Table 1.

Modified generic inclusion criteria.

Not present before cancer diagnosis Pre-existing conditions cannot be considered treatment-related toxicity. For each toxicity, all relevant known pre-existing conditions must be registered to allow for valid statistical analyses (it is not required to screen for such conditions). Relevant pre-existing conditions may either •increase the probability of having a severe toxicity classified (e.g., being blind in one eye so only the other eye needs to be affected during treatment; or having Li-Fraumeni syndrome, relevant for developing second malignant cancer), or •preclude the possibility of a classification as severe toxicity for the patient (e.g., being blind in both eyes before cancer diagnosis)

Symptomatic To ensure equal probability of capturing the condition across different protocols using different screening strategies, the condition must be symptomatic and expected to lead to a clinical diagnosis without use of routine screening. •Compensated cardiac failure detected by routine echocardiogram is not included, whereas severe, symptomatic cardiac failure is included.

Objective The condition must be uniformly classifiable across different patients and by different observers. •Chronic pain, nausea, or fatigue, which are subjective, are not included, although these conditions can represent a substantial burden to the survivor.

Unacceptable severity The condition must be so severe, that it is considered an unacceptable tradeoff for disease control—i.e., had the condition been predictable at cancer diagnosis, it would probably have led to a change in anticancer therapy. •Physical and mental conditions that substantially affect self-care and instrumental activities of daily living or posing substantial threat of early mortality fulfill this criterion. •This consideration mirrors current actions (e.g., as reduction of anthracycline use in patients with Down Syndrome, reduction of thiopurine doses in patients with TPMT deficiency) or concerns related to re-exposure after severe drug-induced toxicity (e.g., re-exposure to asparaginase following asparaginase associated pancreatitis).

Persisting severity or correctable only by unacceptable treatments The condition must have been present for a sustained period or be corrected by a treatment, which itself is considered unacceptable. •Acute events are not included, but sequelae such as severe cognitive deficits following cerebral hemorrhage or amputation of a limb following severe infections, are. •Organ transplantation is an example of an unacceptable treatment since it is itself associated with risk of severe mortality and morbidity, whereas growth hormone replacement is an example of a treatment that is not considered unacceptable.