Early and late morbidity assessment

Physician assessed morbidity will be scored prospectively with the Common Terminology Criteria for Adverse Events (both CTCAE v3.0 and CTCAE v4.0) on a priori selected, clinical relevant endpoints regarding gastro-intestinal, genito-urinary, vaginal and several unspecific symptoms.

Both early morbidity (per definition within the first 90 days after begin of treatment) and late morbidity will be assessed. Early morbidity will be assessed with a short version of the overall morbidity assessment with selected endpoints.

The morbidity endpoints for EMBRACE 2 were selected after a consensus based on yearly interim comprehensive analyses of the EMBRACE 1 material, covering inter alia: longitudinal analyses on manifestation pattern of symptoms, evaluation of the open text reports of the EMBRACE 1 database, cross-validation with the patient reported symptoms from the quality of life assessment, literature research and joint clinical discussions.

Case report forms are available for download at the EMBRACE 2 website: CRF Early Morbidity & CRF Baseline and Late Morbidity.

Morbidity Analyses: Morbidity outcomes will be analyzed if baseline and at least one follow-up assessment have been recorded. Morbidity will be censored at time of any recurrence (local, nodal, systemic) and baseline morbidity will be taken into account in any analysis in order to differentiate between tumor-related and treatment-related symptoms.

Endpoints will be evaluated both for the overall organ at risk (bowel, rectum, bladder, vagina etc.) and for individual symptoms with prevalence rates, crude and actuarial incidences (Kaplan Meier time to event method). For selected endpoints, a dose effect relation will be investigated based on Cox proportional hazard models; independent risk factors for morbidity will be taken into account by multivariate modelling.  

The following time points of assessment are scheduled:

Before start of treatment

During treatmentWeek 4Early morbidity
End of treatmentEnd of treatment

1st year3, 6, 9, 12 monthsLate morbidity
2nd year18, 24 months
3rd year30, 36 months
4th year48 months
5th year60 months

Contact person:

Kathrin Kirchheiner, Kari Tanderup