title: Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.
abstract: The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose-volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7-31.2% depending on the alpha/beta ratio of prostate cancer (p<0.001), and a mean increase in rectal NTCP of 3.0% (p<0.001). If only the DIPTN was dose escalated, the TCP was increased by 6.4-27.5% (p<0.003) and the rectal NTCP was increased by 1.8% (p<0.01). In the dose escalated DIPTN IMRT plans, the highest rectal NTCP was seen in patients with IPTNs in the posterior peripheral zone close to the anterior rectal wall, and the lowest NTCP was seen with IPTNs in the lateral peripheral zone. The ratio of increased TCP to NTCP may represent an improvement in the therapeutic ratio, but was dependent on the position of the IPTN relative to the anterior rectal wall. Improvements in prostate imaging and prostate immobilization are required before clinical implementation would be possible. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.
authors.affiliation: Department of Radiotherapy, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, SM2 5PT, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Nutting
authors.forename: C M
authors.initials: CM
authors.lastname: Corbishley
authors.forename: B
authors.initials: B
authors.lastname: Sanchez-Nieto
authors.forename: V P
authors.initials: VP
authors.lastname: Cosgrove
authors.forename: S
authors.initials: S
authors.lastname: Webb
authors.forename: D P
authors.initials: DP
authors.lastname: Dearnaley
mesh_terms: D000465:Algorithms; D006801:Humans; D008297:Male; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000379:methods*; D014057:Tomography, X-Ray Computed