One in Five Cancer Tumors Grow Before Shrinking: Nivolumab

Ingrid Hein

November 27, 2018

Atypical response — usually tumor enlargement followed by shrinking — is seen in 20% of cancer patients who respond to immunotherapy, according to a study of response patterns in patients with a variety of tumors, including melanoma, genitourinary carcinomas, and lung tumors.

This finding could help radiologists make better diagnoses, said lead researcher Richard Thomas, MBBS, MD, from Brigham and Women's Hospital, in Boston.

"It's important to assess these patients' images properly and not diagnose progressive disease," he told Medscape Medical News.

The tumor appears to be progressing, but it's not, he explained. The size increases because immune cells have entered the tumor, which can make "people think that these patients have worsening disease."

"It's not like chemo," he added. "With immunotherapy, atypical response is quite high."

With a treatment that makes the body's own system attack the tumor, response can be unpredictable. Response times can also vary.

"Many times when we see that patients are not getting better but are doing okay clinically, we just have to wait," Thomas pointed out. He said he has seen an atypical response as long as 24 months after the start of immunotherapy.

Atypical Response

In their retrospective study, Thomas and his colleagues looked at responses in 254 patients being treated with nivolumab alone or in combination with ipilimumab.

The patients had a variety of cancer tumors and were assessed from January 2013 to August 2017, Thomas reported at the Radiological Society of North America 2018 Annual Meeting in Chicago.

To target atypical response to the treatment, only the 166 patients who had stable disease or a clinical response (partial or complete) were included in the analysis.

The researchers looked at follow-up scans to identify the frequency of atypical tumor response and to assess how the tumor changed over time.

Normally, disease is defined as progressive when the tumor increases by 20%. But because "we wanted to identify and study even minor tumor progression," patients whose tumors increased 10% to 20% were included.

Tumor size decreased in 133 (80%) patients. In the remaining 33 (20%) patients, tumor pseudoprogression occurred before the tumor size decreased.

In 15 patients, the sum of the longest diameter (SLD) of the tumor increased 10% to 19% before it fell below baseline. In two patients, the increase in SLD was more than 20% before the tumor fell below baseline. And 16 patients developed new lesions but the SLD of the baseline tumor decreased over at least two consecutive scans.


Time, Patience Needed

All patients eventually responded to treatment and tumor size decreased, but response time was highly variable.

"The important thing to understand here is that you are using the body's own immune cells to attack the tumor, and each immune system has its own way and takes its own time. It's hard to predict when someone will respond; the system can even attack the tumor cells after the drugs are stopped," said Thomas.

Even when tumors are not decreasing, patients are not necessarily clinically worse. "Just wait. It is likely just taking a longer time for the immune cells to enter the tumor," he explained.

Artificial intelligence or deep learning might eventually help predict which patients are going to respond to immunotherapy so that they can be treated appropriately, he added. "This is likely an area that will see a lot of development and research in future."

In some patients, the body develops immunity to checkpoint inhibitors, which is a challenge with this type of treatment. Immune checkpoint inhibitors can increase survival time, "but the cancer cells can develop resistance and come back," he said.

It is also important to be aware of the adverse effects of these drugs. When immune cells are stimulated to attack cancer cells, they can sometimes attack other cells, such as those in the lung or thyroid. Patients have to be monitored. "As soon as we see these side effects, we have to decide whether to give steroids or take them off," Thomas noted.

But this study focused on tumor response, not adverse effects. "The most important finding here is that atypical response is quite high," he pointed out.

As immunotherapy becomes popular for many advanced solid tumors, there has been increased awareness among radiologists about the treatment-response assessment related to checkpoint inhibitors, said Hyesun Park, MD, Harvard Medical School in Boston.

"Recently, immune-related response-assessment criteria, such as iRECIST, have been introduced," she told Medscape Medical News. "The criteria include 'unconfirmed' progression of disease for initial treatment-response assessment." The clinician can then defer the diagnosis decision until after a follow-up scan.

"It is important for a radiologist to recognize the type of anticancer drug that patients are getting when interpreting the images to avoid misinterpretation," Park explained. Not doing so could lead to patients being mistakenly removed from trials.

Thomas and Park disclosed no relevant financial relationships.

Radiological Society of North America (RSNA) 2018 Annual Meeting. Presented November 25, 2018.

Follow Medscape on Twitter @Medscape and Ingrid Hein @ingridhein



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