Increase In Tumor Dose Research Articles

TH-AB-BRB-07: A Feasibility Study for Personalized Fractionation Schedule for Lung Cancer

Purpose: Investigate the feasibility of using spatio-temporal optimization, i.e., fractionation schedule optimization combined with IMRT to select the patient-specific fractionation schedule that best maximizes the tumor biologically equivalent dose (BED). Methods and materials: The optimal fractionation schedule for a patient depends on the tumor and organ at-risk (OAR) sensitivity to fraction size (i.e., α/β), the effective tumor doubling time, and the size and location of tumor target relative to one or more OAR. We used a novel spatio-temporal optimization method to identify the number of fractions N that maximizes the tumor BED using 3D BED distribution for sixteen lung phantom cases. The selection of the optimal fractionation schedule used equivalent 30-fraction OAR constraints for the heart (Dmean < 45 Gy), lungs (Dmean < 20 Gy), cord (Dmax < 45 Gy), esophagus (Dmax < 63 Gy), and unspecified tissues (D05 < 63 Gy). To asses plan quality, we considered the min, mean, max and D95 tumor BED and the equivalent uniform dose (EUD) for optimized plans to the corresponding BED values for a conventional IMRT plan (60 Gy in 30 fractions). A sensitivity analysis was performed to assess the effects on optimal fractionation schedule of the effective tumor doubling time (Td = 3–100 days) and lag-time for accelerated repopulation (Tk = 0 to 10 days) Results: For a tumor α/β = 10Gy, tumor max, min, mean, and D95 BED were about 20% larger than the BED for the conventional prescription. The EUD for the optimized fractionation schedule was up to 17% larger than conventional prescription. For fast proliferating tumor (Td < 10 days), there was no significant increase in tumor dose but the treatment course could be shortened, offering convenience for patients and efficient allocation of resources.

The potential of shape-based treatment plan optimization for pancreatic IMRT treatments to spare organs at risk and allow for dose escalation to the tumor PTV.

316 Background: Due to the low dose tolerance of the organs at risk (OARs) in the abdomen the tumor dose for pancreatic cancer patient is restricted to 50-60 Gy in 1.8-2.0 Gy fractions when combined with chemotherapy. The goal of this study was to develop a system that can determine the minimal radiation dose to the OARs of each individual patient that is achievable while maintaining adequate tumor coverage. This could guide treatment planners to spare the OARs to the fullest extent. When the minimal doses to the OAR are achieved, the total plan can be upscaled until the normal tissue dose constraints are met, allowing for an increase in tumor dose without increased normal tissue toxicity. Methods: The minimal achievable dose to the OARs depends on its proximity to the planning target volume (PTV). The overlap volume histogram (OVH) was used to describe the spatial relation of each OAR to the PTV. A database of 33 patients, treated with IMRT, was queried to find the lowest achieved dose to an organ for any of the prior patients with less favorable PTV-OAR configurations than the current patient. This minimal dose must also be achievable for the OAR of the new patient. For 25 randomly chosen patients the lowest achievable dose to the liver and kidneys was predicted this way. Then the patients were replanned to verify if this dose could be achieved. The new plans were compared to the original clinical plans. Results: After replanning the predicted achievable dose to the liver was realized within 1 and 2 Gy for more than 86% and 96% of the patients respectively. For the kidneys these numbers were 83% and 96%. The average improvement in terms of mean dose was 1.4 Gy (range 0 – 4.6 Gy) for the liver and 1.7 Gy (range 0 – 6.3 Gy) for the kidneys. This would have allowed an increase in PTV dose of on average 5 Gy (range 0-13 Gy) based on the liver and 8.5 Gy (range 0-38 Gy) based on the kidneys compared to the original plan, without an increase in dose to the bowel, cord, and stomach. Conclusions: The lowest achievable dose to the OARs could accurately be predicted for pancreatic cancer patients within seconds. This can guide dosimetrists to spare the OARs or increase the PTV dose by 5 Gy without increased toxicity. [Table: see text]

SU-GG-I-139: Improving the Efficacy of a Radionuclide Targeting Agent by Simulating Its Pharmacokinetics

Purpose: Radionuclide therapy aims to deliver therapeutic doses to a tumor while sparing normal tissues by selective retention of a radionuclide carrying agent in the tumor. We determined how varying tumor and body clearance rates affect the dose delivered to a tumor. Method and Materials: Organ pharmacokinetics were adapted from a model targeting agent while tumor kinetics were simulated. The dosimetry of the normal organs and a tumor in the head-and-neck region was found by using MIRD software, OLINDA 1.0. The tumor percent-injected-dose (%ID) was assigned an instantaneous value of 10, 5, 4, 3 and 1% while the tumor and body washout times were varied over three orders of magnitude: 1, 0.1, and 0.01. Using 1Gy total body dose as the limit, the tumor dose for each simulation was determined. Results: For each tumor ID%, the most important kinetic parameter was tumor washout time. Delivering at least 50 Gy to a tumor when the tumor washout time was 1 did not depend on body washout time but did require that the tumor %ID was greater than 3%. In order to deliver at least 50 Gy when the tumor washout was 0.1 and body washout was 0.01, the tumor %ID needed to be greater than 3%. The greatest increase in tumor dose for each scenario was seen when the body washout was simulated at 0.1 and the tumor washout time was increased from 0.1 to 1. Conclusion: A fast body washout allows for more permissible injected activity and delivered dose. In this experiment, it was possible to achieve meaningful therapy even at a sub-optimal tumor %ID's because fast body washout and slow tumor washout permitted favorable residence times within the body and tumor. When considering the pharmacokinetics of a targeting agent, the tumor kinetics influences therapy more than fast body clearance.

Comparison of simulated annealing algorithms for conformal therapy treatment planning

The efficiency of four fast simulated annealing algorithms for optimizing conformal radiation therapy treatment plans was studied and the resulting plans were compared with each other and to optimized conventional plans. Four algorithms were selected on the basis of their reported successes in solving other minimization problems: fast simulated annealing with a Cauchy generating function, fast simulated annealing with a Lorentzian generating function, variable step size generalized simulated annealing (VSGSA), and very fast simulated reannealing (VFSR). They were tested on six clinical cases using a multiple beam coplanar conformal treatment technique. Relative beam weights were computed that maximized the minimum tumor dose subject to dose-volume constraints on normal organ doses. Following some initial tuning of the annealing parameters, each algorithm was applied identically to each test case. Optimization tests were run using different random number sequences and different numbers of iterations. The VSGSA algorithm consistently produced the best results. Using long run times, it generated plans with the highest minimum tumor dose in five of the six cases. For the short run times, the VSGSA solutions averaged larger minimum tumor doses than those of the other algorithms for all six patients, with increases ranging from 0.4 to 5.9 Gy. For three of the patients, the conformal plan gave a clinically significant increase in the minimum tumor dose over the conventional plan, ranging from 8.2 to 13.0 Gy. In two other cases, there was little difference between the two treatment approaches. For one case, the optimized conventional plan was much better than the conformal plan because the conventional beam arrangement included wedges, which offset the multiple beam advantage of the conformal plans. For equal computing times of both long and short duration, the VSGSA algorithm consistently produced conformal plans that were superior to those produced by the other algorithms. The simple conformal technique used in this study showed a significant potential advantage in the treatment of abdominal tumors. In three of the cases, the conformal plans showed clinically important increases in tumor dose over optimized conventional plans.

CCRT for non-small cell lung cancer: Sensitivity of clinical gains to organ tolerance restrictions

A method is described for allowing the entrance angles of beams to vary along the longitudinal axis of the target volume using a computer controlled radiation therapy (CCRT) treatment technique. The increase in tumor dose potentially available with this technique is evaluated for the case of a non-small cell carcinoma of the lung for which treatment is constrained by a clinically relevant tolerance condition. Tolerance is expressed in terms of that volume of unaffected contralateral lung allowed to receive > 20 Gy. The evaluation is repeated with small changes made to the constraining condition in order to explore the sensitivity of the dose gain to the definition of tolerance. For the chosen example, at least an additional 10 Gy could be prescribed to the tumor with the CCRT technique when the 20 Gy contralateral lung volume was held to less than 30%. A gain of 7 Gy was found when the 20 Gy volume was held to 27% and 1 Gy when the 20 Gy volume was reduced to 25%. CCRT treatment can result in a significant dose gain under a clinically relevant condition for tolerance. Its measured advantage strongly depends on the dose constraints specified. Sensitivity analysis is necessary to meaningfully evaluate the merits of alternative treatment techniques.

90Y · B72.3 Against pancreatic cancer: Dosimetric and biological analysis

Nude mice xenografted with a human pancreatic carcinoma cell line were injected with yttrium-90 ( 90Y) conjugated to diethylene triaminepenta acetic acid (DTPA) alone, and DTPA covalently linked to a monoclonal antibody, B72.3. The animals were sacrificed in temporal sequence to evaluate isotope distribution. Dosimetry was carried out using the principles outlined in MIRD and ICRU Report 32. Results are expressed as percent uptake per unit mass in organs and tumor and as relative absorbed dose normalized to 9°Y uptake in liver at 7 hr. When conjugated to B72.3, an 8-fold increase in isotope localization in the tumor was noted by 24 hr. When the relative absorbed dose is calculated for 90Y and 90Y · B72.3, a 26-fold increase in tumor dose is noted for the 90Y conjugate. Normal tissues show no to modest (<5X) enhanced dose with 90Y · B72.3. B72.3, therefore, deserves further investigation as a potential monoclonal antibody for targeting therapeutic radioisotopes and possibly diagnostic radioisotopes to pancreatic cancer. Radiobiological aspects of the low dose rates from radioimmunotherapy are discussed.

Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the gustave-roussy institute and the princess margaret hospital

This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis, of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an “individual risk” (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.

Repair of Potentially Lethal Radiation Damage: Comparison of Neutron and X-Ray RBE and Implications for Radiation Therapy

Experiments with Chinese hamster cells have shown that neutron irradiation does not result in repair of potentially lethal damage (PLD), i.e., that which can be influenced by changes in environmental conditions following irradiation. Since PLD is presumed to be repaired in tumors but not in normal tissues, this absence of differential sparing of tumor cells relative to normal tissues--a feature characteristic of irradiation with x rays--represents an advantage of neutrons in addition to their reduced oxygen effect. At a given dose, the difference in relative biological effectiveness (RBE) between tumors and normal tissues corresponds to a 5% increase in tumor dose with no concomitant increase in dose to normal tissues, which could be significant in cancer therapy.