A Chronobiological Prognostic Model for Resected Stage I Non-Small-Cell Lung Cancer.

@article{leuzzi2026chronobiological,
  title = {{A Chronobiological Prognostic Model for Resected Stage I Non-Small-Cell Lung Cancer.}},
  author = {Giovanni Leuzzi and Pamela Minicozzi and Paolo Verderio and Chiara Maura Ciniselli and Michele Ferrari and Alessandro Pardolesi and Alessia Stanzi and Jury Brandolini and Luigi Rolli and Matteo Calderoni and Clarissa Uslenghi and Ugo Pastorino and Giuseppe Lo Russo and Claudia Proto and Arsela Prelaj and Teresa Beninato and Daniele Lorenzini and Piergiorgio Solli},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18193208},
  url = {https://europepmc.org/article/MED/42882902},
  note = {CC BY},
}

TY  - JOUR
TI  - A Chronobiological Prognostic Model for Resected Stage I Non-Small-Cell Lung Cancer.
AU  - Giovanni Leuzzi
AU  - Pamela Minicozzi
AU  - Paolo Verderio
AU  - Chiara Maura Ciniselli
AU  - Michele Ferrari
AU  - Alessandro Pardolesi
AU  - Alessia Stanzi
AU  - Jury Brandolini
AU  - Luigi Rolli
AU  - Matteo Calderoni
AU  - Clarissa Uslenghi
AU  - Ugo Pastorino
AU  - Giuseppe Lo Russo
AU  - Claudia Proto
AU  - Arsela Prelaj
AU  - Teresa Beninato
AU  - Daniele Lorenzini
AU  - Piergiorgio Solli
PY  - 2026
DA  - 2026/10/04
JO  - Cancers
DO  - 10.3390/cancers18193208
UR  - https://europepmc.org/article/MED/42882902
AB  - Objectives  Chronobiology may influence outcomes in non-small-cell lung cancer (NSCLC), but its prognostic role in early-stage disease remains unclear. We evaluated the association between perioperative chronobiological variables, systemic inflammation, and long-term outcomes after complete resection for stage I NSCLC.Methods  587 patients who underwent curative-intent resection for pathological stage I NSCLC between 2009 and 2018 were retrospectively reviewed. Chronobiological and inflammatory variables included season of surgery (spring/summer [21st March-22nd September], autumn/winter [23rd September-20th March]), time of day, day of week, and preoperative (CRP0 levels: low ≤ 3 mg/L, high > 3 mg/L) and postoperative day-3 (CRP3 levels: low ≤ 126 mg/L, high > 126 mg/L) C-reactive protein levels. The cohort was randomly divided into training (70%) and testing (30%) sets to develop and validate a prognostic model for overall survival (OS), taking into consideration the follow-up time. Disease-free survival (DFS) was analyzed as a secondary endpoint.Results  Median follow-up was 6.7 years, with 80 deaths and 108 recurrences recorded. In the training set, older age (p = 0.0049), stage IB disease (p = 0.0301), high CRP0 (p = 0.0049), and high CRP3 (p = 0.0280) were associated with worse OS, while surgery performed during autumn/winter was associated with improved OS (p = 0.0312). The multivariate Cox model including age, stage, and season of surgery showed the best prognostic performance (C-index 0.67, 95% Bonferroni-adjusted CI 0.50-0.83) and was internally validated in the testing cohort (C-index 0.69, 95%CI 0.52-0.86). The resulting linear predictor remained associated with both OS and DFS in the overall population.Conclusions  A simple model integrating age, pathological stage, and season of surgery was associated with long-term outcomes after surgery in stage I NSCLC. This model provides an exploratory framework integrating host-, tumor-, and chronobiological dimensions of prognosis. These findings require external validation and further investigation of the biological mechanisms underlying seasonal variation.
SN  - 2072-6694
ER  -