BACKGROUND Histological transformation is one of the numerous mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors(EGFRTKIs).Given its rarity,the underlying transformational...BACKGROUND Histological transformation is one of the numerous mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors(EGFRTKIs).Given its rarity,the underlying transformational mechanisms,clinical features,and therapeutic prognoses are only studied through limited case reports.AIM To analyze the clinical characteristics and underlying mechanisms in non-small cell lung cancer(SCLC)patients with histological transformation after treatment with EGFR-TKIs.METHODS We retrospectively investigated nine patients diagnosed with non-SCLC transforming to SCLC,large-cell neuroendocrine carcinoma(LCNEC),or squamous cell carcinoma on re-biopsy after first-or third-generation EGFR-TKIs.RESULTS The median age of nine patients was 60 years.Among them,six patients had the EGFR 19del mutation,one had the L858R mutation,and one had wild-type EGFR.The level of plasma NSE was measured in six patients with SCLC or LCNEC transformation when transformation occurred,and five patients had elevated plasma NSE levels.All patients received standard chemotherapy after transformation with the exception of one patient who received chemotherapy and anlotinib.CONCLUSION Tumor re-biopsy should be performed routinely when EGFR-TKI therapy fails in lung cancer patients to avoid ignoring histological transformation and to select a subsequent therapeutic strategy.The transformed tumor retained the original EGFR mutation,indicating that histological transformation represents an evolution from the initial tumor.展开更多
Acquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer(mCRC).Histological transformation is an important mechanism underlying the acquired resistance of n...Acquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer(mCRC).Histological transformation is an important mechanism underlying the acquired resistance of non-small cell lung cancer and prostate cancer to targeted therapy.However,no report has examined the role of histological transformation in mCRC.Here,we report the first case of histologically transformed large cell neuroendocrine carcinoma from primary colon adenocarcinoma during antiangiogenesis and anti-PD-1 combination therapy.The histologic conversion was confirmed by the observation that the transformed large cell neuroendocrine carcinoma lesion retained the original mutational signature found in the primary tumor.Sequential tumor biopsy and dynamic changes in tumor markers demonstrated the transformed process.The histological transformation not only resulted in discordant responses to the same treatment but also significantly shortened overall survival.This case calls for more attention to histological transformation in mCRC.Tumor rebiopsy upon disease progression and monitoring dynamic changes in tumor markers would help to identify such cases.展开更多
文摘BACKGROUND Histological transformation is one of the numerous mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors(EGFRTKIs).Given its rarity,the underlying transformational mechanisms,clinical features,and therapeutic prognoses are only studied through limited case reports.AIM To analyze the clinical characteristics and underlying mechanisms in non-small cell lung cancer(SCLC)patients with histological transformation after treatment with EGFR-TKIs.METHODS We retrospectively investigated nine patients diagnosed with non-SCLC transforming to SCLC,large-cell neuroendocrine carcinoma(LCNEC),or squamous cell carcinoma on re-biopsy after first-or third-generation EGFR-TKIs.RESULTS The median age of nine patients was 60 years.Among them,six patients had the EGFR 19del mutation,one had the L858R mutation,and one had wild-type EGFR.The level of plasma NSE was measured in six patients with SCLC or LCNEC transformation when transformation occurred,and five patients had elevated plasma NSE levels.All patients received standard chemotherapy after transformation with the exception of one patient who received chemotherapy and anlotinib.CONCLUSION Tumor re-biopsy should be performed routinely when EGFR-TKI therapy fails in lung cancer patients to avoid ignoring histological transformation and to select a subsequent therapeutic strategy.The transformed tumor retained the original EGFR mutation,indicating that histological transformation represents an evolution from the initial tumor.
基金Beijing Excellent Talent Cultivation Subsidy Young Backbone Individual Project and Science Foundation of Peking University Cancer Hospital,Grant/Award Number:A002226the ethics committee of Peking University Cancer Hospital&Institute(2021KT30).
文摘Acquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer(mCRC).Histological transformation is an important mechanism underlying the acquired resistance of non-small cell lung cancer and prostate cancer to targeted therapy.However,no report has examined the role of histological transformation in mCRC.Here,we report the first case of histologically transformed large cell neuroendocrine carcinoma from primary colon adenocarcinoma during antiangiogenesis and anti-PD-1 combination therapy.The histologic conversion was confirmed by the observation that the transformed large cell neuroendocrine carcinoma lesion retained the original mutational signature found in the primary tumor.Sequential tumor biopsy and dynamic changes in tumor markers demonstrated the transformed process.The histological transformation not only resulted in discordant responses to the same treatment but also significantly shortened overall survival.This case calls for more attention to histological transformation in mCRC.Tumor rebiopsy upon disease progression and monitoring dynamic changes in tumor markers would help to identify such cases.
