The association between diarrhea and serum cytokines in patients with gynecologic cancer treated with surgery and pelvic chemoradiotherapy

Highlights • Gastrointestinal symptoms including diarrhea and constipation are common in patients with gynecologic cancer receiving pelvic chemoradiotherapy. • There was an increase of serum IL-6 levels in patients with ≥grade 2 diarrhea during pelvic chemoradiotherapy. • Serum IL-1β and TNFα levels did not change during pelvic chemoradiotherapy. • Radiotherapy-related and clinical factors affect the development of chemoradiotherapy-induced diarrhea.
Purpose We investigated whether serum cytokines including Interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNFα) are increased during pelvic chemoradiotherapy (CRT) in patients with gynecologic malignancies, and sought to identify prognostic factors for the development of diarrhea during pelvic CRT. Materials and methods Patients with cervical or endometrial cancer receiving postoperative pelvic CRT were eligible for this prospective study. Patients were evaluated weekly during CRT for symptoms, including diarrhea and constipation. Serum cytokine levels were measured using immunoassays 1 week before CRT, and at week 3 and 5–6 during CRT. Radiotherapy-related parameters such as mean dose, minimum dose, and maximum dose to the small bowel were also analyzed. Multivariate logistic regression analysis was used to assess factors associated with development of enteritis symptoms. Results Twenty-six patients were enrolled, all of whom were eligible for symptom and dosimetric parameter evaluation; 24 were eligible for cytokine level measurement. Cytokine levels did not differ between patients with and without diarrhea before CRT. IL-6 levels increased during CRT, and were significantly higher in patients with diarrhea ≥grade 2 than in those with grade 0–1 at week 5–6 (6.771 ± 2.657 pg/mL vs. 3.396 ± 0.499 pg/mL, p = 0.046). Serum IL-1β and TNFα levels did not change during CRT. Diarrhea before CRT and the maximum dose to the small bowel were independent prognostic factors for CRT-induced diarrhea in the multivariate analysis. Conclusions There was an increase of serum IL-6 levels in patients with ≥grade 2 diarrhea during pelvic CRT. Serum IL-1β and TNFα levels did not change during CRT. Radiotherapy-related and clinical factors affect the development of diarrhea during pelvic CRT.