“Isn’t there some kind of blood test we can do?”
It was a question that David Kozono, MD, PhD, of the Department of Radiation Oncology, heard his patients ask frequently. While undergoing radiation therapy to treat their lung cancer, they longed for a simple, noninvasive blood test that could reveal whether their tumor was responding to treatment or predict how likely they were to experience side effects afterward.
No such blood test exists, but it would be great if one did, Kozono would gently tell them.
He hopes he will soon have a different answer, thanks to a department-wide initiative he spearheaded called BROADBAND (BWH Radiation Oncology All-Department Bio-repository to Accelerate New Discoveries). Every patient seen in Radiation Oncology is now asked if they would like to contribute a blood sample for study. His study team also asks patients if they would like to give researchers permission to study various data routinely collected by care providers about the patient’s medical history, details about radiation treatments and responses to quality-of-life surveys.
The breadth and depth of information should help researchers more quickly identify biomarkers that can be used to determine how patients will respond to treatment, Kozono said.
“If we could make predictions with these biomarkers and adjust treatments on the fly, we would be able to better tailor our therapy for each patient and reach the overriding goal we all have: personalized medicine,” he said.
BROADBAND is one of two parallel initiatives in the department aimed at maximizing opportunities for patients to participate in research and increasing the number of novel trials offered within Radiation Oncology, explained Paul Nguyen, MD, the department’s vice chair for Clinical Research.
“We want to learn from every patient who comes through our doors, and, at the same time, patients often appreciate the opportunity to join the fight against cancer by participating in research,” Nguyen said. “The future of cancer care is personalization of therapy and uncovering genomic information that will help us find new targets for cancer treatment.”
For the parallel effort to grow the number of novel trials in the department, Daphne Haas-Kogan, MD, chair of Radiation Oncology, has found one not-so-secret ingredient to be effective: collaboration.
Shortly after joining the Brigham in 2014, she kicked off translational science meetings that brought together physicians and scientists across different departments, sparking new ideas for research.
Fostering multidisciplinary collaboration within Radiation Oncology has also been key, she added. All members of the team – including administrative staff, biologists, child life specialists, doctors, dosimetrists, nurses, physicists, postdocs, residents and therapists, among others – are working to support cutting-edge research and care, Haas-Kogan said.
“All the expertise was present, but it seemed a little siloed,” she said. “Bringing together brilliant, dedicated people to cross-cultivate ideas across different specialties and disciplines has been incredibly instrumental to the success of our goals.”
Meanwhile, collaboration across institutions has also fueled novel trials in the department. Among those are two multi-institutional studies Kozono is working on in coordination with Alliance Foundation Trials, a research organization within the Alliance for Clinical Trials in Oncology. Both studies focus on therapeutics that could augment existing lung cancer treatments.
The first trial looks at a PARP1 inhibitor, a class of drugs that targets enzymes involved in DNA damage repair. Chemotherapy and radiation therapy work by damaging tumor DNA, but the PARP1 enzyme can undo the effects of treatment by triggering a DNA repair response. The second study examines the effects of PD-L1 inhibitors, which trigger the immune system to target cancer cells that may not be eliminated with standard treatments.
More broadly, other researchers in the department have launched clinical trials in the past 18 months that explore the use of new medications and radiation therapies in treating brain, gynecological, pediatric and prostate cancer.
“One hallmark of the Brigham is providing not only fabulous clinical care, but also very effectively translating laboratory findings into new, cutting-edge therapies,” Haas-Kogan said. “There’s a culture here of dedication to research and clinical care – and merging the two to serve patients in the best possible way.”
Partnering with the Biobank
One area where Kozono hopes to see BROADBAND provide insight is in identifying a biomarker that shows which patients are likely to develop radiation pneumonitis as a side effect of lung cancer treatment.
The condition causes lung inflammation and scarring, resulting in shortness of breath, coughing and discomfort. The symptoms typically don’t present until three to six months after treatment, and by that time a lot of the damage is irreversible despite steroid treatment, Kozono said.
“About 10 percent of patients are affected, but we cannot entirely predict who is going to develop this,” he said. “If you could predict who these patients may be, it would be worth it to start them on high-dose steroids early on.”
About 70 percent of Radiation Oncology patients approached about BROADBAND have consented to participate in some form – providing a blood sample, permission to analyze their clinical data or both. While thrilled with the early success, the department hopes to grow that rate.
“We need large numbers of patient samples to conduct meaningful research,” Nguyen said. “We just didn’t have enough, so we decided to invest in the future by offering this to every patient.”
BROADBAND had several predecessors within the department, but they were all smaller, ad hoc efforts targeted to specific patient populations. The project is the first initiative in Radiation Oncology that aims to collect samples from every patient, regardless of demographic or disease type.
To help establish this library of samples, Kozono approached the Partners Biobank team at Partners HealthCare to share resources. Established in 2010, the Biobank is a system-wide research program aimed at advancing investigations in personalized medicine. Three blood samples are collected from consented patients – for analysis of DNA, plasma and serum – and made available for distribution to Partners investigators for studies approved by the Partners Institutional Review Board.
Now, when Radiation Oncology patients come in for an initial radiation planning appointment at BWH, they have the opportunity to simultaneously consent for BROADBAND and the Biobank. Once obtained, the samples are processed and stored in the Biobank facility. Any samples collected during or after treatment are processed and stored at BWH.
“The infrastructure was already there, and they were looking for help getting more samples, so it was a win-win in that respect,” he said.
Having samples at all three points of treatment – before, during and after – will be invaluable to researchers, Kozono said. Being able to study them in conjunction with a patient’s clinical and treatment data “takes it to the next level,” he added.