Core biopsy (bx) accuracy and safety of biopsy and preoperative immunotherapy in predicting histological subtype and nuclear grade in ECOG-ACRIN EA8143 perioperative nivolumab (nivo) versus observation in patients (pts) with renal cell carcinoma (RCC) undergoing nephrectomy.
Bibliographic record
Abstract
4541 Background: PROSPER is a phase 3 National Clinical Trials Network study that accrued pts with clinical stage ≥T2 or TanyN+ RCC of any histology planned for radical/ partial nephrectomy. Pts were randomized to perioperative nivo followed by primary tumor resection and 9 cycles of nivo postoperatively or standard surgery followed by observation. To address concerns that core kidney bx might 1) not provide accurate diagnosis and 2) delay surgery due to adverse events (AEs) or scheduling, the study was amended from requiring all patients to undergo core bx prior to treatment for confirmation of RCC, to only require bx in patients randomized to the nivo arm. Herein, we report the accuracy and safety of primary tumor core bxs in predicting final histology and nuclear grade by both site and central pathology review as well as time from enrollment to surgery. We also report AEs of preoperative nivo. Methods: Concordance of both core bx and primary tumor by site and central pathology review of histology and grade (1-2 vs 3-4) are reported, along with the Cohen’s Kappa value, which measures the agreement and concordance (kappa=0 is no concordance and 1 is highest). AEs relating to core bxs and preoperative nivo, as well as time from enrollment to surgery for each arm, comparing pre- and post-amendment (dropping bx requirement in surgery alone arm) are also reported. Results: 387/404 pts in the nivo arm and 171/415 pts in the surgery alone arm had core bxs. 632 patients had both central pathology and site review available. 41 of all randomized patients (819) were considered as non-RCC and 26/41 were identified via bx. The median times from enrollment to surgery for nivo and control arms pre-amendment were 32d vs 19 d, and post-amendment were 21 d vs 14 d, respectively. The median (25th-75th percentile) number of days from last preoperative nivo to surgery was 14 d (9-20). AEs related to core bx, generally from bleeding, were reported in 13/558 (2.3%) pts. 2/13 bxs resulted in life-threatening complications. 21/353 (6%) of pts receiving nivo pre-surgery had ≥ grade 3-5 AE attributed to nivo. 181/353 (51%) pts had any grade AE attributed to nivo. Concordance between bxs and primary tumor pathologies for determining histological subtype was Kappa = 0.62. Agreement between central pathology and originating site review of primary tumor for determining nuclear grade was Kappa = 0.56, and concordance of histology was Kappa = 0.78. Conclusions: The PROSPER trial use of core bxs in advance of neoadjuvant therapy was generally safe, largely consistent with primary tumor histology and grade, and did not delay resection of the primary tumor. AEs of preoperative nivo were consistent with nivo AEs in metastatic disease. This approach is valid for future neoadjuvant trials. Clinical trial information: NCT03055013 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".