Collaborative research opportunities abound in both the clinical and basic sciences, in conjunction with other Sections at the Medical Center as well as with investigators at the Norris Cotton Cancer Center, the Geisel School of Medicine, the Thayer School of Engineering, The Dartmouth Institute, and the graduate departments of Dartmouth College.
Our Section boasts state-of-the-art treatment technologies and techniques, equipped with six megavoltage linear accelerators (five with electron beam capability), two CT simulators, 19 treatment-planning workstations, HDR remote after-loading capability, and extensive brachytherapy expertise including Pd-103, Ir-192 (HDR & LDR), Y-90 (Zevelin, Therasphere, Pancrit), Sm-153, Ra-223, I-131, and Cs-131.
Innovative radiobiology applications include Velocity deformable registration and RBE formalism, HBO chambers, Cherenkov imaging of humans, EPR oximetry and dosimetry, and several animal-model technologies (e.g. a research accelerator, a Cs-137 irradiator, an advanced small animal imaging facility, and iron nano-particle therapy).
Our Section recently acquired an MRI-based linear accelerator for clinical use (one of the first dozen in the United States) – Viewray’s MRIdian® linear accelerator. It is scheduled for installation in 2019. This new technology represents the very cutting edge of image-based radiation therapy, opening entirely new vistas of research projects and clinical applications for the years ahead.
Our Section has the capacity to do detailed oxygen radiosensitization studies of hyperbaric oxygenation in human subjects in large part due to the proximity of our hyperbaric chambers to the radiation oncology suite – an almost unique capability across the North American continent.
There are numerous research projects ongoing within the Section, as our faculty are engaged in several collaborations across the Medical Center, Dartmouth College, the Thayer School of Engineering, and The Dartmouth Institute.
Just a few examples of faculty-led initiatives include:
- NCI Program Project Grant (P01): Direct and Repeated Clinical Measurement of p02 for Enhancing Cancer Therapy. Co-Principal Investigators: Philip Schaner MD, PhD, Brian Pogue PhD, Benjamin Williams PhD. Grant Number: 5P01CA190193-03. Direct Costs: $5,074,400. In this project, Dr. Schaner and colleagues are investigating the use and development of electron paramagnetic resonance (EPR) imaging technology for measuring and tracking tumor and tissue oxygenation during therapy.
- DoD Breast Cancer Research Program Breakthrough Award. Lymph Node Metastases – Optical Diagnostic and Radiation Therapy. Principal Investigator: Lesley Jarvis, MD, PhD. Grant Number: W81XWH-16-1-0005. $539,278. In this project, Dr. Jarvis and colleagues are investigating the measurement of Cherenkov radiation as a means for obtaining qualitative and quantitative characterizations of breast and axillary tissues during radiation therapy.
- NCI R01. Optical Cherenkov calibration for human radiation therapy. Co-PI: David Gladstone, ScD. Grant Number: R01EB023909. Direct Costs: $423,145. In this project, Dr. Gladstone and colleagues are pursuing the use of Cherenkov imaging as a means for accurate 3-D calibration of radiation dosimetry. It should be noted that, related to this project, Dr. Gladstone’s team was awarded “Best in Physics (Imaging),” at the 2017 annual meeting of the AAPM and the Editors’ Choice Award for best publication in Medical Physics in 2018.
- NCI U01. Overcoming the immune-suppressive tumor microenvironment through in situ vaccination nanotechnology. Co-PI: Jack Hoopes, DVM, PhD. Grant Number: U01CA218292. In this project, Dr. Hoopes and colleagues are studying engineered virus-like nanoparticles derived from plants for use in cancer immunotherapy. Current data demonstrate potent efficacy in mouse models and canines with metastatic cancer.
- NCI UM1. A long term multidisciplinary study of cancer in women: The Nurses’ Health Study. Co-PI: Nirav Kapadia, MD, MS. In this project, Dr. Kapadia and colleagues are investigating large-scale questions that arise from linkage of this data-rich cohort study to Medicare claims and other data sources with potential clinical, public health, and public policy impact.
Many other externally-funded grants focus on applications of radiation therapy. Examples include:
- R01NS095411. Sanchez/Hoopes/Ratner (multi-PI), 12/15-11/19
Targeting Tumors with NF1 Loss.
Develop and test, in brain tumor xenographs, chemotherapeutic agents that will target tumors with NF1. The novel NF1 drugs being produced are being combined with hypofractionated RT.
P30CA023108 NIH/NCI, Leach: PI Hoopes: (Radiation/Imaging Shared Resource PI), 12/15-11/20
NCI designated Norris Cotton Cancer Center CCSG: Irradiation and Imaging Core Grant-Shared Resource Director.
To provide the accurate and safe delivery of experimental ionizing radiation to cells and animals, for cancer researchers and provide oversight and directions of the animal imaging and microscopy program.
NCCC Prouty Grant, Hoopes and Fiering (multi-PI), 12/16-12/18
Magnetic nanoparticle enhancement of radiation and immune therapy for malignant melanoma.
Determine if combined local treatment of a melanoma tumor with both hyperthermia and radiation will stimulate stronger systemic antitumor immune.
NIBIB R01 14080707 (MERIT extension award), Samkoe: PI, Hoopes: Co-I, 09/17-08/24
In vivo optical receptor concentration imaging of EGFR in head and neck carcinoma.
Study is designed to assess, in real-time targeted drug binding in tumors. Hoopes et al will exploit the spontaneous oral SCC canine tumors in this research. Included treatment of canine oral cancers with hypofractionated following imaging
NIH NCI U01CA218292, Steinmetz / Fiering / Hoopes: Multi PI (UCSD/Dartmouth), 09/17-08/22
Overcoming the immune-suppressive tumor microenvironment through in situ vaccination nanotechnology and radiation.
Assess engineered virus-like nanoparticles, from plants, for use in cancer immunotherapy. Data demonstrate potent efficacy in mouse models and canine patients with metastatic cancer.
NIH1R21CA197409, Luke (PI), Hoopes (Co-I), 05/16 – 04/19
Super localization ultrasound imaging with targeted laser activated nanodetectors and ionizing radiation.
Design and test the ability of a specific type of novel ultrasound to identify micrometastasis
R44 CA199681, Ware: PI , Pogue Co:I, 09/15 – 08/18
NIH/National Cancer Institute (DoseOptics SBIR)
Video rate optical verification tool for radiotherapy treatment.
The project goal is to develop a water tank based radiation beam delivery imaging system for regular Quality Audit of radiotherapy systems. The company, DoseOptics LLC, is making the commercial prototype and it will be tested in a subcontract to Radiation Oncology at Dartmouth-Hitchcock Medical Center.
R44 CA232879, Ware: PI, Pogue: CoI, 08/18 – 07/19
NIH/National Cancer Institute (DoseOptics SBIR)
A non-contact optical patient and beam dosimetry system for continuous in vivo radiotherapy verification.
The project goal is to develop a commercial prototype system for combined optical surface mapping and Cherenkov dose imaging, for remote verification of patient position and beam delivery in radiotherapy.
NIH/NIBIB R01 EB024498, Pogue:PI, 08/17 – 04/21
Cerenkov excited luminescence sheet imaging (CELSI).
This project is focused on development of an independent Cherenkov excited luminescence scanned imaging system for high resolution molecular imaging in small animals.
NIH/NCI R01 CA233564-01, Sentman, Hoopes: Co- PI, 06/19 - 04/24
How local tumor radiation therapy enhances CAR T cell efficacy and host anti-tumor immunity.
In this application we propose to understand the mechanism and efficacy potential of NK CAR T cells and hypofractionated / SBRT in solid tumor therapy. Currently resubmitted.
Beyond externally financed projects, through research funds available internally through the Norris Cotton Cancer Center numerous faculty-driven initiatives have developed over the years, some evolving into larger-scale innovations and multi-institutional collaborations and clinical trials.
For example, our team has published innovative work in the exploration of hyperbaric oxygen treatment as a potential radiation sensitizer, recently applied in conjunction with combined modality therapy for head & neck tumors. (Please see Hartford et al, IJROPBP 2017.) We have now extended this work to study HBO in conjunction with stereotactic radiosurgery for the treatment of brain metastases. These project are planned for extension to multi-institutional settings in Phase II-III studies.
Another current example of NCCC-funded work includes radiation predictive assays. In collaboration with basic scientists at the medical school, our group is studying analyses of changes in chromosomal make-up as a predictor of response to pre-operative combined modality therapy in the treatment of esophageal cancer – a potentially important tool in the selection of patients for organ preservation.
Large-scale NCI-funded cooperative group trials
The Section has been a decades-long full member of the RTOG, and into the present continues as a very active participant in NRG/RTOG clinical protocols. Further opportunities for clinical trials’ work and enrollment exist in other NCI-funded cooperative groups, and also through Dartmouth-sponsored initiatives, either initiated through our Section or in collaboration with other investigators. Through its Office of Clinical Research, the NCCC supports a broad collection of clinical trials at Dartmouth-Hitchcock, including active engagement with NRG at the national level.