Diagnostic Impact of PET/CT Over CECT in Post Therapeutic Evaluation of Colorectal Cancer

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1 Med. J. Cairo Univ., Vol. 85, No. 3, June: , Diagnostic Impact of PET/CT Over CECT in Post Therapeutic Evaluation of Colorectal Cancer MOHAMED T. ALI, M.D.; MOHAMED D. HOMOS, M.D. and DOAA M. NABIL, M.D. The Department of Radiodiagnosis, Faculty of Medicine, Cairo University Abstract Objective: To evaluate the effectiveness of FDG PET/CT compared with routinely used MSCT in post therapeutic assessment of colorectal cancer. Patients and Methods: A total number of 70 patients (30 women, 40 men; mean age, 48.7y), referred for re-evaluation of colorectal carcinoma after treatment. Retrospective assessment of cases was done by two experienced readers: First, MSCT, second PET/CT. The number, localization, and diagnostic certainty of lesions were evaluated. In 30 patients, histopathology, imaging, and clinical follow-up were considered as the reference standards. In 40 patients, both clinical follow-up and imaging were considered as the reference standards. Results: The overall comparison between CECT and PET/CT showed significant superiority of PET/CT (sensitivity 90%, specificity 84%, PPV 89% and NPP 85%) as compared to CECT (sensitivity 42%, specificity 29%, PPV 55% and NPP 20%) respectively. Conclusion: 18F-FDGPET/CT has shown its more effectiveness over CECT only in staging and follow-up of patients with colorectal cancer as PET/CT was more sensitive in identifying sites of recurrent or metastatic disease as well as monitoring treatment response so patients with inconclusive CECT findings now are subsequently evaluated by 18FFDG PET/CT. Key Words: Colorectal cancer PET/CT CECT. Introduction COLORECTAL cancer is considered the third leading cause of death worldwide. After colorectal surgery, recurrence mostly occurs in one-third of patients within the first 2 years. It is difficult to stage and assess recurrences by conventional imaging modalities; moreover, frequent non conclusive investigations result in diagnostic and therapeutic delay [1]. In post-operative patients, resection Correspondence to: Dr. Mohamed Talaat Ali, The Department of Radiodiagnosis, Faculty of Medicine, Cairo University of isolated metastases leads to improved survival while multifocal metastatic lesions are associated with poor prognosis [2,3]. Early detection of colorectal carcinoma recurrence became more important in the last past decade, as the options of treatment for localized disease have significantly improved. However, aggressive locoregional interventions (e.g. partial liver resections, Radiofrequency Ablation (RFA) of liver metastases, resections of pulmonary metastases) are considered un-useful in the presence of metastases elsewhere. Therefore, detection of tumour sites throughout the body is needed with high accuracy [4]. The results of CT depend on the site of recurrence, size and morphological appearance of the lesion. Because of its high uptake of 18F-FDG in primary colorectal carcinomas and their recurrences, FDG-PET/CT provides proper information about changes in glucose metabolism raising its detecting ability of recurrence [3] and assessment of therapeutic response Figs. (5,7). Whole body PET/CT imaging is considered the most accurate diagnostic test for detection of colorectal cancer recurrence, and can differentiate resectable from non-resectable disease [5]. The aim of our study is to determine the accuracy of FDG PET/CT compared with commonly used MSCT in post therapeutic assessment of colorectal cancer. Patients and Methods Retrospective study with total number of 70 post-operative or post therapy CRC patients with clinical, laboratory or equivocal imaging findings (between June 2013 to February 2016), came for PET/CT assessment for recurrence detection, restaging and post-treatment evaluation. The study was done after approval of the ethical committee 1159

2 1160 Diagnostic Impact of PET/CT Over CECT in Post Therapeutic Evaluation for retrospective evaluation, and written informed consent was taken from all patients. All data were obtained with a combined PET/CT using (Phillips Gemini Time of flight 64 machines). Techniques and imaging protocol: We performed post-therapy PET at least 4-6 weeks after surgery or chemotherapy and 8-12 weeks after external beam radiation. All patients were asked to fast for six hours prior to scan. The patients were instructed to avoid any kind of strenuous activity prior to the examination and following injection of the radioisotope to avoid physiologic muscle uptake of FDG and the patient was asked to void prior to scanning. We administered one liter of negative oral contrast agent (5% mannitol) approximately one hour before and of 10-20mCi (370 MBq; approximate dose to patient, 3-5MBq/ Kg) 18F-FDG minutes before examination. This period is referred to as the uptake phase and is the necessary amount of time for the FDG to be adequately bio-distributed and transported into the patient's cells. We performed low dose non enhanced CT scan first, then a whole body PET study followed by diagnostic enhanced whole body CT scan. The whole study took approximately minutes. The contrast enhanced helical CT was performed following injection of 125mL of a low- osmolarity iodinated contrast medium at a rate of 4mU/sec by using a power injector. Typical scanning parameters would be a collimator width of 5.0mm, pitch of 1.5, gantry rotation time of 0.8 second, and field of view of 50cm. The helical data are retrospectively reconstructed at 1mm intervals. PET was performed following the CT study without moving the patient. Approximately six to seven bed positions are planned in the threedimensional acquisition mode for scanning the entire patient with 3-5 minute acquisition at each bed position. PET and CT images were first reconstructed, then reformatted into coronal and sagittal images to facilitate image interpretation. For each of these sets of PET and CT images, corresponding fusion images, combining the two types of data, also were generated. Data analysis: Image evaluation was performed in a step wise manner by at least two experienced observers; any differences were resolved by consensus. Reading was performed in 2 successive steps: First, CECT alone was evaluated. In the second step, PET/CT images were evaluated. Results of reading step 1 and 2 were then compared (Table 1). Table (1): Comparison between results of CE CT & PET/CT. CE CT PET/CT Inconclusive Conclusive Total Inconclusive Conclusive Total Local lesions Hepatic lesions Lymph nodes Peritoneal lesions Pulmonary lesions Osseous Adrenal Abdominal wall Skin Muscles Brain Total A- Interpretation of the CE CT findings: Detection of enhancing soft-tissue masses or other suggestive signs (e.g., surrounding tissue extension, localization) was considered as malig- nant. Hypodense liver lesions with irregular outlines and marginal contrast enhancement were considered as malignant. The lymph node assessment used a size of 1.0cm (short axis) for malignancy. Further-

3 Mohamed T. Ali, et al more, lymph nodes with a fatty hilum or with calcifications were considered as benign, whereas a central necrosis was regarded malignant. B- Interpretation of the PET/CT findings: Interpreting PET findings as positive or negative is adequate by visual assessment alone. According to the IHP definitions, residual masses of 2cm or more in maximum transverse diameter with 18F- FDG activity visually more than that of mediastinal blood pool structures are considered PET positive, whereas residual masses 1.1 to 1.9cm are considered PET positive only if their activity was exceeding surrounding background activity. A smaller residual mass or a normal-sized lymph node (eg, <1 X 1cm) was considered positive for disease if its activity is higher than that of the surrounding background. Hepatic or splenic lesions should be considered as positive if their uptake is higher than or equal to that of the liver or spleen, and negative if their uptake is lower than that of the liver and spleen. Lung nodules 5mm in patients should be considered as positive if FDG uptake is exceeding the mediastinal blood pool. Metastasis cannot be excluded in lung nodules >0.5cm. If there were increased FDG uptake in the bone marrow, the patient was considered as PET positive. Reactive bone marrow hyperplasia after chemotherapy can give diffuse pattern of uptake that can mimic or mask diffuse bone marrow involvement; therefore, proper history was crucial. A delay of 3-4 weeks after end of therapy permits the physiologic marrow activity to be regained. C- Diagnostic score and possibility of referral for PET/CT: Images were assessed regarding the number and localization of lesions using a confidence score for diagnosis with a scale ranging from 2 to 2: 2: Benign lesions (e.g., cysts, hemangiomas), calcified lymph nodes. 1: Lesions considered as probably benign (e.g., small pulmonary nodules having no 18F- FDG uptake and no other signs of malignancy were considered as probably benign granulomas). 0: Lesions considered indeterminate (e.g., medium-sized lymph nodes or liver lesions not clearly defined as cysts or metastases). 1: Lesions considered as probably malignant (e.g., liver lesions with ill-defined margins after resection). 2: Lesions considered as malignant (sure malignant criteria). If lesions detected in a CECT scan and documented as 2 or 2 (sure benign or sure malignant), the examination is considered conclusive. When multiple lesions stated as 2 (sure malignant) were detected, this means that the curative therapeutic approach is rather impossible, and thus CECT was reported as conclusive. If one or more lesions documented as 1, 0, or 1 (probably benign, indeterminate, probably malignant), CECT was reported as inconclusive. These cases are referred for PET/CT. D- Comparison of CECT and PET/CT: Detection of lesions by CECT and PET/CT was documented as regards lesion characterization and if there is newly detectable lesions by PET/CT. Reference standard: Follow-up of patients was done to assess the previously treated lesions. Histopathologic evaluation of lesions was done in 30 patients and considered as golden standard. Clinical follow-up was done with all available clinical data (e.g., physical examination, laboratory tests) and imaging procedures, such as CT, PET/CT, and ultrasound were done in the remaining 40 patients. Follow-up was done within 18 months. It included physical examinations, tumor markers (CEA), CECT and PET/CT. Results The study includes 70 post-operative and/or therapy patients of colorectal cancer (30 women, 40 men; mean age 48.7y). As regards the indications (28 patients had abnormal findings in previous imaging, 8 patients had increasing CEA levels and 34 patients were referred for post therapeutic routine follow-up after treatment). As regards the therapeutic procedure (10 patients underwent surgery only, 51 patients had surgery and adjuvant chemo or radiotherapy, 6 patients chemotherapy only and 3 patients had radiotherapy only). The patients had the following extents of disease: (4 patients were free of disease, 30 patients had local lesions at the operative bed, 24 patients had metastatic hepatic lesions, 41 patients had lymph nodes involvement and 20 patients had peritoneal masses, 41 patients had pulmonary nodules and 7 patients had other lesions). Regarding local recurrence 30 patients had local abnormal findings (21 rectal and 9 colonic cancer). CECT was conclusive in 7 (23%) patients and inconclusive in 23 (77%) patients. PET/CT delivered correct additional information in 28 (90%) patients, while in three patients (10%) the PET/CT was inconclusive Figs. (2,3).

4 1162 Diagnostic Impact of PET/CT Over CECT in Post Therapeutic Evaluation Regarding the hepatic metastasis, 24 patients had hepatic lesions (9 patients with single focal lesion and 15 patients had multiple lesions). CECT was considered conclusive in 10 patients (42%) and inconclusive in 14 patients (58%). PET/CT delivered correct additional information in 23 (96%) patients, while in one patient (4%) the PET/CT was false negative because of negative 18F-FDG uptake but the biopsy revealed metastasis Figs. (4,6). Regarding the lymph node involvement 41 patients had lymph nodes (15 larger than 1cm and 26 subcentimetric). CECT was conclusive in 17 patients (41.5%) and inconclusive in 24 patients (58.5%). PET/CT delivered correct additional information in 39 patients, while was inconclusive in 2 patients Fig. (7). Regarding the peritoneal lesions 20 patients (28%) had peritoneal lesions CECT was conclusive in (14 of 20) 70% patients and inconclusive in (6 of 20) 30% patients. PET/CT delivered correct additional information in 24 patients (added 6 new lesions that were overlooked in CECT). In two patients PET/CT was inconclusive warranting close follow-up and correlation with tumor markers. Regarding the pulmonary lesions 40 patients (57%) had pulmonary lesions, CECT was conclusive in 8 patients and inconclusive in 32 patients while PET/CT was conclusive in 27/40 patients inconclusive in 13/40 lesions. Regarding the other metastases were detected in 15 patients (Table 2), each site was calculated separately since five patients had more than one site, so from statistical point of view, we had 20 sites, CECT was conclusive in 11 of 20 lesions while in the remaining 9 lesions CECT was inconclusive while PET/CT was conclusive in 18/20 (90%) patients inconclusive in 2/20 (10%) lesions. Regarding the overall comparison between CECT and PET/CT (Table 3) and Fig. (1), the most important factor is that PET/CT increased diagnostic confidence, allowing the readers to be sure of diagnosed lesions with the possibility of increasing the number of detected lesions. The overall comparison between CECT and PET/CT showed significant superiority of PET/CT (sensitivity 90%, specificity 84%, PPV 89% & NPP 85%) as compared to CECT (sensitivity 42%, specificity 29%, PPV 55% & NPP 20%) respectively CECT Sensitivity PPV PET/CT Specifity NPP Fig. (1): Overall comparison between CECT and PETCT. (A) Fig. (2): (A) Axial CT of the pelvis (B) Axial fused PET/CT image of the pelvis. 54 years old male patient, 13 month after abdomino-perineal resection of rectal cancer, CT revealed presacral mass. The patient came for further PET/CT assessment. No 18F FDG uptake was seen within the presacral abnormality that was identified on CT images (arrows). Findings at biopsy of the mass were negative, and the patient remains disease free. (B)

5 Mohamed T. Ali, et al (A) (B) (C) (D) Fig. (3): (A,B) Axial and sagittal CT images of the pelvis. (C,D) Axial and sagittal fused PET/CT images of the pelvis. (E) Whole body coronal MIP PET image. 56-year-old male underwent resection anastomosis for rectal adenocarcinoma, followed by chemo and radiation therapy. Routine follow-up CT showed recto-sigmoid mural thickening with presacral soft tissue density, the patient came for PET/CT assessment that showed increased FDG uptake (SUVmax.6.5) corresponding to irregular mural thickening at the rectosigmoid junction (open arrows) encased by metabolically non active pre-sacral low attenuation granulation tissue. Metabolically active right internal iliac lymph node is noted (closed arrow). PET/CT detects the metabolically active soft tissue lesion. (E)

6 1164 Diagnostic Impact of PET/CT Over CECT in Post Therapeutic Evaluation (A) (B) (C) Fig. (4): (A) Axial non contrast CT image of the liver (B) Axial post contrast CT image of the liver. (C) Axial fused PET/CT image of the liver. (D) Whole body coronal MIP PET image. 71 years old male patient with history of sigmoid carcinoma treated surgically and he is complaining of elevated CEA level, CT revealed inconclusive hepatic focal lesion, the patient came for PET/CT assessment that showed 18F-FDG-avid (SUV max 9.2) hepatic focal lesion seen in segment VIII. (D) (A) (B) Fig. (5): (A) Axial CT of the pelvis. (B) Axial fused PET/CT of the pelvis (C,D) Sagittal fused PET/CT of the pelvis. 66 year old male after anterior resection of rectal Ca. CT revealed soft tissue density at the operative bed (A), PET/CT revealed increased FDG uptake (SUVmax 6.4) corresponding to the irregular soft tissue thickening related to the anal canal (B). After 6 cycles of chemotherapy the patient came for therapeutic assessment showing metabolic and morphological regression of the irregular soft tissue thickening with current SUVmax measuring 3.2 compared to 6.4 in the previous study (C,D). (C) (D)

7 Mohamed T. Ali, et al Fig. (6): (A) Axial CT images of the abdomen (B,C) Axial fused PET/CT images of the abdomen. 41 year male underwent RFA for hepatic metastatic focal lesion form rectal grade II adenocarcinoma. The ablated hepatic focal lesion is replaced by photopenic areas of coagulative necrosis with residual non-uniform peripheral FDG activity SUVmax 5.5 (closed arrows). FDG avid (SUVmax. 5.4) subcentimetric lymph nodes at the coeliac and porto-caval groups are noted (open arrows). The patient came after 4 cycles of chemotherapy for assessment of the therapeutic response showing newly developed metabolically active (SUVmax 10.2) lesion at segment V with (arrow head) and metabolic progression of the coeliac and porto-caval lymph nodes with SUVmax 5.8 as compared to 5.4 in the previous scan. Fig. (7): (A,B,C) Pretreatment axial fused PET/ CT images. (D,E,F) Posttreatment axial fused PET/ CT images. A 48-year old male patient with metastatic sigmoid colon adenocarcinoma following 3 cycles of chemotherapy. The patient came for assessment of treatment response showing metabolic and morphological regression of the sigmoid colon mural (SUVmax.5.2 compared to 8.7), multiple variable sized FDG avid hepatic focal lesions as well as the right pulmonary nodule (0.7cm with SUVmax 1.7 compared to 1.3cm and SUVmax 6.1 ).

8 1166 Diagnostic Impact of PET/CT Over CECT in Post Therapeutic Evaluation Table (2): Distribution of different sites of other metastatic lesions. Sites Number of patients Percent Osseous 9 45 Adrenal 4 20 Abdominal wall 3 15 Brain 1 5 Skin 1 5 Muscles 2 10 Table (3): Overall comparison between CT & PET/CT. Modality Sensitivity Specificity PPV NPV CECT 42% 29% 55% 20% PET/CT 90% 84% 89% 85% Discussion Early and accurate detection of recurrent colorectal carcinoma with high sensitivity and specificity became very important lastly as the therapeutic options of localized disease have improved significantly [6]. The diagnosis of local recurrence and differentiating it from post-operative changes is challenging for conventional imaging. In previous studies by [7,8]. PET/CT allowed them to differentiate benign lesions from pre-sacral soft tissue abnormality with a sensitivity of 100% and a specificity of 96%. Our results confirm the finding that, lesion detection and evaluation by CECT alone may give inconclusive results that require further diagnostic evaluation by other modality (61.7% of our patient population). The reason for this is mainly related to specificity issues of the modality together with the structural abnormalities found by this modality, these results were in accordance with previous study done by Soyka et al., [9]. In the current study we found that in 16% (5/30 lesions) of the patients with apparently conclusive findings on CECT, the addition of PET/CT led to significant changes in therapy this was in accordance with previous study done by Selzner et al., [10]. Even though, with improving diagnostic confidence with PET/CT, several lesions cannot be definitively detected [11]. In our study two lesions couldn't be certainly assessed warranting follow-up examinations. The post-operative distortion of liver with scar tissue and artificial materials, leads to lower sensitivity and specificity of CT and MRI [12] PET/CT can be of value, in a study done by Selzner et al., 2004 for the detection of liver metastasis after hepatectomy with a sensitivity of 100% and spe- cificity of 89% for PET/CT, while the specificity of contrast enhanced CT dropped to 50% for this type of patients. CT may give false-positive results at the rim of the lesions because of hyper-perfusion after RFA, while FDG-PET remains effective [13]. In the current study CT was inconclusive in 58% of hepatic lesions and PET/CT gave conclusive additional information in 93% of these lesions while in one patient the PET/CT was inconclusive warranting close follow-up and correlation with tumor markers. CECT was reported as conclusive in 42% of hepatic lesions and PET/CT had correct additional findings in 60% of lesions. Reduced sensitivity of CECT for metastatic lymph nodes detection may be due to its small size below 1cm in diameter. In the current study we were able to detect 18F-FDG active subcentimetric lymph nodes in 14 patients (20%), these additional sites of metastatic spread would have been missed if assessment was done using CT alone and this results in down-staging and hence change the management plan in these patients. In recurrent colorectal carcinoma pulmonary deposits are the most extra-hepatic site, detection of these metastases is important as surgical intervention may be possible by doing liver surgery combined with resection of a small number of pulmonary deposits [14]. Both CT and PET/CT are of high sensitivity in detection of pulmonary lesions, but PET/CT may be more helpful in differentiating benign from malignant lesions [15]. In current study PET/CT added correct findings regarding the pulmonary nodules in 27 patients, while in 13 patients it was inconclusive warranting close follow-up and correlation with tumor markers. PET/CT is more valuable than CT in detection of peritoneal lesions, in the current study PET/CT added correct additional information changing 83% of patients with inconclusive CT findings into conclusive lesions as well as adding six new lesions that were overlooked in CECT. PET/CT is more valuable than CT in detection of bone marrow affection, in this study, there were 2 patients showed multifocal foci of increased 18F- FDG marrow uptake, but with no corresponding CT findings (as bone destruction, osteolytic or osteosclerotic areas), this is in accordance with previous study done by Bar-Shalom et al., [16]. Diffuse bone marrow activation occurring in the weeks following chemotherapy leads to limitation in making the correct diagnosis of marrow affection, in 5 patients in this study, it was diffuse and affecting the axial skeleton with a symmetric distribution

9 Mohamed T. Ali, et al as stated by previous study done by Paes et al., [17]. PET/CT is also proved to be of value in followup of cases after chemotherapy. The overall comparison between CECT and PET/CT in the current study showed significant superiority of PET/CT (p,0.0001). CECT detected 175 lesions of which 38.3% were considered conclusive and 61.7% were stated as inconclusive while PET/CT detected overall 186 lesions (11 additional lesions) of which 93.3% were stated as conclusive and 6.7% were stated as inconclusive with sensitivity and specificity of PET/CT was 90% and 84% respectively compared to CECT that was 42% and 29% respectively. The main limitation of this work is the wide gray zone of inconclusive lesions (score 1, 0 & 1) in the used confidence score for assessment of CECT findings and to some extent its retrospective nature. Conclusion: PET/CT is a more sensitive modality than CECT in the detection of tumor recurrence in the presacral space in patients who underwent abdominoperineal resection. It also proved that compared with CT, PET/CT may predict tumor recurrence in the periphery of radiofrequency ablation sites in the liver. PET/CT depicted more metastatic subcentimetric nodes, metastatic marrow infiltration and peritoneal nodules. PET/CT proved useful in follow-up of cases after treatment either by surgery, chemo or radio-therapy. References 1- KAMEL E.M., BURGER C., BUCK A., et al.: Impact of metallic dental implants on CT based attenuation correction in a combined PET/CT scanner. Eur. Radiol., 13: JADVAR H. and PARKER J.A.: Clinical PET and PET/ CT. Book. P: , JADVAR H. and PARKER J.: PET Physics and Instrumentation. In: Clinical PET and PET/CT, Jadvar H & Parker J. eds. Springer-Verlag London Limited, 1: 1-44, VEIT P., KUEHLE C. and BEYER T.: Whole-body PET/ CT tumor staging with integrated experiences in patients with colorectal cancer PET-CT-colonography: Technical feasibility and first. Gut., 55: 68-73, RASMUS K.P, SOREN H., ABASS A. and POUL F.H.: Clinical impact of FDG-PET/CT on colorectal cancer staging and treatment strategy. Am. J. Nucl. Med. Mol. Imaging, 4 (5): , HILLNER B.E., SIEGEL B.A., LIU D., et al.: Impact of PET/CT and positron emission tomography (PET) alone on expected management of patients with cancer: Initial results from the national oncologic PET registry. J. Clin. Oncol., 26: , LONG-BANG CHEN, JIN-LONG TONG, HAI-ZHU SONG, HONG ZHU and YU-CAI WANG: 18F-DG PET/ CT in detection of recurrence and metastasis of colorectal cancer World J. Gastroenterol., October 7; 13 (37): 50259, NUYTTENS J.J., ROBERTSON J.M., YAN D. and MAR- TINEZ A.: The position and volume of small bowel during adjuvant radiation therapy for rectal cancer. Int. J. Radiat. Oncol. Biol. Phys., 51: , SOYKA JAN D., PATRICK VEIT-HAIBACH, KLAUS STROBEL, STEFAN BREITENSTEIN, ALOISTSC- HOPP, KATJA and THOMAS F.: Department of Nuclear Medicine, University of Zuerich, Zurich, Switzerland. J. Nucl. Med., 49: , SELZNER M., HANY T.F., WILDBRETT P., McCOR- MACK L., KADRY Z. and CLAVIEN P.A.: Does the novel PET/CT imaging modality impact on the treatment of patients with metastatic colorectal cancer of the liver? Ann. Surg.; 240: ; discussion , ROSENBAUM S.J., LIND T., ANTOCH G. and BOCK- ISCH A.: False-positive FDG PET uptake: The role of PET/CT. Eur. Radiol., 16: , DROMAIN C., De BAERE T., ELIAS D., et al.: Hepatic tumors treated with percutaneous radio-frequency ablation: CT and MR imaging follow-up. Radiology, 223: , ANTOCH G., VOGT F.M., VEIT P., et al.: Assessment of liver tissue after radiofrequency ablation: Findings with different imaging procedures. J. Nucl. Med., 46: 520-5, KING J., GLENN D., CLARK W., et al.: Percutaneous radiofrequency ablation of pulmonary metastases in patients with colorectal cancer. Br. J. Surg., 91: 217-3, BOHDIEWICZ P.J., WONG C.Y., KONDAS D., GAS- KILL M. and DWORKIN H.J.: High predictive value of F-18 FDG PET patterns of the spine for metastases or benign lesions with good agreement between readers. Clin. Nucl. Med., 28: , BAR-SHALOM R., YEFREMOV N. and GURALNIK L.: Clinical performance of PET/CT in evaluation of cancer: Additional value for diagnostic imaging and patient management. J. Nucl. Med., 44: , PAES F.M., KALKANIS D.G., SIDERAS P.A., et al.: FDG PET/CT of Extranodal Involvement in Non-Hodgkin Lymphoma and Hodgkin Disease. Radio. Graphics, 30: , 2010.

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