Prostate radiotherapy Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer Jan Seppälä a, * , Marko Seppänen b , Eveliina Arponen b , Paula Lindholm a , Heikki Minn a,b a Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland b Turku PET Centre, Turku University Hospital, Turku, Finland article info Article history: Received 27 April 2009 Received in revised form 31 July 2009 Accepted 4 August 2009 Available online 18 September 2009 Keywords: Prostate cancer PET Acetate Dose escalation Probability of uncomplicated control abstract Purpose: To demonstrate the theoretical feasibility of [ 11 C]acetate PET/CT in delineating the malignant intraprostatic lesions (IPL’s) in prostate cancer and to use the data in external beam radiotherapy to boost the biologically defined target volume (BTV). Methods and materials: Twelve men with intracapsular prostate carcinoma were imaged with [ 11 C]acetate PET/CT and the data were used to delineate the BTV. Six dynamic IMRT plans were generated to each patient: a standard IMRT (sIMRT) plan with a 77.9 Gy dose to PTV (prostate gland with a 6-mm margin) and a simultaneous integrated boost IMRT (SIB IMRT ) plan to deliver 77.9 Gy, 81 Gy, 84 Gy, 87 Gy and 90 Gy to the BTV and 72 Gy to the rest of PTV. To study the theoretical dose escalation based on the delin- eation of BTV, tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs) of bladder and rectum were calculated and compared between the treatment plans. Results: [ 11 C]Acetate was used to delineate the IPL’s of all 12 patients. With every patient the TCP was increased with SIB IMRT without increasing the NTCP of the bladder or rectum. The probability of uncom- plicated control (PUC) was increased on average by 28% with the SIB IMRT treatment plans. The highest PUC was achieved with an average dose of 82.1 Gy to the BTV. Conclusions: Our study indicates that [ 11 C]acetate can be used to define the IPL’s and in combination with SIB IMRT the defined areas can theoretically be treated to ultra high doses without increasing the treatment toxicity. These results motivate the formal validation of [ 11 C]acetate PET for biological dose planning in prostate cancer. Ó 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 93 (2009) 234–240 Radiotherapy (RT) is one of the treatment options of localized prostate cancer (PCa). Dose escalation in external beam RT has im- proved treatment outcomes and even doses as high as 90 Gy are recommended to more aggressive tumors [1–4]. The increase in the dose increases the probability of tumor control but the risk of normal tissue toxicity is also increased unless the volume of the high dose area is decreased [4,5]. One of the options to reduce the irradiated volume is to use functional imaging to determine the malignant intraprostatic lesions (IPL) and focus the dose escalation only to the defined IPL’s. Different non-invasive approaches such as dynamic MRI and magnetic resonance spectroscopy (MRS) have been used to visualize the IPL’s to give high doses of radiation to the defined lesions [6,7]. The use of MRI in radiotherapy treatment planning has its limitations since an accurate CT-MRI image regis- tration is often difficult and time consuming owing to the anatomy changes of the prostate [8]. Positron emission tomography (PET) is a 3D imaging technique used for diagnosis, staging and re-staging of various neoplasms and for the evaluation of treatment response of oncological therapies. Altered lipid metabolism in PCa is reflected in increased uptake of carbon-11 labeled tracer [ 11 C]acetate (ACE) [9]. ACE outperforms [ 18 F]fluoro-2-deoxy-gluocose (FDG) in diagnosis and staging of PCa and is being evaluated in patients experiencing PSA relapse after radical prostatectomy or RT [9,10]. ACE PET is found to be more sensitive than MRI in detecting recurrent PCa by some [12] but not all investigators [11]. As a major advantage compared to FDG, acetate is not excreted in the urine and is more sensitive in the detection of PCa [9]. Pre- clinical studies indicate that ACE may detect hypoxic cells common in PCa [13]. The high sensitivity of ACE PET in diagnosing primary and recurrent PCa has already been demonstrated [9,14] but the difference in the uptake of acetate in patients with prostate cancer or with benign prostatic hyperplasia has not found to be statisti- cally significant [15,16].[ 11 C]Acetate PET imaging has also been used to localize the IPL’s [9,17]. Ciernik et al. [18] have shown [ 18 F]choline PET to be feasible to define asymmetric target volumes for external beam RT but to our knowledge, no such studies are available for ACE. We used hybrid PET/CT scanner with [ 11 C]acetate as a tracer to determine the highest concentrations of tumor and with image 0167-8140/$ - see front matter Ó 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2009.08.010 * Corresponding author. Address: Dept of Radiotherapy (821), Turku University Hospital, P.O. Box 52, 20521 Turku, Finland. E-mail address: jan.seppala@tyks.fi (J. Seppälä). Radiotherapy and Oncology 93 (2009) 234–240 Contents lists available at ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com