference up to 5.8 Gy EQD2.
Estimated intraobserver variation for the reported D2cc was 5.5% in the worst-‐case scenario (non-‐significant).
As conclusion, we observed acceptable interobserver variability in EQD2 for D2cc, with strong impacts on clinical threshold levels (D2cc ≤ 75 Gy EQD2) in some cases.
In paper III, we was to evaluate the interobserver variability (IOV) of rectum contouring, and its dosimetric consequences, for high-dose-rate brachytherapy in patients with prostate cancer across multiple institutions. Five radiation oncologists contoured rectums in 10 patients on transperineal ultrasound image sets after establishing a delineation consensus. The D0.1cc, D1cc, and D2cc rectum volume parameters were determined. The mean, standard deviation, and range of each DVH parameter were evaluated for each patient. The IOV was determined using the coefficient of variation, and the dosimetric impacts on the total dose were analysed by estimating the biologically equivalent dose (EQD2a/b =3). The interobserver coefficients of variation (± standard deviation) for the reported D0.1cc, D1cc, and D2cc were 5 ± 1.84%, 4 ± 1.26%, and 4 ± 1.33%, respectively. As for the impact on the total dose, the mean dose differences for D0.1cc, D1cc, and D2cc were 10 Gy, 7.3 Gy, and 6.6 Gy, respectively.
As conclusion, we found that the D2cc is robust as evident by the low IOV (<5%).
However, some variability ranges almost overlap with the clinical threshold level, which may present dosimetric and clinical complications. General rectal contouring guidelines for prostate high-dose-rate brachytherapy are desirable to reduce discrepancies in delineation.
