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 rhythmmay influence the effectiveness of immune checkpoint inhibitors. These drugs help the immune system recognize and attack cancer cells by blocking tumors’ ability to turn off those immune responses.
Now, the new study, published December 8 in the journal Cancershows that the time of day a drug is given also affects extensive-stage small cell lung cancer (ES-SCLC), a fast-growing cancer that is generally associated with a poor prognosis and accounts for about 15% of new lung cancer cases.
This study is “very important,” he said. Dr. Francis Levimedical oncologist and founder of the Chronotherapy Group at the University of Warwickwho did not participate in the work. spreads previous research did it with the same team, which involved different types of lung cancer and different immune checkpoint inhibitors, but produced similar results.
“Early in the day of immune checkpoint inhibitors, as single agents or in combination with chemotherapy or antiangiogenics. [drugs that starve tumors of blood]significantly improves the efficacy of the treatment compared to later dosing times,” Lévi told LiveScience.
Other experts who were not involved in the study agreed that the results were impressive. In a joint statement, the oncologist Dr. Pasquale Innominato and circadian biologist Robert Dallmanboth from the University of Warwick, and oncologist Dr Seline Ismail-Sutton from Ysbyty Gwynedd Hospital in Wales, told LiveScience that they were “struck by the large effect of the time of day the immunotherapy is given on overall survival”, calling it “a very significant difference”.
Adjusting the timing of treatment “represents a simple, low-cost adjustment with the potential to deliver significant improvements in patient outcomes…without adding new medications or complex interventions,” they said.
Earlier treatment, longer survival
In the study, researchers from the Affiliated Cancer Hospital of Xiangya Medical College of Central South University in China analyzed data from nearly 400 patients with ES-SCLC, a cancer with a 14-month median survival rate. All patients received standard initial immunotherapy in combination with chemotherapy between May 2019 and October 2023.
The average treatment time of each patient’s day was calculated based on the first four cycles of therapy. The researchers then compared the survival outcomes of patients treated at different times of the day, between 11 a.m. and 4:30 p.m. They matched the patients to make sure that the main thing that differed between them was the timing of treatment, not baseline characteristics, such as age or sex.
3 in the afternoon marked a critical 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 to those treated later that day.
Even after accounting for other factors that could influence patient outcomes, this earlier treatment time remained a strong and independent predictor of better survival.
The study’s findings align with laboratory studies suggesting that killer T cells (immune cells that can directly kill cancer) tend to migrate to tumors in the morningsaying Dr. Chi Van Dangprofessor 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 LiveScience.
Personalized ‘chronotherapy’
The study’s large sample size was a strength, but the research has some caveats.
Lévi noted that the majority of patients were men, for example. The pronounced time effects did not appear to extend to women in the study, but this may be because there were few women included, the study authors wrote, so it is worth exploring in larger studies.
The study found that patients who received immunochemotherapy before 3 p.m. lived almost twice as long as those treated later in the afternoon. However, this picture is not entirely clear, said Lévi, because the study does not indicate the best cut-off time for care. “This creates uncertainty about the most appropriate cut-off time, which could actually be between 11:30 a.m. and 3:00 p.m.,” he said.
Furthermore, because the study looked at data from previous patients, stronger evidence will still need to be obtained from randomized clinical trials, in which different treatment times are explicitly tested and compared to each other. Most of the evidence for the benefits of early treatment “comes from retrospective studies,” Innominato and colleagues said, “only a prospective trial completed and additional trials now in development.”
Assuming the trials show positive results, there could still be logistical hurdles to overcome. “If treatment were limited to a single time period, such as the morning, clinical units could quickly become overwhelmed,” Innominato and his colleagues said.
It is important to note that the “optimal window” for treatment may not be universal among patients, they added. It may depend in part on the biological rhythms and lifestyle characteristics of each individual.
Chronotyping: categorizing people as “morning larks” or “night owls” — could “align therapy with each patient’s internal clock, taking into account individual variability and thus increasing effectiveness while relieving pressure on clinical units by distributing treatments throughout the day,” they suggested. “The challenge now is to develop rapid and reliable ways to identify chronotype and scale this approach, and specific studies are already underway.”
This article is for informational purposes only and is not intended to provide medical advice.
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