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Radiological, pathological and DNA remission in recurrent metastatic nasopharyngeal carcinoma
© Chan et al; licensee BioMed Central Ltd. 2006
Received: 21 May 2006
Accepted: 31 October 2006
Published: 31 October 2006
Circulating plasma Epstein Barr Virus DNA (EBV-DNA) is a sensitive and specific marker of nasopharyngeal carcinoma (NPC). The mainstay of treatment of metastatic NPC is systemic chemotherapy and resection for solitary metastasis. Despite high response rate to chemotherapy, complete remission is uncommonly seen.
We report a case of recurrent metastatic NPC in a 43-year-old man, who achieved complete remission three times with chemotherapy and surgery. Serial plasma EBV-DNA levels were measured during the course of disease. The patient had three episodes of recurrences of NPC manifested as distant metastasis. Both time, rise in the plasma EBV-DNA level preceded detection of recurrences by imaging. Following systemic chemotherapy, he achieved complete remission each time, of which was confirmed by 18-flourodeoxyglucose positron emission tomography and hepatectomy pathology. The plasma EBV-DNA level dropped to zero copy/ml at the time of each remission.
This case highlights the high chemosensitivity of NPC by illustrating a rare occurrence of complete response of metastatic NPC to chemotherapy. This case also underscores the usefulness of EBV-DNA as a useful tool in monitoring NPC by its ability to detect early recurrence and excellent correlation with treatment response.
The recent development in nucleic acids in serum and plasma has opened up many new areas in molecular diagnosis. In the field of oncology, circulating plasma/serum Epstein Barr Virus (EBV) DNA in nasopharyngeal carcinoma (NPC) is a good example. The real-time polymerase chain reaction (RT-PCR) is a reliable and reproducible technique, which allows a rapid quantification of plasma EBV DNA, thus rendering it an attractive tool in the monitoring of treatment response [1, 2]. The test is highly sensitive because it targets the BamHI-W repeat region of the EBV genome . This test became available for clinical use at our oncology centre in 2002. Though it is uncommon to see patients with metastatic NPC achieve partial response to chemotherapy, it is very rare to observe complete response. Here we report a case which illustrates rare occurrence of complete response to chemotherapy and highlights good correlation between plasma EBV DNA and FDG-PET scan and pathology. Written consent was obtained from the patient for publication of this report.
A 43-year old man was referred to our cancer center in October, 2001 with stage IIb undifferentiated nasopharyngeal carcinoma (T2N1M0). He completed radical radiotherapy in December, 2001, and achieved complete remission afterwards. Although baseline plasma EBV DNA was not available, patient had undetectable plasma EBV DNA which was measured within one week after radiotherapy.
the correlation between plasma EBV-DNA level and clinical status; clinical and radiological remission is associated with falling level of EBV-DNA level to zero copy/ml.
EBV DNA copies/ml
It is observed that patient subsequently developed recurrences though plasma EBV DNA dropped to zero copy/ml when he was having a relatively inactive disease (which is manifested as clinical and radiological remission). This is unlikely due to suboptimal EBV DNA assay because the assay used by our centre is well validated as reported previously [1, 2, 5]. It is noteworthy that although plasma EBV DNA is a sensitive tool in monitoring disease and tumor burden, zero copy/ml of EBV DNA does not necessarily equate complete eradication of disease, and close monitoring of clinical condition and EBV DNA level are still required. The case study also points to the importance of a well standardized and highly sensitive PCR method, because the relatively low level of EBV DNA detected in second and third relapse might be missed with a less sensitive PCR method [1, 10].
Cell-free EBV DNA was first demonstrated in circulation of NPC patient by PCR amplification in 1998 . Dependent on number of PCR cycles, modalities of PCR and various preparations of specimen, different assays of various sensitivity and specificity were subsequently developed for detection of circulating EBV DNA [1, 7–10]. Several characteristics have enabled circulating EBV DNA to be widely used in clinical practice for management of NPC. In our institute, with the use of real time PCR, EBV DNA in plasma had been demonstrated to be a both sensitive (96%) and specific (93%) marker of NPC . EBV DNA is undetectable in healthy individuals and those disease-free patients with history of NPC, while it is raised in plasma of most patients with active disease. Also, plasma EBV DNA has a role in staging and prognostication [11, 12]: higher level of EBV DNA is detected in patient with more advanced UICC stage, and those patients with non-metastatic NPC have poorer prognosis when there is persistent high EBV DNA level after radical radiotherapy to nasopharynx. More importantly, detection of EBV DNA can be used for monitoring of NPC patients for any recurrence or metastasis [2, 13]. It had been reported by that rise in EBV DNA might predate clinical relapse up to few months hence rendering earlier work-up and treatment feasible . Other potential use of circulating EBV DNA remains to be elucidated. For example, the use of EBV DNA in screening general population for NPC is still under active research. There are also ongoing studies addressing the improved accuracy of detecting NPC with combined use of circulating EBV DNA and other serological markers. In our centre, we have already completed a prospective study looking into correlation between plasma EBV DNA and PET-CT imaging before and after radiotherapy in patients with advanced NPC. With this case, apart from reporting an uncommon occurrence of chemotherapy induced complete remission of metastatic nasopharyngeal carcinoma, we hope this case can highlight the good correlation between circulating EBV DNA and FDG-PET scan in disease monitoring of nasopharyngeal carcinoma.
Written consent was obtained from the patient for publication of this report.
The authors are indebted to the patient for providing informed consent and giving kind permission of this report.
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