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Researchers Continue Building Evidence Around Precision Radiation Molecular Tool


NEW YORK (GenomeWeb) – When cancer spreads, the organ site may be a significant factor in whether a patient responds to radiation treatment, suggests data published recently by a team of Moffitt Cancer Center researchers.

In the study, reported in the International Journal of Radiation Oncology, Moffit's Javier Torres-Roca and colleagues analyzed de-identified samples from more than 700 metastatic and 1,300 primary colon cancer lesions using their previously developed 10-gene radiation-sensitivity index (RSI).

The researchers found that metastatic tumors were "slightly more" radiation resistant than primary tumors, based on the RSI score. However, they found that RSI scores varied significantly according to the site of metastases, with tumors spread to the ovaries being most resistant to radiation and lung tumors least so.  

The researchers then assessed if these trends could be seen in an independent cohort of 23 patients with oligometastatic disease — a stage between localized and advanced metastatic cancer — in the lung or liver, and treated with the same radiation dose. In this cohort, lung metastases had better two-year local control rate with radiation treatment than patients with liver metastases.

Although the RSI scores weren't determined in this independent group, the researchers said that it provides indirect support for their finding that radiation sensitivity varies among metastatic tissues according to their anatomical location. "This [finding] is on top of the large evidence [on RSI] we've been building over several years," Torres-Roca told GenomeWeb, noting that his group has gathered direct evidence of RSI's validity in more than 2,000 patients.

Several years ago, Moffitt Cancer Center inked an exclusive worldwide licensing agreement with Torres-Roca's start-up CvergenX for the radiation therapy technology platform, dubbed InterveneXRT. The platform, which currently analyzes the expression of 10 genes using Affymetrix microarrays, has been under development for more than a decade and has received $2 million in research funding, much of it from the National Cancer Institute.

Torres-Roca said CvergenX is on track to launch InterveneXRT in the next year or two. Under the deal with Moffitt, the company will pay the cancer center when commercialization milestones are met, and based on sales of testing services and licensed products.

Anticipating commercialization, Torres-Roca's group has ramped up validation efforts. At the American Society for Therapeutic Radiation and Oncology's annual meeting in San Francisco last year, researchers presented multiple studies on InterveneXRT, showing it could be used to personalize radiation therapy for cancer patients across tumor types. Based on analysis involving several thousand samples, investigators found up to a 20-fold difference in response between the radiation-sensitive and the radiation-resistant cancers.

In the next study accepted for publication, researchers gauged the RSI score and molecular subtype of more than 340 breast cancer patients after they received breast conserving surgery and radiation. They found that the RSI score wasn't associated with risk of local recurrence, but when combined with molecular subtype, it did identify a subgroup of patients with triple-negative disease who were resistant to radiation therapy. Based on these findings, the study authors believe that combining RSI score with molecular subtype might help guided radiotherapy decisions for breast cancer patients.

Meanwhile, the most recent analysis had some weaknesses, noted University of Vermont's Christopher Anker and Massachusetts General Hospital's Jennifer Wo in an accompanying editorial in the International Journal of Radiation Oncology. Anker and Wo underscored, for example, that the independent cohort didn't have their RSI scores calculated. Nonetheless, they found the group's hypothesis-generating findings "provocative," and further noted that if the algorithm is validated "RSI may guide appropriate patient selection for dose escalation."

This is precisely what Torres-Roca is striving for. "We're working on integrating [RSI] into dosing protocols," Torres-Roca said. "We have developed an approach that allows us to estimate the amount of radiation that is required based on the radiosensitivity of the tumor."

CvergenX announced in April that the NCI had selected InterveneXRT to be part of its clinical development assay program, a government-funded effort aiming to identify tests that advance personalized medicine approaches. Under this program, the test will undergo analytical and clinical validation specifically to predict non response to radiation therapy in rectal cancer patients.

However, in Torres-Roca's view, RSI's value as a tool for personalizing radiation treatment cuts across clinical settings. "All molecular diagnostics are developed from the perspective of a specific clinical situation and in a specific clinical need," he said. "What we have developed is a molecular diagnostic for radiation that applies to multiple clinical situations where radiation is used."

Radiation therapy is given to cancer patients in the hopes that it will shrink tumors by damaging the DNA of cancer cells. But depending on the type of tumor tissue being treated, patients get the same dose. However, Torres-Roca's work on the RSI suggests  variability in how patients respond to radiation.

"We're dosing some patients well, but we're certainly not dosing everyone appropriately," Torres-Roca said. Of the 500,000 patients each year in the US who received radiation as their primary treatment, between 50,000 and 75,000 aren't receiving the right dose, he estimates.

Although his group hasn't yet published InterveneXRT's ability to determine radiation doses, that's the next step, Torres-Roca said. The data to date suggests to him that the RSI could be used to optimize dosing for any cancer patient receiving radiation and the tool could help genomically stratify radiation trials. This is "equivalent to a targeted drug … except it doesn't take $10 billion to develop it," he said.

According to one study, radiation treatment can cost $1,700 for a single dose or as much as $16,000, depending on the type of therapy and the schedule. Meanwhile, InterveneXRT will be priced on par with other algorithm-based tests, which on average have reimbursement levels between $2,000 and $4,500, Torres-Roca has previously said.

He estimated that up to 40 percent of cancer patients are able to stave off their disease with radiation therapy, compared to 11 percent of patients who receive targeted treatment. "If there is an opportunity for a highly successful treatment like radiation to actually be optimized, that's a huge opportunity to improve cancer outcomes," Torres-Roca said. "And it's not going to cost $100,000 to give to patients."