Session Item

Month and severity score (MOSES) was developed to model time weightage into the grade of toxicity with an aim to facilitate better correlation between physician reported late adverse effects and patient reported quality of life (QOL). Reanalysis of a phase III trial with a primary endpoint of late toxicity is performed using both Common Toxicity Criteria of Adverse event (CTCAE) reporting and MOSES.

NCT 01279135 randomized patients with cervix cancer to postoperative image guided intensity modulated radiotherapy (IG-IMRT) or three dimensional conformal radiation (3DCRT) to investigate the difference in late grade ≥ 2 gastrointestinal (GI) toxicity. However, the impact of IG-IMRT on all grades of CTCAE and their time course is unknown. The GI, genitourinary (GU) and other late toxicity were reported for intervention effect. CTCAE grade available at predefined time points during follow-up was converted into a mathematical score (Ʃ (P x S)) by imputing proportionate time weightage to CTCAE and thereby determining MOSES for GI, GU/GI and any toxicity. This mathematical score was summated to determine cumulative MOSES (C-MOSES) as representative of multiple system and multiorgan toxicity. Receiver operator characteristics curve analysis was used to identify C-MOSES cut off that predicted for substantial impact on QOL. The late toxicity between study arms was reanalyzed as time-to-event and intention-to-treat analysis using CTCAE grade ≥1 toxicity and C-MOSES≥0.70 as cut off’s. p<0.05 was considered significant.

Three hundred patients were randomized (IG-IMRT 151 and 3DCRT 149). At a median follow up of 48 months 238 (79%) patients had CTCAE grade ≥1 toxicity whereas 147 (49%) patients had C-MOSES score≥0.70. This difference in event rate using CTCAE and C-MOSES demonstrates that imputing time weightage allows discrimination between “isolated events” and “any grade persistent events”.

IG-IMRT was associated with reduced 3-year CTCAE grade≥2 GI toxicity (21.1% vs 42.2% HR 0.46 95% CI 0.29-0.73, p<0.001) in the primary trial. No difference was however, observed in the two arms in the 3-year rates of CTCAE grade≥1 GI toxicity (84.5% vs. 84.2% (HR 0.98 (0.75-1.28), p=0.88). However, using C-MOSES ≥0.70, the 3-year GI toxicity between IG-IMRT and 3DCRT was 54.1% vs. 33.6% (HR=0.63 95% CI 0.41-0.99, p=0.043).The late GU/GI toxicity with CTCAE grade≥1 was 86 % vs. 87.5% (HR 1.01 95% CI: 0.78-1.32, p=0.92) and 54.1 % vs.35.4% (HR =0.68 95% CI: 0.44-1.05 p=0.08) using C-MOSES. The CTCAE rates for any toxicity were 90.7% vs. 93.5% (HR=0.99 95% CI: 0.77-1.28, p=0.94) respectively. The corresponding 3-year rates using C-MOSES≥0.70 was and 77.3% vs. 62.9% (HR=0.72 95% CI: 0.52-0.99, p=0.04). 

By imputing toxicity duration, C-MOSES provides much more comprehensive discrimination of severity and duration between treatment modalities than CTCAE at each organ system level. Further external validation is however needed for MOSES.