Liquid Biopsy New Hope for Precision Therapies for Retinoblastoma Tumours
Retinoblastoma is a type of eye cancer that develops in the light-sensitive lining of the eye, called the retina.
Retinoblastoma can occur at any age but mainly occurs in children younger than 5 years of age and most often in those younger than 2.
In many developing countries where tumours can progress until they literally burst out of eyes, retinoblastoma remains an often fatal diagnosis, whereas in other countries the survival rate has risen to 98%.
Retinoblastoma was one of the first cancers to have its genetic origins identified in the late 1980s — a finding that helped launch the current era of personalised treatments that have transformed treatment of breast, lung, and prostate cancer.
To date though, children who develop these rare tumours have not benefited from that wave of precision diagnostics and therapies. This is mainly due to the fact that doctors have not been able to biopsy the tumours for genetic information that could guide treatment, without removing the very eyes the clinicians are trying so hard to save.
You can read about our own Little Fighter, Helen’s story HERE
The good news is that a young oncologist at Children’s Hospital Los Angeles followed a hunch that there may be a safe, non-invasive way to biopsy retinoblastoma tumours by using fluid that’s removed from the eye during chemotherapy and typically discarded.
According to a small study recently published in JAMA Ophthalmology showed that DNA found in the fluid matched the DNA found in tumours – a discovery that could lead to a new liquid biopsy.
Dr. Jesse Berry, 36, has long been frustrated by not being able to tell the parents of her young retinoblastoma patients what to expect. Even in cases that look identical, some patients quickly respond to standard chemotherapy, while others don’t respond after years of difficult treatments. In other cancers, biopsies can guide oncologists toward the best treatment options.
Doing a biopsy on tumours in the retina, the thin layer of nerve cells in the back of the eye, risks spreading cancer by unleashing tumour particles into the rest of the body and the brain.
“It’s ironic. The retinoblastoma gene … opened up a huge, huge area of research that benefited so many cancer patients,” Berry said. “But not retinoblastoma patients.”
A few years ago, Berry was performing a routine chemotherapy injection into the eye of a retinoblastoma patient that required her to first withdraw a tiny amount of fluid.
“I discarded the fluid and syringe and just had a thought — maybe there’s something in the fluid,” said Berry, a paediatric ocular oncologist at CHLA and assistant professor at the University of Southern California’s Roski Eye Institute.
“I started writing my research proposal that night.”
Damian Salgado, who Berry treated in 2015, had a tumour that was so large and advanced, that his right eye had to be immediately removed. Damian’s mother Kati decided to allow Damian’s eye and eye fluid to be used in Berry’s proof-of concept study (he was one of three patients involved) because she hates to think of other parents going through what she did.
Few people thought the team would be able to find tumour DNA in the fluid of the eye, or aqueous humor, Berry said. The fluid sits in a different chamber of the eye where tumour cells cannot migrate. And they knew that even if any DNA from the tumour had made it to the fluid, it would only be in tiny fragments that are difficult to detect.
Working with James Hicks, a biologist at USC, the team was able to detect tumour DNA in tiny fragments that had likely been loosed as tumour cells died and broke up.
The new liquid biopsy technique could be the first step toward offering more personalized, genetic-based cancer treatments to retinoblastoma patients from the very start, potentially saving more eyes and vision. In the case of very aggressive tumours, it could allow doctors to advise quickly removing eyes to spare children from years of needless chemotherapy when eyes are unlikely to be salvageable.
“It can be devastating as a doctor to make that call,” Berry said. “You’ve fought for three years to save the eye.”
Outside retinoblastoma experts say they’re excited about the finding because they’ve never been able to grab samples of the tumours they treat without removing the eye. But they warn that any new treatments are many years away.
“It won’t cure children on its own, but it is a step toward saving eyes,” said Dr. Brenda Gallie, an expert on the genetics of retinoblastoma at the Hospital for Sick Children in Toronto.
About 50 – 70 % of patients with aggressive tumours do not respond to standard chemotherapy and suffer recurring tumours, Berry said.
“A major issue is that our therapies are not targeted,” said Dr. Jonathan Kim, who directs the retinoblastoma program at CHLA and the ocular oncology service at USC’s Roski Eye Institute and was part of the research team.
Standard chemotherapy agents don’t work specifically on blocking retinoblastoma tumours but instead broadly inhibit DNA replication. That means lots of side effects, such as anaemia, infections, lost hair, and damage to bone marrow.
“Children often get sick on chemotherapy for retinoblastoma. It’s considered fairly toxic,” Kim said.
For children who don’t respond to chemotherapy, there is cryotherapy and laser treatment and radiation available — and of course removal of the affected eye. But what Kim and Berry really want in their arsenal are precision treatments that target specific pathways in the retinoblastoma tumour, as well as information on which tumours might be resistant to chemotherapy.
While there is no genetic diagnostic test yet available based on their findings, Kim and Berry said it is relatively simple for an ophthalmologist to remove eye fluid that could then be analysed at a genetic lab with the proper expertise.
Since completing the initial paper published Thursday, the team has analysed 50 more samples from eye fluid of retinoblastoma patients, including those with less aggressive tumours whose eyes were saved, to get a start on determining what factors might be at play in tumour progression. (That paper is expected to be published soon.)
Berry plans to spend the next decade immersed in the data trying to develop diagnostic tests and better treatments based on the genetic material that now appears easy to obtain. “It’s a very fertile area,” said Kim. “It will take her career.”
Posted on 18 October, 2017, in Blog, Research and tagged Child Cancer Awareness, childhood cancer, Childhood Cancer Awareness, Children with Cancer, LFCT, Little Fighters Cancer Trust, paediatric cancer, Pediatric cancer, pediatric cancer awareness, Retinoblastoma, south africa. Bookmark the permalink. Leave a comment.