D.J. Krauss

Comparison of dose-escalated, image-guided radiotherapy vs. dose-escalated, high-dose-rate brachytherapy boost in a modern cohort of intermediate-risk prostate cancer patients

PURPOSE We compared outcomes in intermediate-risk prostate cancer patients treated with dose-escalated adaptive image-guided radiation therapy (IGRT) or dose-escalated high-dose-rate brachytherapy boost (HDR-B). METHODS AND MATERIALS Patients with intermediate-risk prostate cancer by National Comprehensive Cancer Network criteria were treated with either CT-based off-line adaptive IGRT (n = 734) or HDR-B (n = 282). IGRT was delivered with 3D-conformal or intensity-modulated radiation therapy with a median dose of 77.4 Gy. For HDR-B, the whole pelvis received a median 46 Gy, and the prostate 2 implants of 9.5 Gy (n = 71), 10.5 Gy (n = 155), or 11.5 Gy (n = 56). RESULTS Median followup was 3.7 years for IGRT and 8.0 years for HDR-B (p < 0.001). Eight-year biochemical control was 86% for IGRT and 91% for HDR-B (p = 0.22), disease-free survival 67% for IGRT and 79% for HDR-B (p = 0.006), and overall survival 75% for IGRT and 86% for HDR-B (p = 0.009). Cause-specific survival (8-year, 100% vs. 99%), freedom from distant metastases (98% vs. 97%), and freedom from local recurrence (98% vs. 98%) did not differ (p > 0.50 each). A worse prognosis group was defined by percent positive prostate biopsy cores >50%, perineural invasion, or stage T2b-c, encompassing 260 (35%) IGRT and 171 (61%) HDR-B patients. These patients evidenced a 5-year biochemical control of 96% for HDR-B and 87% for IGRT (p = 0.002). CONCLUSIONS Dose-escalated IGRT and HDR-B both yield excellent clinical outcomes for patients with intermediate-risk prostate cancer. Improved biochemical control with HDR-B for patients with worse pretreatment characteristics suggests that a subgroup of intermediate-risk prostate cancer patients may benefit from dual-modality treatment.

Have we reached proton beam therapy dosimetric limitations? – A novel robust, delivery-efficient and continuous spot-scanning proton arc (SPArc) therapy is to improve the dosimetric outcome in treating prostate cancer

During the recent years, proton beam therapy practice has been dramatically advanced from passive-scattering (PS) to Pencil Beam Scanning (PBS) technique [1]. Such evolution not only has improved the dosimetric quality [2], but also has simplified the operation and workflow of proton therapy centers [3]. As a result, most of the new proton therapy centers are equipped with PBS only [4]. Nevertheless, challenges still remain. More recently, there have been several discussions regarding whether the proton beam therapy has reached its dosimetric limitation [5] due to its lateral penumbra (spot size) [6], range uncertainties [7] and deliver efficiency [8]. Although, there have been a lot of efforts on defining the role of proton arc therapy via developing different techniques such as Distal Edge Tracking (DET) [9], mono-energetic arc delivery [10] or static multiple fields [11], none of the above proposed techniques could address the plan robustness, beam delivery efficiency, and the continuous rotation-delivery at the same time. Hence, there have been concerns in our scientific community that whether proton arc therapy is needed or feasible in our clinical practice [12]. Recently, our group proposed a novel Spot-Scanning Proton Arc (SPArc) algorithm to address the above three main challenges in proton arc therapy through an interactive inverse planning approach. A potential dosimetric improvement was presented over current IMPT technique especially resulting in reduction of body integral dose, better target conformity as well as a practical achievable arc treatment delivery time [13]. Herein we propose the first systematic study to exploit this novel technique of SPArc in treating prostate cancer.

SU-F-J-192: A Quick and Effective Method to Validate Patient's Daily Setup and Geometry Changes Prior to Proton Treatment Delivery Based On Water Equivalent Thickness Projection Imaging (WETPI) for Head Neck Cancer (HNC) Patient

PURPOSE With the implementation of Cone-beam Computed-Tomography (CBCT) in proton treatment, we introduces a quick and effective tool to verify the patients daily setup and geometry changes based on the Water-Equivalent-Thickness Projection-Image(WETPI) from individual beam angle. METHODS A bilateral head neck cancer(HNC) patient previously treated via VMAT was used in this study. The patient received 35 daily CBCT during the whole treatment and there is no significant weight change. The CT numbers of daily CBCTs were corrected by mapping the CT numbers from simulation CT via Deformable Image Registration(DIR). IMPT plan was generated using 4-field IMPT robust optimization (3.5% range and 3mm setup uncertainties) with beam angle 60, 135, 300, 225 degree. WETPI within CTV through all beam directions were calculated. 3%/3mm gamma index(GI) were used to provide a quantitative comparison between initial sim-CT and mapped daily CBCT. To simulate an extreme case where human error is involved, a couch bar was manually inserted in front of beam angle 225 degree of one CBCT. WETPI was compared in this scenario. RESULTS The average of GI passing rate of this patient from different beam angles throughout the treatment course is 91.5 ± 8.6. In the cases with low passing rate, it was found that the difference between shoulder and neck angle as well as the head rest often causes major deviation. This indicates that the most challenge in treating HNC is the setup around neck area. In the extreme case where a couch bar is accidently inserted in the beam line, GI passing rate drops to 52 from 95. CONCLUSION WETPI and quantitative gamma analysis give clinicians, therapists and physicists a quick feedback of the patients setup accuracy or geometry changes. The tool could effectively avoid some human errors. Furthermore, this tool could be used potentially as an initial signal to trigger plan adaptation.

SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor

PURPOSE To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. METHODS FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function of pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. RESULTS Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. CONCLUSION Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.

SU-F-T-205: Effectiveness of Robust Treatment Planning to Account for Inter- Fractional Variation in Intensity Modulated Proton Therapy for Head Neck Cancer

PURPOSE To evaluate the potential benefits of robust optimization in intensity modulated proton therapy(IMPT) treatment planning to account for inter-fractional variation for Head Neck Cancer(HNC). METHODS One patient with bilateral HNC previous treated at our institution was used in this study. Ten daily CBCTs were selected. The CT numbers of the CBCTs were corrected by mapping the CT numbers from simulation CT via Deformable Image Registration. The planning target volumes(PTVs) were defined by a 3mm expansion from clinical target volumes(CTVs). The prescription was 70Gy, 54Gy to CTV1, CTV2, and PTV1, PTV2 for robust optimized(RO) and conventionally optimized(CO) plans respectively. Both techniques were generated by RayStation with the same beam angles: two anterior oblique and two posterior oblique angles. The similar dose constraints were used to achieve 99% of CTV1 received 100% prescription dose while kept the hotspots less than 110% of the prescription. In order to evaluate the dosimetric result through the course of treatment, the contours were deformed from simulation CT to daily CBCTs, modified, and approved by a radiation oncologist. The initial plan on the simulation CT was re-replayed on the daily CBCTs followed the bony alignment. The target coverage was evaluated using the daily doses and the cumulative dose. RESULTS Eight of 10 daily deliveries with using RO plan achieved at least 95% prescription dose to CTV1 and CTV2, while still kept maximum hotspot less than 112% of prescription compared with only one of 10 for the CO plan to achieve the same standards. For the cumulative doses, the target coverage for both RO and CO plans was quite similar, which was due to the compensation of cold and hot spots. CONCLUSION Robust optimization can be effectively applied to compensate for target dose deficit caused by inter-fractional target geometric variation in IMPT treatment planning.

TH-CD-202-10: Tumor Metabolic Control Probability & Dose Response Mapping for Adaptive Dose Painting by Number

PURPOSE Adaptive dose-painting-by-number (DPbN) requires a dose-response-mapping (DRM) obtained early in the treatment course. To obtain DRM, voxel-by-voxel tumor dose response needs to be quantified. Our recent study has demonstrated that voxel-by-voxel radio-sensitivity of patient tumor can be determined using tumor-metabolic-ratio measured early during the treatment using FDG-PET images. In this study, the measurements were utilized to construct tumor metabolic control probability (TMCP) and DRM for DPbN. METHODS FDG-PET/CT images of 18 HN cancer patients obtained pre- and weekly during the treatment were used. Spatial parametric images of tumor-metabolic-ratio (dSUV) were constructed following voxel-by-voxel deformable image registration. Each voxel value in dSUV was a function of baseline SUV and delivered dose. Utilizing all values of dSUV in the controlled tumor group at the last treatment week, a cut-off function between the baseline SUV and dSUV was formed, and applied in early treatment days on dSUV of all tumors to model the TMCP. At the treatment week k, TMCP was constructed with respect to the tumor voxel dSUV appeared at the week using the maximum likelihood estimation for all dose levels, and used for DRM construction. RESULTS TMCPs estimated in the week 2 & 3 have D50 =11.1∼47.6Gy; γ50 =0.55∼0.92 respectively with respect to dSUV=0.3∼1.2. The corresponding DRM between tumor voxel dSUV and the expected treatment dose has sigmoid shape. The expected treatment dose are 26∼40Gy (for 95% TMCP) for high sensitive tumor voxels with dSUV=0.3∼0.5; and 65∼110Gy for low sensitive tumor voxels with the dSUV>1.0 depending on the time of the estimation. CONCLUSION TMCP can be constructed voxel-by-voxel in human tumor using multiple FDG-PET imaging obtained in early treatment days. TMCP provides a potential quantitative objective of tumor DRM for DPbN to plan the best dose, escalate or de-escalate, in tumor adaptively based on its own radio-sensitivity.