November 5, 2020

Study finds that every month delay in cancer treatment can raise risk of death by around 10 per cent

Dr. Tim Hanna, Radiation Oncologist at the Cancer Centre of Southeastern Ontario, Faculty of Queen’s Cancer Research Institute, OICR Clinician Scientists and lead of the study.

Research led by Dr. Timothy Hanna suggests that minimizing delays to treatment could improve cancer survival rates

Many countries have needed to defer cancer surgeries, radiotherapy and other treatments through the COVID-19 pandemic, which has brought the impact of treatment delays into sharp focus. In a study published today in The BMJ, Dr. Timothy Hanna and collaborators report that people whose cancer treatment is delayed by even four weeks have in many cases a six to 13 per cent higher risk of dying – a risk that keeps rising the longer their treatment does not begin.

“We know that delay matters and now we understand how much it matters,” says Hanna, Radiation Oncologist at the Cancer Centre of Southeastern Ontario, Faculty of Queen’s Cancer Research Institute, OICR Clinician Scientists and lead of the study. “With these data, we can now quantify the impact of treatment delays – including those that we’re experiencing now throughout the COVID-19 pandemic.”

The research group reviewed and analyzed relevant studies from around the world that were published over the last two decades. They found that there was a significant impact on a person’s risk of death if their treatment was delayed, whether the treatment was surgical, chemotherapy or radiotherapy. They observed this impact across all seven types of cancer analyzed – breast, bladder, colon, rectum, lung, cervix and head and neck cancers.

For example, with cancer surgery, they saw a six to eight per cent increase in the risk of death for every four-week treatment delay, meaning that a three-month delay could increase the risk of death by about 25 per cent. The impact was even greater for specific treatments – such as bowel cancer chemotherapy – where a three-month delay could cause a 44 per cent increase in risk of death.

“As we move towards the second COVID-19 wave in many countries, the results emphasize the need to prioritize cancer services including surgery, drug treatments and radiotherapy as even a four-week delay can significantly increase the risk of cancer death,” says Dr. Ajay Aggarwal, co-lead of the study from King’s College London and the London School of Hygiene and Tropical Medicine.

Hanna hopes this study will help inform cancer treatment backlog management and prioritization. His prior work on prioritizing treatment during COVID-19, published in Nature Reviews Clinical Oncology, has been incorporated into health system planning and management in Ontario and around the world.

“The impact of cancer treatment delays will persist long after the threat of this pandemic subsides,” says Hanna. “As a clinician, a patient, an administrator or a decision-maker in our cancer care system, these results should encourage us all to put resources and efforts in place to minimize system level delays in cancer treatment.”

March 12, 2020

The complexities of head and neck cancers may be simpler than we thought

Drs. Sampath Loganathan and Daniel Schramek.

Toronto-based research team uncovers dozens of rare mutations found in head and neck cancers converge on a single molecular pathway, amplifying the need to shut down this critical cancer-causing mechanism

With the advancement of DNA sequencing technology, researchers have discovered hundreds of genes that, when mutated, can drive cancer progression. Despite these discoveries, we don’t yet fully understand how the majority of cancer-causing genes work, leaving a large gap between the discovery of a gene mutation and the discovery of a new therapy. Dr. Daniel Schramek is filling that gap.

In a recent study, published in Science, Schramek and collaborators, including Dr. Trevor Pugh, Director of Genomics at OICR, analyzed the function of nearly 500 gene mutations found in head and neck cancers. Remarkably, they discovered that the many of these mutations affected one key molecular process within cancer cells. They shut down NOTCH signaling.

“While we see many different mutations in different genes across different patients, we found that many mutations, surprisingly, tend to do the same thing,” says Schramek, who is an investigator at Sinai Health’s Lunenfeld-Tanenbaum Research Institute (LTRI). “This means the complexities of head and neck cancers may be simpler than we thought”

Schramek reasons that focusing on correcting the NOTCH pathway, rather than correcting the effects of each individual gene mutation, could simplify and focus the search for new and improved cancer therapies. He estimates that approximately 70 per cent of people with head and neck cancers have tumours that are affected by this pathway. Thus, a large majority of these patients could benefit from NOTCH-correcting cancer drugs.

“Every patient’s tumour is made up of different gene mutations and combinations of these mutations,” says Dr. Sampath Loganathan, first author of the study and Postdoctoral Fellow in the Schramek Lab. “Some of the more common, well-understood mutations are druggable – meaning they can be blocked with drugs – but there are hundreds of rarer, but important, mutations that we don’t yet understand.”

It is challenging to understand how a single mutation causes damage within a cell and ultimately leads to cancer. It is tremendously more challenging to understand the function of hundreds of mutations.

Our findings present a new way of thinking about precision oncology

Dr. Daniel Schramek

Schramek’s lab, however, developed an experimental system that allowed them to accelerate traditional functional testing for a fraction of the cost. Their system could test hundreds of gene mutations in a single mouse model. What would take several millions and decades in research and development, could now be done in one year for a fraction of the cost. Equipped with their powerful tools, this research group was the first to systematically look at rare mutations in head and neck cancers.

Schramek and collaborators are now working to identify key elements within the NOTCH pathway that can be blocked with chemicals. Their ultimate goal is to develop these chemicals into new drugs to help those with head, neck and other types of cancers. They will also continue to explore this phenomenon in other cancers such as breast and pancreatic cancers.

“Our findings present a new way of thinking about precision oncology,” Schramek says. “Instead of matching patients with specific mutations to specific treatments, researchers could focus on shutting down or restoring the pathways involved with those genes – hence, a pathway-centric model of precision oncology. We’re excited by this progress, and we look forward to bringing our ideas to future patients.”

This research was done in collaboration with OICR and was supported by the Canadian Institutes of Health Research, the Terry Fox Research Institute and the Human Frontier of Science Program. Schramek is a Kierans/Janigan Cancer Research Scientist and holds a Canada Research Chair in functional cancer genomics in the Department of Molecular Genetics at the University of Toronto.

Read more about this work in the Lunenfeld-Tanenbaum Research Institute’s news story.