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Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer

  • Authors:
    • Özge Kaya Korkmaz
    • Yaren Sari Çataldaş
    • Nazlican Saltik Barel
    • Mehmet Büyükevli
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Etlik City Hospital, University of Health Sciences, Ankara, Ankara 06010, Turkey, Department of Thoracic Surgery, Etlik City Hospital, University of Health Sciences, Ankara, Ankara 06010, Turkey
    Copyright: © Kaya Korkmaz et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 312
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    Published online on: May 22, 2026
       https://doi.org/10.3892/ol.2026.15667
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Abstract

Recent neoadjuvant trials in lung cancer have demonstrated meaningful survival advantages, highlighting the need for standardized assessment of pathologic response in resected specimens. Only two systems are currently recommended for evaluating post‑treatment response, namely the International Association for the Study of Lung Cancer (IASLC) tumor regression grading system and the immune‑related pathologic response criteria (irPRC). The present study aimed to review and apply histopathologic parameters for assessing tumor regression in non‑small cell lung carcinoma (NSCLC) specimens resected after neoadjuvant therapy. A total of 30 NSCLC resections obtained after neoadjuvant therapy between 2022 and 2025 were analyzed. Gross and microscopic evaluations were performed according to IASLC recommendations. Residual viable tumor, fibrosis, inflammation and necrosis were semi‑quantitatively assessed according to IASLC and irPRC principles. Major pathologic response (mPR) was defined as ≤10% viable tumor and pathologic complete response (pCR) as 0% viable tumor. Associations with demographic features, treatment modalities and survival outcomes were analyzed. Compared with chemotherapy (CT) alone, chemo‑immunotherapy (CIT) exhibited a trend toward a deeper pattern of tumor regression, reflected by lower median viable tumor percentages (7.5 vs. 55.0%) and higher mPR rates (62.5 vs. 22.7%), although these differences did not reach statistical significance. pCR occurred in 37.5% of patients treated with CIT and in 13.6% of patients treated with CT. CIT specimens demonstrated more prominent immune‑mediated stromal changes, including greater intratumoral inflammation (32.5 vs. 10.0%) and more frequent lymphocytic patterns. Fibrosis strongly correlated with response (P<0.001), whereas necrosis did not. Spread through air spaces positivity was found to be significantly reduced in cases of mPR (P<0.001). Therefore, neoadjuvant CIT may be associated with deeper pathologic regression compared with CT, characterized by increased fibrosis and immune activation. Major pathologic response remains a potential prognostic indicator and integration of IASLC and irPRC criteria, together with tumor microenvironment assessment, may improve the evaluation of treatment response in resectable NSCLC.
View Figures

Figure 1

Gross assessment and mapping of the
tumor bed following neoadjuvant therapy. The specimen was
systematically sectioned and subdivided into grid areas (A-U) for
representative sampling according to International Association for
the Study of Lung Cancer recommendations.

Figure 2

Representative histologic image
demonstrating manual annotation of viable tumor (red), stromal
component (blue) and necrotic areas (yellow) using QuPath software
for quantitative assessment (scale bar, 500 µm).

Figure 3

Waterfall plot to visualize the depth
of pathologic response for each patient. CT, chemotherapy; CIT,
chemo-immunotherapy.

Figure 4

Major pathological response in the
tumor bed. (A) Dense fibrosis and chronic inflammatory infiltrates
(magnification ×4). (B) Cholesterol clefts within the regressed
tumor bed (H&E staining; original magnification ×10). (C)
Foreign body-type giant cell reaction (H&E staining; original
magnification ×4). (D) Prominent histiocytic accumulation (H&E
staining; original magnification ×4). (E) Microcalcifications
within the fibrotic stroma (H&E staining; original
magnification ×4).

Figure 5

Distribution of viable tumor
percentage, necrosis, and stromal components in the chemotherapy
and chemo-immunotherapy groups after neoadjuvant treatment. The
central line indicates the median, the box represents the
interquartile range, and whiskers denote the minimum and maximum
values. Outliers are indicated by black diamond symbol.
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Spandidos Publications style
Kaya Korkmaz Ö, Sari Çataldaş Y, Saltik Barel N and Büyükevli M: Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer. Oncol Lett 32: 312, 2026.
APA
Kaya Korkmaz, Ö., Sari Çataldaş, Y., Saltik Barel, N., & Büyükevli, M. (2026). Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer. Oncology Letters, 32, 312. https://doi.org/10.3892/ol.2026.15667
MLA
Kaya Korkmaz, Ö., Sari Çataldaş, Y., Saltik Barel, N., Büyükevli, M."Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer". Oncology Letters 32.1 (2026): 312.
Chicago
Kaya Korkmaz, Ö., Sari Çataldaş, Y., Saltik Barel, N., Büyükevli, M."Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer". Oncology Letters 32, no. 1 (2026): 312. https://doi.org/10.3892/ol.2026.15667
Copy and paste a formatted citation
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Spandidos Publications style
Kaya Korkmaz Ö, Sari Çataldaş Y, Saltik Barel N and Büyükevli M: Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer. Oncol Lett 32: 312, 2026.
APA
Kaya Korkmaz, Ö., Sari Çataldaş, Y., Saltik Barel, N., & Büyükevli, M. (2026). Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer. Oncology Letters, 32, 312. https://doi.org/10.3892/ol.2026.15667
MLA
Kaya Korkmaz, Ö., Sari Çataldaş, Y., Saltik Barel, N., Büyükevli, M."Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer". Oncology Letters 32.1 (2026): 312.
Chicago
Kaya Korkmaz, Ö., Sari Çataldaş, Y., Saltik Barel, N., Büyükevli, M."Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer". Oncology Letters 32, no. 1 (2026): 312. https://doi.org/10.3892/ol.2026.15667
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