3 Tesla multiparametric MRI for GTV-definition of Dominant Intraprostatic Lesions in patients with Prostate Cancer – an interobserver variability study

Hans Christian Rischke 0 1 Ursula Nestle 1 Tobias Fechter 1 Christian Doll 1 Natalja Volegova-Neher 1 Karl Henne 1 Jutta Scholber 1 Stefan Knippen 1 Simon Kirste 1 Anca L Grosu 1 Cordula A Jilg 2 0 Department of Nuclear Medicine, University of Freiburg , Hugstetter Strasse 55, 79106 Freiburg , Germany 1 Department of Radiation Oncology, University of Freiburg , Robert Koch Str. 3, 79106 Freiburg , Germany 2 Department of Urology, University of Freiburg , Hugstetter Strasse 55, 79106 Freiburg , Germany Purpose: To evaluate the interobserver variability of gross tumor volume (GTV) - delineation of Dominant Intraprostatic Lesions (DIPL) in patients with prostate cancer using published MRI criteria for multiparametric MRI at 3 Tesla by 6 different observers. Material and methods: 90 GTV-datasets based on 15 multiparametric MRI sequences (T2w, diffusion weighted (DWI) and dynamic contrast enhanced (DCE)) of 5 patients with prostate cancer were generated for GTV-delineation of DIPL by 6 observers. The reference GTV-dataset was contoured by a radiologist with expertise in diagnostic imaging of prostate cancer using MRI. Subsequent GTV-delineation was performed by 5 radiation oncologists who received teaching of MRI-features of primary prostate cancer before starting contouring session. GTV-datasets were contoured using Oncentra MasterplanW and iplanW Net. For purposes of comparison GTV-datasets were imported to the ArtiviewW platform (AquilabW), GTV-values and the similarity indices or Kappa indices (KI) were calculated with the postulation that a KI > 0.7 indicates excellent, a KI > 0.6 to < 0.7 substantial and KI > 0.5 to < 0.6 moderate agreement. Additionally all observers rated difficulties of contouring for each MRI-sequence using a 3 point rating scale (1 = easy to delineate, 2 = minor difficulties, 3 = major difficulties). Results: GTV contouring using T2w (KI-T2w = 0.61) and DCE images (KI-DCE = 0.63) resulted in substantial agreement. GTV contouring using DWI images resulted in moderate agreement (KI-DWI = 0.51). KI-T2w and KI-DCE was significantly higher than KI-DWI (p = 0.01 and p = 0.003). Degree of difficulty in contouring GTV was significantly lower using T2w and DCE compared to DWI-sequences (both p < 0.0001). Analysis of delineation differences revealed inadequate comparison of functional (DWI, DCE) to anatomical sequences (T2w) and lack of awareness of non-specific imaging findings as a source of erroneous delineation. Conclusions: Using T2w and DCE sequences at 3 Tesla for GTV-definition of DIPL in prostate cancer patients by radiation oncologists with knowledge of MRI features results in substantial agreement compared to an experienced MRI-radiologist, but for radiotherapy purposes higher KI are desirable, strengthen the need for expert surveillance. DWI sequence for GTV delineation was considered as difficult in application. - Introduction Radiotherapy (RT) of primary prostate cancer (PCa) has been modified in the past decade by using image-guided radiotherapy (IGRT) and intensity modulated radiotherapy (IMRT) techniques [1]. Whole gland dose escalation with IMRT proved to be safe in respect of acute and late toxicities [2-4]. Although prostate cancer is typically a multifocal disease, histopathologic studies revealed that most patients with prostate cancer have at least one or two dominant intraprostatic tumor lesions (DIPL) [5,6]. For patients scheduled for primary radical radiotherapy obtaining high irradiation doses of the whole prostate are crucial to achieve high biochemical and clinical control rates [7]. However the risk of toxicity, especially in the rectal mucosa inevitably increases with dose escalatation [8], thus requiring highly precise and accurate radiation techniques. There is evidence that local prostate cancer recurrence after primary radiotherapy develops from the origination of the primary tumor or from the initial dominant intraprostatic tumor burden [9,10]. Experience with IMRT has led to the concept of focal dose-escalation using simultaneous integrated boost of DIPL. Local dose escalation on DIPL may result in significant improved disease control without increasing normal tissue complication probability (mainly acute and chronic rectal mucositis/ proctitis). This therapeutic approach has been calculated by Niyazi et al. in a mathematical model based on different assumptions of responsiveness of prostate cancer to irradiation and different sensitivities and specificities of an appropriate imaging method considering choline PET [11]. Many studies with histopathologic comparison on wholemount sections as reference standard have shown that Magnetic Resonance Imaging (MRI) using anatomic and functional sequences like Magnetic Resonance Spectroscopy (MRS), Dynamic Contrast Enhanced MRI (DCEMRI) and Diffusion weighted Imaging (DWI) results in high accuracies in detecting primary prostate cancer due to excellent spatial resolution with clear depiction of anatomy/pathoanatomy in combination with visualization of functional properties of prostatic lesions [12-23]. DWIMRI in conjunction with T2-weighted showed accuracies of 81% and 89% at 1.5 Tesla respectively [17,18]. DCEMRI showed a sensitivity and specificity for identification of cancer foci > 0.5 mL of 86% and 94%, respectively [19]. Furthermore a combination of two functional sequences at 1.5 Tesla resulted in a significantly improved area under the receiver operating characteristic (ROC) curve compared to a single functional parameter when whole-mount sections with histologically defined tumor outlines were used as reference standard. Using the combination of apparent diffusion coefficient and initial area under the gadolinium plasma concentration-time curve for detection of cancer foci resulted in an area under the ROC curve of 0.94 reflecting high accuracy. Combination of all three functional parameters (DWI, DCE-MRI and MRS) showed no further improvement [20]. Using T2w sequences at 3 Tesla results in reported sensitivities and specificities of 80%88% and 96%100%, respectively [24]. Prostate imaging at 3 Tesla benefits from higher signal to noise ratio (SNR), enables higher quality imaging than obtained at 1.5 Tesla and moreover the use of an endorectal coil can be obviated with satisfying image quality [25] and without distortion of pelvic anatomy which is important for radiotherapy planning [26]. Recently the European Society of Urogenital Radiology (ESUR) published MR guidelines for imaging in prostate cancer and structured reporting [27]. MRI-Criteria to identify an intraprostatic tumor lesion are different throughout the MRI-sequences [27]. Few studies based on consensus reading of a radiologist and radiation oncologist using functional MRI sequences for definition of DIPL have shown that focal dose escalation results in low acute toxicities [28,29] with better sparing of the rectal wall [30]. We wondered if knowledge and application of MRIcriteria (Table 1, that are cl (...truncated)