To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (HL) using clinical factors known at diagnosis.
Although early response as measured by CT and/or PET scan has proven useful in the allocation of patients to therapy (eg. eliminating radiation or augmenting chemotherapy) (D Friedman, ASH 2010), stratification at diagnosis may allow earlier modification of treatment approach. The International Prognostic Score (D. Hasenclever, N Engl J Med, 1998) has been used effectively in adults with advanced stage disease, but includes predictors that may not be applicable to the pediatric and adolescent population. 1721 patients with intermediate risk HL (excludes IA and IIA without bulk disease and IIIB/IVB) were treated on AHOD0031, a Children's Oncology Group study using a dose dense, response based algorithm. 770 patients who were randomized or assigned to receive the same treatment (4 ABVE-PC and IFRT) serve as the basis for this report.
Patients <21 years with intermediate risk HL were eligible for COG AHOD0031. The study evaluated the tailoring of treatment by early response to 2 ABVE-PC. Rapid early response (RER) was a 2-dimensional tumor reduction of >60% after 2 cycles of ABVE-PC. Complete response (CR) was a >80% 2-diminsional reduction by CT, and resolution of nuclear imaging abnormalities. RER who achieved CR after 2 additional ABVE-PC were randomized to +/− 21Gy. Slow early responders (SER) were randomized to +/− DECA in addition to the 4 ABVE-PC/21 Gy.
Cox regression analysis was used to evaluate potential predictors of EFS (gender, age, race, stage, mediastinal mass, B symptoms, hemoglobin, sedimentation rate, albumen, histology). Continuous variables were dichotomized by clinical significance or quartiles of the population. Multivariable predictive modeling was performed using univariate predictors with a p<0.25. In instances of collinearity, the most robust variable was used. A stepwise selection algorithm was used to identify predictors with a p<0.15.
Four predictors (stage 4, large mediastinal adenopathy, albumen<3.5 and fever) were identified as predictive of adverse EFS. Since the Hazard Ratios were similar, the CHIPS (Childhood Hodgkin IPS) score was devised that gave 1 point for each of the 4 adverse predictors. EFS based on score was found to predict an excellent outcome of nearly 90% for those with CHIPS 0 or 1 (N=589) vs. 78% or 62% for those with CHIPS 2 or 3 respectively (N= 141 and 32).
The CHIPS score identifies a subset of patients accounting for 22% of an intermediate risk population who are predicted to have an EFS <80%. Early augmentation of therapy may improve outcome for this cohort. After further validation of this approach in historical cohorts, future studies will evaluate the utility of the CHIPS in additional cohorts of newly diagnosed patients.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.