Uncomplicated Control Probability Research Articles

Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer

To demonstrate the theoretical feasibility of [(11)C]acetate PET/CT in delineating the malignant intraprostatic lesions (IPL's) in prostate cancer and to use the data in external beam radiotherapy to boost the biologically defined target volume (BTV). Twelve men with intracapsular prostate carcinoma were imaged with [(11)C]acetate PET/CT and the data were used to delineate the BTV. Six dynamic IMRT plans were generated to each patient: a standard IMRT (sIMRT) plan with a 77.9 Gy dose to PTV (prostate gland with a 6-mm margin) and a simultaneous integrated boost IMRT (SIB(IMRT)) plan to deliver 77.9 Gy, 81 Gy, 84 Gy, 87 Gy and 90 Gy to the BTV and 72 Gy to the rest of PTV. To study the theoretical dose escalation based on the delineation of BTV, tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs) of bladder and rectum were calculated and compared between the treatment plans. [(11)C]Acetate was used to delineate the IPL's of all 12 patients. With every patient the TCP was increased with SIB(IMRT) without increasing the NTCP of the bladder or rectum. The probability of uncomplicated control (PUC) was increased on average by 28% with the SIB(IMRT) treatment plans. The highest PUC was achieved with an average dose of 82.1 Gy to the BTV. Our study indicates that [(11)C]acetate can be used to define the IPL's and in combination with SIB(IMRT) the defined areas can theoretically be treated to ultra high doses without increasing the treatment toxicity. These results motivate the formal validation of [(11)C]acetate PET for biological dose planning in prostate cancer.

Comparisons of treatment optimization directly incorporating random patient setup uncertainty with a margin‐based approach

The purpose of this study is to incorporate the dosimetric effect of random patient positioning uncertainties directly into a commercial treatment planning system's IMRT plan optimization algorithm through probabilistic treatment planning (PTP) and compare coverage of this method with margin-based planning. In this work, PTP eliminates explicit margins and optimizes directly on the estimated integral treatment dose to determine optimal patient dose in the presence of setup uncertainties. Twenty-eight prostate patient plans adhering to the RTOG-0126 criteria are optimized using both margin-based and PTP methods. Only random errors are considered. For margin-based plans, the planning target volume is created by expanding the clinical target volume (CTV) by 2.1 mm to accommodate the simulated 3 mm random setup uncertainty. Random setup uncertainties are incorporated into IMRT dose evaluation by convolving each beam's incident fluence with a sigma = 3 mm Gaussian prior to dose calculation. PTP optimization uses the convolved fluence to estimate dose to ensure CTV coverage during plan optimization. PTP-based plans are compared to margin-based plans with equal CTV coverage in the presence of setup errors based on dose-volume metrics. The sensitivity of the optimized plans to patient-specific setup uncertainty variations is assessed by evaluating dose metrics for dose distributions corresponding to halving and doubling of the random setup uncertainty used in the optimization. Margin-based and PTP-based plans show similar target coverage. A physician review shows that PTP is preferred for 21 patients, margin-based plans are preferred in 2 patients, no preference is expressed for 1 patient, and both autogenerated plans are rejected for 4 patients. For the PTP-based plans, the average CTV receiving the prescription dose decreases by 0.5%, while the mean dose to the CTV increases by 0.7%. The CTV tumor control probability (TCP) is the same for both methods with the exception of one case in which PTP gave a slightly higher TCP. For critical structures that do not meet the optimization criteria, PTP shows a decrease in the volume receiving the maximum specified dose. PTP reduces local normal tissue volumes receiving the maximum dose on average by 48%. PTP results in lower mean dose to all critical structures for all plans. PTP results in a 2.5% increase in the probability of uncomplicated control (P+), along with a 1.9% reduction in rectum normal tissue complication probability (NTCP), and a 0.7% reduction in bladder NTCP. PTP-based plans show improved conformality as compared with margin-based plans with an average PTP-based dosimetric margin at 7100 cGy of 0.65 cm compared with the margin-based 0.90 cm and a PTP-based dosimetric margin at 3960 cGy of 1.60 cm compared with the margin-based 1.90 cm. PTP-based plans show similar sensitivity to variations of the uncertainty during treatment from the uncertainty used in planning as compared to margin-based plans. For equal target coverage, when compared to margin-based plans, PTP results in equal or lower doses to normal structures. PTP results in more conformal plans than margin-based plans and shows similar sensitivity to variations in uncertainty.

4. Optimization of dose distribution with individual beam compensators

Purpose C++ written module for dose distribution (DD) optimization based on data exchange with Theraplan Plus (TPP) is presented. Method An CT based radiotherapy treatment plan is prepared using the TPP system. Patient data (contours, densities) and beams geometry are exported to the TPP Export File. The compensators for each beam are designed using TPP Export File. The dose D n at n–th point is given by total primary dose: D n =∑ J W j •I jn •isq jn • exp(-μ(d r,jn -d r,max )), where J is the total number of beams, W j is the weight of the j-th beam, I jn is the relative energy fluence (REF) of jn-th pencil beam, isq is the inverse square factor, d r,jn , d r,max are radiological depths of n-th point and max dose respectively. The Probability of Uncomplicated Control (Pun) function is used as an objective function: Pun=TCP•II L (1v I •NCTP I ) where L is the number of critical organs in question, V I is the relative gravity of the injury. In the course of iteration the changes of REF values are performed sequentially for all beams. For one beam the value of Pun function for each ray is calculated separately and compared to the previous one. The new REF gives the max value of Pun. After the calculations for one beam are completed, the dose distribution for this beam is calculated with the new values of REF and process is continued for next beam until the objective function reaches its minimum. Results The program was tested for a number of real H&N cases with a U-shaped target, the spinal cord being the critical organ. It has been assumed that for an ideal DD the Pun values is 0.5. After optimization, the Pun values was never less than 0.46. Obtaining the optimal DD required usually 15 to 30 iterations and took about 5 minutes. Conclusions Theraplan Plus is an ideal tool for the user who wishes to designe his own algorithms of the DD optimization. A rapid raytracing approach developed and implemented by the authors allows for an effective optimization of the DD.

Complications of fast neutron therapy.

The purpose of the study was to identify the tissues and organs at risk following high-energy neutron-beam therapy for selected radioresistant tumors, estimating the separate probabilities of both normal tissue injury and of tumor recurrence, each in relation to the absorbed dose. Published statistical and anecdotal reports on the incidence of serious complications observed following fast neutron treatment directed to the cranium, head and neck, chest, upper abdomen, pelvis, and extremities are reviewed and dose-response parameters derived using bivariate probit or logistic analyses. We then calculate the conditional probability of uncomplicated control (PUC) at various doses, assuming that tumor cure and late injury are stochastically independent events. The median effective doses and coefficients of variation, derived for neutron irradiation of human brain and spinal cord, oropharynx, lung, stomach and bowel, rectum and bladder, and extremities, are tabulated and tentative "tolerance limits" estimated. Tolerance doses are shown to depend on several factors including beam quality, chemical composition, cell cycling rate, fraction-size, and follow-up time. In patients followed over 5 years, safe tolerance doses appear to range from < 14 GY for the central nervous system up to 22 GY in the oropharynx and mandible. Given well-determined dose-response data for specific normal tissues and the associated tumors, the separate probabilities of tumor control and of normal tissue injury at a given dose can be estimated. The particular treatment scheme yielding the highest PUC can usually be identified. The maximum PUC for neutron therapy, compared with other modalities, is a measure of both efficacy and safety for the procedure under study and thus provides a useful guide for comparing various modalities and treatment plans and for designing more effective treatment strategies.