김문현

238

￭

￭

Circulating tumor cell as a surrogate biomarker in advanced gastric cancer with bone marrow invasion

1세브란스병원 종양내과, ²연세 송당 암 연구센터, ³BK21 플러스 연세의과학사업단

*

김문현

, 이가든

, 이기쁨

, 권우선

, 정현철

, 라선영

In AGC, initial presentation with bone metastasis is rare (bone 3.8~12%, bone marrow 0.024~0.9%). These subset of patients have poor outcome with a median survival of less than three months. Although tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are used as biomarkers in AGC, their role in predicting responses to chemotherapy is variable and inconclusive in clinical practice. Here, we report a case which cir- culating tumor cells (CTCs) was a useful surrogate biomarker in predicting clinical outcome. A 58-year-old woman was admitted to the hospital due to poor oral intake, nausea, back pain and weight loss of 8 kg over 3 months. Laboratory study revealed anemia (8.3g/dL) and thrombocytopenia (23,000/uL).

Gastroduodenoscopy and CT scan confirmed AGC with multiple lymph nodes and bone metastasis. Bone marrow biopsy, which was performed to rule out other hematologic causes of thrombocytopenia, revealed metastatic signet ring cell carcinoma from stomach. Immunohistochemistry showed that HER2 was negative, but with high level of PD-L1 expression (PD-L1 expression 95%). Blood sampling was done serially to check circulating tumor cells (CTCs).

Before treatment, CTCs were elevated (1777 CTC per mL). This was unusually high since patients with metastatic disease have typically 1-10 CTC per mL of whole blood. The patient was then treated with capecitabine and oxaliplatin combination. Initially, she responded well to treatment. Platelet count in- creased within a week, reaching 197,000/uL at second cycle. In addition, CTCs markedly decreased from 1777 to 12. However, CTCs steadily increased from 38 to 317. Thereafter, CT scans confirmed disease progression after four cycles. Next-generation sequencing (NGS) and Global Screening Array (Illumina©) analysis revealed germline FGFR4 (G338R) mutation and somatic FGFR2 (K659N) alteration. Thereafter, the patient was enrolled in a clinical trial and received nivolumab and paclitaxel, but eventually died from disease progression after 7 months of treatment. Our case showed that serial follow up of CTCs may be a surrogate marker in predicting therapeutic responses and prognosis in patients.

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￭

Heart transplantation for HF in a patient with breast cancer exposed to low cumulative dose of AC

1울산대학교 의과대학 서울아산병원 내과, ²울산대학교 의과대학 서울아산병원 종양내과

*

조성현

, 정재호

Background: The risk of cardiotoxicity has long been recognized to correlate with the cumulative anthracycline (AC) dose. Total cumulative doses of AC in breast cancer are typically lower than limited dose. Here, we report a rare case of heart transplantation for cardiomyopathy in a patient with breast cancer who was treated with low cumulative doses of AC (240 mg/m²). Case report: A previously healthy 54-year-old woman underwent breast-conserving sur- gery for left breast cancer. The tumor was found to be an invasive ductal carcinoma measuring 1.7×1.5×1.5 cm (nuclear grade 2/3, histologic grade 2/3), and the sentinel lymph node was negative for metastasis (pT1N0M0). Immunohistochemistry of the tumor was positve for estrogen receptor, progesterone receptor, and negative for human epidermal growth factor receptor 2 expression. She subsequently received four cycles of adjuvant chemotherapy with dox- orubicin (total cumulative dose: 240 mg/m²), and cyclophosphamide. One month after completion of chemotherapy, she visited our emergency department with general weakness. Systolic and diastolic pressure were 67, and 14 mmHg, respectively, and laboratory findings revealed acute kidney injury. She was referred to intensive care unit for shock management. At that time, echocardiography showed reduced ejection fraction (EF: 15%), suggesting cardiogenic shock. Since all other causes of heart failure (HF) including coronary artery disease, arrhythmia, and infection were ruled out, we considered AC induced cardiomyopathy. HF became worse, eventually requiring extracorporeal membrane oxygenation (ECMO) treatment. Heart transplantation were performed as a definitive treatment for decompensated HF two weeks later because the heart function did not improve despite ECMO treatment. The patient was dis- charged with clinical improvement, 2 months after heart transplantation. She has been on immunosuppressants for heart transplantation, and anastrozole for breast cancer, since then. Conclusion: When a patient treated with AC developed unexpected severe heart failure, AC should be suspected as the cause of cardiomyopathy even if total cumulative dose is typically lower than limited dose.

238

￭

￭

Circulating tumor cell as a surrogate biomarker in advanced gastric cancer with bone marrow invasion

1세브란스병원 종양내과, ²연세 송당 암 연구센터, ³BK21 플러스 연세의과학사업단

*

김문현

, 이가든

, 이기쁨

, 권우선

, 정현철

, 라선영

In AGC, initial presentation with bone metastasis is rare (bone 3.8~12%, bone marrow 0.024~0.9%). These subset of patients have poor outcome with a median survival of less than three months. Although tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are used as biomarkers in AGC, their role in predicting responses to chemotherapy is variable and inconclusive in clinical practice. Here, we report a case which cir- culating tumor cells (CTCs) was a useful surrogate biomarker in predicting clinical outcome. A 58-year-old woman was admitted to the hospital due to poor oral intake, nausea, back pain and weight loss of 8 kg over 3 months. Laboratory study revealed anemia (8.3g/dL) and thrombocytopenia (23,000/uL).

Gastroduodenoscopy and CT scan confirmed AGC with multiple lymph nodes and bone metastasis. Bone marrow biopsy, which was performed to rule out other hematologic causes of thrombocytopenia, revealed metastatic signet ring cell carcinoma from stomach. Immunohistochemistry showed that HER2 was negative, but with high level of PD-L1 expression (PD-L1 expression 95%). Blood sampling was done serially to check circulating tumor cells (CTCs).

Before treatment, CTCs were elevated (1777 CTC per mL). This was unusually high since patients with metastatic disease have typically 1-10 CTC per mL of whole blood. The patient was then treated with capecitabine and oxaliplatin combination. Initially, she responded well to treatment. Platelet count in- creased within a week, reaching 197,000/uL at second cycle. In addition, CTCs markedly decreased from 1777 to 12. However, CTCs steadily increased from 38 to 317. Thereafter, CT scans confirmed disease progression after four cycles. Next-generation sequencing (NGS) and Global Screening Array (Illumina©) analysis revealed germline FGFR4 (G338R) mutation and somatic FGFR2 (K659N) alteration. Thereafter, the patient was enrolled in a clinical trial and received nivolumab and paclitaxel, but eventually died from disease progression after 7 months of treatment. Our case showed that serial follow up of CTCs may be a surrogate marker in predicting therapeutic responses and prognosis in patients.

￭

￭

Heart transplantation for HF in a patient with breast cancer exposed to low cumulative dose of AC

1울산대학교 의과대학 서울아산병원 내과, ²울산대학교 의과대학 서울아산병원 종양내과

*

조성현

, 정재호

Background: The risk of cardiotoxicity has long been recognized to correlate with the cumulative anthracycline (AC) dose. Total cumulative doses of AC in breast cancer are typically lower than limited dose. Here, we report a rare case of heart transplantation for cardiomyopathy in a patient with breast cancer who was treated with low cumulative doses of AC (240 mg/m²). Case report: A previously healthy 54-year-old woman underwent breast-conserving sur- gery for left breast cancer. The tumor was found to be an invasive ductal carcinoma measuring 1.7×1.5×1.5 cm (nuclear grade 2/3, histologic grade 2/3), and the sentinel lymph node was negative for metastasis (pT1N0M0). Immunohistochemistry of the tumor was positve for estrogen receptor, progesterone receptor, and negative for human epidermal growth factor receptor 2 expression. She subsequently received four cycles of adjuvant chemotherapy with dox- orubicin (total cumulative dose: 240 mg/m²), and cyclophosphamide. One month after completion of chemotherapy, she visited our emergency department with general weakness. Systolic and diastolic pressure were 67, and 14 mmHg, respectively, and laboratory findings revealed acute kidney injury. She was referred to intensive care unit for shock management. At that time, echocardiography showed reduced ejection fraction (EF: 15%), suggesting cardiogenic shock. Since all other causes of heart failure (HF) including coronary artery disease, arrhythmia, and infection were ruled out, we considered AC induced cardiomyopathy. HF became worse, eventually requiring extracorporeal membrane oxygenation (ECMO) treatment. Heart transplantation were performed as a definitive treatment for decompensated HF two weeks later because the heart function did not improve despite ECMO treatment. The patient was dis- charged with clinical improvement, 2 months after heart transplantation. She has been on immunosuppressants for heart transplantation, and anastrozole for breast cancer, since then. Conclusion: When a patient treated with AC developed unexpected severe heart failure, AC should be suspected as the cause of cardiomyopathy even if total cumulative dose is typically lower than limited dose.