A patient receiving chemotherapy

A study published in the Journal of Clinical Oncology has found that the level of a person’s immune cells may provide an indication of whether they would benefit from chemotherapy in a type of cancer called oropharyngeal squamous cell carcinoma (OPSCC).

These cells, called lymphocytes, are a type of white blood cell that form an essential part of the immune system.

The current standard of care for OPSCC involves radiotherapy and chemotherapy. However, the use of cisplatin chemotherapy increases the amount and severity of side effects, compared to radiotherapy alone.

To avoid the potential side effects associated with chemotherapy, researchers have been searching for a kinder approach to treatments for oropharyngeal cancers.

Now, this latest study has found that measuring someone’s lymphocyte count before beginning their treatment may be able to help identify which patients with oropharyngeal cancer could be successfully treated with radiotherapy alone.

The work, funded by Cancer Research UK, was conducted by researchers at the Christie NHS Foundation Trust in collaboration with the University of Manchester and the Leeds Teaching Hospitals NHS Trust.

What is oropharyngeal cancer?

Oropharyngeal cancer starts in the oropharynx, which is the part of the throat just behind the mouth. It includes cancers of the back of the tongue and tonsil.

Some cases of oropharyngeal cancer are associated with a virus known as Human Papilloma Virus (HPV) and people with HPV positive oropharyngeal cancers tend to have a better outlook than people with HPV negative oropharyngeal cancers.

“These types of cancer are becoming increasingly common. And the good news is that they’re usually curable,” says Dr James Price, clinical oncologist at the Christie NHS Foundation Trust and lead author of the study.

“The less good news is that in order to do that, we treat them very intensively with high dose radiotherapy, and chemotherapy as well, and that can lead to severe side effects, both during treatment and in the long-term.

“So internationally, researchers think that we could de-escalate treatment for these patients, i.e., treat them less intensively. The question with that is, who would you treat less intensively? And that’s where our research comes in.”

Results from the study

The study found that the number of lymphocytes a person has in their blood before treatment (absolute lymphocyte count or ALC) is indicative of their overall survival.

People with low levels of lymphocytes in their blood had a lower chance of cure when treated with radiotherapy alone, but that was improved by the addition of chemotherapy.

On the other hand, people who have higher levels of lymphocytes in the blood may not require the addition of chemotherapy for the same chance of cure.

“Patients with high immune cells in their blood tend to do really well, whether they’re given chemotherapy or not,” says Price.

“So, what we’ve found is this group of patients with a good immune system, high immune cells in the blood, who might not need the addition of chemotherapy, and if they don’t have the chemotherapy, then the side effects will be less severe. Consequently, in the future, they would have a better quality of life.”

But the findings don’t only highlight who may not need chemotherapy. Equally important is the finding that in those with low lymphocyte count, additional treatment with chemotherapy does increase their chance of survival.

What are the implications?

A low pre-treatment ALC is associated with poor survival outcomes in a number of solid cancers. However, this is the first time that an interaction between lymphocyte count and use of subsequent chemotherapy has been shown.

This raise questions about how treatments can be better tailored to individual patients. As lymphocyte count can be determined from a routine blood test, it could provide a simple way of determining a patient’s treatment path.

As well as the development of the drug type known as immunotherapies, which harnesses the body’s own immune system to treat cancer, there has been an increased interest in how an individual’s own immune response impacts the chance of successfully treating their cancer.

“Patients who don’t have a good immune system seem to be much better when you give them chemotherapy. So, the question was is the chemotherapy, as well as doing what we know it does in terms of helping the radiotherapy, also modulating a patient’s immune system?” adds Price.

“And there is emerging evidence that shows that cisplatin does do that. It may modulate the immune system and make it more capable of killing the cancer itself.”

Although this advancement is exciting, it’s still early days for Price and the team.

Moving forward, researchers may be able to use ALC as a way of selecting patients for a treatment de-escalation trial to further investigate these findings. In addition, future research will investigate what is happening to the immune cells in and around the tumour itself during radiotherapy.

“We haven’t before had data that show a patient’s immune cells not only determine radiotherapy treatment outcomes, but also the benefit of using chemotherapy alongside radiotherapy to cure the cancer,” says Dr David Thomson, Clinical Director of the Greater Manchester Head and Neck Cancer Pathway Board.

“It still needs more research,” he adds “We’re now looking at biopsies before and during treatment to understand what happens to the immune cells in and around the tumour itself. That will take us forward even further in understanding how a patient’s own immune cells interact with radiotherapy to affect the chance of cure.”


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