167 Assessment of pathologic complete response following neoadjuvant therapy in patients with resectable lung cancer is equivalent across scoring systems
Bibliographic record
Abstract
Background Neoadjuvant/perioperative chemoimmunotherapy is a standard of care for treating patients with resectable non-small lung cancer (NSCLC) based on several phase III registrational clinical trials demonstrating improvement in rates of pathologic complete response (pCR, 0% residual viable tumor, RVT, in the resection specimen), event-free survival (EFS), and overall survival (OS) in patients treated with chemoimmunotherapy vs chemotherapy alone. However, pathologic response assessment criteria varied amongst these trials, with some studies reporting scoring by pan-tumor pathologic response criteria (irPRC) described in 2018 1 and others using criteria described by the International Association for the Study of Lung Cancer published in 2020.2 Despite the fact that these criteria are very similar in their approach to pathologic response assessment, some investigators have questioned whether cross-trial differences exist with regard to the value of pCR due to the different scoring systems used. The purpose of this study was to determine whether pCR assessed by these two scoring systems was associated with differential pCR rates across these trials and/or predictive value in the form of hazard ratios (HR) for the association of pCR with EFS.Methods A literature review was performed to identify phase III trials in patients with resectable NSCLC treated with chemoimmunotherapy in the neoadjuvant/perioperative setting. pCR rates and HR of pCR for predicting EFS were extracted from each trial manuscript. If the latter was not provided, data from the published Kaplan-Meier survival curves were converted to patient-level data using R package IPDfromKM with iterative Kaplan-Meier method3 and a HR was calculated.Results Five trials met criteria for inclusion 4–8 (table 1). All studies defined pCR as 0% RVT in both the primary tumor and lymph nodes. pCR rates across these studies were similar (range 17-25%). HRs for pCR predicting EFS were also comparable (range 0.13-0.16; table 1), indicating that pCR as assessed by either method had similar associations with EFS.Conclusions Regardless of criteria used for assessment of pCR, equivalent rates of pCR and HRs measuring the association between pCR and EFS were found across five phase III registrational trials in patients with resectable lung cancer treated with neoadjuvant/perioperative chemoimmunotherapy. This finding thus supports meta-analyses assessing the association between pCR and EFS.References Cottrell TR, Thompson ED, Forde PM, Stein JE, Duffield AS, Anagnostou V, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann Oncol. 2018 Aug 1;29(8):1853–1860.Travis WD, Dacic S, Wistuba I, Sholl L, Adusumilli P, Bubendorf L, et al. IASLC multidisciplinary recommendations for pathologic assessment of lung cancer resection specimens after neoadjuvant therapy. J Thorac Oncol. 2020 May;15(5):709–740.Liu N, Zhou Y, Lee JJ. IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2021 Jun 1;21(1):111.Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, et al. Perioperative durvalumab for resectable non-small-cell lung cancer. N Engl J Med. 2023 Nov 2;389(18):1672–1684.Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, et al. Perioperative nivolumab in resectable lung cancer. N Engl J Med. 2024 May 16;390(19):1756–1769.Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022 May 26;386(21):1973–1985.Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med. 2023 Aug 10;389(6):491–503.Lu S, Zhang W, Wu L, Wang W, Zhang P; Neotorch Investigators. Perioperative toripalimab plus chemotherapy for patients with resectable non-small cell lung cancer: the neotorch randomized clinical trial. JAMA. 2024 Jan 16;331(3):201-211.Abstract 167 Table 1Phase III trials investigating neoadjuvant/perioperative chemoimmunotherapy in NSCLCpCR = pathologic complete response; HR = hazard ratio, EFS = event-free survival; CI = confidence interval; chemo = chemotherapy; IASLC = International Association for the Study of Lung Cancer; irPRC = pan-tumor pathologic response criteria*HR and/or survival curves by pathologic response not published
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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 | 0.008 | 0.027 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".