PATTERNS OF PRESENTATION AND OUTCOMES IN STAGE IV HODGKIN LYMPHOMA: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP (COG) AHOD1331 TRIAL
Bibliographic record
Abstract
Introduction: Outcomes for high-risk pediatric and adolescent and young adult (AYA) classic Hodgkin lymphoma (cHL) improved substantially with the addition of brentuximab vedotin (Bv) to AVEPC (adriamycin, vincristine, etoposide, prednisone, cyclophosphamide) chemotherapy. As patients with stage IV disease have poor outcomes, we evaluated the prognostic implications of sites contributing to stage IV disease. Methods: On AHOD1331 (NCT02166463), patients age 2–21 years with high-risk cHL (stage IIB with bulk, IIIB, IVA, and IVB) were randomized to 5 cycles of AB (bleomycin)VE-PC versus Bv-AVE-PC, and consolidative radiotherapy based on interim response and large mediastinal adenopathy at diagnosis. Patients with stage IV disease, as determined by protocol defined and centrally reviewed PET-CT, were identified. Stage IV was defined as disseminated involvement of ≥1 extralymphatic organ or tissues (with or without lymph node involvement) or isolated extralymphatic organ involvement with distant nodal involvement. E-lesions were distinguished from sites of stage IV involvement in the lung, but any liver and/or bone marrow involvement, regardless of contiguity, was considered stage IV. Central review was performed to confirm institutional classification of stage, upstaging 33 patients to stage IV and downstaging 17 among the 353 enrolled and stratified as Stage IV by the institution. Baseline characteristics and progression-free survival (PFS) were compared by pattern of metastatic involvement (lung only, bone only, bone marrow only, or multi-site, defined as >1 site of involvement). Results: 369 patients (median age 15 years, range 3–22) with stage IV disease treated on AHOD1331 were included, of which 183 (50%) were treated with ABVE-PC and 186 (50%) with Bv-AVE-PC. Patterns of disease included: isolated involvement of lung (185; 50%); bone marrow (5; 1%); or bone (8; 2%), and 171 (46%) had multi-site involvement. B symptoms were present in 80% and 88% with bone marrow or bone involvement respectively, 50% of those with lung, and 57% with multi-site disease. The 3 year-PFS (95% CI) by site of involvement was: 88.0% (82.3, 91.9) for lung, 100% for isolated bone marrow or bone, and 82.5% (75.8, 87.5) for multi-site (p = 0.21). Bv-AVE-PC significantly improved PFS among stage IV patients compared to ABVE-PC (3-year PFS 90.2% vs. 81.5%, p = 0.01). Among those with isolated lung involvement, there was a non-significant increased PFS with Bv (3-year PFS 91.2% vs. 84.7%, p = 0.16), while those with multi-site metastatic disease experienced significantly improved PFS with Bv (3 year-PFS 88.1% vs. 77.1%, p = 0.05). Conclusions: Among pediatric and AYA patients with stage IV cHL, PFS was notably improved with Bv among patients with multi-site metastatic involvement. These results will help guide future efforts to understand strategies to improve outcomes among children with stage IV disease. The research was funded by: Supported in part by grants from the National Institutes of Health (U10CA098543, U10CA180899, and U10CA180886; all to the Children’s Oncology Group), the Quality Assurance Review Center (U10CA29511), Imaging and Radiology Oncology Core Rhode Island (U24CA180803), and St. Baldrick’s Foundation (to the Children’s Oncology Group) Keywords: Hodgkin lymphoma, molecular targeted therapies, Lymphoid Cancers - Other No conflicts of interests pertinent to the abstract.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".