Research Efforts Examining Novel Radiation Approaches Flourish at Fox Chase Cancer Center

Eric M. Horwitz, MD, FABS, FASTRO

Advances made in the field of radiation oncology are allowing patients with cancer to derive greater benefit with fewer toxicities, according to Eric M. Horwitz, MD, FABS, FASTRO, and Stephanie E. Weiss, MD, FASTRO. Many efforts being made at Fox Chase Cancer Center seek to further move the needle forward across several tumor types.

“The technology in radiation oncology has gotten so much better over the years. We have levels of precision that just didn't exist 2 decades ago,” Horwitz, the chair of radiation oncology, a professor, and Gerald E. Hanks Endowed Chair in Radiation Oncology, said. “We can now give really big doses of radiation to really small areas. It works really well, has potentially fewer adverse effects [AEs], and it's also quicker. That’s a good thing, especially during a pandemic. The less time that people have to spend in hospitals, the better.”

In an interview with OncLive^®, Horwitz and Weiss, who is the chief of the Division of Neurologic Oncology, a professor in the Department of Radiation Oncology, and the director of the Radiation Oncology Residency and Fellowship Training Program at Fox Chase Cancer Center, highlighted ongoing research efforts with radiation therapy that are generating excitement at their institution.

OncLive^®: What research efforts in the radiation space have you participated in at Fox Chase Cancer Center?

Horwitz: For prostate cancer and breast cancer, in our department, we have been studying [hypofractionated radiation] since the early 2000s. We have done our own phase 2 and 3 clinical trials, [in addition to] having actually [performed] other Cooperative Group [trials] across the United States. Last year, we published the 10-year update of our own phase 3 randomized prospective clinical trial for hypofractionation in prostate cancer [NCT00062309]. What we saw was that one is equally effective compared to conventionally fractionated treatment, and the AEs are basically the same. For us, it is the standard, and it really has become the national standard in prostate cancer. It is exciting that this is what we have been doing and studying for years, not just for prostate cancer.

SBRT therapy just reflects giving a few big doses of radiation, but we now know from treating different sites of metastatic disease for different cancers, that this is really effective. We can control disease and delay the initiation or the continuation of systemic therapy. It is also much easier to coordinate with systemic therapy because we are not giving somebody 8 weeks of radiation. It can be done over a week, or a week and a half. There has also been a lot of large national and international clinical trials that have supported the use of SBRT, where it works well [and is] well tolerated. The medical world is using SBRT to treat oligometastatic disease. That is a big thing that we internally have been very interested in over the years. [However], in radiation oncology as a whole, it has really become a new standard and is a new way of treating people, which is very exciting. Primary treatment of prostate cancer, breast cancer, and other sites, plus using this technology to treat metastatic disease, is a big direction that radiation oncology is headed. We [could] already be there.

In our department [we have] a project that has been going on for almost 7 years now. We are testing, potentially, a new way of treating cancer [called] radiodynamic therapy. Photodynamic therapy, which is an FDA-approved treatment where you use a certain wavelength of light to activate a drug that then creates little molecules that attack cancer cells, [was] approved for treating certain surface tumors and certain lung tumors. The limitation is that the light can only penetrate millimeters, [and] can only treat things on the surface. There are not that many indications for it. [However], with high energy X-rays, there is no limitation to the distance.

A group, initially in China, discovered that a certain energy of radiation has the same effect that the laser light does, but you can aim the radiation anywhere. We call this radiodynamic therapy; it has never been [used] outside of China, except now, it is being [investigated] at Fox Chase. It requires a high energy accelerator to make the X-rays that activate the drug. We have what is called a racetrack microtron in our department now, which is just a big accelerator that generates 45 MV photons. Traditionally, in radiation oncology, we use 6 or 10 [MV photons]. Sometimes we use 18 MV, at most, so [we are producing] high energy X-rays. It is actually very low dose radiation, but the high energy X-rays activate the drug. We have a phase 1 trial going on right now for all different cancers, from head and neck [to] the chest, abdomen, and pelvis. [In the] trial we are investigating safety but based on what we expect to see and what we are seeing [thus far], there are many different options we are going to have as we move forward into future studies.

Right now, we are looking at it for patients who have [progressed on] either conventional, or other investigational therapies, and potentially have no other options. We started accruing patients this year. It is a cancer center study, not just a radiation oncology study, so we are working with our colleagues in medical oncology, surgical oncology, and in the lab.

What are some of the ongoing research efforts being made at Fox Chase that your colleagues should look out for?

Stephanie E. Weiss, MD, FASTRO

Weiss: [We have] a few projects [with radiation therapy where] the goal is to fully dose, and therefore, optimally treat the cancer while sparing normal tissue. A few investigations are looking into that [concept]. [For example,] Charles Lee, MD, PharmD, is looking at the constraints, with respect to dose, that go to the mandible for head and neck cancers. The hypothesis is that after adopting these more stringent mandibular constraints—which we have—we are going to see a lower rate of osteoradionecrosis; this is essentially death of the bone in the mandible after head and neck radiation and is, unfortunately, a relatively common AE. We hope to do this without compromising coverage.

Rebecca Shulman, MD, is [also] looking at head and neck osteoradionecrosis, and she is interrogating our retrospective experience to look at the timing of this, how it is best managed, and how long before patients will subsequently need to undergo surgery, which is one of the treatment [approaches] for this. She is also interrogating a national database and looking at the prevalence of osteoradionecrosis to get a baseline [understanding] of what occurs out there, or at least, what gets reported. We can compare that with what we are doing [at Fox Chase and in practice].

Dr Schulman [is also] looking at the radiation response of some cultured cells in vitro, and the actual treatment response in real patients who have breast cancers with BRCA1 mutations. BRCA1 genotyping is thought to predict treatment response, but it is a relatively underexplored concept; this would really extend our routine distinction between sporadic and hereditary breast cancers.

Abigail Copella, MD, is looking at [the effect of] chemotherapy after stereotactic body radiotherapy [SBRT] on survival in patients with early non–small cell lung cancer. With this approach, we are essentially able to use a shortened course of radiation, and a higher dose per day, keeping that therapeutic ratio in mind. These patients were able to [be treated] very successfully with SBRT in terms of local control. However, the question is, if you have cells that have escaped that local region, and just doing radiation to that area is not going to help, [are they] going to need systemic therapy? That is not well studied in conjunction with SBRT. The aim [of this research] is to look at using adjuvant chemotherapy to improve failure elsewhere in the body, and overall survival. The second part of that study will look at hypofractionation, a shortened course of radiotherapy, in central, non–small cell cancers, which are essentially lesions that are near a lot of normal, soft tissue; it will evaluate what we are able to do safely.

Aneesh Pirlamarla, MD, is looking at pulsed low-dose rate [LDR] radiation and its use for reradiation in rectal and anal cancers. [This is the] same principle [that other studies] in prostate [cancer have evaluated]. Before, we used to say the normal tissues just had as much dose as it can tolerate; [however,] it looks like we can retreat. With pulsed LDR, we are looking to see whether this is a good, effective treatment with acceptable toxicity.

Nina Burbure, MD, PhD, is looking at a rare tumor: hypopharyngeal cancer. She is interrogating a national database to see whether certain treatments, specifically radiation vs surgery, improve survival [in this cancer], as well as what the role of human papillomavirus is in the prognosis for these patients.

Another [ongoing] project [at Fox Chase] is essentially looking at early-stage oropharyngeal cancer. Investigators seek to determine in patients who are receiving a single-modality fraction—for instance, just radiotherapy—whether any demographics or any tumor characteristics are associated with greater survival if they receive chemoradiation. Again, it's asking that dual versus single modality question.