KEY POINTS
- REQUITE prospectively enrolled 530 patients with nonmetastatic lung cancer treated with curative-intent radiotherapy at 16 centers in Europe and the USA between 2014 and 2017. The cohort included 159 women and 371 men treated with conventional RT, chemoradiotherapy or SBRT.
- Follow-up declined substantially over time: 309 patients remained evaluable at 12 months and 151 beyond one year. By 12 months, 32.7% of women and 38.7% of men had died, creating important survivorship and attrition bias in later toxicity estimates.
- During the first 3–6 months, women had more overall grade ≥2 toxicity than men (46% vs 37%). Grade ≥2 pulmonary events occurred in 40% versus 30%, while grade ≥2 oesophageal events occurred in 15% versus 6%, respectively.
- Across follow-up, the most frequent grade ≥2 pulmonary symptoms were dyspnoea (18% overall) and cough (15%). Women had more grade ≥2 chest wall pain (13.8% vs 5.9%) and grade ≥3 dyspnoea (6.6% vs 2.4%); pneumonitis itself was grade ≥2 in 11.3% of women versus 8.1% of men.
- After adjustment for multiple testing, exploratory sex differences persisted for acute oesophageal toxicity in several subgroups, particularly SBRT/SABR, no chemotherapy, stage I–II disease, age >70 years, non-current smokers and patients without COPD. Late grade ≥3 differences were largely driven by pulmonary events after SBRT/SABR and in early-stage disease.
- Patient-reported outcomes documented substantial long-term functional burden. At 12 months, 45% of women versus 21% of men reported not feeling active; beyond 12 months, 47% versus 32% reported difficulty maintaining physical activity. Shortness of breath, cough, fatigue and limitations in daily activities remained common.
- The study was explicitly descriptive and was not designed to establish biological sex as an independent cause of radiation toxicity. Treatment technique, smoking, COPD, stage, chemotherapy, age, baseline symptoms and differential survival all varied, while later assessments involved a progressively selected survivor population.
CLINICAL TAKEAWAY
Lung radiotherapy toxicity extends well beyond pneumonitis alone: dyspnoea, cough, chest wall symptoms, fatigue and activity limitation remained clinically important during survivorship. The sex-specific signals are useful for generating hypotheses and structuring follow-up, but should not yet drive sex-based dose constraints or treatment selection.