Patterns of response to anti-PD1 treatment: Comparison of three radiological response criteria and effect on overall survival (OS) in metastatic melanoma patients (MM).
Bibliographic record
Abstract
9073 Background: Radiological assessment of patterns of response (R) to checkpoint inhibitors remain imperfect. irRC accounts for pseudoprogression but does not evaluate change in density. We aimed to evaluate individual lesion and inter patient R by RECIST 1.1, irRC, CHOI and modified CHOI (mCHOI) and correlate R with OS. Methods: 37 patients (pts) with 567 measurable lesions treated with pembrolizumab in a phase 1 trial were studied. Bidimensional tumor diameter and density measurements were obtained at baseline and serial assessment CT scans. Overall R was assigned as per final CT scan assessment. Association of each criterion with OS was determined. Results: R varied according to site of metastases; lung lesions had the highest rate of complete response (CR) compared to other sites (69/163 (42%) lesions vs 71/404 (18%) p < .0001) and R varied at first assessment by RECIST compared to irRC (table). Delayed R post first scan were seen in 2/37 (5%) deemed PD by RECIST and 2/14 (14%) pts deemed PD by irRC at 1st assessment. 1/6 pts deemed to have PD by irRC at second assessment also had delayed R. 24 (65%) pts met CHOI density and size criteria for R at first follow-up. mCHOI criteria (> 15% density decrease and decrease in tumor size > 10%) showed R of 38% (14/37). Change in tumor size and density on 1st follow-up assessment was associated with OS with each 1000 mm2 increase in tumor size from baseline increasing the hazard of dying by 25.9% (HR = 1.259, [95% CI = 1.116-1.420], p = 0.0002). Similarly each 100HU increase in density increased the HR by 99% (HR = 1.99, [95% CI 1.246-3.176], p = 0.0039). R defined by any criteria had superior OS (CHOI, p = 0.0084; mCHOI, p = 0.0183; irRC, p < 0.0001 and RECIST, p = 0.0003). Conclusions: R by any criteria was prognostic and pseudoprogression was seen. The novel patterns of R and changes on treatment in tumor density suggest complex anti-tumor R of immunotherapy and require further validation. CR (%) PR/SD/PD (%) Site of Metastases Lung 42 58 Liver 24 76 Other solid organ 22 78 Peritoneal 37 63 Node 7 93 Subcutaneous 21 79 Other 11 89 R at first assessment scan RECIST 1.1 9/12/16 (24/32/44) irRC 10/13/14 (27/35/38)
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 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".