Dose-escalation using intensity-modulated radiotherapy for prostate cancer – Evaluation of the dose distribution with and without 18F-choline PET-CT detected simultaneous integrated boost

doi:10.1016/j.radonc.2009.07.014

Radiotherapy and Oncology

Volume 93, Issue 2, November 2009, Pages 213-219

https://doi.org/10.1016/j.radonc.2009.07.014 Get rights and content

Abstract

Background and purpose

The aim of the study was to evaluate the impact of a dose escalation to an ¹⁸F-choline PET-CT defined simultaneous integrated boost (IB) on the dose distribution and changes of the equivalent uniform dose (EUD).

Materials and methods

PET-CT was performed in 12 consecutive patients for treatment planning. An intraprostatic lesion was defined by a tumour-to-background uptake value ratio >2 (GTV_PET). Dose escalation was focused only on the intraprostatic lesion. Two comparisons were evaluated: whole prostate irradiation to 76 Gy ± boost to 80 Gy (C1) and whole prostate irradiation to 66.6 Gy ± boost to 83.25 Gy (C2).

Results

PTV/GTV_PET + margins were covered by a mean EUD of 75.9/76.1 Gy vs. 77.1/80.1 Gy (C1) and 66.5/66.2 Gy vs. 71.1/82.9 Gy (C2) (p < 0.01, respectively). Concerning the organs at risk, EUD increased slightly with an additional boost (mean EUD for bladder: C1 53.2 Gy vs. 53.8 Gy; C2 43.0 Gy vs. 45.1 Gy; for rectum: C1 52.0 Gy vs. 52.6 Gy; C2 43.0 Gy vs. 45.4 Gy; p < 0.01, respectively). The distance to the organs at risk had a significant impact on the respective maximum doses in the treatment plans with IB.

Conclusions

Treatment planning with IB allows an individually adapted dose escalation. The therapeutic ratio can be improved by a considerable dose escalation to the macroscopic tumour, but only minor EUD changes to the bladder and rectum.

Section snippets

Imaging

PET-CT (Phillips Gemini TF 16) with ¹⁸F-choline was performed in 12 consecutive prostate cancer patients for treatment planning. Patients presented with the histological result and no evidence of metastases. After a choline-poor diet for 5 days the patients have fasted at least for 6 h before PET acquisition. Whole body image acquisition in supine patient position followed 1 h after the injection of 178–355 MBq ¹⁸F-choline and hydration with 250 ml electrolyte solution and 10 mg furosemide,

Results

GTV_PET and GTV_PET + margins have been found to be significantly larger for high risk vs. intermediate/low risk patients (mean GTV_PET of 9 cm³ vs. 3 cm³ and mean GTV_PET + margins of 25 cm³ vs. 12 cm³; p = 0.03, respectively). Both volumes were likewise larger for patients with a T-stage >2a vs. ⩽2a (defined before PET-CT; mean GTV_PET of 11 cm³ vs. 3 cm³ and mean GTV_PET + margins of 28 cm³ vs. 13 cm³; p < 0.01) and a biopsy Gleason score >6 vs. ⩽6 (mean GTV_PET of 8 cm³ vs. 3 cm³ and mean GTV_PET + margins of 24 cm³ vs.

Discussion

Advances in radiotherapy treatment techniques, including IMRT and IGRT, and imaging modalities offer new opportunities for an individualized treatment of prostate cancer patients. A dose-volume effect is a well-known radiobiological phenomenon – larger doses are needed for local control of larger tumour volumes [29]. Specifically for prostate cancer, the problem of local recurrences exactly at the primary localization before treatment has been reported [10]. Furthermore, a dose–response

Conclusions

Treatment planning with a simultaneous integrated boost allows an individually adapted dose escalation. The boost volume, as defined by a tumour-to-background uptake ratio >2 in a PET-CT with choline, was found to correlate with several well-established prognostic parameters. The therapeutic ratio can be improved by a considerable dose escalation to the macroscopic tumour site without considerably increasing the NTCP for the rectum and bladder. In contrast to a minor impact of the prescription

References (38)

A. Al-Mamgani et al.
Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer
Int J Radiat Oncol Biol Phys
(2008)
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)
H.A. McNair et al.
A comparison of the use of bony anatomy and internal markers for offline verification and an evaluation of the potential benefit of online and offline verification protocols for prostate radiotherapy
Int J Radiat Oncol Biol Phys
(2008)
G.O. De Meerleer et al.
Radiotherapy of prostate cancer with or without intensity modulated beams: a planning comparison
Int J Radiat Oncol Biol Phys
(2000)
V. Vitolo et al.
Assessment of carotid artery dose in the treatment of nasopharyngeal cancer with IMRT versus conventional radiotherapy
Radiother Oncol
(2009)
J. Wang et al.
The clinical feasibility of online cone beam computer tomography-guided intensity-modulated radiotherapy for nasopharyngeal cancer
Radiother Oncol
(2009)
N. Cellini et al.
Analysis of intraprostatic failures in patients treated with hormonal therapy and radiotherapy: implications for conformal therapy planning
Int J Radiat Oncol Biol Phys
(2002)
G.M. Villeirs et al.
Magnetic resonance imaging anatomy of the prostate and periprostatic area: a guide for radiotherapists
Radiother Oncol
(2005)
P.A. Kupelian et al.
Hypofractionated intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: long-term outcomes
Int J Radiat Oncol Biol Phys
(2005)
D.J. Brenner
Fractionation and late rectal toxicity
Int J Radiat Oncol Biol Phys
(2004)

C.A.F. Lawton et al.

RTOG GU radiation oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate cancer

Int J Radiat Oncol Biol Phys

(2009)

Q. Wu et al.

Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose

Int J Radiat Oncol Biol Phys

(2002)

P.B. Dunscombe et al.

The equivalent uniform dose as a severity metric for radiation treatment incidents

Radiother Oncol

(2007)

B. Emami et al.

Tolerance of normal tissue to therapeutic irradiation

Int J Radiat Oncol Biol Phys

(1991)

C. Burman et al.

Fitting of normal tissue tolerance data to an analytic function

Int J Radiat Oncol Biol Phys

(1991)

T. Rancati et al.

Fitting late rectal data using different NTCP models: results from an Italian multi-centri study (AIROPROSO101)

Radiother Oncol

(2004)

E.N. van Lin et al.

IMRT boost dose planning on dominant intraprostatic lesions: gold marker-based three-dimensional fusion of CT with dynamic contrast-enhanced and 1H-spectroscopic MRI

Int J Radiat Oncol Biol Phys

(2006)

V. Fonteyne et al.

Intensity-modulated radiotherapy as primary therapy for prostate cancer: report on acute toxicity after dose escalation with simultaneous integrated boost to intraprostatic lesion

Int J Radiat Oncol Biol Phys

(2008)

M. Bolla et al.

Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911)

Lancet

(2005)

Cited by (70)

Value of 18F-fluorocholine PET/CT in predicting response to radical radiotherapy in patients with localized prostate cancer
2021, Clinical and Translational Radiation Oncology
This study aims to establish whether metabolic parameters obtainable from FCH PET/CT can predict long-term response to radical radiotherapy (rRT) in patients with localized prostate cancer (PCa).
Drawing on a single-center database, we retrospectively reviewed the pre-treatment FCH PET/CT scans of 50 patients who underwent rRT between 2012 and 2017. Patients were enrolled if they had a follow-up of at least 3 years after rRT. Various metabolic parameters were considered for each PET/CT, including FCH multifocality. rRT was administered to all patients for a total equivalent dose of 76–80 Gy, using a standard or hypofractionated schedule. Patients were classified as disease-free (DF) if their PSA levels after rRT rose by <2 ng/mL vis-à-vis their PSA nadir, or as not disease free (NDF) if their PSA levels rose by more than 2 ng/ml.
A multifocal FCH uptake in the prostate gland was identified in 27 patients (54%). At 3-year follow-up, 37 patients (74%) were judged DF, and 13 (26%) were NDF. The SUVmax and SUVmean, and the sum of the two values in all FCH foci in the prostate gland were significantly higher for NDF patients than for DF patients (all p < 0.005). The sum of the TLCKA levels in all FCH foci was likewise significantly higher in patients who were NDF than in those found DF (median 54.5 vs. 29.4; p < 0.05). At univariate analysis, the most of PET-metrics and Gleason Score were predictors of biochemical relapse after 3-year follow-up (all p < 0.05).
Higher SUVs seems predict a worse outcome for patients with multifocal intraprostatic lesions who are candidates for rRT.
Margin verification for hypofractionated prostate radiotherapy using a novel dose accumulation workflow and iterative CBCT
2020, Physica Medica
Hypofractionated radiotherapy for prostate cancer reduces the inconvenience of an extended treatment course but the appropriate treatment margin to ensure tumor control while minimizing toxicity is not standardized. Using a novel dose accumulation workflow with iterative CBCT (iCBCT) images, we were able to validate treatment margins.
Sixteen patients treated to the prostate on a hypofractionated clinical trial were selected. Prescription dose was 3625 cGy to > 95% of the PTV in 5 fractions with a boost to 4000 cGy to the high risk GTV (if applicable). PTV margin expansion was 5 mm isotropic except 3 mm posterior, no margin for the GTV. Daily iCBCT images were obtained while practicing strict bladder and rectal filling protocols. Using a novel adaptive dose accumulation workflow, synthetic CTs were created and the daily delivered dose was recalculated. The daily dose distributions were accumulated and target coverage and organ dose were assessed.
Although the PTV coverage dropped for the accumulated dose, the prostate coverage was not compromised. The differences in bladder and anorectum dose were not significantly different. Four patients received a boost to the GTV and a significant decrease in coverage was noted in the accumulated dose.
The novel dose accumulation workflow demonstrated that daily iCBCT images can be used for dose accumulation. We found that our clinical treatment margins resulted in adequate dose to the prostate while sparing OARs. If the goal is to deliver the full dose to an intra-prostatic GTV, a margin may be appropriate.
Prostate irradiation with focal dose escalation to the intraprostatic dominant nodule: a systematic review
2018, Prostate International
Radiation therapy (RT) is a curative treatment option for localized prostate cancer. Prostate irradiation with focal dose escalation to the intraprostatic dominant nodule (IDN) is an emerging treatment option that involves the prophylactic irradiation of the whole prostate while increasing RT doses to the visible prostatic tumor. Because of the lack of large multicentre trials, a systematic review was performed in an attempt to get an overview on the feasibility and efficacy of focal dose escalation to the IDN.
A bibliographic search for articles in English, which were listed in MEDLINE from 2000 to 2016 to identify publications on RT with focal directed boost to the IDN, was performed. The review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
Twenty-two articles describing 1,378 patients treated with RT using focal boost were identified and fulfilled the selection criteria. Intensity-modulated radiation therapy (IMRT) was used in 720 patients (52.3%), volumetric modulated arc therapy was used in 45 patients (3.3%), stereotactic body radiation therapy (SBRT) in 113 patients (8.2%), and low–dose rate and high–dose rate brachytherapy (BT) were used in 305 patients (22.1%) and 195 patients (14.1%), respectively. Use of androgen deprivation therapy varied substantially among series. Biochemical disease-free survival at 5 years was reported for a cohort of 812 (58.9%) patients. The combined median biochemical disease-free survival for this group of patients was 85% (range: 78.8–100%; 95% confidence interval: 77.1–82.7%).
The average occurrence of grade III or worse gastrointestinal and genitourinary late toxicity was, respectively, 2.5% and 3.1% for intensity-modulated RT boost, 10% and 6% for stereotactic body RT, 6% and 2% for low–dose rate BT, and 4% and 4.3% for high–dose rate BT.
This review shows encouraging results for focal dose escalation to the IDN with acceptable short- to medium-term side effects and biochemical disease control rates. However, owing to the heterogeneity of patient population and the short follow-up, the results should be interpreted with caution. Considering that the clinical endpoint in the studies was biochemical recurrence, the use and duration of androgen deprivation therapy administration should be carefully considered before driving definitive conclusions. Randomized trials with long-term follow-up are needed before this technique can be generally recommended.
PET/Computed Tomography for Radiation Therapy Planning of Prostate Cancer
2017, PET Clinics
Citation Excerpt :
Of articles that reported PET/CT-guided planning of EBRT, most used radiolabeled choline PET/CT.18 Six articles evaluated localized prostate cancer and reported 178 patients with PET/CT-guided planning of a boost to GTVPET.18 In 3 articles, Pinkawa and colleagues27–29 simultaneously integrated a boost with 80 Gy for the GTVPET with a dose of 76 Gy for the whole prostate. The small boost did not increase toxicity for normal organs at risk.
Combining high dose external beam radiotherapy with a simultaneous integrated boost to the dominant intraprostatic lesion: Analysis of genito-urinary and rectal toxicityToxicity after integrated boost for prostate cancer
2016, Radiotherapy and Oncology
Local recurrences after radiotherapy are dose-dependent and occur in the dominant intraprostatic lesion (DIL). The purpose of this study was to evaluate the impact of a simultaneous integrated boost (SIB) to the magnetic resonance imaging (MRI)-defined DIL on toxicity.
Four-hundred and ten patients were treated with intensity-modulated radiotherapy. A median dose of 78 Gy was prescribed to the prostate. A SIB of 82 Gy to the DIL was performed in 225 patients (SIB+). Genitourinary and rectal toxicity on fixed time points up to 8 years were compared between SIB− (185 patients) and SIB+ patients. Chi-square, Fisher’s exact and Kaplan–Meier statistics were applied.
With a median follow up of 72 months, the six-year actuarial risk of genitourinary and rectal toxicity grade ⩾ 2 was 31% and 12% respectively. The actuarial risk of developing toxicity and incidence of symptoms at fixed time points were not increased with a SIB.
Performing a SIB did not increase genitourinary or rectal toxicity up to 8 years’ follow-up.
Dose escalation to dominant intraprostatic lesions with MRI-transrectal ultrasound fusion High-Dose-Rate prostate brachytherapy. Prospective phase II trial
2016, Radiotherapy and Oncology
To demonstrate the feasibility, safety and effectiveness of dose escalation to intraprostatic lesions with MRI-transrectal ultrasound fusion High-Dose-Rate (HDR) brachytherapy.
15 patients with intermediate-high risk prostate cancer and visible dominant intra-prostatic nodule on mpMRI have been treated. The treatment consisted of combined MRI-TRUS fusion HDR-brachytherapy (1 fraction of 1500 cGy) and hypofractionated external beam (3750 cGy in 15 fractions).
A dose of 1875 Gy was delivered to at least 98% of the DIL volume.
Median prostate volume was 23.8 cc; median number of needles was 16 (13–18). Dose escalation to DIL was feasible in 14/15 patients (93%) without violating dosimetric constraints and 1 patient presented a minimal deviation of dosimetric restrictions.
With a median follow-up of 18 months (17–24), none of the patients developed acute urinary retention or grade ⩾3 toxicity.
In addition to standard PSA follow-up, response has been assessed by mpMRI at 12 months. All patients presented adequate morphological responses on anatomical and functional sequences.
HDR brachytherapy using MRI-transrectal ultrasound fusion for image guidance is a suitable technique for partial prostate dose escalation. Tolerance and toxicity profiles are excellent and results are encouraging in terms of biochemical, morphological and functional response.

View all citing articles on Scopus

View full text

Prostate radiotherapyDose-escalation using intensity-modulated radiotherapy for prostate cancer – Evaluation of the dose distribution with and without 18F-choline PET-CT detected simultaneous integrated boost

Abstract

Background and purpose

Materials and methods

Results

Conclusions

Section snippets

Imaging

Results

Discussion

Conclusions

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

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

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Lancet

Prostate radiotherapy
Dose-escalation using intensity-modulated radiotherapy for prostate cancer – Evaluation of the dose distribution with and without ¹⁸F-choline PET-CT detected simultaneous integrated boost