Tumor control probability (TCP) in prostate cancer: role of radiobiological parameters and radiation dose escalation.

The objective of this work was to assess the relative impact of radiobiological parameters and radiation dose escalation on Tumor Control Probability for prostate cancer patients treated with radiation. Radiobiological parameters included alpha/beta ratios, cell surviving fraction at 2 Gy (SF(2) and clonogenic cell density (CCD). Using the Niemierko method, TCP was calculated in ten prostate cancer patients as a function of increasing radiation doses (70-140 Gy), alpha/beta ratios (1.5-20), SF(2) (0.3-0.7) and CCD (10-20 million cells/cm(3). At 70 Gy and CCD of 10 million/cm(3), TCP was above 99% for SF(2) of 0.3 or 0.4, 97.4%-98.6% for SF(2) of 0.5 and less than 2% for SF(2) of 0.6 or 0.7. With dose escalation, TCP values above 99% were demonstrated at 80 Gy for SF(2) of 0.5 and 100 Gy for SF(2) of 0.6. For SF(2) of 0.7, TCP above 99% was demonstrated with 100 Gy and CCD of 10(4)cells/cm(3) or 140 Gy and CCD of 10(7) cells/cm(3). TCP decreased with lower alpha/beta of 1.5, but at a much smaller scale compared to SF(2) changes. TCP modeling predicts that SF(2) and CCD are dominant predictors of radioresistance in prostate cancer. Radiation doses of 100 Gy or greater may be required for tumors with SF(2) of 0.6 or above. Relating clinical tumor prognostic indicators such as Gleason score and PSA to radiobiological parameters will allow us to identify subsets of patients in need of higher radiation doses and adjuvant therapy to maximize treatment outcomes.

Intensity modulated radiation therapy versus three-dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison.

The present study compared the dosimetry of intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) techniques in patients treated for high-grade glioma. A total of 20 patients underwent computed tomography treatment planning in conjunction with magnetic resonance imaging fusion. Prescription dose and normal-tissue constraints were identical for the 3D-CRT and IMRT plans. The prescribed dose was 59.4 Gy delivered at 1.8 Gy per fraction using 4-10 MV photons. Normal-tissue dose constraints were 50-54 Gy for the optic chiasm and nerves, and 55-60 Gy for the brainstem. The IMRT plan yielded superior target coverage as compared with the 3D-CRT plan. Specifically, minimum and mean planning target volume cone down doses were 54.52 Gy and 61.74 Gy for IMRT and 50.56 Gy and 60.06 Gy for 3D-CRT (p < or = 0.01). The IMRT plan reduced the percent volume of brainstem receiving a dose greater than 45 Gy by 31% (p = 0.004) and the percent volume of brain receiving a dose greater than 18 Gy, 24 Gy, and 45 Gy by 10% (p = 0.059), 14% (p = 0.015), and 40% (p < or = 0.0001) respectively. With IMRT, the percent volume of optic chiasm receiving more than 45 Gy was also reduced by 30.40% (p = 0.047). As compared with 3D-CRT, IMRT significantly increased the tumor control probability (p < or = 0.005) and lowered the normal-tissue complication probability for brain and brainstem (p < 0.033). Intensity-modulated radiation therapy improved target coverage and reduced radiation dose to the brain, brainstem, and optic chiasm. With the availability of new cancer imaging tools and more effective systemic agents, IMRT may be used to intensify tumor doses while minimizing toxicity, therefore potentially improving outcomes in patients with high-grade glioma.