Histopathology-derived modeling of prostate cancer tumor control probability: Implications for the dose to the tumor and the gland.

PURPOSE: To evaluate the impact of GTV-CTV dose differentiation by simulating response of prostate patients to radiotherapy, considering histopathology of prostatectomy specimens. MATERIAL AND METHODS: Tumors' cell numbers (N0) and Gleason Scores (GS) were derived from histopathology of 25 specimens. Index lesions and tumors ⩾0.5cm(3) were considered GTV. Satellites <0.5cm(3) constituted the tumor load in the CTV. Each patient's tumor control probability (TCP) was simulated using the linear quadratic model and considering the N0 while assuming either a constant or GS-dependent α and ß. RESULTS: 19/25 patients had multi-focal disease. In 11 patients the CTV contained GS 4+3 or 4+4 tumors. Compared to the GTV, the CTV pathology was more favorable. For an α=0.140Gy(-1), a GTV dose of 79Gy with a CTV dose of 72Gy achieved an 80% TCP in the population. Varying α between 0.160-0.118Gy(-1) with GS, a GTV and CTV dose of 80Gy and 70Gy also gave an 80% TCP. CONCLUSIONS: Considering only N0, our simulations suggest that a GTV-CTV dose differentiation of 7Gy would not compromise TCP of the patient population. When assuming an increased radiosensitivity with lower GS, a further dose differentiation of 10Gy might be feasible.

Gross tumor volume and clinical target volume in prostate cancer: How do satellites relate to the index lesion.

PURPOSE: There is an increasing interest for dose differentiation in prostate radiotherapy. The purpose of our study was to analyze the spatial distribution of tumor satellites inside the prostate. METHODS AND MATERIALS: 61 prostatectomy specimens were stained with H&E. Tumor regions were delineated by the uro-pathologist. Volumes, distances and cell densities of all delineated tumor regions were measured and further analyzed. RESULTS: Multifocal disease was seen in 84% of the patients. The median number of tumor foci was 3. The median distance between the index lesion and the satellites was 1.0 cm, with a maximum of 4.4 cm. The index lesions accounted for 88% of the total tumor volume. The contribution of tumor foci<0.1 cm(3) to the total tumor volume was 2%. The median cell density of the index lesion and all satellites, regardless of size, were significantly higher than that of the prostate. CONCLUSIONS: Satellites do not appear in a limited margin around the index lesion (GTV). Consequently, a fixed CTV margin would not effectively cover all satellites. Thus if the aim is to treat all tumor foci, the entire prostate gland should be considered CTV.