Initial Staging of Hodgkin’s Disease

The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin’s disease (HD). Forty patients (18 men and 22 women, mean age 30 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard. No significant differences were found at staging between PET/ ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor). Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients. (Medicine 93(8):e50) Abbreviations: CHT = chemotherapy, F FDG = 2-deoxy-2(F18) fluoro-D-glucose, PET/ldCT = positron emission tomography/low-dose computed tomography, CT = computed tomography, ceCT = contrast-enhanced computed tomography, HD = Hodgkin’s disease, NHL = non-Hodgkin lymphoma, CTDI = computed tomography dose index, DLP = dose-length product, ABVD = adriamycin, bleomycin, vinblastine, dacarbazine. INTRODUCTION Hodgkin’s disease (HD) is a lymphoproliferative disorder presenting an incidence in the United Kingdom and the United States of 2.7–2.8 per 100,000 and the proper staging of the disease, that is the aim of our study, is actually of great impact when planning radiotherapy and chemotherapy (CHT). In particular, in HD the CHT treatment consisting of adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) greatly differs in toxic collateral effects from that of other CHT schemes as bleomycin, etoposide, adriamycin cyclophosphamide, vincristine (Oncovin), procarbazine, prednisone regimens that is usually reserved in selected case of advanced disease. Recent studies showed that the principal short-term toxic effect of ABVD treatment is represented by neutropenia and hair loss while skin, liver, and lung complications are reported in a few patients only and no permanent impairment of brain glucose metabolism has been reported in patients treated with this CHT. The Ann Arbor system is used to stage HD taking into account the sites of involvement and systemic symptoms due to lymphoma. As far as staging imaging procedure is concerned, 2-deoxy-2-(F18) fluoro-D-glucose positron emission tomography/computed tomography (F FDG PET/CT) provides crucial metabolic information in staging lymphoma, adding functional features to morphologic staging and modifying the treatment strategy in one-third of HD patients when compared with other imaging modalities. Contrast-enhanced computed tomography (ceCT, with oral and contrast administration) lack good sensitivity while evaluating lymph nodal disease, and intravenous contrast administration does not present an added value when investigating bone marrow involvement. Integrated positron emission tomography/contrast-enhanced computed tomography (PET/ceCT), in which a full-ring-detector clinical positron emission tomography (PET) scanner and ceCT are combined, makes it possible to acquire both metabolic and anatomic imaging data using a single device in a single diagnostic session and provides precise anatomic localization of suspicious area of increased 2-deoxy-2-(F18) fluoro-D-glucose (F FDG) uptake. The additional availability of ceCT data increases the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT), especially when clear anatomic information are required (as in the case of head and neck and pelvic cancer). In particular, as compared with positron emission tomography/low-dose computed tomography (PET/ldCT), PET/ceCT shows an elevated diagnostic accuracy Editor: Julhash U Kazi. Received: May 20, 2014; revised and accepted: June 17, 2014. From the Department of Biomedicine and Prevention, University Tor Vergata, Rome (AC, RD, CRC, LT, MC, MG, AO, GS, OS); Azienda Ospedaliera S. Coce e Carle, Hematology, Cuneo (AG); and IRCCS Neuromed, Pozzilli (OS), Italy. Correspondence: Agostino Chiaravalloti, Department of Biomedicine and Prevention, University Tor Vergata, Viale Oxford 81, 00133 Rome, Italy (e-mail: [email protected]). The authors have no funding information to disclose. The authors declare that they have no conflict of interest. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work noncommercially, as long as the author is credited and the new creations are licensed under the identical terms. ISSN: 0025-7974 DOI: 10.1097/MD.0000000000000050 Medicine • Volume 93, Number 8, August 2014 www.md-journal.com | 1 for lymph node staging in patients with rectal cancer and allows a more definitive diagnosis in laryngeal carcinoma. To the best of our knowledge, few studies have investigated the conjunction of PET/ldCT with ceCT for staging HD. Most of the papers in this field show that PET/ ceCT is able to improve the diagnostic accuracy in the assessment of HD in spleen and liver, leading to a significantly more intensive treatment in these patients, whereas in other studies the differences at staging did not reach statistical significance showing a good correlation between the different imaging modalities (PET/ceCT and PET/ldCT). The aim of this study is the evaluation of the differences at staging for both nodal and extranodal sites of HD localization by means of PET/ldCT and PET/ceCT performed in the same examination session. Next, we investigated the performance of PET/ldCT and PET/ceCT compared with ceCT alone because, to the best of our knowledge, this imaging modality is often performed in clinical routine especially for its availability and relatively low costs. MATERIALS AND METHODS Patients Forty patients (18 men and 22 women, mean age 30 9.6 years old) with biopsy-proven HD underwent a PET/ldCT and a ceCT for staging HD in the same examination session. Patients with other oncologic or HIV history were excluded from the study. No patient was suffering from liver or renal disease, nor was any patient pregnant or breastfeeding. After 20 5 days post first-line CHT (ABVD 2 cycles—dose intensity 100%—that consist of doxorubicin 25mg/m iv, Bleomycin 10,000 units/m, Vinblastine 6mg/m, and dacarbazine 375mg/m for 2mo) all the patients were evaluated in order to assess treatment response (see below). The study has been approved by the local ethics committee and a written informed consent has been obtained in all cases from the patients themselves in accordance with the Declaration of Helsinki. PET/ldCT Scanning All patients fasted for at least 5 hours before F FDG intravenous injection; serum glucose level was normal in all of them ( 107mg/mL). As already reported in our similar study in this field, patients were injected with 370–450MBq of F FDG intravenous and hydrated (500mL of iv saline sodium chloride, 0.9%) to reduce pooling of the radiotracer in the kidneys. The PET/CT system Discovery ST16 (GE Medical Systems, TN) was used for the whole population under examination. The system combines a high-speed ultra 16-detectorrow (912 detectors per row) computed tomography (CT) unit and a PET scanner with 10,080 bismuth germanate crystals in 24 rings. Axial FWHM 1cm radius is 5.2mm in 3-dimensional (3D) mode and axial field of view (FOV) is 157mm. For the PET/ldCT a low-amperage CT scan was acquired for attenuation correction of PET images (80mA, 140 kV, FOV about 420– 500mm, and CT slice thickness 3.75). The computed tomography dose index (CTDI) for low-dose computed tomography (ldCT) was 4.0175 ( 0.84) mGy and the dose-length product (DLP) was 473.296 ( 161.09) mGy-cm. After nonenhanced CT, total-body PET examination in the caudocranial direction from upper thighs to vertex was performed (3.5min per bed). Reconstruction was performed using the 3D reconstruction method of ordered subset expectation maximization with 30 subsets and 2 iterations. ceCT Scanning At staging, ceCT scan with 120–140kV, automatic milliampere (limit 330–350mA), thickness 3.750mm reconstructed at 1.25mm, acquisition mode 27.50/1.375:1, gantry rotation time 0.6 s, large FOV, matrix 512 512) was carried out with intravenous administration of nonionic iodinated contrast material (100–120mL, 370mgI/mL, 420mgI/kg at 3mL/s), obtaining 2 successive stacks of scans. In order to investigate the presence of any rapid/low enhancing lesion of liver or kidneys, the first comprised the upper abdomen with a 30-second delay from the injection onset leading to 18.85 ( 0.14) mGy for CTDI and 883.11 ( 161.40) mGy-cm for DLP; the second extended from the neck to the pelvis with a 60-second delay leading to 18.5 ( 0.47) mGy for CTDI and 1607.88 ( 148.02) mGy-cm for DLP. Brain ceCT was also obtained 3 minutes after intravenous contrast administration: CTDI1⁄4 80.76 ( 0.02) mGy and DLP1⁄4 1292.19 ( 0.02). Image Analysis The nuclear medicine physician and the radiologist were unaware of the PET/ldCT and ceCT results, respectively. According to other similar reports in this field, the visual analysis of PET/ldCT and ceCT images has been performed on a dedicated workstation by a nuclear physician and a radiologist, both aware of the clinical history of the patient. Any focus of increased F FDG uptake over background not located in areas of normal F FDG uptake (central nervous system, heart, digestive tract, thyroid, and muscles) and/or excretion (urinary tract) was considered positive for tumor (Figure 1 and Figure 2). For ceCT, standard CT criteria for individual lymph node groups (when >10mm in short axis), lung, liver, and spleen were used to determine the site of suspect HD localization. For bone marrow involvement, any lytic area that usually appears as a region of soft-tissue attenuation with irregular margins that usually breach the cortex or any sclerotic lesions that appear hyperdense and irregular has been considered pathologic (Figure 2). For nodal involvement, a datasheet indicating the nodal stations was filled for PET/ldCT and ceCT results. As far as the extranodal site is concerned, the physicians were required to sign the presence or absence of disease (regardless of diffuse or focal) in lung, liver, spleen, bone marrow, skin, and brain. A third datasheet was then generated, including functional (PET) and ceCT data. The clinical stage of the patients was assessed in agreement with Ann Arbor classification. Follow-up Data as the Reference Standard Any area of residual F FDG uptake in interim PET has been evaluated by 2 experienced nuclear medicine physicians (AC and OS) by means of qualitative analysis according to the Deauville 5 point score. All the positive findings in interim PET have been confirmed by means of mediastinum or upper cervical lymph node(s) biopsy (because these were the sites of no-therapy response or recurrence detected in PET/CT). All the findings detected in staging PET/ldCT, ceCT, and PET/ceCT were compared with those obtained after CHT: the absence or decrease of F FDG uptake and the 2 | www.md-journal.com ã 2014 Lippincott Williams & Wilkins Chiaravalloti et al Medicine • Volume 93, Number 8, August 2014