Physics Contribution
Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using 11C-choline Positron Emission Tomography Scans

https://doi.org/10.1016/j.ijrobp.2012.01.087Get rights and content

Purpose

To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using 11C-choline positron emission tomography PET scans in patients with localized prostate cancer.

Methods and Materials

This was an RT planning study of 8 patients with prostate cancer who had 11C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV60% and SUV70%). Three IMRT plans were generated for each patient: PLAN78, which consisted of whole-prostate radiation therapy to 78 Gy; PLAN78-90, which consisted of whole-prostate RT to 78 Gy, a boost to the SUV60% to 84 Gy, and a further boost to the SUV70% to 90 Gy; and PLAN72-90, which consisted of whole-prostate RT to 72 Gy, a boost to the SUV60% to 84 Gy, and a further boost to the SUV70% to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCPPET) and on prostatectomy-defined volumes (TCPpath), and rectal normal tissue complication probabilities (NTCP) were compared between the plans.

Results

All plans for all patients reached prescription doses while adhering to dose constraints. TCPPET values for PLAN78, PLAN78-90, and PLAN72-90 were 65%, 97%, and 96%, respectively. TCPpath values were 71%, 97%, and 89%, respectively. Both PLAN78-90 and PLAN72-90 had significantly higher TCPPET (P=.002 and .001) and TCPpath (P<.001 and .014) values than PLAN78. PLAN78-90 and PLAN72-90 were not significantly different in terms of TCPPET or TCPpath. There were no significant differences in rectal NTCPs between the 3 plans.

Conclusions

IMRT dose painting for localized prostate cancer using 11C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.

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)

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    Citation 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].

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Conflict of interest: none.

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