THE 23‐GENE GENE EXPRESSION‐BASED ASSAY DOES NOT PREDICT INTERIM PET SCAN RESULTS AFTER ABVD IN ADVANCED STAGE CLASSICAL HODGKIN LYMPHOMA IN THE US INTERGROUP S0816 TRIAL
Bibliographic record
Abstract
Introduction: Recently, we described a 23-gene gene expression-based biomarker that was prognostic for overall survival (OS) in patients (pts) with locally extensive and advanced stage classical Hodgkin lymphoma treated with ABVD chemotherapy (Scott et al. J Clin Oncol2013). The observation that the results of PET scan after 2 cycles (PET2) of ABVD is highly prognostic of progression free survival (PFS) has led to the design of response-adapted trials, where pts with a positive PET2 receive more intensive regimens aiming to improve outcomes. The purpose of this study was to test whether the 23-gene assay could predict PET2 results, allowing rational selective escalation of treatment from the time of diagnosis. The US Intergroup S0816 trial was a response-adapted trial in advanced stage (III and IV) classical Hodgkin lymphoma, with escalation to escBEACOPP where the PET2 was Deauville 4 or 5 (Press et al. J Clin Oncol 2016). Methods: The 23-gene assay was applied to RNA extracted from the formalin-fixed paraffin-embedded (FFPE) diagnostic biopsies of 276 pts from the S0816 trial. Patients were categorized into low- and high-risk groups using previously described assay thresholds. The primary endpoint was the comparison of the proportion of PET2 positive pts in the two risk groups. The secondary endpoint explored whether the risk groups were predictive of PFS in the context of response-adapted treatment. Results: Adequate gene expression was obtained in 217/276 (79%) biopsies – 119/164 (73%) from archival slides and 98/112 (88%) FFPE blocks. The patient characteristics of the 217 pts were not significantly different from the remainder of the total trial population of 336 pts. 142 (65%) pts were assigned to the low- and 75 (35%) to the high-risk gene expression group. 38 (18%) pts had a positive PET2. The assay did not identify pts at greater risk of PET2 positivity with 21% and 11% of pts having a positive PET2 in the low- and high-risk group, respectively. To test whether this was the result of a suboptimal threshold, we examined the area under the curve (AUC) of the receiver operator characteristic curve. The AUC of 0.41 (95% CI 0.31 – 0.51) demonstrates that the assay is not predictive of PET2 positivity. Furthermore, the assay was not predictive of PFS, with a 2-year PFS of 80% and 84% in the low- and high-risk groups, respectively (log rank P = 0.65). There were not sufficient events to test the prognostic power of the assay for OS. Conclusions: The 23-gene assay, trained on the endpoint of OS, was not predictive of PET2 results. Furthermore, it was not predictive of PFS in this trial of response-adapted treatment. These results provide strong evidence that this assay should not be used for risk stratification where response-adapted therapy is utilized. Support: National Cancer Institute (NCI), National Clinical Trials Network (NCTN) grants CA180888, CA180819, CA180821, and CA180820; Lymphoma Research Foundation. Keywords: classical Hodgkin lymphoma (cHL); gene expression profile (GEP); positron emission tomography (PET).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.002 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".