Kenneth Sutherland

A Mathematical Study to Select Fractionation Regimen Based on Physical Dose Distribution and the Linear–Quadratic Model

PURPOSE Hypofractionated irradiation is often used in precise radiotherapy instead of conventional multifractionated irradiation. We propose a novel mathematical method for selecting a hypofractionated or multifractionated irradiation regimen based on physical dose distribution adding to biologic consideration. METHODS AND MATERIALS The linear-quadratic model was used for the radiation effects on tumor and normal tissues, especially organs at risk (OARs). On the basis of the assumption that the OAR receives a fraction of the dose intended for the tumor, the minimization problem for the damage effect on the OAR was treated under the constraint that the radiation effect on the tumor is fixed. RESULTS For an N-time fractionated irradiation regimen, the constraint of tumor lethality was described by an N-dimensional hypersphere. The total dose of the fractionated irradiations was considered for minimizing the damage effect on the OAR under the hypersphere condition. It was found that the advantage of hypofractionated or multifractionated irradiation therapies depends on the magnitude of the ratio of α/β parameters for the OAR and tumor in the linear-quadratic model and the ratio of the dose for the OAR and tumor. CONCLUSIONS Our mathematical method shows that multifractionated irradiation with a constant dose is better if the ratio of α/β for the OAR and tumor is less than the ratio of the dose for the OAR and tumor, whereas hypofractionated irradiation is better otherwise.

What is the appropriate size criterion for proton radiotherapy for hepatocellular carcinoma? A dosimetric comparison of spot-scanning proton therapy versus intensity-modulated radiation therapy

BackgroundWe performed a dosimetric comparison of spot-scanning proton therapy (SSPT) and intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma (HCC) to investigate the impact of tumor size on the risk of radiation induced liver disease (RILD).MethodsA number of alternative plans were generated for 10 patients with HCC. The gross tumor volumes (GTV) varied from 20.1 to 2194.5 cm3. Assuming all GTVs were spherical, the nominal diameter was calculated and ranged from 3.4 to 16.1 cm. The prescription dose was 60 Gy for IMRT or 60 cobalt Gy-equivalents for SSPT with 95% planning target volume (PTV) coverage. Using IMRT and SSPT techniques, extensive comparative planning was conducted. All plans were evaluated by the risk of RILD estimated using the Lyman-normal-tissue complication probability model.ResultsFor IMRT the risk of RILD increased drastically between 6.3–7.8 cm nominal diameter of GTV. When the nominal diameter of GTV was more than 6.3 cm, the average risk of RILD was 94.5% for IMRT and 6.2% for SSPT.ConclusionsRegarding the risk of RILD, HCC can be more safely treated with SSPT, especially if its nominal diameter is more than 6.3 cm.

Radiotherapy using a laser proton accelerator

Laser acceleration promises innovation in particle beam therapy of cancer where an ultra-compact accelerator system for cancer beam therapy can become affordable to a broad range of patients. This is not feasible without the introduction of a technology that is radically different from the conventional accelerator-based approach. The laser acceleration method provides many enhanced capabilities for the radiation oncologist. It reduces the overall system size and weight by more than one order of magnitude. The characteristics of the particle beams (protons) make them suitable for a class of therapy that might not be possible with the conventional accelerator, such as the ease for changing pulse intensity, the focus spread, the pinpointedness, and the dose delivery in general. A compact, uncluttered system allows a PET device to be located in the vicinity of the patient in concert with the compact gantry. The radiation oncologist may be able to irradiate a localized tumor by scanning with a pencil-like particle beam while ascertaining the actual dosage in the patient with an improved in-beam PET verification of auto-radioactivation induced by the beam therapy. This should yield an unprecedented flexibility in the feedback radiotherapy by the radiation oncologist. Laser accelerated radiotherapy has a unique niche in a current world of high energy accelerator using synchrotron or cyclotron.

Intrafractional Baseline Shift or Drift of Lung Tumor Motion During Gated Radiation Therapy With a Real-Time Tumor-Tracking System

PURPOSE To investigate the frequency and amplitude of baseline shift or drift (shift/drift) of lung tumors in stereotactic body radiation therapy (SBRT), using a real-time tumor-tracking radiation therapy (RTRT) system. METHODS AND MATERIALS Sixty-eight patients with peripheral lung tumors were treated with SBRT using the RTRT system. One of the fiducial markers implanted near the tumor was used for the real-time monitoring of the intrafractional tumor motion every 0.033 seconds by the RTRT system. When baseline shift/drift is determined by the system, the position of the treatment couch is adjusted to compensate for the shift/drift. Therefore, the changes in the couch position correspond to the baseline shift/drift in the tumor motion. The frequency and amount of adjustment to the couch positions in the left-right (LR), cranio-caudal (CC), and antero-posterior (AP) directions have been analyzed for 335 fractions administered to 68 patients. RESULTS The average change in position of the treatment couch during the treatment time was 0.45 ± 2.23 mm (mean ± standard deviation), -1.65 ± 5.95 mm, and 1.50 ± 2.54 mm in the LR, CC, and AP directions, respectively. Overall the baseline shift/drift occurs toward the cranial and posterior directions. The incidence of baseline shift/drift exceeding 3 mm was 6.0%, 15.5%, 14.0%, and 42.1% for the LR, CC, AP, and for the square-root of sum of 3 directions, respectively, within 10 minutes of the start of treatment, and 23.0%, 37.6%, 32.5%, and 71.6% within 30 minutes. CONCLUSIONS Real-time monitoring and frequent adjustments of the couch position and/or adding appropriate margins are suggested to be essential to compensate for possible underdosages due to baseline shift/drift in SBRT for lung cancers.

In vivo imaging of clock gene expression in multiple tissues of freely moving mice

Clock genes are expressed throughout the body, although how they oscillate in unrestrained animals is not known. Here, we show an in vivo imaging technique that enables long-term simultaneous imaging of multiple tissues. We use dual-focal 3D tracking and signal-intensity calibration to follow gene expression in a target area. We measure circadian rhythms of clock genes in the olfactory bulb, right and left ears and cortices, and the skin. In addition, the kinetic relationship between gene expression and physiological responses to experimental cues is monitored. Under stable conditions gene expression is in phase in all tissues. In response to a long-duration light pulse, the olfactory bulb shifts faster than other tissues. In Cry1−/− Cry2−/− arrhythmic mice circadian oscillation is absent in all tissues. Thus, our system successfully tracks circadian rhythms in clock genes in multiple tissues in unrestrained mice.

Evaluation of the Effectiveness of the Stereotactic Body Frame in Reducing Respiratory Intrafractional Organ Motion Using the Real-Time Tumor-Tracking Radiotherapy System

PURPOSE To evaluate the effectiveness of the stereotactic body frame (SBF), with or without a diaphragm press or a breathing cycle monitoring device (Abches), in controlling the range of lung tumor motion, by tracking the real-time position of fiducial markers. METHODS AND MATERIALS The trajectories of gold markers in the lung were tracked with the real-time tumor-tracking radiotherapy system. The SBF was used for patient immobilization and the diaphragm press and Abches were used to actively control breathing and for self-controlled respiration, respectively. Tracking was performed in five setups, with and without immobilization and respiration control. The results were evaluated using the effective range, which was defined as the range that includes 95% of all the recorded marker positions in each setup. RESULTS The SBF, with or without a diaphragm press or Abches, did not yield effective ranges of marker motion which were significantly different from setups that did not use these materials. The differences in the effective marker ranges in the upper lobes for all the patient setups were less than 1mm. Larger effective ranges were obtained for the markers in the middle or lower lobes. CONCLUSION The effectiveness of controlling respiratory-induced organ motion by using the SBF+diaphragm press or SBF + Abches patient setups were highly dependent on the individual patient reaction to the use of these materials and the location of the markers. They may be considered for lung tumors in the lower lobes, but are not necessary for tumors in the upper lobes.

Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: A simulation study

PURPOSE In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic x ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues. However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on tumor-control probability (TCP). METHODS A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. The markers were with two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of single-field uniform dose (SFUD) were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCP(r)) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model, α∕β values of 1.5, 3, and 10 Gy (RBE) were considered. RESULTS It was found that the marker of 1.5 mm diameter does not affect the TCPs with all α∕β values when two or more fields are used. On the other hand, if the marker diameter is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCP(r) by less than 3%. This is especially true when multiple (two or three) markers are used for alignment of a patient. CONCLUSIONS It is recommended that 1.5-mm markers be used to avoid the reduction of TCP as well as to spare the surrounding critical organs, as long as the markers are visible on x-ray fluoroscopy. When 2-mm markers are implanted, more than two fields should be used and the markers should not be placed close to the distal edge of any of the beams.

A feasibility study of novel plastic scintillation dosimetry with pulse-counting mode

The purpose of this study was to develop a novel scintillation dosimeter for in vivo dosimetry in Ir-192 brachytherapy via the pulse-counting mode. The new dosimeter was made from a plastic scintillator shaped into a hemisphere of diameter 1 mm and connected to the tip of a plastic optical fiber. The relationship between pulse counts and absorbed dose was derived based on the assumption that scintillation photons from the incident gamma ray are proportional to the absorbed dose. An equation for the conversion of pulse counts to water-equivalent dose was deduced wherein the pulse height spectrum from scintillation photons was assumed to be exponential. To confirm its accuracy, the dose rate distribution in a water phantom was measured by the present dosimeter and this was compared with Monte Carlo simulations, resulting in a discrepancy of less than 1.97%. It was found that the dosimeter has a wide dynamic range of linearity up to an order of magnitude of almost 10(3), including corrections for loss of counts due to pile-up.

Optimization of fluoroscopy parameters using pattern matching prediction in the real-time tumor-tracking radiotherapy system

In the real-time tumor-tracking radiotherapy system, fluoroscopy is used to determine the real-time position of internal fiducial markers. The pattern recognition score (PRS) ranging from 0 to 100 is computed by a template pattern matching technique in order to determine the marker position on the fluoroscopic image. The PRS depends on the quality of the fluoroscopic image. However, the fluoroscopy parameters such as tube voltage, current and exposure duration are selected manually and empirically in the clinical situation. This may result in an unnecessary imaging dose from the fluoroscopy or loss of the marker because of too much or insufficient x-ray exposure. In this study, a novel optimization method is proposed in order to minimize the fluoroscopic dose while keeping the image quality usable for marker tracking. The PRS can be predicted in a region where the marker appears to move in the fluoroscopic image by the proposed method. The predicted PRS can be utilized to judge whether the marker can be tracked with accuracy. In this paper, experiments were performed to show the feasibility of the PRS prediction method under various conditions. The predicted PRS showed good agreement with the measured PRS. The root mean square error between the predicted PRS and the measured PRS was within 1.44. An experiment using a motion controller and an anthropomorphic chest phantom was also performed in order to imitate a clinical fluoroscopy situation. The result shows that the proposed prediction method is expected to be applicable in a real clinical situation.

Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose–volume histograms

PURPOSE Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose-volume histograms for tumor and normal tissues of organs around the tumor. METHODS Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose-volume histogram. RESULTS It was found that the optimization of fractionation scheme incorporating the dose-volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8-32 fractions with a daily dose of 2.2-6.3 Gy. CONCLUSIONS It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose-volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.