Cancer Treatment Assessment Could Potentially Be Inaccurate, Outdated

Outdated measurements of cancer drug response could prevent some patients from receiving beneficial treatments.

A study published by Frontiers in Oncology suggests that metabolic imaging may be more accurate assessing treatment response than tumor shrinkage. Since tumors increase their metabolism to proliferate and grow, physicians could potentially use this method to assess the treatment earlier and more precisely than by measuring tumor size.

“What we have been using for decades is called RECIST -- it measures the dimensions of a tumor and it does a good job of showing a patient's response to chemotherapy and radiation,” said researcher Natalie Serkova, PhD. “These therapies (called cytotoxic) kill cells and so if they are working, we see the tumor shrink.”

Newer treatments inhibit the ability of cancer cells to grow and proliferate through cessation of metabolic rates, and do not kill cancer cells immediately, according to the study. Another study found that 15% of patients taken out of clinical trials due to perceived nonresponse to the drug are not actually non responders, but are responding in a way that cannot be captured by RECIST.

“With this criteria, it doesn't look like the new experimental drug is working. But it may be the criteria and not the drug that is failing in trials of these new targeted therapies," said the current study’s senior author S Gail Eckhardt, MD, FASCO. “One possible solution is to image a tumor's metabolic rate, such as glucose uptake.”

Researchers said that since cancer cells need glucose to drive growth, they burn it much faster than healthy cells. Certain treatments such as anti-EGFR drugs stop the ability of cancer cells to overuse glucose, according to the study.

“These new therapies stop a cancer cell's glucose uptake within 24 hours after the first dose, but changes in tumor volume happen months later,” said Dr Eckhardt.

Since these treatments can take months to appear successful by RECIST criteria, a new assessment that watches a tumor’s glucose use could be more effective at determining treatment response. Researchers also said that the uptake of phospholipids could more accurately assess response.

Proliferation of cancer cells means building cell membranes that are made from phospholipids. Drugs that slow a tumor’s use of phospholipids are successful prior to meeting RECIST criteria.

Researchers said that there is an overwhelming need for criteria to assess immunotherapies.

“With useful immunotherapies like PD1 and PDL1 checkpoint inhibitors, we can actually see an initial increase in tumor size. A successful immune response against a tumor is marked by inflammation which might mimic an increase in tumor dimensions,” Dr Serkova said. “With RECIST criteria that prioritizes tumor volume, inflammation can make it look like these drugs have made the cancer worse.”

Researchers caution that assessing treatment success just through RECIST criteria may prevent patients from receiving critical treatment due to perceived failures. They suggested using metabolic imaging to provide alternative ways of determining treatment success.

“RECIST will remain the gold standard to measure the success of classic, cytotoxic therapies like chemotherapy and radiation -- therapies whose singular goal is cell death,” Dr Serkova concluded. “And it remains useful in characterizing the response to these new targeted therapies after they have had months to eventually result in tumor shrinkage. But new measures are needed to show before months have passed whether these drugs are working.”