Cancer care can gobble up hours on the clock. The time spent traveling to the cancer center, as well as the time spent sitting in waiting rooms and dealing with adverse events and other problems, eat into the precious time that a cancer patient has left ― which, depending on the cancer and the stage, may not be long.

The problem has been termed “time toxicity,” and a growing number of oncologists are suggesting that it to be discussed with patients as they consider treatment.

Dr Arjun Gupta

Time lost to cancer care can be considerable. It is of particular concern for terminal patients. People with advanced gastrointestinal cancer, for instance, can spend 1 of every 4 of their remaining days going back and forth between the hospital, said Arjun Gupta, MD, a gastrointestinal oncologist at the University of Minnesota, Minneapolis.

That’s enough to offset the improvement in survival ― often around 2–3 extra months ― that patients with advanced solid tumors can expect with the latest treatments, he said.

A Lack of Data

How patients spend their time while receiving treatment has been fairly well studied in cardiology and some other specialties, but the issue has only recently been gaining traction in oncology.

Perhaps the oncology field has been too busy “celebrating” and incorporating “the marginal survival gains” from recent advances to pay much attention to the “everyday time demands of cancer care,” Gupta told Medscape Medical News.

Overall, “our community does not do a good job of acknowledging, quantifying, or weighing…the impact of time toxicity,” he and his colleagues write in a Journal of Clinical Oncology editorial.

Dr Tim Brown

That should change, they say. In addition to discussing survival benefits, adverse events, and out-of-pocket costs, patients should be told up front about the time demands they can expect with various treatments so they can best weigh their options. Opting for a more involved treatment isn’t necessarily wrong; rather, patients “should have the option to spend the time how they see fit,” said Tim Brown, MD, a hematology/oncology fellow at the University of Pennsylvania, Philadelphia.

The problem in oncology is that very little research has been conducted to quantify the time burdens of cancer care, so outside of their own personal experience, oncologists don’t have much information to pass along to patients.

As a result, time toxicity remains “a very, very hidden cost of cancer care,” Gupta said.

An FDA Mandate?

A move is afoot now to close the data gap. Gupta’s team is currently analyzing completed clinical trials to estimate how much time patients spent on care-related activities. Analysis of the first trial is due to be published soon in the Journal of Clinical Oncology.

The team’s next step is to engage with cooperative groups to include time toxicity as a prospective endpoint in future studies.

Ultimately, Gupta would like to see the US Food and Drug Administration (FDA) require a measurement of time toxicity in cancer clinical trials. His team has proposed “days at home” as a metric that is easy to measure and understand.

“We’ve had generally very encouraging reactions” to the idea “from all stakeholders and, most importantly, patients and patient advocates,” he said.

“We are still in the early phases,” but overall, “we are building consensus in a body of work” showing that it is possible to quantify time toxicity.

“We are making it more formalized…so [that] the science can move forward,” Gupta said.

Lessons From the Loss of a Loved One

Other groups are also moving the science forward.

In a recent preprint publication, investigators led by Vinay Prasad, MD, from the University of California, San Francisco, reviewed pivotal trials of 13 metastatic cancer drugs approved by the FDA from 2009–2022. They found that patients in the investigative arms spent a median of an extra 16 hours per month on trial-related activities in comparison with patients who received best supportive care. Of that time, 5.3 hours were spent traveling.

The extra time was spread over a minimum of 4–5 days a month. The calculation did not include time spent for infusions, since most of the drugs were taken orally, and it also did not include time spent on treating adverse events.

Across the trials, the median improvement in overall survival was just about 2 months.

In an echo of what Gupta’s team is saying, Prasad and colleagues concluded that future trials “should prospectively assess actual time on care…and calculate actual home days gained.”

Similarly, a team from East Carolina University, in Greenville, North Carolina, recently conducted a trial involving patients with locoregional pancreatic cancer who were treated with curative intent. The mean overall survival was 17.5 months, but the analysis showed that 11% of the patients’ days were spent in clinical encounters.

The finding was similar to those from an earlier study that found that metastatic pancreatic cancer patients spend about 10% of their remaining days in healthcare encounters. A significant chunk of that time was spent traveling and waiting.

Dr Rebecca Snyder

For some patients, the time burden is even greater. In the Carolina University study, a small subset of patients with comorbidities spent much more time interacting with providers, said senior investigator and pancreatic surgeon Rebecca Snyder, MD, incoming faculty at the MD Anderson Cancer Center, Houston.

For Snyder, time toxicity is a personal issue: her mother died of advanced lung cancer. In a JAMA essay, Snyder wrote very movingly about how the disease progressed quickly.

Snyder recalls how her mother “lived a very short time” and did not have much quality of life because her treatments, which she came to regret undergoing, made her severely ill. “It really had an impact on me,” Snyder said, and it “frames how I think about this.”

Time toxicity is an “outcome measure that is very relevant to patients,” she commented. It is information that patients “should know when they make their decisions,” she added.

A Proactive Approach

A group of clinicians based in Philadelphia are taking a different tack on time toxicity ― they are using a text-message app to save cancer patients time.

Co-investigator Timothy Brown, MD, from the Penn Center for Cancer Care Innovation at the University of Pennsylvania, explained that they are using the app to survey patients for signs and symptoms of toxicity to immunotherapy. If patients report that they are doing well, the app lets them skip a routine checkup.

The team recently reported in JAMA Network Open that the approach is safe, with a 0% rate of false negatives. The next step is to study how much time patients save by using the app.

Regarding time toxicity, Brown says: “I think it’s really important to take a step back and make sure what we are proposing and prescribing for patients isn’t overly burdensome and is in line with their treatment goals.

“I think understanding time toxicity gives us another tool to do that,” he said.

The physicians interviewed for this story have disclosed no relevant financial relationships.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is also an MIT Knight Science Journalism fellow. Email: [email protected]

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