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 rhythmmay influence the effectiveness of immune checkpoint inhibitors. These drugs help the immune system recognize and attack cancer cells by blocking the ability of tumors to inhibit these immune responses.
In several cancers – such as kidney, liver, stomach, esophagus, head and neck cancers, as well as melanoma – giving this treatment in the morning has been associated with better results than giving it in the late afternoon or evening.
Now the new study, published Dec. 8 in the journal Cancershows that the time of day a drug is administered also affects extensive-stage small cell lung cancer (ES-SCLC) – a fast-growing cancer that is usually associated with a poor prognosis and accounts for approximately 15% of new cases of lung cancer.
This study is “very important”, said Dr Francis Lévimedical oncologist and founder of Chronotherapy Group at the University of Warwickwho did not participate in the work. It extends previous research he did it with the same team, which involved different types of lung cancer and different immune checkpoint inhibitors, but produced similar results.
“At the start of the day, immune checkpoint inhibitors, as monotherapy or in combination with chemotherapy or antiangiogenics [drugs that starve tumors of blood]significantly improves treatment efficacy compared to subsequent dosing times,” Lévi told Live Science.
Other experts 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 Live Science they were “impressed by the significant effect of time of immunotherapy administration on overall survival”, calling it a “very significant difference”.
Adjusting the treatment schedule “represents a simple, inexpensive adjustment with the potential to make 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 School of Central South University in China analyzed data from nearly 400 patients with ES-SCLC, a cancer with median survival rate of 14 months. All patients received standard initial immunotherapy in combination with chemotherapy between May 2019 and October 2023.
Each patient’s average treatment time per day was calculated based on the first four therapy cycles. The researchers then compared the survival outcomes of patients treated at different times of day, between 11 a.m. and 4:30 p.m. They compared the patients to ensure that the main difference between them was the timing of treatment, not baseline characteristics, such as age or gender.
3 p.m. marked a critical point. Patients who typically received treatment before 3 p.m. survived significantly longer without their cancer progress. They also had longer overall survival over the next five years, compared to those treated later in the day.
Even after accounting for other factors that might influence patient outcomes, this earlier treatment duration remained a strong, independent predictor of better survival.
The study results are consistent with laboratory studies that suggest that killer T cells (immune cells capable of directly killing cancer) tend to migrate into tumors in the morningsaid Dr Chi Van Dangprofessor of cancer medicine at Johns Hopkins University, who was not involved in the study. Therefore, aligning immunotherapy with this migration could help it work better, he told Live Science.
Personalized “chronotherapy”
The study’s large sample size is a strength, but the research has some caveats.
Lévi pointed out that most of the patients were men, for example. The pronounced temporal effects did not appear to extend to the women in the study, but that may be because few women were included, the study authors wrote, making it therefore 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, that picture isn’t entirely clear, Lévi said, because the study doesn’t specify the best cutoff time for care. “This leads to uncertainty about the most appropriate cut-off time, which could actually be between 11:30 a.m. and 3:00 p.m.,” he said.
Additionally, because the study looked at previous patient data, stronger evidence will still need to come from randomized clinical trials, in which different treatment schedules are explicitly tested and compared to each other. Most evidence for the benefits of early treatment “comes from retrospective studies,” Innominato and colleagues said, “with only a prospective trial completed and additional trials currently in development.
Assuming the trials yield positive results, there could still be logistical hurdles to overcome. “If treatment were limited to a single time window, such as the morning, clinical units could quickly become overwhelmed,” Innominato and colleagues said.
It is important to note that the “optimal window” for treatment may not be universal among patients, they added. This 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 thereby increasing efficiency while alleviating pressure on clinical units by spreading treatments throughout the day”, they suggested. “The challenge now is to develop rapid and reliable ways to identify chronotype and scale up this approach, and dedicated studies are already underway.”
This article is for informational purposes only and is not intended to offer medical advice.
