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Small-cell lung cancer with a rare epidermal growth factor receptor gene mutation showing "wax-and-wane" transformation.

Takagi Y, Nakahara Y, Hosomi Y, Hishima T - BMC Cancer (2013)

Bottom Line: Given the staging of cT2aN3M1b (Stage IV) and histological diagnosis, first-line chemotherapy with cisplatin plus irinotecan was initiated, and partial response was achieved.Erlotinib was started, but multiple brain metastases and enlarged mediastinal lymph nodes subsequently appeared.Amrubicin therapy achieved partial response after two cycles, with the shrinkage lasting for eight months.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan. ytakagi-tmd@umin.net.

ABSTRACT

Background: Small-cell lung cancer with epidermal growth factor receptor (EGFR) gene mutation typically manifests as a transformation occurring after EGFR tyrosine kinase inhibitor therapy for adenocarcinoma with EGFR mutation, whereas primary small-cell lung cancer showing EGFR mutation is extremely rare. Second biopsy of EGFR-mutated tumor has been broadly recognized as necessary, but is not always performed in daily practice, mainly due to the imbalance between the potential risk of the diagnostic procedure and the therapeutic impact of the biopsy result.

Case presentation: A 70-year-old woman who had never smoked was referred to our hospital with chief complaints of cough and back pain. Transbronchial lung biopsy from the primary tumor of the left upper lobe revealed combined small-cell lung cancer and adenocarcinoma, a subtype of small-cell lung cancer. EGFR L861Q mutation was detected in both small-cell lung cancer and adenocarcinoma components. Given the staging of cT2aN3M1b (Stage IV) and histological diagnosis, first-line chemotherapy with cisplatin plus irinotecan was initiated, and partial response was achieved. Seven months after initial diagnosis, the primary tumor enlarged again, and a second biopsy from the enlarged lesion detected only adenocarcinoma with the L861Q mutation. Erlotinib was started, but multiple brain metastases and enlarged mediastinal lymph nodes subsequently appeared. Whole-brain radiation therapy was performed, and endobronchial ultrasonography-guided transbronchial biopsy from the lymph node revealed reverse transformation to small-cell lung cancer with the L861Q mutation. Amrubicin therapy achieved partial response after two cycles, with the shrinkage lasting for eight months. Serum sialyl Lewis X antigen level increased when the adenocarcinoma component was dominant, whereas plasma pro-gastrin-releasing peptide level increased when the small-cell lung cancer component became dominant.

Conclusions: Transformation of the tumor correlates with the difference between small-cell lung cancer and adenocarcinoma in sensitivity to therapies, so repeated biopsies are beneficial for choosing appropriate treatments. Noninvasively obtainable parameters such as tumor markers can support the need for biopsy.

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EGFR L861Q amplification curve for each specimen by the peptide nucleic acid-locked nucleic acid PCR clamp test. A) Small-cell lung cancer component of the specimen at the time of initial diagnosis. B) Adenocarcinoma component of the specimen at the time of initial diagnosis. C) Adenocarcinoma at the time of disease progression after cisplatin-irinotecan therapy. D) Small-cell lung cancer at the time of disease progression after erlotinib therapy.
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Figure 3: EGFR L861Q amplification curve for each specimen by the peptide nucleic acid-locked nucleic acid PCR clamp test. A) Small-cell lung cancer component of the specimen at the time of initial diagnosis. B) Adenocarcinoma component of the specimen at the time of initial diagnosis. C) Adenocarcinoma at the time of disease progression after cisplatin-irinotecan therapy. D) Small-cell lung cancer at the time of disease progression after erlotinib therapy.

Mentions: A 70-year-old Japanese woman was referred to our hospital with chief complaints of cough and back pain. She had never smoked and had no history of malignancy. Computed tomography (CT) revealed a 4-cm-diameter mass in the left upper lobe, enlargement of mediastinal lymph nodes, and left pleural dissemination (Figure 1). Asymptomatic brain metastasis was also detected on magnetic resonance imaging. A transbronchial lung biopsy (TBLB) specimen from the left upper lobe showed combined SCLC and adenocarcinoma (Figure 2), and the TNM classification of the tumor was cT2aN3M1b(BRA). The TBLB specimens were analyzed using a peptide nucleic acid-locked nucleic acid PCR clamp test, and EGFR exon 21 L861Q mutations were detected in both SCLC and adenocarcinoma components (Figure 3).


Small-cell lung cancer with a rare epidermal growth factor receptor gene mutation showing "wax-and-wane" transformation.

Takagi Y, Nakahara Y, Hosomi Y, Hishima T - BMC Cancer (2013)

EGFR L861Q amplification curve for each specimen by the peptide nucleic acid-locked nucleic acid PCR clamp test. A) Small-cell lung cancer component of the specimen at the time of initial diagnosis. B) Adenocarcinoma component of the specimen at the time of initial diagnosis. C) Adenocarcinoma at the time of disease progression after cisplatin-irinotecan therapy. D) Small-cell lung cancer at the time of disease progression after erlotinib therapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4228323&req=5

Figure 3: EGFR L861Q amplification curve for each specimen by the peptide nucleic acid-locked nucleic acid PCR clamp test. A) Small-cell lung cancer component of the specimen at the time of initial diagnosis. B) Adenocarcinoma component of the specimen at the time of initial diagnosis. C) Adenocarcinoma at the time of disease progression after cisplatin-irinotecan therapy. D) Small-cell lung cancer at the time of disease progression after erlotinib therapy.
Mentions: A 70-year-old Japanese woman was referred to our hospital with chief complaints of cough and back pain. She had never smoked and had no history of malignancy. Computed tomography (CT) revealed a 4-cm-diameter mass in the left upper lobe, enlargement of mediastinal lymph nodes, and left pleural dissemination (Figure 1). Asymptomatic brain metastasis was also detected on magnetic resonance imaging. A transbronchial lung biopsy (TBLB) specimen from the left upper lobe showed combined SCLC and adenocarcinoma (Figure 2), and the TNM classification of the tumor was cT2aN3M1b(BRA). The TBLB specimens were analyzed using a peptide nucleic acid-locked nucleic acid PCR clamp test, and EGFR exon 21 L861Q mutations were detected in both SCLC and adenocarcinoma components (Figure 3).

Bottom Line: Given the staging of cT2aN3M1b (Stage IV) and histological diagnosis, first-line chemotherapy with cisplatin plus irinotecan was initiated, and partial response was achieved.Erlotinib was started, but multiple brain metastases and enlarged mediastinal lymph nodes subsequently appeared.Amrubicin therapy achieved partial response after two cycles, with the shrinkage lasting for eight months.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan. ytakagi-tmd@umin.net.

ABSTRACT

Background: Small-cell lung cancer with epidermal growth factor receptor (EGFR) gene mutation typically manifests as a transformation occurring after EGFR tyrosine kinase inhibitor therapy for adenocarcinoma with EGFR mutation, whereas primary small-cell lung cancer showing EGFR mutation is extremely rare. Second biopsy of EGFR-mutated tumor has been broadly recognized as necessary, but is not always performed in daily practice, mainly due to the imbalance between the potential risk of the diagnostic procedure and the therapeutic impact of the biopsy result.

Case presentation: A 70-year-old woman who had never smoked was referred to our hospital with chief complaints of cough and back pain. Transbronchial lung biopsy from the primary tumor of the left upper lobe revealed combined small-cell lung cancer and adenocarcinoma, a subtype of small-cell lung cancer. EGFR L861Q mutation was detected in both small-cell lung cancer and adenocarcinoma components. Given the staging of cT2aN3M1b (Stage IV) and histological diagnosis, first-line chemotherapy with cisplatin plus irinotecan was initiated, and partial response was achieved. Seven months after initial diagnosis, the primary tumor enlarged again, and a second biopsy from the enlarged lesion detected only adenocarcinoma with the L861Q mutation. Erlotinib was started, but multiple brain metastases and enlarged mediastinal lymph nodes subsequently appeared. Whole-brain radiation therapy was performed, and endobronchial ultrasonography-guided transbronchial biopsy from the lymph node revealed reverse transformation to small-cell lung cancer with the L861Q mutation. Amrubicin therapy achieved partial response after two cycles, with the shrinkage lasting for eight months. Serum sialyl Lewis X antigen level increased when the adenocarcinoma component was dominant, whereas plasma pro-gastrin-releasing peptide level increased when the small-cell lung cancer component became dominant.

Conclusions: Transformation of the tumor correlates with the difference between small-cell lung cancer and adenocarcinoma in sensitivity to therapies, so repeated biopsies are beneficial for choosing appropriate treatments. Noninvasively obtainable parameters such as tumor markers can support the need for biopsy.

Show MeSH
Related in: MedlinePlus