A test that detects changing levels of tumour fragments in the blood may be an easy, non-invasive and quick way to predict who will benefit from immunotherapy, University of Toronto researchers say.
Immunotherapy canshrink tumours and prolong survival for patients for whom other treatments have failed. But it only helps about 20 to 30 per cent of patients and so far, clinicians have been unable to predict who will benefit.
Since immunotherapy can have severe side effects in a small percentage of patients, knowing whether to begin or continue would be helpful for patients weighing different treatment options.
A team of scientists and clinicians addressed this question with a novel study evaluating various cancer patients response to a specific immunotherapy drug usinga customized test based on each patients tumour profile.
They found that individual response to treatment can be predicted within weeks, based on increasing or decreasing levels of DNA fragments which are shed from the tumour into the blood.
Genomic testing with powerful new technologies can detect the same genetic mutations in the fragments circulating in the blood as in the actual tumour. These fragments are called circulating DNA or ctDNA.
Specifically, the study found that a decrease in these circulating tumour DNA fragments at six toseven weeks after treatment with the immunotherapy drug pembrolizumab was associated with a beneficial response to the drug and longer survival.
The study, Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab, was published in Nature Cancer this week.
Dr. Lillian Siu, a professor in the department of medicine at U of T's Faculty of Medicine, senior scientist and medical oncologist at Princess Margaret Cancer Centre and BMO Chair in Precision Cancer Genomics, noted that the study is one of the first studies across a broad spectrum of tumours to show that measuring levels of ctDNA could be useful as a predictor of who responds well to immunotherapy.
Its like a molecular CT scan that gives us a molecular dimension, an added layer of information to know whether a tumour is growing or not, saidSiu, a co-senior author of the paper. Thats why this is so exciting. It helps to predict early on what may happen over time. Although important, computerized tomography (CT) and other scans alone will not tell us what we need to know quickly or accurately enough.
Dr. Scott Bratman, an associate professor of radiation oncology and medical biophysics and first author on the paper, saidit may take many months to detect whether a tumour is shrinking with various imaging scans.
New next-generation sequencing technologies can detect and measure these tiny bits of cellular debris floating in the blood stream accurately and sensitively, allowing us to pinpoint quite quickly whether the cancer is active, said Bratman, a radiation oncologist and senior scientist at Princess Margaret.
The prospective study analyzed the change in ctDNA from 74 patients, with different types of advanced cancers, being treated with pembrolizumab.
To customize or personalize the test, all the genes from the tumour biopsy tissue of each patient were sequenced or decoded, with specific attention to the mutations that occur in cancer.These mutations ranged from dozens to tens of thousands of mutations per tissue sample, differing according to cancer type.
Sixteen genetic mutations for each patient were then selected for a specific test to be developed and customized to detect personalized ctDNA of each patient via a simple blood sample.
When we looked at all 20,000 genes in each cancer, the range of mutations in different individuals was huge due to the many different cancer types in the study, saidDr. Trevor Pugh. Aco-senior author on the paper and an associate professor in the department of medical biophysics, he is alsoa senior scientist at Princess Margaret and director of genomics at the Ontario Institute for Cancer Research.
The novelty is that, rather than taking a one-size-fits-all approach, we designed a personalized blood test for each person based on their own cancers mutation list, Pugh said.
Of the 74 patients, 33 had a decrease in ctDNA levels from their original baseline levels to week six to seven after treatment with the drug. These patients had better treatment responses and longer survival. Even more striking was that all 12 patients who had clearance of the ctDNA to undetectable levels during treatment were still alive at a median follow-up of 25 months.
Conversely, a rise in ctDNA levels was linked to a rapid disease progression in most patients, and poor survival.
Few studies have used a clinical biomarker across different types of cancers, saidSiu, who is also the clinical lead for the Tumor Immunotherapy Program at the Princess Margaret, adding that the observation that ctDNA clearance during treatment and its link to long-term survival is novel and provocative, suggesting that this biological marker can have broad clinical impact.
This research was funded by the Princess Margaret Cancer Foundation, Ontario Institute for Cancer Research, Terry Fox Research Institute, Gattuso-Slaight Personalized Cancer Fund, BMO Chair in Precision Cancer Genomics, Canada Research Chair in Translational Genomics, Canada Foundation for Innovation, Ontario Ministry of Research and Innovation, and Merck for the study drug.
Read more:
Blood test could predict who will benefit from immunotherapy, researchers find - News@UofT
- North Korea Wants to Convince the World It Can Nuke Hawaii. Donald Trump Is Happy to Oblige. - The Intercept - May 3rd, 2017 [May 3rd, 2017]
- Does Donald Trump Have Dementia? - The Root - May 3rd, 2017 [May 3rd, 2017]
- Donald Trump's peculiar obsession with authoritarian leaders - Chicago Tribune - May 3rd, 2017 [May 3rd, 2017]
- 'South Park' Creators Skirt Donald Trump Next Season Because Monkey Running Into Wall Can't Be Made Funnier - Deadline - May 3rd, 2017 [May 3rd, 2017]
- Donald Trump Has Been Lying About The Size Of His Penthouse - Forbes - May 3rd, 2017 [May 3rd, 2017]
- This is the best news Donald Trump has had in a while - CNN - May 3rd, 2017 [May 3rd, 2017]
- AFT President: Betsy DeVos and Donald Trump Are Dismantling Public Education - TIME - May 3rd, 2017 [May 3rd, 2017]
- The Donald Trump Zone of Uncertainty shows up in the health-care debate - Washington Post - May 3rd, 2017 [May 3rd, 2017]
- Donald Trump Predicts Mideast Peace Is 'Not As Difficult As People Have Thought' - Huffington Post - May 3rd, 2017 [May 3rd, 2017]
- Make America Great Again! | Donald J Trump for President - May 3rd, 2017 [May 3rd, 2017]
- Donald Trump Rage Tweets Against Media For Taking Seriously His Tweets - Deadline - June 6th, 2017 [June 6th, 2017]
- Roger Stone: I Hooked Up Nigel Farage With Donald Trump - Mother Jones - June 6th, 2017 [June 6th, 2017]
- Accused leaker Reality Winner called Trump an 'orange fascist' on Twitter - CNN International - June 6th, 2017 [June 6th, 2017]
- Donald Trump's Approval Rating Is Better Than Bill Clinton's at This Point in His First Term - Newsweek - June 6th, 2017 [June 6th, 2017]
- London, Qatar, Donald Trump: Your Tuesday Briefing - New York Times - June 6th, 2017 [June 6th, 2017]
- Donald Trump Escalates Qatar Crisis - HuffPost - June 6th, 2017 [June 6th, 2017]
- How Donald Trump Shifted Kids-Cancer Charity Money Into His Business - Forbes - June 6th, 2017 [June 6th, 2017]
- No, Donald Trump doesn't have 110 million people following him on social media - Washington Post - June 6th, 2017 [June 6th, 2017]
- Donald Trump is the best 2020 recruiter Democrats could hope for - CNN - June 6th, 2017 [June 6th, 2017]
- It's Time to Demand Donald Trump's Resignation - RollingStone.com - June 6th, 2017 [June 6th, 2017]
- A brief history of Donald Trump's feud with Sadiq Khan, London's first Muslim mayor - Washington Post - June 7th, 2017 [June 7th, 2017]
- Donald Trump has a lot of feelings about fame - CNN - June 7th, 2017 [June 7th, 2017]
- Donald Trump Is Never to Blame - New York Times - June 7th, 2017 [June 7th, 2017]
- Donald Trump will do whatever it takes to distract you from the Comey hearing - CNN - June 7th, 2017 [June 7th, 2017]
- President Trump's Approval Rating Hit Another New Low - TIME - June 7th, 2017 [June 7th, 2017]
- The Potemkin Policies of Donald Trump - The Atlantic - June 7th, 2017 [June 7th, 2017]
- Jeff Sessions committed the one sin Donald Trump can't forgive - CNN - June 7th, 2017 [June 7th, 2017]
- James Comey just went nuclear on Donald Trump - CNN International - June 7th, 2017 [June 7th, 2017]
- Vladimir Putin, Hillary Clinton and the true cause of Donald Trump's legitimacy crisis his own actions - Salon - June 9th, 2017 [June 9th, 2017]
- Donald Trump Proposes Covering Mexican Border Wall With Solar Panels - Futurism - June 9th, 2017 [June 9th, 2017]
- Tell Your Senators: Don't Let Donald Trump Take Our Cuba Policy Backwards - The Nation. - June 9th, 2017 [June 9th, 2017]
- Donald Trump Wrote a Cookbook - New York Times - June 9th, 2017 [June 9th, 2017]
- Donald Trump is destroying America's standing in the world and may end up destroying the world - Salon - June 9th, 2017 [June 9th, 2017]
- Donald Trump hasn't tweeted in a very long time - CNN - June 9th, 2017 [June 9th, 2017]
- Experts: Trump's Comey Firing 'Possibly Lawful, But Awful' - NBCNews.com - June 9th, 2017 [June 9th, 2017]
- Karl Rove, Erick Erickson slam Donald Trump - Salon - June 9th, 2017 [June 9th, 2017]
- The Real Scandal Is Still Russia - Slate Magazine - June 9th, 2017 [June 9th, 2017]
- 5 times UK Labour leader Jeremy Corbyn slammed Donald Trump - Politico - June 9th, 2017 [June 9th, 2017]
- 9 questions Donald Trump needs to answer at today's news conference - CNN - June 9th, 2017 [June 9th, 2017]
- So is Donald Trump secretly recording conversations or not? - CNN - June 9th, 2017 [June 9th, 2017]
- Watch Donald Trump Throw Binders Full of Highway Environmental Reviews on the Floor - Slate Magazine (blog) - June 10th, 2017 [June 10th, 2017]
- This week in Donald Trump's conflicts of interest: Kushner may have problems, but Trump's hotel raises lots of questions - Salon - June 10th, 2017 [June 10th, 2017]
- Historian Ruth Ben-Ghiat: Donald Trump looks like Mussolini but can be overcome - Salon - June 10th, 2017 [June 10th, 2017]
- This One Tweet May Lead to Donald Trump's Impeachment - National Review - June 10th, 2017 [June 10th, 2017]
- Fact Check: Donald Trump's Claims About Infrastructure - New York Times - June 10th, 2017 [June 10th, 2017]
- The Worst of Donald Trump's Toxic Agenda Is Lying in Wait A Major US Crisis Will Unleash It - The Intercept - June 10th, 2017 [June 10th, 2017]
- Boy Scout James Comey is no match for Donald Trump - Washington Post - June 10th, 2017 [June 10th, 2017]
- Justice Department: Trump Can Take Payments From Foreign Governments - TIME - June 11th, 2017 [June 11th, 2017]
- Marc Kasowitz, Donald Trump's lawyer, has clients with Kremlin ties - The Denver Post - June 11th, 2017 [June 11th, 2017]
- Yes, Donald Trump is an incompetent buffoon but he's still a major threat to democracy - Salon - June 11th, 2017 [June 11th, 2017]
- Democrats bet on Trump in Virginia governor's race - Politico - June 11th, 2017 [June 11th, 2017]
- Will Donald Trump's anti-Muslim words on travel ban hurt his case? - USA TODAY - June 11th, 2017 [June 11th, 2017]
- Donald Trump's State Visit To The UK Now In Doubt - HuffPost - June 11th, 2017 [June 11th, 2017]
- Donald Trump Jr.: There's 'no ambiguity' in my father's orders - CNN - June 11th, 2017 [June 11th, 2017]
- Ivanka condemns Donald Trump's 'vicious critics' - BBC News - June 13th, 2017 [June 13th, 2017]
- Donald Trump Surrogate Lays Out POTUS Case For Sacking Special Counsel Robert Mueller - Deadline - June 13th, 2017 [June 13th, 2017]
- Russia, Theresa May, Donald Trump: Your Tuesday Briefing - New York Times - June 13th, 2017 [June 13th, 2017]
- Donald Trump in Wonderland: Literally everything our president says and does reflects the opposite of reality - Salon - June 13th, 2017 [June 13th, 2017]
- Donald Trump Is Turning Young Voters Off the GOPand Maybe Forever - Daily Beast - June 13th, 2017 [June 13th, 2017]
- Trump's Own Tweets Help Kill His Government's Travel Ban, Again - Fortune - June 13th, 2017 [June 13th, 2017]
- Donald Trump's Approval Rating Sinks Further As Disapproval Hits Record High - Newsweek - June 13th, 2017 [June 13th, 2017]
- When Jeff Sessions met Donald Trump: The origins of an alliance now strained - Washington Post - June 13th, 2017 [June 13th, 2017]
- Donald Trump just held the weirdest Cabinet meeting ever - CNN - June 13th, 2017 [June 13th, 2017]
- Donald Trump to mayor of island sinking due to climate change: Don't worry about it! - Salon - June 14th, 2017 [June 14th, 2017]
- Trump son tweet connects shooting to NYC 'Julius Caesar' play - CNN - June 14th, 2017 [June 14th, 2017]
- Newt Gingrich, Donald Trump Jr. rush to blame Kathy Griffin and the left for baseball shooting - Salon - June 14th, 2017 [June 14th, 2017]
- Donald Trump's Biggest Mistake Might Have Been Getting Elected - Vanity Fair - June 14th, 2017 [June 14th, 2017]
- Congress Shooter Is Dead - TMZ.com - June 14th, 2017 [June 14th, 2017]
- Trump faces first big domestic moment - Politico - June 14th, 2017 [June 14th, 2017]
- Tiny mark on Melania Trump's birthday card to Donald Trump sparks wild theories - AOL - June 16th, 2017 [June 16th, 2017]
- Donald Trump Is Now Facing Three Emoluments Lawsuits - Slate Magazine - June 16th, 2017 [June 16th, 2017]
- Play Video - TIME - June 16th, 2017 [June 16th, 2017]
- Donald Trump Blocked Me on Twitter for Telling Him He's Not as Cool as Witches - Newsweek - June 16th, 2017 [June 16th, 2017]
- Senate passes Russia sanctions bill, pushing back against Trump - CNN - June 16th, 2017 [June 16th, 2017]
- Australian leader is on the hot seat for making fun of Donald Trump - Washington Post - June 16th, 2017 [June 16th, 2017]
- Flattery is Donald Trump's cocaine he's addicted to it - USA TODAY - June 16th, 2017 [June 16th, 2017]
- Moving to Scuttle Obama Legacy, Donald Trump to Crack Down on Cuba - New York Times - June 16th, 2017 [June 16th, 2017]
- Donald Trump doesn't get the special counsel investigation. And he's never going to. - CNN - June 16th, 2017 [June 16th, 2017]
- Memo to Donald Trump: The election ended 219 days ago. You won. - CNN - June 16th, 2017 [June 16th, 2017]
- Who in the White House Will Turn Against Donald Trump? - The New Yorker - June 17th, 2017 [June 17th, 2017]