It’s been a dozen years since D. Ross Camidge, MD, PhD, of the University of Colorado Cancer Center and his colleagues first published on the use of tightly-focused radiation to attack isolated active cancer sites in lung cancer patients who otherwise were responding well to targeted therapies. In the years since, that breakthrough has transformed cancer care.
“We’re changing the way we think about cancer progression,” says Camidge, a medical oncologist and the Joyce Zeff Chair in Lung Cancer Research at the CU Cancer Center. “We’re challenging the idea that cancer is either ‘You’re alive and thriving’ or ‘You’re dying.’ The traditional thinking was, the targeted treatment’s not working, so stop it. We’re saying there’s a middle ground where you’re maintaining a balance. The treatment is working, the cancer is still submissive, but you’re weeding the garden with local radiation where it’s not.”
And now he’s back with an update, drawing on a larger data set, showing fresh evidence of the efficacy of local radiation where needed alongside targeted therapies known as tyrosine kinase inhibitors (TKI) in an era when TKIs have evolved to target multiple different molecular drivers of cancer.
His article, “The Role of Local Therapy for Oligo-Progressive Disease in Oncogene-Addicted Non-Small-Cell Lung Cancer,” is appearing in the July issue of the journal Advances in Radiation Oncology.
Exploring crazy new ideas
Camidge refers to the article as just an update, but it was interesting enough to those in his field that his tweet about it has received 22,000 views to date.
Camidge pioneered the idea that, if TKI drugs are successful in suppressing cancer at all but one or a few sites, then those isolated sites can be dosed with focused radiation, while leaving the patient on targeted therapies.
That way, isolated occasional outbreaks of cancer growth can be treated with radiation one at a time as they occur, rather than taking the patient off TKIs and switching to another treatment, such as chemotherapy, that might not stop cancer from rampaging throughout the body.
It’s an idea that has changed the standard of care for certain kinds of non-small-cell lung cancer.
Camidge credits his CU Cancer Center colleague, Brian Kavanagh, MD, MPH, chair of the CU Department of Radiation Oncology, for collaborating with him and supporting work that went against prevailing wisdom in the radiation-oncology field. “We should all be so lucky to live in a time with colleagues open to exploring crazy new ideas,” Camidge says.
Darwinian oncology
The story goes back to the early 2010s. “We started to have an explosion of subdividing non-small-cell lung cancer into different molecular subtypes based on dominant mutations or gene rearrangements in the cancer,” Camidge says. “And you could pair that with specific inhibitors of the pathways involved by those mutations or gene rearrangements. When you did that, giving the right drug to the right people, you would get these dramatic responses.”
The question was what to do if cancer became active again in patients on targeted therapies.
Camidge – who started his career in the United Kingdom as a radiation oncologist before pivoting to medical oncology – says that the thinking at the time was “you don’t use radiation in advanced-stage disease because the cat was out of the bag. Back in the days when people would get chest X-rays, seeing something growing a little bit and throwing radiation at it didn’t work because you didn’t know whether there were 57 other active sites.”
But targeted therapies were getting better at controlling the disease throughout a patient’s body. Meanwhile, imaging – particularly positron emission tomography (PET) scanning – was getting more accurate, making it easier to pinpoint isolated sites where the cancer was growing. And the development of stereotactic body radiation therapy (SBRT) enabled the delivery of very precise radiation doses to isolated cancer sites with potentially fewer side effects.
“What Dr. Kavanagh and I started to see in people on the targeted therapies is that most of the disease would be under control, and only a small number of sites would be progressing,” Camidge says. “This hadn’t really been described before. It was Darwinian oncology because it was like evolution in real time. If the body is the Galapagos Islands, we’re changing the environment with the drug, and the cancer on most of the islands is still suppressed, but on one little island, there’s an adaptation and the cancer is able to grow there.”
Camidge and Kavanagh coined a term for cancer progression at only a few sites in patients with otherwise suppressed disease: Oligo-progression. “Oligos” in ancient Greek means “few.”
Healthy skepticism
All of these developments led to the theory that focused radiation could be used to attack isolated sites of progressing cancer. “And we kept people on the targeted drugs, and that kept the other sites of disease still suppressed,” Camidge says.
For patients on clinical trials given drugs in development, the norm at the time was to take patients off developmental drugs at the first sign of cancer progression; Camidge persuaded some drug companies to keep the patients on those therapies.
Their first publication on oligo-progression in 2012 reported on ALK-positive and EGFR-mutant non-small-cell lung cancers, for which early targeted therapies were available at the time. In their latest publication, Camidge and his colleagues report expanded data that includes several additional genetic-mutation cancer drivers and newer-generation therapies.
They found that over half of the patients they studied who underwent local radiation to a single active cancer site at the time of first progression had only one active site the next time their cancer progressed – the disease had not expanded to additional sites.
“Our latest update is saying, this phenomenon of oligo-progression, of seeing localized evolution occur in the presence of an otherwise effective drug, is a general phenomenon across many different types of targeted therapy,” Camidge says. And he has been hearing of similar findings by other researchers involving other cancers.
Camidge recalls that their early findings were met at first with “healthy skepticism,” but acceptance has grown over time. “The concept of oligo-progression, local radiation therapy and treatment beyond progression is now relatively well established across multiple tumor types, so that’s a success,” he says.
In addition to Camidge and Kavanagh, CU Cancer Center members who co-authored the new paper are Tejas Patil, MD; Dexiang Gao, PhD; Erin Schenk, MD, PhD; and Chad Rusthoven, MD.
Photo at top: D. Ross Camidge, MD, PhD, examines patient scans at the Anschutz Cancer Pavilion on the CU Anschutz Medical Campus. Photo by Casey A. Cass | University of Colorado.
