To Market, To Market: Product Ideation to Fruition in Radiation Oncology

The end of the 19th century brought the discovery of x-rays and, within 3 years, the use of radiation to treat cancer. Over the next 125 years, radiation therapy (RT) technologies have considerably advanced in tandem with the field’s understanding of tumors and healthy tissue response. Globally, pioneers have painstakingly toiled to uncover improved radiation delivery methods and save patient lives.

The evolution of RT-related technologies and treatment techniques, from the simple to complex, is far from complete. For innovators to make a lasting impact, conceiving a groundbreaking idea is merely the first step. Numerous efforts are required to bring an invention to market, necessitating preparation, resolve, and creativity, says Cedric Yu, DSc, professor emeritus at the University of Maryland School of Medicine (UMSOM) in Baltimore

“It’s very important to think outside the box about what’s possible,” says Dr. Yu, who holds more than 20 patents. “Don’t limit yourself with what you have. Be a little wild! If you believe you have a good idea, push for it.”

Javier F. Torres-Roca, MD, senior member in the Department of Radiation Oncology at Moffitt Cancer Center in Tampa, and professor of Oncologic Sciences in the University of South Florida Morsani College of Medicine, likewise has a proclivity for unconventional ideas, honed with persistence over 20 years of scientific development. That grit helped lead to his co-founding of Cvergenx Inc., a genomic technology company that provides decision support to optimize RT delivery through individualized radiation response. 

“As stewards of radiation therapy, we have a duty to improve its efficacy. A key way you do that is by integrating biology into the field,” says Dr. Torres-Roca.

As these thought leaders share their unique journeys of innovation, an attorney addresses intellectual property (IP) considerations for an informed development process.

A Pursuit of Valid Ideas

As a medical physicist, Dr. Yu invented intensity-modulated arc therapy (IMAT),¹ a rotational form of intensity-modulated radiation delivery that has been widely adopted for cancer treatment. Using rotational beams was a simple idea, he says.

“If the patient were transparent and we could see the tumor and its surrounding organs, we would find that certain directions are better for shooting the tumor than others, and within a given direction, a certain area is better than others,” Dr. Yu says. “If you have the beam rotating around the patient and changing the shape of the port and the intensity of the beam, you get the best results in a very short treatment time.”

When these and other transformative concepts were met with resistance or doubt, he would critically re-examine their validity. “I asked myself, ‘Is the idea fundamentally valid or invalid?’ If your idea is valid, it is worth pursuing with patience and perseverance,” he says.

Dr. Yu is also CEO of Xcision Medical Systems LLC, in Columbia, Md., which was founded on idea he had as a physicist at Michigan’s William Beaumont Hospital to improve treatment for women with early stage breast cancer. As an alternative to a lengthy course of surgery and radiation, the hospital used radioactive interstitial treatment with a dozen needles inserted through the breast.

“I thought ‘This is too brutal and painful just to look at it; there’s got to be a better way,’” he recalls. He came up with the idea of aiming the radiation from all around a “big bowl” at a common point, and having the breast dropped into the bowl to be treated, enabling highly focused dose distribution. The method is a stereotactic body radiation therapy-based (SBRT) approach that spares healthy tissue and helps improve quality of life and outcomes.

Dr. Yu’s initial grant application for developing the idea was unscored. By keeping track of clinical research on breast cancer treatments, he found that the idea of SBRT for breast cancer was valid. With support from UMSOM, he launched Xcision and licensed the exclusive rights to his patent from UMSOM to develop the idea. After he applied for a grant and received $4M from the National Institutes of Health, Xcision developed the GammaPod System, which was FDA approved in 2017 and has been used on about 1,000 patients. One GammaPod treatment can be delivered postoperatively to replace weeks of RT² or preoperatively as an ablative treatment,³ both with very low toxicities. 

Everyone is proud of what they’ve created, and they want to share it. Don’t! Your innovation can end up in the public domain.

“When one has an idea that could be translated to clinical impact, he should first have the idea patented through his employer,” Dr. Yu says. This makes it more attractive for commercial companies to turn the idea into a product to gain competitive advantage in the market.

Steven Miller, MD, JD, a partner at IPath PLC, agrees that strong intellectual property is vital for both protection and growth.

“As a startup, put yourself in the shoes of a [big medical device company]: What would make your innovation — your product and everything that goes with it — most attractive? The answer is some level of global IP protection,” Miller says, suggesting an international application filing under the Patent Cooperation Treaty (PCT).  

“Even relatively simple devices or systems are potentially very profitable,” he adds, “creating a high incentive for others to copy a product.”

Wisely, Dr. Yu was aware of IP and ownership with his IMAT invention, for which he has two patents licensed by two leading companies in radiation therapy.

“Whether or not one should develop an idea by starting a business or licensing to another company is a complicated question with far too many considerations,” Dr. Yu explains. “Most ideas are not sufficient or commercially viable to support a commercial venture by itself. And starting a business is one of the most difficult tasks [to] take on in life.”

A Biologic Paradigm Shift

More than two decades ago, Dr. Torres-Roca identified a void in radiation oncology: the failure to incorporate individualized biology in RT treatment decisions. His quest became including a biological component to quantify the effect of radiation as an opportunity to optimize treatment.

“We’ve seen that medical oncology has adapted their treatment [with] immunotherapy and biomarker-driven decision-making. But in radiation, we’re still stuck in this old paradigm of giving the same dose of radiotherapy to everyone. There is no way this can be optimal for each individual patient,” he says, even when using dose escalation and other techniques. When the uniform dose coming out of the machine interacts with the patient, the biological effect is different depending on whether the patient is sensitive or resistant to the dose.

Dr. Torres-Roca’s current technology, genomic-adjusted radiation dose (GARD), essentially quantifies the difference between those patients by combining two algorithms — the linear-quadratic model, which helps identify dosing strategies, and the radiosensitivity index (RSI), which evaluates expression levels of 10 genes that predict tumor radiosensitivity.⁴ He and Moffitt colleagues started developing the signature in 2003 using a public database with access to baseline gene expression for dozens of cell lines. The researchers developed algorithmic models of genes that were good at predicting radiation response and in subsequent years integrated complexity into the modeling using systems biology and scale-free network principles.

Dr. Torres-Roca has determined that GARD outperforms physical dose in terms of predicting patient outcomes,⁵ and that it can predict the therapeutic benefit for each patient to quantify how likely the patient is to benefit from radiotherapy and whether adjusting the dose may be of value. In turn, this will enable a more intelligent design of clinical trials.

The RSI/GARD technology is established at the CLIA laboratory at Moffitt. Three ongoing prospective clinical trials are evaluating GARD-based RT dose optimization in soft-tissue sarcoma (NCT 05301283), triple-negative breast cancer (NCT 05528133) and non-small cell lung cancer (NCT 05873439), says Dr. Torres-Roca, noting that development in molecular diagnostics can be a lengthy and tedious process.

“We’ve been forced to develop a long scientific validation path that is almost equivalent to a drug, but you’re not going to charge as much as a drug — a significant barrier to commercial development of RSI and GARD in a very technology-driven industry,” he says.

Financial and Legal Considerations

Indeed, the ability to monetize an invention is a key consideration. “For a venture to be successful, it has to be better for the patients, cost-effective, and make the hospital money,” says Dr. Yu, noting that financial planning for development typically “takes longer and costs more than you thought.”

“Don’t underestimate the premarket costs of developing a new medical device,” agrees Miller, which include IP, FDA or regulatory approval, manufacturing, a CMS code for reimbursement, a patent clearance search, opinion work, and other expenses.  

“The process of prosecuting IP is long and expensive,” adds Dr. Torres-Roca. “International patents very often need to be translated to the language of each jurisdiction where they are being prosecuted … [which is] a critical business decision. Once granted, there are maintenance fees to maintain the patent,” he explains, adding that when patents expire, inventors must file again — sometimes repeatedly — with refinements to protect the invention.

Additional advice is to keep details zipped. Miller has worked with clients who have lost all rights to their invention after disclosing elements at a scientific meeting, in an article, or through shop talk.

“Everyone is proud of what they’ve created, and they want to share it. Don’t!” Miller emphasizes. “Your innovation can end up in the public domain.”

Miller highly recommends consulting with a medical device IP attorney from the get-go about the complex considerations of ownership. “The more you understand about the process ahead of time, the better,” he says.

Talking with other innovators can also help researchers become mentally and financially prepared to bring a technology to market, says Dr. Yu. “You’ll learn a lot,” he says. “Although it’s hard, it’s a very rewarding experience.”

“People shouldn’t be afraid to try and change,” concludes Dr. Torres-Roca. “I’d rather fail trying to do something that can make a difference than succeed at doing what everyone else is doing.”

References

1. Yu CX. Intensity modulated arc therapy using dynamic multileaf collimation: an alternative to tomotherapy. Phys Med Biol. 1995;40(9):1435-1449.
2. Trovo M, Reverberi C, Prisco A, et al. PD-0234 Single-fraction stereotactic radiotherapy for partial breast irradiation using the GammaPod system. Radiother Oncol. 2023;182:S169-S170. doi:1016/S0167-8140(23)08823-0
3. Rahimi A, Leitch M, Dogan B, et al. (2023) Early results of a phase I pre-operative single fraction ablative trial for early stage breast cancer. Int J Rad Oncol Biol Phys. 2023;117(4):E7-E8. doi: 10.1016/j.ijrobp.2009.06.014
4. Eschrich SA, Pramana J, Zhang H, et al. A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int J Radiat Oncol Biol Phys. 2009;75(2):489-496. doi:10.1016/j.ijrobp.2009.06.014
5. Scott JG, Berglund A, Schell MJ, et al. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol. 2017; 18(2):202-211. doi:10.1016/S1470-2045(16)30648-9