Histologic transformation in lung cancer: when one door shuts, another opens

Abstract

Histologic transformation (HT) is a major cause of drug resistance to therapy in patients with lung cancer. HTs to small-cell lung cancer (SCLC) have been reported frequently in patients with epidermal growth factor receptor ( EGFR)-mutated lung cancer. Although HTs have an impact on the clinical outcomes in patients owing to a high refractoriness to treatments, there is limited data on the prevalence, causes, mechanisms, treatment efficacy, and future treatment strategies. In this review, we assess the literature regarding HTs comprehensively, including those describing EGFR-tyrosine kinase inhibitors, other molecular targeted drugs, and immune checkpoint inhibitors. Furthermore, we discuss the mechanisms of HTs and the lineage plasticity to SCLC and squamous cell carcinoma in lung cancer. In addition, we summarize the treatment efficacy and future perspectives of HTs in patients with lung cancer, and propose better management strategies for this group of patients.

A Real-World Analysis of Anti-Programmed Death-Ligand 1 (PD-L1) Immune Checkpoint Inhibitor Treatments Combined with Chemotherapy in Untreated Extensive Stage Small Cell Lung Cancer

“…Our results showed that patients who received rst-line treatment with atezolizumab or durvalumab in combination with chemotherapy experienced no signi cant difference in OS. The chemotherapy regimen of cisplatin combined with etoposide is the standard rst-line treatment for extensive-stage SCLC [20]. The results of our study indicated that using atezolizumab or durvalumab combined with standard chemotherapy regimens as rst-line therapy in extensive-stage SCLC is effective and feasible in clinical practice.…”

Sequential treatment in advanced epidermal growth factor receptor-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with 1st/2nd-generation EGFR-tyrosine kinase inhibitors

“…For the 3 patients who underwent liquid biopsies only in this study, all of them were controlled by subsequent osimertinib treatments. Small cell transformation has also been reported as a resistance mechanism to prior osimertinib therapy in a previous study ( 44 ). According to the clinical treatment response to osimertinib in the 3 patients who underwent liquid biopsies only, the possibility of small cell transformation was very low, and the 3 patients were still included in this study.…”

“…Small cell lung cancer transformation is a rare (<5%) acquired resistance to previous EGFR-TKI treatment ( 44 ). In this study, 2 patients had small cell transformation according to tissue rebiopsy and were excluded from further analysis.…”

“…In this study, 2 patients had small cell transformation according to tissue rebiopsy and were excluded from further analysis. For advanced EGFR-mutated NSCLC patients who experienced small cell transformation after previous EGFR-TKI treatments, chemotherapy with platinum-based regimens combined with etoposide is recommended if the patient has acceptable performance status ( 44 ). For the 3 patients who underwent liquid biopsies only in this study, all of them were controlled by subsequent osimertinib treatments.…”

Conversion therapy with immunotherapy plus chemotherapy achieves a pathological complete response in stage IIIC NSCLC

“…As the resection criteria are controversial among locally advanced lung cancer in the era of immunotherapy, the optimal assessment criteria for operability following conversion therapy are also transformation is a major mechanism of drug resistance in lung cancer patients. Small-cell lung cancer (SCLC) transformation has been reported frequently in NSCLC patients after targeted therapy (33). However, histologic transformation between adenocarcinoma and squamous cell carcinoma after ICIs treatment is unusual.…”