International Journal of Radiation Oncology*Biology*Physics
Physics ContributionIntensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using 11C-choline Positron Emission Tomography Scans
Introduction
There is a clear dose-response relationship between radiation dose and biochemical tumor control rates in prostate cancer. A meta-analysis (1) showed that an increase of radiation therapy (RT) dose from 70 Gy up to 80 Gy resulted in an increase in biochemical prostate-specific antigen control rates by 19% in patients with high-risk prostate cancer. An extrapolation of that data suggests that in this population, doses higher than 90 Gy may be necessary to maximize tumor control rates. However, such high doses are impossible to deliver using conventional external beam RT without an unacceptably high risk of severe toxicity 1, 2.
“Dose painting” (3) is a strategy that has been proposed to enable the delivery of such high RT doses without giving an unacceptably high risk of toxicity. This is the concept of using functional imaging to identify regions within the conventional target volumes that may have different biology and thus may require escalated doses of radiation to achieve tumor control.
Previous studies of local recurrence patterns indicate that strategies such as dose painting may be beneficial. Pucar et al (4) showed that dominant intraprostatic lesions (DILs) identified on pretreatment magnetic resonance imaging (MRI) are the main sites of local recurrence following whole-prostate RT (4). It is reasonable then to hypothesize that if higher doses of radiation are delivered to DILs, lower local recurrence rates may result.
Previous studies have examined the use of dose painting in prostate cancer, using various imaging modalities ranging from dynamic contrast-enhanced (DCE) MRI (5), MR spectroscopy (MRS) (5), 18F-fluorocholine PET (6), and 11C acetate PET (7). This study examines the use of dose painting in prostate cancer by using 11C-choline PET scans.
This study is an extension of a previous study performed at Austin Health (8). In that study, 11C-choline PET scans were compared with prostatectomy specimens to quantify the degree of correlation for the purposes of target volume definition for prostate RT. The current study uses the contouring methods developed from that study to determine the technical feasibility of using 11C-choline PET for dose painting by contours.
Section snippets
Study design
The RT planning study cohort consisted of 8 patients with intermediate to very high-risk prostate cancer who had 11C-choline PET scans prior to radical prostatectomy. Their characteristics are described in Table 1.
Image coregistration
11C-choline PET scans and CT scans were acquired and coregistered. Following radical prostatectomy, transverse sections were taken of the prostate. A single pathologist outlined each tumor focus on the histological sections and then scanned the sections directly on a flatbed scanner.
Results
In all 24 RT plans generated, the target volume objectives as well as the OAR dose constraints were met without exception. The dose distributions for the 3 plans for a representative patient (patient 8) are shown in Fig 2. The TCPPET and TCPpath values for each patient for each plan are shown in Table 3.
The mean TCPPET values for PLAN78, PLAN78-90, and PLAN72-90 were 65%, 97%, and 96%, respectively. PLAN78-90 had a 49% higher TCPPET than PLAN78, and this difference was statistically significant
Discussion
This study demonstrates the technical feasibility of dose painting for localized prostate cancer. Two dose painting approaches were compared with standard RT, and both were found to be achievable while staying within published dose constraints. Both dose painting approaches had TCPs superior to standard RT while not having significantly different NTCPs. There was also no significant difference in TCPs and NTCPs between the 2 dose painting strategies; however, 1 patient’s TCPpath decreased when
Conclusions
Dose painting by contours using 11C-choline PET scans is technically feasible. This study evaluated biological modeling based on both PET-defined DILs and pathologically defined DILs, showing that both PLAN78-90 and PLAN72-90 resulted in higher TCPs than PLAN78, while having similar NTCPs. As such, both PLAN78-90 and PLAN72-90 have higher therapeutic ratios. Caution should be applied in using the dose escalation/de-escalation strategy as evidenced by the drop in TCPpath for a single patient
Acknowledgment
We are grateful to Graham Hepworth, Statistical Consulting Centre, University of Melbourne, for assistance with statistical analyses; Brad Warkentin, University of Alberta, for assistance with biological modeling; and Tim Liu for help with the RT planning.
References (20)
- et al.
Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials
Int J Radiat Oncol Biol Phys
(2009) - et al.
Use of normal tissue complication probability models in the clinic
Int J Radiat Oncol Biol Phys
(2010) - et al.
Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality
Int J Radiat Oncol Biol Phys
(2000) - et al.
Clinically significant prostate cancer local recurrence after radiation therapy occurs at the site of primary tumor: magnetic resonance imaging and step-section pathology evidence
Int J Radiat Oncol Biol Phys
(2007) - 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) - et al.
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
Radiother Oncol
(2009) - et al.
Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer
Radiother Oncol
(2009) - et al.
Histopathological correlation of 11C-choline PET scans for target volume definition in radical prostate radiotherapy
Radiother Oncol
(2011) - et al.
How low is the alpha/beta ratio for prostate cancer?
Int J Radiat Oncol Biol Phys
(2003) - et al.
Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations
Int J Radiat Oncol Biol Phys
(1991)
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Value of 18F-fluorocholine PET/CT in predicting response to radical radiotherapy in patients with localized prostate cancer
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2018, Physics and Imaging in Radiation OncologyCitation Excerpt :The role of 11C and 18F choline PETCT in the diagnosis of primary PCa is controversially discussed as some studies have shown a low sensitivity for detection of primary PCa, whereas other studies reported a higher sensitivity [96–98]. In a planning study Chang et al. compared mpMRI with [11C] choline-PET/CT for GTV-delineation based on histology reference and postulated a superiority of choline PET/CT [99]. However, more recent data showed that 11C choline PET/CT failed to distinguish between PCa and non-PCa tissue in the prostate [100,101].
Conflict of interest: none.