A fundamental challenge in the treatment planning process of multi-fractional external-beam radiation therapy (EBRT) is the tradeoff between tumor control and normal tissue sparing in the presence of geometric uncertainties (GUs). To accommodate GUs, the conventional way is to use an empirical planning treatment volume (PTV) margin on the treatment target. However, it is difficult to determine a near-optimal PTV margin to ensure specified target coverage with as much normal tissue protection as achievable. Coverage optimized planning (COP) avoids this problem by optimizing dose in possible virtual treatment courses with GU models directly incorporated. A near-optimal dosimetric margin generated by COP was reported to savvily accommodate setup errors of target and normal tissues for prostate cancer treatment. This work further develops COP to account for (1) deformable organ motion and (2) delineation uncertainties for high-risk prostate cancer patients. The clinical value of COP is investigated by comparing with two margin-based planning techniques: (i) optimized margin (OM) technique that iteratively modifies PTV margins according to the evaluated target coverage probability and (ii) fixed margin (FM) technique that uses empirically selected constant PTV margins. Without patient-specific coverage probability estimation, FM plans are always less immune to the degraded effect of the modeled GUs than the COP plans or the OM plans. Empirical PTV margins face more risks of undesirable target coverage probability and/or excessive dose to surrounding OAR. The value of COP relative to OM varies with different GUs. As implemented for deformable organ motions, COP has limited clinical benefit. Due to optimization tradeoffs, COP often results in target coverage probability below the prescribed value while OM achieves better target coverage with comparable normal tissue dose. For delineation uncertainties, the clinical value of COP is potentially significant. Compared to OM, COP successfully maintains acceptable target coverage probability by exploiting the slack of normal tissue dose in low dose regions and maximally limiting high dose to normal tissue within tolerance.

IMRT uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI), a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or “blurred” dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUDf has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques. Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

IMRT uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI), a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or “blurred” dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUDf has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques. Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

IMRT uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI), a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or “blurred” dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUDf has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques. Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

IMRT uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI), a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or “blurred” dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUDf has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques. Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.