R Yao

Optimization for high-dose-rate brachytherapy of cervical cancer with adaptive simulated annealing and gradient descent

PURPOSE To validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)-based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer. METHODS Eight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose-volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program. RESULTS The ASA plans are higher on bladder V75% and D2cc (p=0.034) and lower on rectum V75% and D2cc (p=0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p=0.034), lower overdose index (p=0.005), and lower rectum gEUD and normal tissue complication probability (p=0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose-volume histogram could have different dose distributions. CONCLUSIONS Our optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA.

Biological Planning for High-Dose-Rate Brachytherapy: Application to Cervical Cancer Treatment

Cervical cancer has a high mortality rate approximately 35 percent in the United States and is difficult to treat successfully. One promising treatment is high-dose-rate brachytherapy, which entails delivering high-dose radiation to the tumor via the temporary implantation of radioactive seeds. This treatment promises to be particularly effective in eradicating tumors while preserving the organs. Yet, major obstacles to successful treatment remain, especially 1 determining the best seed type, spatial configuration of seeds, and seed dwelling time, and 2 improving the probability that the treatment will eliminate all malignant cells. We developed an advanced planning model to simultaneously address both of these issues. To permit taking advantage of the best available information, our model works with inputs from positron emission tomography. We begin with a multiobjective, nonlinear, mixed-integer programming model that is initially intractable. To solve the model, we introduce an original branch-and-cut and local-search approach that couples new polyhedral cuts with matrix reduction and intelligent geometric heuristics. The result has been accurate solutions that are obtained rapidly. Clinical trials at Rush University Medical Center demonstrated superior medical outcomes. These analytical techniques are applicable not only to cervical cancer, but also to other types of cancer, including breast, lung, and prostate cancer.

WE-AB-207B-11: Optimizing Tumor Control Probability in Radiation Therapy Treatment - Application to HDR Cervical Cancer

PURPOSE The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor-control-probability(TCP) with an acceptable normal-tissue-complication probability(NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. We design treatment plans that optimize TCP directly and contrast them with the clinical dose-based plans. PET image is incorporated to evaluate gain in TCP for dose escalation. METHODS We build a nonlinear mixed integer programming optimization model that maximizes TCP directly while satisfying the dose requirements on the targeted organ and healthy tissues. The solution strategy first fits the TCP function with a piecewise-linear approximation, then solves the problem that maximizes the piecewise linear approximation of TCP, and finally performs a local neighborhood search to improve the TCP value. To gauge the feasibility, characteristics, and potential benefit of PET-image guided dose escalation, initial validation consists of fifteen cervical cancer HDR patient cases. These patients have all received prior 45Gy of external radiation dose. For both escalated strategies, we consider 35Gy PTV-dose, and two variations (37Gy-boost to BTV vs 40Gy-boost) to PET-image-pockets. RESULTS TCP for standard clinical plans range from 59.4% - 63.6%. TCP for dose-based PET-guided escalated-dose-plan ranges from 63.8%-98.6% for all patients; whereas TCP-optimized plans achieves over 91% for all patients. There is marginal difference in TCP among those with 37Gy-boosted vs 40Gy-boosted. There is no increase in rectum and bladder dose among all plans. CONCLUSION Optimizing TCP directly results in highly conformed treatment plans. The TCP-optimized plan is individualized based on the biological PET-image of the patients. The TCP-optimization framework is generalizable and has been applied successfully to other external-beam delivery modalities. A clinical trial is on-going to gauge the clinical significance. Partially supported by the National Science Foundation.

Thermal effusivity: a promising imaging biomarker to predict radiation-induced skin injuries.

Abstract An effective screening technology is needed to triage individuals at the time of radiation incidents involving a large population. Three-dimensional thermal tomography is a relatively new development in active thermal imaging technology that produces cross-sectional images based on the subject’s ability to transfer heat—thermal effusivity—at the voxel level. This noninvasive imaging modality has been used successfully in nondestructive examination of complex materials; also it has been shown to predict the severity of radiation-induced skin injuries several days before the manifestation of severe moist desquamations or blister formation symptoms in mice at 40 Gy. If these results are confirmed at lower dose levels in human subjects, a thermal tomography imaging device may be an ideal screening tool in radiation emergencies. This imaging method is non-invasive, relatively simple, easily adaptable for field use, and when properly deployed, it will enhance public emergency preparedness for incidents involving unexpected radiation exposure.

SU‐E‐CAMPUS‐J‐03: Thermal Effusivity Changes Predict Radiation Exposure

Purpose: To evaluate an imaging technique to measure thermal effusivity changes following radiation exposure using 3‐dimensional temperature tomography (3DTT). Potential applications include early detection of skin reactions in cancer patients undergoing radiotherapy or large scale monitoring following a radiation disaster. Methods: We have designed an infrared (IR) imaging system and calibrated with high emissivity materials. The system consisted of an IR camera coupled with two 5000W photographic flash lamps and a portable computer. By inducing a surface temperature change with a flash lamp and measuring the thermal response by taking a rapid set of images using an IR camera, a three dimensional effusivity image can be computed. Four to five week old female SKH‐1 hairless mice were irradiated to different doses levels (20 Gy, 10 Gy, 5 Gy and 2 Gy) to the dorsal surface of the right hind thigh in a single fraction using a 1.0 cm Leipzig applicator with an Ir‐192 source. Images were obtained 30 minutes pre‐irradiation and 0.5 and 1 hour post‐irradiation. A 1.0 cm region of interest (ROI) was drawn around the irradiated region at 400 micrometer depth. Mean and standard deviations of apparent effusivity in the ROI were calculated over different time points. A plastic phantom was placed next to mice for reference. Results: The relative effusivity was computed by taking ratios of effusivities from mouse to that from the phantom. Each mouse s relative effusivity at different time points was normalized to that from pre‐irradiation. A12% increase in relative effusivity from the 20 Gy mouse and a 5% from the 2Gy mouse was seen. Conclusion: The effusivity values are increased following radiation exposure. These preliminary data suggest application of 3DTT in early prediction of radiation exposure. More experiments are warraαααnted to confirm these findings to extend the study to human subjects. This work was supported by CMCR/NIAID/NIH.

SU‐D‐500‐01: TCP‐Driven Biological Planning for High‐Dose Rate Brachytherapy

PURPOSE Tumor control probability(TCP) measures the probability that no malignant cells are left in the affected organ. It is an important clinical metric for measuring treatment success. Zaider and Minerbo provide a complex yet important TCP formalism which links the treatment duration, dose deposit, radiobiology of tumor cells and cell life characteristics. We perform feasibility tests on TCP-driven biological planning for high-dose-rate brachytherapy(HDR) where the objective maximizes TCP of the treatment plans. Plan robustness is tested, and plan quality and potential outcome significance are evaluated. METHODS CT and 18F-fluorodeoxyglucose based-PET images are obtained for 15 cervical cancer patients. All received prior external-beam radiation. The CTV prescribed dose is 5Gy for 4 fractionations, with the PET-identified pockets prescribed an escalated-dose ranging from 7.5-9.0Gy per fraction. The treatment model determines the dwell time and seed location that maximizes TCP while constraining PTV coverage, the lower/upper dose, and dose-volume shape for organs-at-risk and PTV. We contrast the standard HDR plan and PET-pocket escalated plan. RESULTS TCP ranges from 48-63% for standard plans versus 82-99% for PET-guided escalated plans. The increase is most significant with the smallest PET-identified pockets. Uniformly, urethra and rectum receive 5-8% reduced dose. There is marginal difference in PTV dose between standard and escalated plans. All resulting TCP-driven plans are clinically acceptable. CONCLUSION TCP can be a very important objective for treatment plan optimization. With advances in biological/functional imaging, there is an urgent need to incorporate radiobiological parameters and TCP within planning. This study marks the first use of TCP as the driving objective for treatment planning. The optimization problem is very difficult to solve and requires computational breakthroughs. The resulting plans improve significantly the overall local tumor control, and reduce organs-at-risk dose. Rush University began clinical studies in 2011. A long term outcome study must be carried out to gauge the overall impact.

TH‐A‐WAB‐10: Blood Perfusion of the Skin as An Indicator of Radiation‐Induced Skin Reaction

PURPOSE The oxygenation state of tissue is known to correlate with radiation-induced effects. We hypothesize that local blood perfusion of skin is directly related to the local oxygen concentration; thus blood perfusion may serve as an effective indicator for radiation-induced skin reactions. Recent advances in near-infrared laser imaging allows near real time non-invasive detection of blood perfusion in the skin. We report a preliminary study of laser imaging for its ability to detect variations in blood perfusion under different environmental, physical, and physiological conditions. METHODS A Moor instrument utilizing near-infrared laser (Moor Instruments, Devon, UK) is utilized for the investigation of perfusion in both motile phantom and human palm. The device projects a speckle pattern on the skin and measure the degree of speckle sharpness in real time. The phantom consists of two cylinders one filled with a motile standard and the other is a static reflector. The phantom is shaken for 10 seconds then is allowed to settle for 2 minutes prior to imaging. We performed laser imaging under conditions such as skin scratching, cold, or exercise. RESULTS The 10 second scan from the phantom scan shows a higher perfusion than the 20 and 30 seconds but has a lower standard deviation than that of the 20 and 30 second scans. This is probably due to the settling down of the particles in the phantom over time resulting in reduced perfusion for the 20 and 30 measurements. The palm images shows a decreased perfusion following the application of the cold pack and an increased perfusion after exercise. CONCLUSION We have demonstrated the feasibility of using near-infrared imaging to monitor skin blood perfusion. It may provide a useful tool to monitor and mitigate radiation-induced skin reactions. CMCR/NIAID/NIH.

Thermal Effusivity Changes as a Precursor to Moist Desquamation

Skin toxicity is a ubiquitous side effect in radiotherapy and can be difficult to predict. Moist desquamation in cancer patients can decrease quality of life and occasionally demand unplanned treatment breaks thus worsening outcome. In breast cancer patients, moist desquamation occurs approximately one-third of the time, and while avenues such as intensity-modulated radiation therapy exist to decrease skin side effects, they may be prohibitively expensive to distribute widely. To selectively target patients who are at risk for high skin toxicity, toxicity prediction beyond heuristics is required. This study presents 3D thermal tomography, a translation technology that employs active thermal imaging to map the thermal effusivity of skin. Irradiated mice were imaged throughout reaction development to establish a correlation between effusivity changes and eventual toxicity severity. Female hairless mice (n = 11) were anesthetized and irradiated to 40 Gy in one fraction using a 1 cm Leipzig brachytherapy applicator with an Ir-192 source. After irradiation, thermal imaging was conducted daily with a flash lamp and infrared camera. Effusivity was calculated using custom software and tracked within irradiated and contralateral control regions. Mice were retrospectively grouped into high-grade (moist desquamation present, n = 6) and low-grade (n = 5). All mice showed an increase in the relative average effusivity difference among the treated and control regions between irradiation and peak reaction between 12 and 15 days after irradiation. The high-grade group showed an earlier increase in relative average effusivity difference (mean 1.7 days after irradiation versus 4.4 days after irradiation) than the low-grade group, and had a significantly greater relative average effusivity difference between 2–5 days after irradiation. We concluded that 3D thermal tomography is quick, non-invasive, non-ionizing and exhibited a correlative difference between mice that eventually developed moist desquamation and those that only presented dry desquamation. With further development, it may prove to be a useful tool in the clinic for differentiating patients who require preventative measures to reduce skin toxicity.

SU‐E‐T‐426: Comparison of HDR Brachytherapy for Cervix Cancer Using an Adaptive Simulated Annealing Program and Oncentra‐ for Simultaneously Integrated Boost

PURPOSE High dose rate (HDR) volumetric brachytherapy is an effective method of treating advanced cervix carcinoma. Local failure is associated with multiple factors including higher maximal standardized uptake value (SUV) values in fluorodeoxyglucose positron emission tomography (FDG- PET) scans. The purpose of this study is to evaluate the ability to simultaneously boost regions of high SUV values using an in-house adaptive simulated annealing (ASA) algorithm and the Oncentra® (Nucletron V.B., Veenendaal, The Netherlands) treatment planning system, thereby potentially improving local control. METHODS Five cervix cancers were evaluated for brachytherapy treatment (tandem/ring and/or interstitial needles). MRI and PET images were obtained post-implant and fused with treatment planning CTs to define a high-risk (HR) CTV (cervix and tumor on MRI) and GTV (volume with >50% of the maximum SUV on PET). The prescribed dose was 5-6 Gy to the HR CTV and 7-9 Gy to the GTV. Treatment plans were first generated in Oncentra® with IPSA followed by manual graphic optimization by the physician. Plans were also independently optimized using the ASA program. The two plans were compared side by side and one was chosen for treatment. Dose-volume parameters including D90, V100 of targets, D2cc to the critical organs, and generalized equivalent uniform dose (gEUD) of all structures were compared between the ASA and the Oncentra plans. RESULTS Both ASA and Oncentra plans were considered acceptable by the physician in four of five cases. Two ASA plans were chosen due to better critical organ sparing and tumor coverage. Two Oncentra plans were preferred because of lower doses to critical organs. One ASA plan was not accepted because of a higher bowel dose. CONCLUSIONS Both ASA and Oncentra® planning methods produce acceptable treatment plans for optimized brachytherapy of cervix carcinoma. Continued studies are warranted to further determine the relative strength of each method. This study was supported in part by a research grant from Varian Medical System Inc.

SU‐E‐T‐642: PET‐Image TCP‐Driven Biological Planning for Cervical Cancer High‐ Dose Rate Brachytherapy

Purpose: Tumor metabolic activities obtained from PET studies may facilitate targeted dose delivery to improve local tumor control. We perform feasibility tests on TCP‐driven PET‐image‐guided dose escalation in high‐ dose‐rate‐brachytherapy(HDR). Quality and robustness of plans, TCP, and potential outcome significance are evaluated. Methods: CT and 18F‐ fluorodeoxyglucosebased‐PET images are obtained for cervical cancer patients. Planning‐target‐volumes(PTV) and critical structures are delineated. Enhanced PET signal defines boost‐target‐volume(BTV). HDR plans are optimized to deliver 35Gy Ir‐192 to PTV and 37–40Gy to BTV following 45Gy external‐beam‐radiotherapy. Each dwell location is modeled via two variables: a binary variable to indicate whether a radioactive seed will be deposited and a continuous variable to denote dwell time. The treatment planning model ensures 95% PTV‐coverage. The objective seeks rapid dose fall‐off from the prescribed dose while maximizing TCP. For each patient‐case, we compare 3 plans: 1)standard HDR plan, 2)escalation with same PTV prescription dose, and 3)escalation with reduced PTV prescription dose. Results: Standard plans have TCP values 48% to 73%. In all patients(15), escalated plans of >=37Gy to BTV result in slight reduction in rectum and bladder dose, and 40Gy for over 99% of BTV. TCP values range from 81% to 96%. When BTV is less than 15% of PTV, dose escalation and standard plans have virtually identical PTV dose. When BTV occupies over 20% of PTV, dose escalation to PET intrinsically increases PTV dose(1–5%). When PTV is prescribed 33Gy, independent of BTV, escalation can be achieved while dose to PTV, bladder and rectum are reduced. Conclusions: The presented algorithm allows for PET‐enhanced treatment, which facilitates targeted delivery of escalated dose and potential improvements in clinical outcome. Our study reveals significant improvement in tumor control and organs‐at‐risk dose reduction. Clinical studies for PET hot‐HDR dose re‐steering are in progress to test its feasibility, validate its importance, and measure potential gain in clinical outcome. The work of the first author is partially supported by funds from the National Science Foundation.