Overview of Clinical and Research Activities at Georgetown University Hospital Dalong Pang, Ph.D. Department of Radiation Medicine Georgetown University Hospital
Clinical Operation Two Varian linear accelerators Varian IX Varian Trilogy
3-D CRT IMRT VMAT Electron
Two Cyberknives
SRS, SBRT lung prostate Brain
One Gamma-Med HDR unit Mostly Gyn using vaginal cylinders
Prostate Seed Implant B&K ultrasound, Variseed planning, Pd-103, either Mono (125 Gy) or boost (76 Gy)
Cs-137 LDR Implant Ir-192 LDR Implant
Electronic Brachytherapy Carl Zeiss Intra-Beam System (IORT) Robotic arm applicators X-ray source
Intra-Beam RT Surgical removal of the tumor Applicator with X-ray probe positioned in the lumpectomy site. Treatment last for about 20 to 50minute to deliver 20Gy in single fraction to the applicator surface
Basic Characteristics A single fraction RT to lumpectomy wall X-ray energy: 50 kvp Dose: 20 Gy at cone surface and 7 Gy at 1-cm depth Treatment time (20-60 minutes) depends on cone size (1.5 cm to 6 cm)
SIR-Spheres Y-90 Resin Microspheres Use of Radioactive Y-90 resin spheres for the treatment of metastatic colorectal cancer in the liver.
Y-90: beta emitter, half life: 64 hours, mean energy: 0. 93 MeV, mean range: 2.5 mm. Intra-arterial delivery Amount of activity depends on patient size, weight, liver lobe volume and lesion volumes BSA 2 0.725 0.425 m 0.20247 ht m wt(kg)
Basic and Clinical Research 1. Atomic Force Microscopy (AFM) investigation of DNA fragmentation by high-let charged particles DNA is the critical cellular target of radiation; DNA DSBs are the most lethal DNA lesions. Higher LET leads to higher RBE- rationale for heavy charged particle therapy High-LET radiation induces complex DSB lesions that are more difficult to repair.
Method for Quantifying DSBs: AFM
Irradiation of DNA Molecules at Various Laboratories Georgetown: Electron AFRRI: Neutron Oak Ridge: Beryllium Chiba Japan: Argon
AFM Measurement of Irradiated DNA e - n 0 Be ++ Ar ++
DNA Fragment Size Distributions of Electron and Neutron Irradiated DNA e - n0 Be ++ Ar ++
Average DSB and DSB Spatial Distribution can be derived from the size distribution profiles. DSB clustering can be demonstrated <DSB>= n/n 0 Sparely: Low-LET Clustered: High-LET
Significance of Research 1. Direct visualization of individual DNA fragments 2. Experimental demonstration of clustered DNA DSB 3. Correlation of DNA clustering with LET of radiation 4. Data aid in theoretical modeling of DNA damage: Monte Carlo simulation, Microdosimetry 5. DNA damage repair
2. Circulating Cell-Free DNA: a Potential Biomarker for Cancer Diagnosis and Treatment Response? 1. Cancer Diagnosis 2. Treatment Response 3. Similar genetic or mutational information in DNAs extracted
Quantitative-PCR is the primary method for studies of cfdna: Concentration Mutation DNA fragment size index Cancer vs. no cancer Concentration is significantly greater in patients with cancer There is a difference in fragment size index Treatment response Successful treatment results in reduced concentration
Hypothesis: DNA fragment size distributions may reveal more information on tumor characteristics AFM used to measure DNA sizes
Our Focus: Radiation Treatment Response Blood samples collected from patients with pancreatic cancer, metastatic colorectal cancer, prostate cancer before and after treatments. blood spin Extraction of ccfdna and AFM imaging Measurement of fragment size distribution
Construction of a Nanofluidic device for rapid DNA size measurement (T. Kole, MD) In collaboration with NIST nanofabrication Lab Working on image process software for automatic fragment size measurement
4. Treatment Planning Automation: Knowledge-Based Optimization Continuation and expansion of OVH-driven treatment planning optimization (Binbin Wu, PhD) Application in Cyberknife Planning Application of IMRT database to VMAT planning Application in plan generation for different institutions
OVH-based optimization aid in Cyberknife planning A data base containing 500 cyberknife plans OVH calculated, PTV, OAR volumes compiled New plans generated retrospectively and prospectively Comparison to existing plans showed equal or better plan quality
Comparison of OVH Plans with Clinical Plans Mean dose to bladder reduces from 17.4Gy in CPs to 13.8Gy in APs 20.7% (3.6Gy) reduction Mean dose to rectum reduces from 16.8Gy in CPs to 14.8Gy in APs 12% (2Gy) reduction
Use of one institution s database to generate plans for another institution 1. H&N plans from a Dutch hospital: 45 patient H&N plans using 7 beam IMRT. SIB-IMRT, 68Gy and 50.3Gy. 2. New plan generated for each patient using JUH database 178 H&N SIB-IMRT plans with three-dose-level: 70Gy, 63Gy and 58.1Gy. 3. Comparison between the plans on DVH demonstrates comparable quality between the OVH-driven plans and the Dutch plans.
100 100 90 90 CP 80 PTV50.3 PTV68 80 AP 70 60 50 40 30 20 10 CP AP Cord 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 74 Dose (Gy) 100 90 80 70 Larynx CP AP 70 60 50 40 30 20 10 Brainstem Mandible 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 74 Dose (Gy) 100 90 80 70 AP CP 60 Oral cavity 60 50 40 30 50 40 30 I Parotid 20 10 20 10 C Parotid 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 74 Dose (Gy) 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 Dose (Gy)
New Development Construction for a Mevion S250 proton system underway
Treatment room Planar X-ray panels Mobile CT
Project Progress current December, 2016
Thank You!