It matters what time of day you get cancer treatment, study suggests

A new study suggests that giving immunochemotherapy earlier in the day helps patients with an advanced type of lung cancer live longer.

Previous studies suggested that the body's internal clock, the circadian rhythm, can influence how well immune checkpoint inhibitors work. These drugs help the immune system recognize and attack cancer cells by blocking tumors' ability to shut those immune responses down.

In several cancers — such as kidney, liver, stomach, esophagus, and head and neck cancers, as well as melanoma — giving this treatment in the morning has been associated with better outcomes than giving it in the late afternoon or evening.

Now, the new study, published Dec. 8 in the journal Cancer, shows that the time of day a drug is delivered also affects extensive-stage small cell lung cancer (ES-SCLC) — a fast-growing cancer that is typically associated with a poor prognosis and accounts for about 15% of new lung cancer cases.

This study is "very important," said Dr. Francis Lévi, a medical oncologist and founder of the Chronotherapy Group at Warwick University, who was not involved in the work. It extends earlier research he did with the same team, which involved different lung cancer types and different immune checkpoint inhibitors but produced similar results.

"Early time of day of immune checkpoint inhibitors, as single agents or combined with chemotherapy or antiangiogenics [drugs that starve tumors of blood], significantly improves treatment efficacy compared to later dosing times," Lévi told Live Science.

Other experts not involved in the study agreed that the results were impressive. In a joint statement, oncologist Dr. Pasquale Innominato and circadian biologist Robert Dallmann, both at Warwick University, and oncologist Dr. Seline Ismail-Sutton at the Ysbyty Gwynedd Hospital in Wales, told Live Science they were "impressed by the large effect of time-of-day of immunotherapy administration on overall survival," calling it "a very meaningful difference."

Tweaking treatment timing "represents a simple, low-cost adjustment with the potential to deliver meaningful improvements in patient outcomes … without adding new drugs or complex interventions," they said.

Earlier treatment, longer survival

In the study, researchers from the Affiliated Cancer Hospital of Xiangya School of Medicine at Central South University in China analyzed data from nearly 400 patients with ES-SCLC, a cancer with a median survival rate of 14 months. All the patients received a standard, initial immunotherapy in combination with chemotherapy between May 2019 and October 2023.

Each patient's average treatment time of day was calculated based on the first four therapy cycles. The researchers then compared survival outcomes for patients treated at different times of day, between 11 a.m. and 4:30 p.m. They matched the patients to ensure that the main thing that differed between them was the treatment timing, not baseline characteristics, such as age or sex.

3 p.m. marked a critical cutoff point. Patients who generally received treatment before 3 p.m. survived significantly longer without their cancer progressing. They also had longer overall survival over the next five years, compared with those treated later in the day.

Even after accounting for other factors that could influence the patients' outcomes, this earlier treatment time remained a strong, independent predictor of better survival.

The study findings align with laboratory studies that suggest killer T cells — immune cells that can directly kill cancer — tend to migrate into tumors in the morning, said Dr. Chi Van Dang, a professor of cancer medicine at Johns Hopkins University, who was not involved in the study. Therefore, aligning immunotherapy with this migration may help it work better, he told Live Science.

Personalized 'chronotherapy'

The large sample size of the study was a strength, but the research has some caveats.

Lévi pointed out that most patients were men, for example. The pronounced timing effects did not seem to extend to the women in the study, but this may come down to there being few women included, the study authors wrote, so it bears exploring in larger studies.

The study found that patients who received immunochemotherapy before 3 p.m. lived nearly twice as long as those treated later in the afternoon. However, this picture isn't completely clear, Lévi said, because the study doesn't pinpoint the best cutoff time for care. "This results in an uncertainty regarding the most appropriate cut off time, that actually could be located between 11:30 and 15:00," he said.

Additionally, because the study looked back at past patient data, stronger evidence will still need to come from randomized clinical trials, in which different treatment timings are explicitly tested and compared against one another. Most evidence of the benefits of early treatment "comes from retrospective studies," Innominato and colleagues said, "with only one prospective trial completed and additional trials now in development."

Assuming trials show positive results, there could still be logistical hurdles to overcome. "If treatment were restricted to a single time window, such as the morning, clinical units could quickly become overwhelmed," Innominato and colleagues said.

It's important to note that the "optimal window" for treatment may not be universal among patients, they added. It may partially depend on each individual's biological rhythms and lifestyle characteristics.

Chronotyping — categorizing people as "morning larks" or a "night owls” — could "align therapy with each patient's internal clock, accounting for individual variability and thus boosting efficacy while easing pressure on clinical units by distributing treatments across the day," they suggested. "The challenge now is to develop quick, reliable ways to identify chronotype and scale this approach, and dedicated studies are already underway."