A new study suggests that giving immunochemotherapy earlier in the day helps patients with advanced lung cancer live longer.
Previous studies suggested that the body's internal clock, circadian rhythmmay affect the effectiveness of immune checkpoint inhibitors. These drugs help the immune system recognize and attack cancer cells by blocking tumors' ability to suppress these immune responses.
IN several types of cancer — such as kidney, liver, stomach, esophagus, head and neck cancers, and melanoma — giving this treatment in the morning was associated with better results than giving it in the afternoon or evening.
Now a new study published December 8 in the journal Cancershows that the time of day the drug is administered also influences the advanced stage of small cell lung cancer (ES-SCLC), a fast-growing cancer that is typically associated with a poor prognosis of about 15% of new lung cancer cases.
The research is “very important,” he said. Dr. Francis Levyoncologist and founder Chronotherapy Group at the University of Warwickwho did not take part in the work. He expands earlier studies he did this with the same team, which used different types of lung cancer and different immune checkpoint inhibitors but produced similar results.
“Early time of day of immune checkpoint inhibitors, either as single drugs or in combination with chemotherapy or antiangiogenic agents. [drugs that starve tumors of blood]significantly increases the effectiveness of treatment compared to later doses,” Levy told Live Science.
Other experts not involved in the study agreed that the results were impressive. In a joint statement, the oncologist Dr. Pasquale Unnamed and circadian biologist Robert Dallmannboth from the University of Warwick, and oncologist Dr Celine Ismail-Sutton from Ysbyty Gwynedd Hospital in Wales told Live Science they were “impressed by the large effect of time of day of immunotherapy on overall survival”, calling it a “very significant difference”.
Changing the timing of treatment “is a simple, low-cost adjustment that has the potential to provide significant improvements in patient outcomes… without adding new drugs or complex interventions,” they said.
Earlier treatment, higher survival rate
In their study, scientists from the Cancer Hospital of Xiangya Medical School of Central South University in China analyzed data from almost 400 patients with ES-SCLC, a cancer with median survival 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 cycles of therapy. The researchers then compared the survival outcomes of patients treated at different times of the day, from 11 a.m. to 4:30 p.m. They matched the patients to ensure that the main difference between them was the timing of treatment, not baseline characteristics such as age or gender.
15:00 marked the critical cut-off point. Patients who typically received treatment before 3 p.m. survived significantly longer without treatment. Cancer progresses. They also had higher overall survival over the next five years compared to those treated later in the day.
Even after controlling for other factors that may have influenced patient outcomes, earlier treatment time remained a strong and independent predictor of better survival.
The study results are consistent with laboratory studies that suggest that killer T cells—immune cells that can directly kill cancer—tend to migrate to tumors in the morningsaid Dr. Chi Van Dangprofessor of cancer medicine at Johns Hopkins University who was not involved in the study. So matching immunotherapy to this migration could help it work better, he told Live Science.
Personalized “chronotherapy”
The study's large sample size was a strength, but the study has some caveats.
Levy noted that most patients, for example, were men. The large time effects did not appear to apply to the women in the study, but this may be because there were few women in the study, the study authors wrote, so it deserves to be explored in larger studies.
The study found that patients who received immunochemotherapy before 3 pm lived almost twice as long as those who received treatment in the afternoon. However, this picture is not entirely clear, Levy said, because the study does not determine the best time to end care. “This leads to uncertainty as to the most appropriate termination time, which could actually be between 11:30 a.m. and 3:00 p.m.,” he said.
Additionally, since the study looked at data from past patients, more convincing evidence would still need to come from randomized clinical trials in which different treatment periods are explicitly tested and compared with each other. According to Innominato and colleagues, most evidence for the benefits of early treatment “comes from retrospective studies,” “only with one prospective study completed and additional trials currently in development.”
Assuming the trial shows positive results, there may still be logistical hurdles to overcome. “If treatment were limited to a single time window, such as the morning, clinical departments could quickly become overwhelmed,” Innominato and colleagues say.
It's important to note that the “optimal window” of treatment may not be universal among patients, they added. This may partly depend on the biological rhythms and lifestyle characteristics of each person.
Chronotyping is the classification of people by “morning larks” or “night owls” — could “match therapy to each patient’s internal clock, accounting for individual variability and thus increasing efficiency while reducing the burden on clinical departments by spreading treatment throughout the day,” they suggested. “The challenge now is to develop rapid and reliable ways to determine chronotype and scale up this approach, and dedicated studies are already underway.”
This article is for informational purposes only and is not intended to provide medical advice.
