Point S (sigmoid) doses and correlation with late recto-sigmoid adverse events in patients undergoing image-based...

Image-guided brachytherapy (BT) recommendations define dose limits for 2 cc of rectum and sigmoid; however, while rectal dose correlations with toxicity are well-established, similar evidence for the sigmoid dose is lacking. Due to its high positional variability, we previously proposed a surrogate marker, the "sigmoid point" (Point S), which now requires prospective validation for its association with late recto-sigmoid adverse events (AEs).

Cervical cancer patients treated with chemoradiation and MRI-based intracavitary or hybrid BT were included. Late recto-sigmoid AEs were prospectively recorded per CTCAE v4. Point S was retrospectively identified on BT plans. Equivalent dose in 2 Gy fractions (EQD2) for rectum 2 cc, sigmoid 2 cc/0.1 cc, and Point S were calculated. Univariate analysis assessed correlations between these doses and late AEs.

Sixty patients were analyzed with a median follow-up of 48 months. Nine (15%) developed grade ≥2 recto-sigmoid bleeding. Median EQD2 doses for patients with grade <2 versus grade ≥2 AEs were: rectum 2 cc: 67.4 versus 72 Gy₃ (p = 0.39); sigmoid 2 cc: 70.4 versus 71.3 Gy₃ (p = 0.65); sigmoid 0.1 cc: 91.8 versus 94.5 Gy₃ (p = 0.40); Point S: 74.4 versus 92.3 Gy₃ (p = 0.017). On univariate analysis, only Point S dose ≥75 Gy₃ was significantly associated with increased risk of recto-sigmoid bleeding (p = 0.017). Logistic regression confirmed higher Point S dose increased the likelihood of grade ≥2 bleeding (p < 0.003).

Point S is a promising surrogate for sigmoid dose estimation during BT. A Point S dose ≥75 Gy₃ is significantly associated with higher risk of grade ≥2 recto-sigmoid toxicity.