I’m excited to share that I’ll be joining AdventHealth Cancer Institute on December 1, 2025, as the Director of Cutaneous & Connective Tissue Malignancies. I’m deeply grateful for the opportunity to continue advancing care, research, and education in this space. As I make this transition, I’ll keep reflecting here on the science and details that shape how we care for patients—because often, it’s the “small things” that matter most.
In oncology, I’ve learned to be cautious about assuming the “small” things don’t matter.
Years ago, I would have said:
- Antibiotics? Surely a necessary safeguard, unlikely to change long-term outcomes.
- PD-L1 testing? Probably too blunt to meaningfully guide care.
- ctdna testing? Probably wouldn’t impact care.
Today, I know both assumptions were wrong.
- Antibiotics matter. We now understand that antibiotics given around the time of immune checkpoint inhibitors (ICIs) can disrupt the gut microbiome, blunting immune response and worsening survival outcomes. Being judicious with antibiotics has become part of how I think about patient care.
- PD-L1 matters. While imperfect, PD-L1 expression helps us decide who is most likely to benefit from ICIs in many solid tumors. It shapes real-world treatment decisions every day.
- CtDNA matters. We can escalate or de-escalate treatments based on clearance or lack thereof prior to gold standard imaging. We can assess high risk post surgical or post IO MRD.
These are lessons in humility: sometimes what seems minor—an antibiotic prescription, a biomarker testing—proves central to outcomes.
And now, I think we’re facing another “small thing” that might not be small at all: the time of day we give immunotherapy.
Why timing could plausibly matter
Immune function doesn’t run on a flat line—it runs on a clock. Circadian biology regulates how dendritic cells process antigens, how T cells traffic between blood and tissues, and even how CD8⁺ T cells infiltrate tumors. These processes peak at different times of day, suggesting there may be windows when the immune system is more primed to respond to ICIs.
What the newest clinical signals show
1) Randomized NSCLC trial (ASCO 2025, Abstract 8516).
Patients with stage IIIC–IV NSCLC, no driver mutations, were randomized to receive chemo-IO either before 3:00 p.m. or after 3:01 p.m. Early dosing nearly doubled PFS and improved OS and response rate. Benefits were consistent across subgroups. (Peer review pending, but notable for being randomized.)
2) Bicentric, bicontinental real-world NSCLC (EBioMedicine 2025).
In ~700 patients treated with 1L chemo-IO in France and China, completing the first four cycles before ~11:30 a.m. was linked to OS of 33 vs 19.5 months for later dosing, with better PFS and response rates as well.
3) Large single-centre, pan-tumor cohort (JCO 2025; Bosetti et al., Abstract 2662).
Among 2,631 patients with lung, melanoma, renal, H&N, and urothelial cancers, those who received ≥50% of ICI infusions after 12:49 p.m. had significantly shorter OS (13.1 vs 21.4 months) than those treated earlier. Importantly, the effect was clearest with ICI alone or ICI + TKI, but not with chemo-containing regimens—reminding us that context matters.
Together, these studies point in the same direction: earlier infusions may mean better outcomes.
How I interpret this in practice
- When feasible, can we aim for morning ICIs, especially the first 2–4 cycles. That’s where the data signal is strongest.
- I don’t treat it as dogma. The Bosetti study reminds us that regimen and tumor type influence whether timing matters.
- I balance feasibility. Mandating morning-only slots could reduce access; we need to be pragmatic and patient-centered.
The bigger lesson
If antibiotics and PD-L1/ctdna taught us anything, it’s this: don’t underestimate the details. Chronobiology may turn out to be another detail that profoundly impacts outcomes. And if a simple scheduling shift of starting infusion in the AM can help, it’s worth our attention. I’ll quote what Dr Mark Socinski (Medical Oncology Advent Health) said at the end of his presentation and after discussing one of the previous abstracts at the Best of ASCO session… “I too would like my IO in the AM!”
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.
Disclosures:
Dr. Thomas serves as a speaker for Bristol Myers Squibb (BMS), Merck, Ipsen, Natera, Immunocore, Pfizer, and SpringWorks. He also receives industry grants in support of numerous clinical trials.