Rates of rectal toxicity in patients treated with high dose rate brachytherapy as monotherapy compared to dose-escalated external beam radiation therapy for localized prostate cancer

doi:10.1016/j.radonc.2020.03.033

Radiotherapy and Oncology

Volume 147, June 2020, Pages 123-129

https://doi.org/10.1016/j.radonc.2020.03.033 Get rights and content

Highlights

•
High dose rate brachytherapy reduces rectal toxicity in prostate cancer treatment.
•
Rectal toxicity lower with brachytherapy than external beam radiotherapy.
•
Biochemical control similar for brachytherapy and external beam radiotherapy.

Abstract

Background

Using a prospectively collected institutional database, we compared rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer.

Methods

2683 patients treated with HDR or EBRT between 1994 and 2017 were included. HDR fractionation was 38 Gy/4 fractions (n = 321), 24 Gy/2 (n = 96), or 27 Gy/2 (n = 128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2–82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). EBRT patients underwent 3D image guidance via an off-line adaptive process.

Results

Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 545 patients (20.3%) received HDR brachytherapy and 2138 (79.7%) EBRT. 69.1% of EBRT patients received IMRT. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥2 diarrhea (0.7% vs. 4.5%, p < 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p < 0.001), and rectal bleeding (0% vs. 1.6%, p = 0.001). Rates of chronic grade ≥2 rectal bleeding (1.3% vs. 8.7%, p < 0.001) and radiation proctitis (0.9% vs. 3.3%, p = 0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥2 were 2.4% vs. 10.5% (p < 0.001) for HDR versus EBRT, respectively. In those treated with IMRT, acute and chronic rates of any grade ≥2 GI toxicity were significantly reduced but remained significantly greater than those treated with HDR.

Conclusions

In appropriately selected patients with localized prostate cancer undergoing radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing rectal toxicity.

Section snippets

High dose rate brachytherapy treatment

Between March 1999 and January 2017, 545 patients underwent HDR brachytherapy with the use of iridium-192 as monotherapy at a single institution. Three different dose schedules were utilized: 38 Gy in 4 fractions, 24 Gy in 2 fractions, and 27 Gy in 2 fractions. Patients selected for brachytherapy as monotherapy typically had National Comprehensive Cancer Network (NCCN) low- or favorable intermediate-risk disease.

A technical description of this institution’s HDR technique has been published

Results

Patient characteristics are presented in Table 1. Of the 545 patients treated with HDR, 321 were treated with 38 Gy in 4 fractions, 128 were treated with 27 Gy in 2 fractions, and 96 were treated with 24 Gy in 2 fractions. In the IGART group, 660 patients were treated with 3DCRT (30.9%) and 1478 (69.1%) of the patients were treated with IMRT. 780 patients were treated to the prostate alone (group 1) and 1351 were treated to the prostate and seminal vesicles (group 2). In group 1, 443 patients

Discussion

To our knowledge, the current study is the first to report improved acute and chronic rectal toxicities in localized prostate cancer patients receiving HDR brachytherapy as monotherapy when compared directly to external beam radiation therapy in the context of image guidance and dose escalation. Given the long natural history and excellent outcomes with prostate cancer, this constitutes an important clinical finding.

Our study adds to the growing body of evidence demonstrating low GI toxicity in

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (29)

D.A. Kuban et al.
Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer
Int J Radiat Oncol Biol Phys
(2008)
D.J. Brenner et al.
Fractionation and protraction for radiotherapy of prostate carcinoma
Int J Radiat Oncol Biol Phys
(1999)
D.J. Demanes et al.
High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy's 10-year results
Int J Radiat Oncol Biol Phys
(2005)
A.A. Martinez et al.
Phase II prospective study of the use of conformal high-dose-rate brachytherapy as monotherapy for the treatment of favorable stage prostate cancer: a feasibility report
Int J Radiat Oncol Biol Phys
(2001)
R. Khor et al.
Direct 2-arm comparison shows benefit of high-dose-rate brachytherapy boost vs external beam radiation therapy alone for prostate cancer
Int J Radiat Oncol Biol Phys
(2013)
O. Marina et al.
Comparison of dose-escalated, image-guided radiotherapy vs. dose-escalated, high-dose-rate brachytherapy boost in a modern cohort of intermediate-risk prostate cancer patients
Brachytherapy
(2014)
P.J. Hoskin et al.
Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer
Radiother Oncol
(2012)
J. Fowler et al.
Is alpha/beta for prostate tumors really low?
Int J Radiat Oncol Biol Phys
(2001)
D.J. Brenner et al.
Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue
Int J Radiat Oncol Biol Phys
(2002)
D. Yan et al.
An off-line strategy for constructing a patient-specific planning target volume in adaptive treatment process for prostate cancer
Int J Radiat Oncol Biol Phys
(2000)

A.A. Martinez et al.

Improvement in dose escalation using the process of adaptive radiotherapy combined with three-dimensional conformal or intensity-modulated beams for prostate cancer

Int J Radiat Oncol Biol Phys

(2001)

G.K. Edmundson et al.

Concurrent treatment planning for outpatient high dose rate prostate template implants

Int J Radiat Oncol Biol Phys

(1993)

M. Roach et al.

Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference

Int J Radiat Oncol Biol Phys

(2006)

I.S. Grills et al.

High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity compared to low dose rate palladium seeds

J Urol

(2004)

Cited by (10)

Application of a Radiopaque Viscous Hydrogel Spacer for Prostate Cancer Radiation Therapy: A Prospective Phase 2 Study
2024, Practical Radiation Oncology
The aim of this study was to evaluate the application of a radiopaque viscous spacer (RVS) for prostate cancer radiation therapy (RT), including injection procedure, toxicity, treatment planning, image guidance, and imaging results up to 12 months after RT.
RVS (median, 10 mL) was injected between prostate and rectal wall in 30 patients. Cone beam computed tomography (CT) was performed during the course of RT, a magnetic resonance imaging 3 and 12 months after RT. Injection and treatment tolerability were analyzed. The resulting distribution was compared with a control group of 30 patients with an initially fluid spacer.
Procedure- or device-related adverse events were not observed. Signs of hydrogel migration were not found in any case. The volume decreased by 25% at 3 months after RT, and small residues were detected at 12 months after RT in 3 cases (10%). The median rectal volume percentage within the 90% isodose was 3.0% (interquartile range, 1.5%-4.5%). Acute and late gastrointestinal toxicities were found in 17% and 3%, respectively (all grade 1). The median distance between prostate and rectum at the base/midplane/apex was greater for RVS in comparison to initially fluid spacer (14/12/11 mm vs 12/10/10 mm, respectively), the gel symmetry (right vs left from midline) was comparable. The application was assessed to be easier to control by the users, and visibility in cone beam CT as good.
The injection of a radiopaque viscous hydrogel spacer resulted in a prostate-rectum distance of >10 mm in most cases. The resulting rectum volume within the high-dose region and RT toxicity were very low. Advantages in comparison to the conventional hydrogel spacer are predominantly an improved placement control during the injection process and good visibility on CT.
High-dose-rate brachytherapy as monotherapy versus as boost in unfavorable intermediate-risk localized prostate cancer: A matched-pair analysis
2023, Brachytherapy
High-dose-rate brachytherapy as monotherapy (HDR-M), or as a boost combined with external beam radiotherapy (HDR-B), are both suitable treatments for intermediate-risk prostate cancer. However, data directly comparing these two approaches for men with unfavorable intermediate-risk (UIR) patients are lacking.
Patients with NCCN-defined UIR prostate cancer treated from 1997 to 2020 were identified in a prospectively maintained, single institution database. HDR-M and HDR-B patients were matched using three factors: age ±3 years; Gleason score (major and minor); and clinical T stage. Biochemical failure was defined as PSA nadir (nPSA) + 2. Available acute and chronic toxicities are additionally reported.
A total of 247 patients were identified (170 receiving HDR-B, 77 receiving HDR-M), ultimately yielding 70 matched pairs (140 patients) for inclusion. The median followup time was 5.2 years for HDR-M compared with 9.3 years for HDR-B (p < 0.001). The two cohorts had similar calculated prostate EQD2 (HDR-B 118 Gy vs. HDR-M 115 Gy, p = 0.977). No significant differences in OS, CSS, DM, LRR, or FFBF were identified. HDR-B had an increased rate of any acute grade 2+ gastrointestinal toxicity and worse acute dysuria and diarrhea. Chronic gastrointestinal and genitourinary toxicity was similar.
These data suggest that HDR brachytherapy as monotherapy is an effective treatment option for selected patients with unfavorable intermediate-risk prostate cancer and provides a more favorable gastrointestinal toxicity profile than HDR-B. Prospective trials should be conducted to refine the selection process for this heterogeneous cohort of patients.
A comparative study of rectal volume variation in patients with prostate cancer: A tertiary care center study
2023, Radiography
Every day variations in rectal filling in prostate cancer radiotherapy can significantly alter the delivered dose distribution from what was intended. The goal of this study was to see if the time of treatment delivery affected the rectal filling.
This is a retrospective study which included 50 patients with localized prostate cancer treated with volumetric modulated arc therapy (VMAT) to the primary and regional lymph nodes. Cone Beam Computed Tomography (CBCT) image-sets were done for all patient's daily setup verification. The radiation therapist contoured the rectum on all CBCT image sets. The rectal volumes delineated on CBCT and the planning CT image sets were compared. The change in rectal volumes between morning and afternoon treatments were calculated and compared.
A total of 1000 CBCT image sets were obtained on 50 patients in the morning and afternoon. The percentage variation of the CBCT rectal volumes over the planning CT scan was 16.57% in the AM group and 24.35% in the PM group.
The percentage change in rectal volume was significantly lesser in AM group compared to PM group and therefore morning treatments may result in dose distribution that is close to the intended dose distribution.
In prostate cancer radiotherapy our study suggests that a simple technique of changing the time of treatment from afternoon to morning can help to reduce the rectal volume.
Normal Tissue Integral Dose as a Result of Prostate Radiation Therapy: A Quantitative Comparison Between High-Dose-Rate Brachytherapy and Modern External Beam Radiation Therapy Techniques
2023, Advances in Radiation Oncology
Quantification of integral radiation dose delivered during treatment for prostate cancer is lacking. We performed a comparative quantification of dose to nontarget body tissues delivered via 4 common radiation techniques: conventional volumetric modulated arc therapy, stereotactic body radiation therapy, pencil-beam scanning proton therapy, and high-dose-rate brachytherapy.
Plans for each radiation technique were generated for 10 patients with typical anatomy. For brachytherapy plans, virtual needles were placed to achieve standard dosimetry. Standard planning target volume margins or robustness margins were applied as appropriate. A “normal tissue” structure (entire computed tomography simulation volume minus planning target volume) was generated for integral dose computation. Dose-volume histogram parameters for targets and normal structures were tabulated. Normal tissue integral dose was calculated by multiplying normal tissue volume by mean dose.
Normal tissue integral dose was lowest for brachytherapy. Pencil-beam scanning protons, stereotactic body radiation therapy, and brachytherapy resulted in 17%, 57%, and 91% absolute reductions compared with standard volumetric modulated arc therapy, respectively. Mean nontarget tissues receiving 25%, 50%, and 75% of the prescription dose were reduced by 85%, 76%, and 83% for brachytherapy relative to volumetric modulated arc therapy, by 79%, 64%, and 74% relative to stereotactic body radiation therapy, and 73%, 60%, and 81% relative to proton therapy. All reductions observed using brachytherapy were statistically significant.
High-dose-rate brachytherapy is an effective technique for reducing dose to nontarget body tissues relative to volumetric modulated arc therapy, stereotactic body radiation therapy, and pencil-beam scanning proton therapy.
Outcomes of salvage high dose-rate brachytherapy with or without pelvic external beam radiotherapy in patients with palpable local recurrence of prostate cancer after radical prostatectomy
2023, Brachytherapy
This study aims to evaluate the outcomes and toxicities in patients with palpable local recurrence of prostate cancer after radical prostatectomy (RP), who were treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT).
This retrospective review included patients with palpable local recurrence of prostate cancer after RP who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N = 4) or 1500 cGy x 1 (N = 2) combined with EBRT; or monotherapy with 950 cGy x 4 (N = 1) or 800 cGy x 2 (N = 1). Toxicity was graded according to CTCAE Version 5.0.
A total of 8 patients were included. Median follow-up was 49 months (range: 9–223 months). Median age at time of salvage brachytherapy was 68 years (range: 59–85 years). Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient developed acute grade 3 urinary obstruction requiring catheterization, which lasted for 1 day postbrachytherapy. One patient developed late grade 3 urinary incontinence 18 months after brachytherapy. There were no other grade 2+ toxicities.
This study demonstrates the safety and efficacy of salvage HDR-BT in the setting of palpable local recurrence of prostate cancer after RP, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy after prior radical prostatectomy.
Complications and side effects of high-dose-rate prostate brachytherapy
2021, Brachytherapy
Citation Excerpt :
Grade 3 toxicities were all <1%. These low rates of toxicity support data from a large series of 2,638 patients who received with HDR-BT (38 Gy in four fractions, 24 Gy in two fractions or 27 Gy in two fractions) compared with EBRT (70.2–82.8 Gy in 1.8 Gy fractions) by Parzen et al.; significantly lower rates of Grade 2 or higher acute and chronic rectal toxicity were noted in HDR-BT cohort (14). Tenesmus in the immediate post-BT period is often related to prostatic edema and resolves within several weeks.
To describe technical challenges and complications encountered during and after high-dose-rate prostate brachytherapy (HDR-BT) and review management of these complications.
The authors performed a systematic review of the literature on toxicities encountered after prostate HDR-BT +/− external beam radiotherapy. A total of 397 studies were identified, of which 64 were included. A focused review of literature regarding the management of acute and late toxicities also performed.
Most acute toxicities include grade 0–2 genitourinary and gastrointestinal toxicity. Overall, Grade 3+ Common Terminology Criteria for Adverse Events toxicity after HDR-BT was low [genitourinary: 0–1%; gastrointestinal 0–3%]. Rates of fistula formation were <1%, and radiation cystitis/proctitis were <14% and more commonly reported in cohorts treated with HDR-BT boost and external beam radiotherapy.
HDR-BT both as monotherapy or combined with external beam radiotherapy for prostate cancer is well tolerated. Serious complications are rare.

View all citing articles on Scopus

View full text

Original ArticleRates of rectal toxicity in patients treated with high dose rate brachytherapy as monotherapy compared to dose-escalated external beam radiation therapy for localized prostate cancer

Highlights

Abstract

Background

Methods

Results

Conclusions

Section snippets

High dose rate brachytherapy treatment

Results

Discussion

Declaration of Competing Interest

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

Brachytherapy

Radiother Oncol

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

J Urol

Original Article
Rates of rectal toxicity in patients treated with high dose rate brachytherapy as monotherapy compared to dose-escalated external beam radiation therapy for localized prostate cancer