Rectal toxicity and rectal dosimetry in low-dose-rate 125I permanent prostate implants: A long-term study in 1006 patients

doi:10.1016/j.brachy.2011.05.007

Brachytherapy

Volume 11, Issue 3, May–June 2012, Pages 199-208

https://doi.org/10.1016/j.brachy.2011.05.007 Get rights and content

Abstract

Objective

To describe the acute and late rectal toxicity in 1006 prostate brachytherapy patients implanted 1998–2003. To determine whether rectal dose–volume histogram as well as patient and treatment factors were associated with rectal toxicity.

Methods and materials

Median followup was 60.7 months. Rectal dosimetry was calculated as dose–volume histogram of the rectum using Day 28 CT-based dosimetry and expressed as volume of the rectum in cc receiving 50%, 100%, and 150% of the prescription dose (VR_50cc, VR_100cc, and VR_150cc, respectively). Univariate and multivariate analyses were performed to examine the influence of patient, implant, dosimetry, and learning curve factors on the development of acute and late toxicities using a modified Radiation Therapy Oncology Group (RTOG) scale. Acute toxicity was analyzed using logistic regression and late toxicity using Cox proportional hazards regression. Analysis of variance was used to examine the association between rectal toxicity and rectal dose.

Results

Rectal dosimetry in 93.5% and rectal toxicity in 96.2% have been recorded. Median VR₁₀₀ = 1.05 cc. Late RTOG Grades 0, 1, 2, 3, and 4 were recorded in 68%, 23%, 7.3%, 0.9%, and 0.2% patients, respectively. On multivariate analysis, acute RTOG ≥2 rectal toxicity was associated with urinary retention (p = 0.036) and learning curve (p = 0.015); late RTOG ≥2 was associated with the presence of acute toxicity (p = 0.0074), higher VR₁₀₀ (p = 0.030) and learning curve (p = 0.027).

Conclusions

Late rectal RTOG ≥2 rectal toxicity in this cohort was 8%. Increased VR₁₀₀, presence of acute rectal toxicity, and learning curve were associated with higher rate of late RTOG ≥2 toxicity. Severe late rectal toxicity after prostate brachytherapy was rare.

Introduction

Prostate brachytherapy (PB) is a standard treatment modality for localized prostate cancer. Long-term biochemical outcomes and toxicity profile are very favorable [1], [2], [3], [4], [5]. Several groups have reported on rectal complications after PB and its relationship to rectal dose [6], [7], [8], [9], [10], [11]. Reported incidence of Grade 2 radiation proctitis after PB is 2–10%, with an onset usually between 6 and 18 months after the procedure [9], [12], [13]. The relationship between rectal dose and rectal toxicity is, however, not straightforward. For example, only a minority of patients with high rectal doses will develop severe rectal complications [9], [13], and some patients with relatively low doses to the rectum may develop significant rectal toxicity (14). The relationship between various patient and treatment factors, apart from rectal doses, has been subject to limited investigation and is not well described. In this study, we describe the rectal toxicity in 1006 consecutive uniformly treated PB patients with long followup from our institution. We describe patients, treatment, and dosimetric factors associated with acute and late rectal toxicity.

Section snippets

Methods and materials

The Prostate Brachytherapy Program at the British Columbia Cancer Agency (BCCA) was established in November 1997 and performed its first implants in July 1998. As of December 2010, more than 3250 patients have undergone PB. Outcome analysis of the first 1006 consecutive patients revealed a 5-year actuarial Kaplan–Meier freedom from biochemical failure of 95.7% [15], [16]. The program maintains a large prospective database containing baseline clinical and dosimetric data, as well as followup

Results

One thousand six patients were implanted between July 1998 and October 28, 2003. Of 1006 patients, 97.4% have postimplant CT-based prostate dosimetry and 93.5% have rectal dosimetry. Both mean and median followup are 60.7 months (range, 0.7–123.7). Of a total of 8624 patient visits, rectal toxicity was recorded 83% of the time; only 38 patients (3.8%) have no rectal toxicity recorded at all. Patient characteristics, planning characteristics, and postimplant dosimetry characteristics are given

Discussion

In summary, we describe rectal toxicity in 1006 consecutive uniformly treated PB patients implanted, with median followup of 60.7 months. To our knowledge, this is the largest published report that examines the association between rectal dosimetry and toxicity and the association between rectal toxicity and various patient, planning and treatment factors.

Like many others [6], [7], [9], [10], [11], [13], [14], we have con-firmed the association between higher rectal dose and subsequent rectal

Conclusions

Late rectal RTOG ≥2 toxicity in this cohort was 8%. Prolonged catheterization and larger prostate size were associated with a higher rate of any acute rectal toxicity. Higher rectal dose, acute rectal toxicity, and effects of learning curve (implant order) were associated with late RTOG ≥2 rectal toxicity. Severe late rectal toxicity (RTOG 3: 0.9%; RTOG 4: 0.2%) after PB in our cohort was rare.

Acknowledgments

BC Cancer Agency Prostate Brachytherapy Program: Radiation Oncology: Drs Mira Keyes (program head), W. James Morris (QA chair), Michael McKenzie, Alexander Agranovich, Tom Pickles, Eric Berthelet, Howard Pai, Winkle Kwan, Mitchell Liu, Jonn Wu, Ross Halperin, Alexander Abraham, David Kim, David Petrik, Juanita Crook, Arthur Cheung, Stacy Miller. Medical Physics: Ingrid Spadinger (physics head), Cynthia Araujo, Yen Pham, Parminder Basran, Nick Chng, Rustom Dubash, Michelle Hilts, Isabelle M.

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Cited by (56)

A Randomized Trial Comparing Quality of Life After Low-Dose Rate or High-Dose Rate Prostate Brachytherapy Boost With Pelvic External Beam Radiation Therapy
2024, International Journal of Radiation Oncology Biology Physics
To compare health-related quality of life (QoL) in urinary, bowel, and sexual domains after combined external beam radiation therapy (EBRT) and either low-dose rate (LDR) or high-dose rate (HDR) prostate brachytherapy (BT).
Eligible men with intermediate or high-risk prostate cancer treated with combined pelvic EBRT and BT were randomly assigned to either HDR (15 Gy) or LDR (110 Gy) boost. International Prostate Symptom Score, Index of Erectile Function, and Expanded Prostate Cancer Composite were collected at baseline, 1, 3, 6, and 12 months, every 6 months to 3 years and then annually along with prostate-specific antigen/testosterone. Fisher's exact test compared categorical variables and the Mann-Whitney U test Expanded Prostate Cancer Index Composite (EPIC) domain scores.
From January 2014 to December 2019, a random number generator assigned 195 men: 108 to HDR and 87 to LDR. Median age was 71 years. Risk group was high in 57% and unfavorable intermediate in 43%. Androgen deprivation (used in 74%) began with 3 months neoadjuvant and continued for median 12 months. Baseline EPIC scores were similar for the LDR/HDR cohorts: 89 and 88 respectively for Genito-urinary; 92 and 93 for Gastro-intestinal. EPIC urinary scores decreased at 1 month for HDR but recovered promptly to a steady state by 6 months. LDR scores reached a nadir at 3 months with slow recovery to 18 months, after which urinary QoL was similar for HDR and LDR. Bowel QOL scores fell in both cohorts reaching respective nadirs at 12 months. HDR patients recovered close to baseline and maintained higher scores than LDR patients to 5 years. The decline for LDR patients remained more than the minimum clinically important difference out to 5 years.
The patient experience for combined EBRT and prostate BT is improved with HDR BT. Urinary QoL improves over time to be equivalent between the 2 modalities after 18 months, but LDR patients report lasting bowel symptoms.
Acute and late side-effects after low dose-rate brachytherapy for prostate cancer; incidence, management and technical considerations
2021, Brachytherapy
To review common reported side effects and complications after primary LDR-BT (monotherapy) and discuss some of the technical aspects that could impact the treatment outcomes.
A literature search was undertaken using medical subject headings (MeSH) complemented by the authors’ personal and institutional expertise.
The reported incidence of acute and late grade 2 or above urinary, bowel and sexual side effects is very variable across the literature. The learning curve and the implant quality have a clear impact on the toxicity outcomes. Being aware of some of the technical challenges encountered during the procedure and ways to mitigate them could decrease the incidence of side effects. Careful planning of seed placement and seed deposition allow sparing of the organs at risk and a lower incidence of urinary and gastro-intestinal toxicity.
Low dose-rate brachytherapy remains a standard monotherapy treatment in the setting of favorable-risk prostate cancer. High disease control and low long-term toxicities are achievable in expert hands with a good technique.
Live implant dosimetry may be an effective replacement for postimplant computed tomography in localized prostate cancer patients receiving low dose rate brachytherapy
2021, Brachytherapy
To determine if Live Implant Dosimetry (LIDO) utilizing intraoperative transrectal ultrasound (TRUS) is equivalent to postimplant CT dosimetry (either day 0 or day 30) in patients with localized prostate cancer (PC) treated with low dose rate (LDR) prostate seed brachytherapy.
The treated population consisted of 628 men with localized (T1-T2) PC. All d'Amico risk categories (low, intermediate, and high) were included, and 437 patients were treated with monotherapy (160 Gy) [low and low tier intermediate], and the remainder (191) [high tier intermediate and high risk] with an implant boost (106 Gy) post external beam radiation, to a volume including the prostate and seminal vesicles (46 Gy). LIDO with intraoperative TRUS, postimplant CT (day 0 and day 30) were performed in all cases. Prostate volumes (V), V₁₀₀ (prostate) and dose (D) D₉₀ (prostate), D₃₀ (urethra), and Rectum D_2cc, were recorded. No urinary catheter was used on Day 30 CT.
More than 91.33% of monotherapy patients reached the target D₉₀ according to LIDO while only 82.99% of Day 0 CT and 92.82% of Day 30 CT achieved target D₉₀. When considering V₁₀₀, monotherapy patients recorded target dosimetry in 90.93%, 82.31%, and 92.02% of cases assessed by LIDO, Day 0 CT and Day 30 CT, respectively. Strong correlations are observed in D₉₀, Rectum D_2cc and Urethra D₃₀ across imaging modalities but V₁₀₀ and V₁₅₀ were poorly correlated due to the relative quantification of this parameter and high degree of error in measurement. Of all monotherapy patients with satisfactory dosimetry on LIDO, 94.82% reached target D₉₀ at day 30 CT and 94.19% reached target V₁₀₀.
LIDO and CT are both effective tools for assessing postimplant dosimetry. Patients with satisfactory LIDO dosimetry are highly likely to have equivalent dosimetry on CT at follow-up, indicating that postimplant CT may be eliminated in PC a patients implanted with this technique.
The impact of a rectal hydrogel spacer on dosimetric and toxicity outcomes among patients undergoing combination therapy with external beam radiotherapy and low-dose-rate brachytherapy
2021, Brachytherapy
Rectal hydrogel spacers have been shown to decrease rectal radiation dose and toxicity. In this study, we compared prostate and rectal dosimetry and acute toxicity outcomes in patients who had and had not received a rectal hydrogel spacer prior to combination therapy with external beam radiotherapy and low-dose-rate brachytherapy.
All patients with intermediate-risk and high-risk prostate cancer who received combination therapy at our institution were identified between 2014 and 2019. Dosimetric outcomes of brachytherapy implants and quality of life (QOL) outcomes were compared between patients who had and had not received a hydrogel spacer.
A Total of 168 patients meeting our inclusion criteria were identified. Twenty-two patients had received a rectal hydrogel spacer, among whom the mean separation between the rectum and prostate was 7.5 mm, and the V100_rectum was reduced by 47% (0.09 cc vs. 0.17 cc, p = 0.04). There was no difference in the percentage of patients achieving a D90 of ≥100 Gy between those who had and had not received a spacer. The mean rate of change in I-PSS and SHIM scores did not differ between the two groups at 2 months after PID.
LDR brachytherapy appears feasible after the placement of a rectal hydrogel spacer. While there was a significantly reduced V100_rectum among patients who had received a hydrogel spacer, there was no statistically significant difference in patients achieving a D90_prostate of ≥100 Gy. Although there was no difference appreciated in QOL scores, the length of follow-up was limited in the rectal-spacer group.
Placement of an absorbable rectal hydrogel spacer in patients undergoing low-dose-rate brachytherapy with palladium-103
2018, Brachytherapy
Rates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity.
Between January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance).
On average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V_100%), dose to 1 cc of rectum (D_1cc), and dose to 2 cc of rectum (D_2cc) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V₁₀₀ and dose to 90% of gland (D₉₀) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D₂₀, D_5cc, and D_1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity—6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding.
Injection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity.
Evaluation and results of ablative therapies in prostate cancer
2017, Progres en Urologie
Établir un état des lieux des modalités d’évaluation et des résultats actuels des traitements ablatifs in situ dans le cancer de la prostate localisé.
Une recherche bibliographique à partir de Medline (http://www.ncbi.nlm.nih.gov) et Embase (http://www.embase.com) a été réalisée et les articles ont été sélectionnés sur leur méthodologie, leur langue de publication (anglais/français) et leur pertinence. Après sélection, 102 articles ont été analysés.
L’interprétation des résultats des traitements ablatifs est souvent difficile au regard de l’hétérogénéité des indications, des techniques et des modalités d’évaluation. Cependant, les séries les plus récentes et les plus homogènes rapportent des résultats encourageants, tant sur le plan carcinologique que fonctionnel. Sur le plan carcinologique, les biopsies post-thérapie ablative, qui représentent le critère essentiel, sont indemnes de cellules tumorales en zone traitée dans 75 à 95 % des cas. Parallèlement, le statut fonctionnel urinaire et sexuel préopératoire est préservé (ou retrouvé précocement) en postopératoire dans plus de 90 % des cas. Les différentes études mettent en évidence des résultats qui dépendent également du type d’énergie selon le volume prostatique et la localisation de l’« index lésion » ciblée.
L’évaluation histologique post-traitement par des biopsies de contrôle guidées par IRM (voire, dans le futur, par des techniques d’échographie innovantes) représente la clé de l’évaluation carcinologique des thérapies ablatives dans le cancer de prostate localisé. Les essais en cours permettront d’harmoniser les méthodes d’évaluation et de préciser les indications et les modalités techniques pour optimiser les résultats pour un patient donné.
To perform a state of the art about methods of evaluation and present results in ablative therapies for localized prostate cancer.
A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 102 articles were analysed.
Analyse the results of ablative therapies is presently difficult considering the heterogeneity of indications, techniques and follow-up. However, results from the most recent and homogeneous studies are encouraging. Oncologically, postoperative biopsies (the most important criteria) are negative (without any tumor cells in the treated area) in 75 to 95%. Functionally, urinary and sexual pre-operative status is spared (or recovered early) in more than 90% of the patients treated. More and more studies underline also the correlation between the results and the technique used considering the volume of the gland and, moreover, the “index lesion” localization.
The post-treatment pathological evaluation by biopsies (targeted with MRI or, perhaps in a near future, with innovative ultrasonography) is the corner stone of oncological evaluation of ablative therapies. Ongoing trials will allow to standardize the follow-up and determine the best indication and the best techniques in order to optimize oncological and functional results for each patient treated.

View all citing articles on Scopus

: Presented at American Brachytherapy Society, Atlanta, GA, USA, May 2010. Canadian Association of Radiation Oncology, Vancouver, BC, Canada, September 2010.

: Conflict of interest: none.

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Rectal toxicity and rectal dosimetry in low-dose-rate 125I permanent prostate implants: A long-term study in 1006 patients

Abstract

Objective

Methods and materials

Results

Conclusions

Introduction

Section snippets

Methods and materials

Results

Discussion

Conclusions

Acknowledgments

Semin Radiat Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Brachytherapy

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Urology

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Rectal toxicity and rectal dosimetry in low-dose-rate ¹²⁵I permanent prostate implants: A long-term study in 1006 patients