Pathologic responses to neoadjuvant chemoimmunotherapy in primary limited-stage small-cell lung cancer

Abstract

Background: Immunotherapy has been proved to have a large effect on extensive-stage small cell lung cancer, but the role of immunotherapy in limited-stage small-cell lung cancer (LS-SCLC) is still unknown.

Methods: A retrospective study of six patients with LS-SCLC who were treated with neoadjuvant chemoimmunotherapy (durvalumab plus etoposide combined with cisplatin) was performed. Patients were evaluated by the safety, feasibility and pathologic responses of neoadjuvant chemoimmunotherapy.

Results: Neoadjuvant durvalumab combined chemotherapy was associated with few immediate adverse events and did not delay planned surgery. All patients achieved partial pathologic response (pPR) instead of major pathologic response, or pathologic complete response. No association was observed between programmed death-ligand 1 expression in tumor specimens and the pathologic response. However, tumors with high expression of immune cells such as CD4+ T cells, CD8+ T cells and FoxP3+ Tregs tended to have better pathologic responses than tumors with low expression of immune cells.

Conclusions: Neoadjuvant durvalumab combined chemotherapy could induce pPR with few side effects in resectable LS-SCLC. The immune cells in the tumor microenvironment might play an important role in neoadjuvant chemoimmunotherapy in resectable LS-SCLC.

Keywords: PD-L1; limited-stage small-cell lung cancer (LS-SCLC); neoadjuvant chemoimmunotherapy; partial pathologic response; surgery.

FIGURE 1

Timelines of patients

FIGURE 2

Representative pathologic responses to neoadjuvant durvalumab plus chemotherapy in primary tumor specimens of LS‐SCLC (patient 5). (a) The characteristics of pathologic response at ×20 magnifications. (b) The characteristics of pathologic response at ×100 magnifications. The white dotted line separates the tumor cells from the degenerated tissues. The left side indicates the tumor cells, the right side indicates the degenerated tissues such as lymphocytes

FIGURE 3

Correlation of pathologic response with pre‐neoadjuvant radiographic tumor size (A) and the PD‐L1 expressions of the primary tumor (B, C). Each dot indicates one patient

FIGURE 4

Patterns of radiologic and pathologic response to neoadjuvant chemoimmunotherapy. Left column: patient 5 (PR), 30% of RVT in the resected specimen; right column, patient 6 (SD), 80% of RVT in the resected specimen. (A, C) Chest CT imaging of patient 5 before and after the administration of neoadjuvant chemoimmunotherapy. (E) Representative sections of tumor specimens after HE staining in patient 5. (B, D) Chest CT imaging of patient 6 before and after the administration of neoadjuvant chemoimmunotherapy. (F) Representative sections of tumor specimens after HE staining in patient 6. The black star indicates the RVT and the black arrow indicates the lymphocytes. Magnifications×20

FIGURE 5

Scatter diagram of the correlation of immune cells with %RVT. (a) Correlation of CD4+ T cells with %RVT. (b) Correlation of CD8+ T cells with %RVT. (c) Correlation of FoxP3+ Tregs with %RVT

FIGURE 6

Immunofluorescent staining of immune cells to neoadjuvant chemoimmunotherapy in resected primary tumors. The orange fluorescence indicates the CD4+ T cells

FIGURE 7

Immunofluorescent staining of immune cells to neoadjuvant chemoimmunotherapy in resected primary tumors. The green fluorescence indicates the CD8+ T cells

FIGURE 8

Immunofluorescent staining of immune cells to neoadjuvant chemoimmunotherapy in resected primary tumors. The pink fluorescence indicates the FoxP3+ Tregs