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EBV Conference 2008 Guangzhou - Baylor College of Medicine

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205 (RegID: 1292)<br />

Jaap Middeldorp<br />

Institution: VU University medical center, Dept.Pathology<br />

e-mail: j.middeldorp@vumc.nl<br />

<strong>EBV</strong>-DNA LOAD MONITORING IN NASOPHARYNGEAL (NP) BRUSHINGS AND WHOLE<br />

BLOOD DURING AND AFTER THERAPY OF NASOPHARYNGEAL CARCINOMA (NPC).<br />

Linda Adham, Alida Harahap, I.Bing Tan, Sabine C Fleig, Astrid E Greijer and Jaap M Middeldorp.<br />

Posterabstract:<br />

NPC is a leading cancer in SE-Asia and nearly 100% <strong>EBV</strong>-associated, allowing use <strong>of</strong> <strong>EBV</strong>-based<br />

diagnostic techniques. Recently we described a non-invasive NP-brush and whole blood approach<br />

combined with <strong>EBV</strong>-DNA load measurement for the diagnosis <strong>of</strong> NPC (Stevens, 2005, 2006), yielding<br />

better sensitivities in NP-brushings.<br />

Purpose: In this study we evaluate the use <strong>EBV</strong>-DNA load monitoring in consecutive whole blood samples<br />

and NP brushings taken at diagnosis and defined time points during and after chemoradiation therapy in a<br />

series <strong>of</strong> 235 NPC patients. <strong>EBV</strong>-IgA serology was also done at all timepoints and routine clinical<br />

examinations, CT-scan, nasendoscopy and biopsy were performed on a regular basis during follow-up.<br />

Results: In all confirmed NPC cases, <strong>EBV</strong>-DNA load in NP-brushings at diagnosis showed strongly<br />

elevated levels in nearly 98% <strong>of</strong> patients, with sometimes extreme high levels (>50x106c/brush), whereas<br />

<strong>EBV</strong>-DNA was detectable in parallel blood samples mostly at low levels, being above the 2000c/ml<br />

cut-<strong>of</strong>f in only 40% <strong>of</strong> cases.<br />

During therapy rapid and significant declines (>1000-fold) <strong>of</strong> <strong>EBV</strong>-DNA load in NP-brushings associated<br />

with good clinical responses, whereas cases with partial response and persistent disease showed stable or<br />

rising <strong>EBV</strong>-DNA levels. In patients without whole blood <strong>EBV</strong>-DNA load at diagnosis, fluctuating positive<br />

levels were detected during therapy, but varied strongly per patient. Patients with detectable <strong>EBV</strong>-DNA<br />

loads before therapy maintained fluctuating levels during and post- therapy.<br />

<strong>EBV</strong>-IgA serology was not predictive <strong>of</strong> therapy outcome at short term but may be useful to (cheaply)<br />

monitor for disease relapse at longer intervals post-therapy.<br />

Conclusions: Our results indicate that <strong>EBV</strong>-DNA load monitoring in NP-brushings provides highly<br />

relevant data reflecting tumor behaviour in situ and can be used for assessment <strong>of</strong> treatment effect.<br />

<strong>EBV</strong>-DNA in blood is less informative, more variable and was useful in only a limited number <strong>of</strong> patients.<br />

<strong>EBV</strong>-DNA in blood possibly reflects the apoptosis sensitivity/activity <strong>of</strong> the tumor, showing significant<br />

individual variation. The non-invasive NP-brush technique allows repeated sampling without much<br />

discomfort to the patient, and can replace the invasive biopsy, while providing more relevant information<br />

on presence and activity <strong>EBV</strong>+ NPC in situ.<br />

<strong>EBV</strong> <strong>Conference</strong> <strong>2008</strong> <strong>Guangzhou</strong><br />

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