Childhood Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Diagnosis and Staging
Table 2. Criteria Used for the Classification of Risk Groups in Childhood Hodgkin Lymphoma Clinical Trialsa
|Trial||Low Risk||Intermediate Risk||High Risk|
|E = extralymphatic.|
|a Adapted from Kelly.|
|Children's Oncology Group|
|AHOD0031|| ||IA bulk or E; IB; IIA bulk or E; IIB; IIIA, IVA|| |
|AHOD0431||IA, IIA with no bulk|| || |
|AHOD0831|| || ||IIIB, IVB|
|C5942||IA, IB, IIA with no bulk, no hilar nodes and <4 sites||IA, IB, IIA with bulk, hilar nodes or ≥4 sites; III||IV|
|C59704|| || ||IIB/IIIB with bulk, IV|
|P9425/P9426||IA, IIA with no bulk||IB, IIA, IIIA1 with bulk; IIIA2||IIB, IIIB, IV|
|GPOH-HD 95; GPOH-HD 2002;PHL-C1[3,22,23]||1A/B, IIA||IE A/B;IIE A; IIB; IIIA||IIE B; IIIE A/B; IIIB; IV|
|Stanford/St. Jude/Dana-Farber Cancer Institute Consortium|
|HOD05|| ||IB, IIIA, IA/IIA with E, ≥3 sites or bulk|| |
|HOD08||IA, IIA with no bulk, E and <3 sites|| || |
|HOD99|| || ||IIB, IIIB, IV|
Although all major research groups classify patients according to clinical criteria, such as stage and presence of B symptoms, extranodal involvement, or bulky disease, comparison of outcomes across trials is further complicated because of differences in how these individual criteria are defined.
Further refinement of risk classification may be performed through assessment of response after initial cycles of chemotherapy or at its completion.
Interim response assessment
The interim response to initial therapy, which may be assessed on the basis of volume reduction of disease, functional imaging status, or both, is an important prognostic variable in both early- and advanced-stage pediatric Hodgkin lymphoma.[24,25] Definitions for interim response are variable and protocol specific, but can range from volume reductions of greater than 50% to the achievement of a complete response with a volume reduction of greater than 95% by anatomic imaging or resolution of FDG-PET avidity.[3,18,21]
The rapidity of response to early therapy has been used in risk stratification to tailor therapy in an effort to augment therapy in higher-risk patients or to reduce the late effects while maintaining efficacy.
Results of selected trials using interim response to titrate therapy
- The Pediatric Oncology Group used a response-based therapy approach consisting of dose-dense ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide-prednisone, cyclophosphamide) for unfavorable advanced-stage patients in combination with 21 Gy involved-field radiation therapy (IFRT). The dose-dense approach permitted reduction in chemotherapy exposure in 63% of patients who achieved a rapid early response after three ABVE-PC cycles. Five-year event-free survival (EFS) was comparable for rapid early responders (86%; treated with three cycles of ABVE-PC) and slow early responders (83%; treated with five cycles of ABVE-PC) followed by 21 Gy IFRT.
- The Children's Cancer Group (CCG) (CCG-59704) evaluated response-adapted therapy featuring four cycles of the dose-intensive BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) regimen followed by a gender-tailored consolidation for pediatric patients with stage IIB, IIIB with bulky disease, and IV Hodgkin lymphoma. For rapid early responding girls, an additional four courses of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, vinblastine) (without IFRT) was given in an effort to reduce breast cancer risk. Rapid early responding boys received two cycles of ABVD followed by IFRT. Slow early responders received four additional courses of BEACOPP and IFRT. Rapid early response (defined by resolution of B symptoms and >70% reduction in tumor volume) was achieved by 74% of patients after four BEACOPP cycles and 5-year EFS among the cohort was 94% (median follow-up, 6.3 years).