- Email: [email protected]
CT in re-staging of patients with non Hodgkin lymphoma and monitory response to therapy in Egypt
The Egyptian Journal of Radiology and Nuclear Medicine xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
The Egyptian Journal of Radiology and Nuclear Medicine journal homepage: www.elsevier.com/locate/ejrnm
Original Article
FDG-PET/CT in re-staging of patients with non Hodgkin lymphoma and monitory response to therapy in Egypt R.A. Elshafey , N. Daabes, S. Galal ⁎
Tanta, Egypt
ARTICLE INFO
ABSTRACT
Keyword: PET-CT Lymphoma Staging
Aim: Assessment of the clinical benefit of [18F]-FDG PET/CT examinations in restaging of patients with non Hodgkin lymphoma (NHL) in Egypt. Patients, methods: This study was performed on 45 patients with NHL. PET-CT and CECT were analyzed after end of chemotherapy regimen, using 12 months follow-up as standard of reference. Results: Follow-up of patients with NHL after 12 months of treatment revealed significant differences between staging by CT versus PET/CT (P = 0.0001). Disease was upstaged by PET/CT in 36% (mostly in stages I and II) and downstaged in only 2% of patients. Agreement between PET-CT & CECT were usually in stage III and IV. Evaluation showed a sensitivity of 77% for CT alone, 95% for FDG-PET-CT. Conclusion: FDG PET-CT significantly improved sensitivity and specificity in restaging of NHL and therefore should be used routinely in follow up of patients with lymphoma.
1. Introduction Malignant lymphoma is considered the most prevalent primary hematopoietic malignancy [1]. WHO classification system had classified prognosis and malignancy grade of lymphoma [2]. The most appropriate therapy of patients of lymphoma depends on accurate prognostic groups classification [3]. CT scans were considered established for staging and restaging of lymphoma. In staging before treatment, CT gives good sensitivity and specificity, but has low specificity in response to therapy assessment. CT scan detect the size and location of masses, but not viable tumor from necrotic tissue [4]. PET with or without CT, using 18-fluorodeoxyglucose (FDG) is based on the principle of increased glucose metabolism in malignant tumors [5]. Combined FDG PET/CT reveal higher specificity in diagnosis, evaluation of treatment response, and prognosis in Hodgkin and non Hodgkin lymphoma patients [2]. Treatment response in many cancers, including malignant lymphoma was been evaluated using Integrated PET/CT which can also predict response to therapy, and it provides essential clinical information [6,7]. FDG PET had many applications in disease staging, detection of
recurrenced, and treatment response assessment in patients with malignant lymphoma. However, infiltrated normal-sized lymph nodes, spleen, bone marrow and extra-nodal tissues revealed limited sensitivity by contrast enhanced CT [8]. Also whole body CT has high radiation dose up to 30 mSv, more than PET scan which has a radiation dose of total of 15 mSv for CT and PET [1]. Recent evidence suggests that PET/CT can replace whole-body CT in patients with lymphoma. PET/CT increased the patient care management decisions than CT alone especially in HD patients [9,7]. So, the aim of this study was to evaluate the clinical significance of combined 18 FDG positron emission tomography and computed tomography (FDGPET/CT) in restaging of patients with NHL in Egypt and monitoring response to therapy. 2. Patients and methods 2.1. Patients This is a prospective study, which was conducted on 45 patients with NHL (29 males and 16 females). Patients were recruited from Radiodiagnosis, Nuclear medicine departments. The regional ethics committee approved the study and written
Peer review under responsibility of The Egyptian Society of Radiology and Nuclear Medicine. ⁎ Corresponding author. E-mail address: [email protected] (R.A. Elshafey). https://doi.org/10.1016/j.ejrnm.2018.06.003 Received 18 March 2018; Accepted 6 June 2018 0378-603X/ © 2018 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Please cite this article as: Elshafey, R.A., The Egyptian Journal of Radiology and Nuclear Medicine, https://doi.org/10.1016/j.ejrnm.2018.06.003
The Egyptian Journal of Radiology and Nuclear Medicine xxx (xxxx) xxx–xxx
R.A. Elshafey et al.
injection and high-fat, low-carbohydrate, protein-permitted diet before the examination.
Table 1 Characters of 45 patients with NHL included in the study. Characteristics
No.
Percentage 64.4% 35.5%
Sex
Male Female
29 16
Age
Median range
48.2 19–78
Types of NHL
Diffuse large B-cell Follicular lymphoma Marginal zone B-cell Precursor T-lymphoblastic Anaplastic large cell
18 11 8 7 1
40% 24.4% 17.7% 15.5% 2.2%
Initial staging
I II
12 9 7 10 2 5
26.6% 20% 15.5% 22.2% 4.4% 11.1%
III IV
II IIE III IIIE
2.6. Dosage administration One liter of negative oral contrast agent (5% mannitol) approximately one hour before the exam. A dose of 3–7 MBq/Kg (10 mci) of 18F-FDG IV injection 45–90 min before examination was administered. This is the uptake phase period which is the necessary time for the FDG to be appropriately bio-distributed and transferred into the patient’s cells. Patients were asked to rest in a quiet room, out of disturbance, and they were also asked to keep calm, to decrease physiologic uptake of FDG into skeletal muscle, which can confuse disease interpretation. 2.7. Patient position Patients must be positioned comfortably on the examination pallet with arms up. 2.8. CT technique
informed consent were obtained from all participants.
Contrasted enhanced CT was performed by injection of 120 mL (at a rate of 4 m/sec) of iodinated low-osmolarity contrast medium. Whole body PET-CT study, scanning began at skull level and extended caudally to upper thigh level. The width of collimation was 5.0 mm, pitch of 1.6, and time of gantry rotation 0.8 s and field of view of 55 cm. reconstruction of helical images are retrospectively done at 1 mm interval.
2.2. Inclusion criteria
• All patients had histopathological diagnosis of NHL diagnosed by biopsy whatever surgically or image guided. • Staging of patients were assessed according to the Ann Arbor staging criteria [10]. • All the patients had complete physical examination and laboratory
2.9. PET technique
testing including (LDH, ESR, CBC, LFTs and RFTs) for good estimation and evaluation before the start of treatment as well as before imaging the patients for more diagnosis.
PET was done following the CT study in the same patient position. Three dimensional acquisition mode are planned with six to seven bed positions (3–5 min at each bed position) for entire patient scanning.
2.3. Exclusion criteria
• Pregnant woman. • Patients with chronic renal impairment (high serum creatinine).
2.10. PET/CT fusion Axial PET and CT images were initially developed, then reformatted into coronal and sagittal images to facilitate image interpretation. Fusion images were generated for PET and CT sets of images. The estimated acquisition time for fused scan was approximately 20–35 min. Reconstruction for attenuation correction of PET image data sets using CT data were done and images were displayed using special software.
2.4. Imaging Exams were done and data were obtained using Siemens Bio-graph true point PET/CT scanner. These dedicated systems integrate a PET scanner with a 64 multi-section helical CT scanners permit the acquisition of co-registered CT and PET images in one session.
2.11. Timing of exam
2.5. Imaging protocol
CECT and PET/CT scan were performed at 10 days after the 3rd cycle of chemotherapy. CECT and PET/CT were underwent within less than one week apart of each other.
2.5.1. Patient preparation
• All patients were asked to fast for six hours prior to scan. All metallic items were removed from the patients. • Patients were asked to empty the urinary bladder before the procedure. • An I.V. cannulation for administration of 18F-FDG. • The patients were instructed to stay out of any kind of hard activity • • •
2.12. PET/CT interpretation All images were interpretated by a consensus of nuclear medicine physicians and radiologists. The PET and CT images were interpreted for the presence and degree of 18F-FDG uptake in nodal and extranodal organs in the initial studies and follow up during/after therapy. SUVmax values for 18-FDG uptake were estimated for each group of enlarged nodes or mass lesion. Diffuse pattern of bone marrow 18-FDG uptake considered reactive bone marrow hyperplasia after chemotherapy. While bone marrow multifocal uptake was considered as PET positive.
before the examination and after injection of the radioisotope to avoid physiologic muscle uptake of FDG. The patient was instructed to void prior to scan. Serum glucose was routinely measured prior to 18F-FDG injection, and fasting levels were 70–170 ng/dl. The strategies for decreasing brown fat were; providing a controlledtemperature (warm) environment for patients before 18F-FDG
2
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Fig. 1. (a) Axial CECT. (b) Axial fused PET-CT. (c) PET MIP (maximum intensity projection) A 33 years male with NHL stage IIA for follow up after end of chemotherapy treatment. The patient reveal complete remission by CECT (stage 0) [18F]fluorodeoxyglucose positron emission tomography/computed tomography scan correctly identified the presence of pathological tracer uptake (max. SUV 5.2) in a solitary lymph node in the cardio-phrenic recess of the left side and so upstage the disease to stage I.
2.13. Treatment
• •
Patients in this study received chemotherapy as the treatment protocol varies from (ABVD, CHOP, RCHOP, MINE) or other according to the oncology decision. Patients were carefully prepared before each cycle as regarding blood picture, liver function and kidney function. Proper evaluation was done after 3 cycles of treatment to categorize the patient response which defined as:
multiplying the maximum long diameter by the longest perpendicular diameter which mean regressive disease. Progressive Disease (PD) was expressed as more than 25% target lesion increase or new lesion appearance. Stable or stationary Disease (SD) was expressed as 50% decrease or less than 25% increase of the measurable lesion.
2.14. Data analysis Statistical results were explained in terms of range, mean ± standard deviation ( ± SD), median, frequencies (number of cases) and percentages when appropriate. Kruskal Wallis analysis of variance
• Complete Cure (CC) if there was disappearance of known disease. • Partial Response (PR) (≥50% decrease in tumor area) calculated by 3
The Egyptian Journal of Radiology and Nuclear Medicine xxx (xxxx) xxx–xxx
R.A. Elshafey et al.
Fig. 2. (A) Axial CECT (b and c) Coronal and axial fused PET-CT A 19 years male with NHL for restaging and treatment assessment. CECT reveal amalgamated lymphamatous adenopathies involving the left inguinal and left femoral lymph node stations (arrows) (stage II). Restaging by PET-CT revealed the CECT detected lymph nodes with additional pathological tracer uptake at right supraclavicular lymph node (max SUV 4.7) and so upstage the disease to stage III.
(ANOVA) test was used for comparison of quantitative variables between the study groups. Statistical calculations were done using Microsoft Excel 2013 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 16 for Microsoft Windows.
revealed solitary lymph node FDG uptake by PET-CT and upstaged them to stage I and one case upstaged to stage II (Fig. 1). PET-CT upstaged 2 cases from stage II to stage IV by detecting metastatic FDG avid osseous deposits confirmed by MRI especially in bone marrow involvement, another 3 cases upstaged from stage II to stage IIE, III & IIIS by detecting extranodal extension & splenic involvement (confirmed by US) (Fig. 2). In contrast, one case downstaged from stage IV to stage II, false positive bone marrow FDG-PET pathological uptake at biopsy (mastocytosis bone uptake). One case was downstaged by PET scan from stage IIE to stage II due to false positive residual mass results by CT (fibrosis). Otherwise PET-CT agreed with CECT which were mainly stage III and IV (Fig. 3). Differences between FDGPET/CT and CECT were statistically significant (P < 0.001) (Table 2).
3. Results Patient characteristics: The study included 45 patients with NHL, with their age ranging from 19 to 78 years at the time of diagnosis (median 48.2 years). Most of their tumors were of diffuse large B-cell type. Most of cases were stage II or greater, and male sex, (Table 1). The 45 patients included in this study underwent CECT & PET/CT scanning to monitor treatment response after 4 cycles of chemotherapy with 12 months follow up as standard of reference. 19 cases revealed complete remission by CECT while 2 of them
4
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3.1. Change of treatment after PET-CT
accuracy over CT or MRI standard imaging. They found that true positive value of FDG-PET was 90%, with an upstaging percentage from 8% to 17% while downstaging from 2% to 23%. Our Results agree with these studies, as the true positive results of PET/CT is 95% with an upstaging percentage is 17.7%, and downstage percentage is 2.2%. Freudenberg et al. [14] who found an improvement in sensitivity and specificity of combined FDG-PET/CT over each imaging modality alone in the restaging of lymphoma patients. The accuracy of FDG-PET was expressed to be 95% and CT accuracy was 84%. Their study is coinciding with our results as the accuracy of CT in our study is 86% while slightly different as we report higher accuracy of combined PET/ CT. The similarity in staging between 18F-FDG-PET and CT was reported to be 80–90% [15–17]. This is agreeing with our results and found mainly in stage III and IV. The study of Isohashi et al. [12] demonstrated that positive findings in both 18F-FDG-PET and CT/MRI was especially low in relation to the treatment response, and most of the different findings were perfectly diagnosed by 18FFDG-PET as changes in glucose metabolism occur before morphologic alterations [18–21]. The results of our study reveal also that PET/CT reveal no tumor activity in a case of residual soft tissue mass revealed by CECT and downstage it as its SUV equal to 1.9. The limitation of this study is the systemic nature of the disease and difficulty of Detecting and validating lesions in lymphoma. Also, very small lesions can be missed by PET scan. Difficulty in proper interpretation of abdominal FDG uptake because of bowel physiological
The oncological treatment was modified according to PET-CT results. In two patients upstaged to stage IV with bone involvement, involved-field radiation of the bone lesions was added to chemotherapy. In three patients (two with iliac nodes and splenic infiltration and one with liver infiltration), reinforced chemotherapy protocol was done in two cases and stem cell implantation was added in the third case due to disease relapse. The course of the disease was divided into three groups according to PET-CT results which was done after CECT (Table 3). PET-CT improve The sensitivity, specificity, Positive predictive value, negative predictive value and overall accuracy of restaging of NHL and detection response to therapy (Table 4). 4. Discussion A significant progress in treatment and diagnosis of malignant lymphomas in the last few years due to the rapid evolution of recent imaging techniques as well as medical oncology [11]. 18F-FDG-PET is expected to play an important role in the diagnosis and treatment of malignant lymphoma patients [12]. FDG-PET has a high diagnostic accuracy in staging and restaging in lymphoma patients [13]. In the study of Isasi et al. [13] who evaluated the diagnostic accuracy of FDG-PET in the staging of patients with lymphoma using a meta-analysis of 20 studies, concluding its high
Fig. 3. (a) Axial CECT (b–f) axial fused PET-CT, (g) PET MIP 54 years male with NHL stage IV for restaging and treatment assessment. CECT revealed multiple enlarged groups of abdominal LNs. PET-CT in accordance with CECT (max SUV 10) in the abdominal LNs (stage IV). Also, pathological FDG tracer uptake in Metastatic osseous deposits are seen in right femoral mid shaft (max SUV 19), outer aspect of right iliac crest max SUV 11), medial and lateral ends of left clavicle (max SUV 9) and left humeral head (max SUV 12).
5
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Fig. 3. (continued) Table 2 Comparison between CECT and PET-CT in restaging of 45 patients with NHL after 4 cycles of chemotherapy. Stage (0) (I) (II) (III) (IV)
I II IIE III IIIE IIIS
CECT
PET-CT
19 2 cases 7 cases 3cases 4 cases 2 cases 2 cases 6case
16 4 cases 5 cases 3 cases 5 cases 2cases 3 cases 7 cases
Table 3 Chart of comparison between CT and PET-CT in assessment of treatment response.
uptake of FDG combined with mobility of the bowel during examination. The points of strength in our study as we focused on NHL type and restrict the study on Egypt as Non-Hodgkin lymphoma was among the 5 most common cancers in Lower Egypt. 5. Conclusion FDG-PET/CT improved the sensitivity and accuracy in restaging of NHL after initial treatment and prediction of response to therapy. Therefore, FDGPET/CT imaging is a promising technique for better management of the patient after treatment.
Chart (1): comparison between CECT & PET-CT as regarding response to treatment.
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Table 4 Analysis of PET/CT results in the studied cases.
Sensitivity Specificity Positive predictive value Negative predictive value Overall accuracy
PET-CT
CT
97.7% 66.6% 97.7% 66.6% 100%
82.2% 66.6% 97.7% 20% 86.6%
2006;17:117–22. [8] Stéphane V, Samuel B, Vincent D, et al. Comparison of PET-CT and magnetic resonance diffusion weighted imaging with body suppression (DWIBS) for initial staging of malignant lymphomas. Eur J Radiol 2011;82(11):7. [9] D’souza MM, Jaimini A, Bansal A, et al. FDG-PET/CT in lymphoma. Indian J Radiol Imag 2013;23(4):354–65. [10] Armitage.. Costwoold modification of Ann Arbor staging system. CA Cancer J Clin 2005;55:368–76. [11] Chavdarova LI1, Tzonevska AD, Piperkova EN. Discrepancies and priorities in staging and restaging malignant lymphoma by SPET, SPET/CT, PET/CT and PET/MRI. Hell J Nucl Med 2013;16(3):223–9. [12] Isohashi K, Tatsumi M, Higuchi I, et al. 18F-FDG-PET in patients with malignant lymphoma having long-term follow-up: staging and restaging, and evaluation of treatment response and recurrence. Ann Nucl Med 2008;22(9):795–802. [13] Isasi CR, Lu P, Blaufox MD. A metaanalysis of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography in the staging and restaging of patients with lymphoma. Cancer 2005;104:1066–74. [14] Freudenberg LS, Antoch G, Schutt P, et al. FDG-PET/CT in re-staging of patients with lymphoma. Eur J Nucl Med Mol Imag 2004;31:325–9. [15] Moog F, Bangerter M, Diederichs CG, et al. Extranodal malignant lymphoma: detection with FDG PET versus CT. Radiology 1998;206:475–81. [16] Juweid G, Beguin Y, Najjar F, et al. Positron emission tomography (PET) with 18Ffluorodeoxyglucose (18F-FDG) for the staging of low grade non-Hodgkin’s lymphoma (NHL). Ann Oncol 2001;12:825–30. [17] Tatsumi M, Cohade C, Nakamoto Y, et al. Direct comparison of FDG PET and CT fi ndings in patients with lymphoma: initial experience. Radiology 2005;237:1038–45. [18] Wahl RL, Zasadny K, Helvie M, et al. Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 1993;11:2101–11. [19] Canellos GP. Residual mass in lymphoma may not be residual disease. J Clin Oncol 1988;6:931–3. [20] Jerusalem G, Beguin Y, Fassotte MF, et al. Whole-body positron emission tomography using 18F-fl uorodeoxyglucose for posttreatment evaluation in Hodgkin’s disease and non-Hodgkin’s lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 1999;94:429–33. [21] Kostakoglu L, Goldsmith SJ. Fluorine-18 fluorodeoxyglucose positron emission tomography in the staging and follow-up of lymphoma: is it time to shift gears? Eur J Nucl Med Mol Imag 2000;27:1564–78.
Conflict of interest The authors declared that there is no conflict of interest. References [1] Adams JA, Nievelstein AJ, Kwee C. Systematic review on the additional value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography in staging follicular lymphoma. J Comput Assist Tomogr 2017;41(1):98–103. [2] Mueller PR, Ferrucci JT, Harbin WP, Kirkpatrick RH, Simeone JF, Wittenberg J. Appearance of lymphomatous involvement of the mesentery by ultrasonography and body computed tomography: the “sandwich sign”. Radiology 1980;134(2):467–73. [3] Margolis DJ, Hoffman JM, Herfkens RJ, Jeffrey RB, Quon A, Gambhir SS. Molecular imaging techniques in body imaging. Radiology 2007;245(2):333–56. [4] Newman JS, Francis JR, Kaminski MS, Wahl RL. Imaging of lymphoma with PET correlation with CT. Radiology 1994;190(1):111–6. [5] Metser U, Dudebout J, Baetz T, Hodgson DC, Langer DL, MacCrostie P, et al. [18F]FDG PET/CT in the staging and management of indolent lymphoma: a prospective multicenter PET registry study. Cancer 2017;123:2860–6. [6] Kazama T, Faria SC, Varavithya V, Phongkitkarun S, Ito H, Macapinlac HA. FDG PET in the evaluation of treatment for lymphoma: clinical usefulness and pitfalls. Radio Graph 2005;25(1):191–207. [7] Raanani P, Shasha Y, Perry C, et al. Is CT scan still necessary for staging in Hodgkin and non-Hodgkin lymphoma patients in the PET/CT era? Ann Oncol
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Contents lists available at ScienceDirect
The Egyptian Journal of Radiology and Nuclear Medicine journal homepage: www.elsevier.com/locate/ejrnm
Original Article
FDG-PET/CT in re-staging of patients with non Hodgkin lymphoma and monitory response to therapy in Egypt R.A. Elshafey , N. Daabes, S. Galal ⁎
Tanta, Egypt
ARTICLE INFO
ABSTRACT
Keyword: PET-CT Lymphoma Staging
Aim: Assessment of the clinical benefit of [18F]-FDG PET/CT examinations in restaging of patients with non Hodgkin lymphoma (NHL) in Egypt. Patients, methods: This study was performed on 45 patients with NHL. PET-CT and CECT were analyzed after end of chemotherapy regimen, using 12 months follow-up as standard of reference. Results: Follow-up of patients with NHL after 12 months of treatment revealed significant differences between staging by CT versus PET/CT (P = 0.0001). Disease was upstaged by PET/CT in 36% (mostly in stages I and II) and downstaged in only 2% of patients. Agreement between PET-CT & CECT were usually in stage III and IV. Evaluation showed a sensitivity of 77% for CT alone, 95% for FDG-PET-CT. Conclusion: FDG PET-CT significantly improved sensitivity and specificity in restaging of NHL and therefore should be used routinely in follow up of patients with lymphoma.
1. Introduction Malignant lymphoma is considered the most prevalent primary hematopoietic malignancy [1]. WHO classification system had classified prognosis and malignancy grade of lymphoma [2]. The most appropriate therapy of patients of lymphoma depends on accurate prognostic groups classification [3]. CT scans were considered established for staging and restaging of lymphoma. In staging before treatment, CT gives good sensitivity and specificity, but has low specificity in response to therapy assessment. CT scan detect the size and location of masses, but not viable tumor from necrotic tissue [4]. PET with or without CT, using 18-fluorodeoxyglucose (FDG) is based on the principle of increased glucose metabolism in malignant tumors [5]. Combined FDG PET/CT reveal higher specificity in diagnosis, evaluation of treatment response, and prognosis in Hodgkin and non Hodgkin lymphoma patients [2]. Treatment response in many cancers, including malignant lymphoma was been evaluated using Integrated PET/CT which can also predict response to therapy, and it provides essential clinical information [6,7]. FDG PET had many applications in disease staging, detection of
recurrenced, and treatment response assessment in patients with malignant lymphoma. However, infiltrated normal-sized lymph nodes, spleen, bone marrow and extra-nodal tissues revealed limited sensitivity by contrast enhanced CT [8]. Also whole body CT has high radiation dose up to 30 mSv, more than PET scan which has a radiation dose of total of 15 mSv for CT and PET [1]. Recent evidence suggests that PET/CT can replace whole-body CT in patients with lymphoma. PET/CT increased the patient care management decisions than CT alone especially in HD patients [9,7]. So, the aim of this study was to evaluate the clinical significance of combined 18 FDG positron emission tomography and computed tomography (FDGPET/CT) in restaging of patients with NHL in Egypt and monitoring response to therapy. 2. Patients and methods 2.1. Patients This is a prospective study, which was conducted on 45 patients with NHL (29 males and 16 females). Patients were recruited from Radiodiagnosis, Nuclear medicine departments. The regional ethics committee approved the study and written
Peer review under responsibility of The Egyptian Society of Radiology and Nuclear Medicine. ⁎ Corresponding author. E-mail address: [email protected] (R.A. Elshafey). https://doi.org/10.1016/j.ejrnm.2018.06.003 Received 18 March 2018; Accepted 6 June 2018 0378-603X/ © 2018 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Please cite this article as: Elshafey, R.A., The Egyptian Journal of Radiology and Nuclear Medicine, https://doi.org/10.1016/j.ejrnm.2018.06.003
The Egyptian Journal of Radiology and Nuclear Medicine xxx (xxxx) xxx–xxx
R.A. Elshafey et al.
injection and high-fat, low-carbohydrate, protein-permitted diet before the examination.
Table 1 Characters of 45 patients with NHL included in the study. Characteristics
No.
Percentage 64.4% 35.5%
Sex
Male Female
29 16
Age
Median range
48.2 19–78
Types of NHL
Diffuse large B-cell Follicular lymphoma Marginal zone B-cell Precursor T-lymphoblastic Anaplastic large cell
18 11 8 7 1
40% 24.4% 17.7% 15.5% 2.2%
Initial staging
I II
12 9 7 10 2 5
26.6% 20% 15.5% 22.2% 4.4% 11.1%
III IV
II IIE III IIIE
2.6. Dosage administration One liter of negative oral contrast agent (5% mannitol) approximately one hour before the exam. A dose of 3–7 MBq/Kg (10 mci) of 18F-FDG IV injection 45–90 min before examination was administered. This is the uptake phase period which is the necessary time for the FDG to be appropriately bio-distributed and transferred into the patient’s cells. Patients were asked to rest in a quiet room, out of disturbance, and they were also asked to keep calm, to decrease physiologic uptake of FDG into skeletal muscle, which can confuse disease interpretation. 2.7. Patient position Patients must be positioned comfortably on the examination pallet with arms up. 2.8. CT technique
informed consent were obtained from all participants.
Contrasted enhanced CT was performed by injection of 120 mL (at a rate of 4 m/sec) of iodinated low-osmolarity contrast medium. Whole body PET-CT study, scanning began at skull level and extended caudally to upper thigh level. The width of collimation was 5.0 mm, pitch of 1.6, and time of gantry rotation 0.8 s and field of view of 55 cm. reconstruction of helical images are retrospectively done at 1 mm interval.
2.2. Inclusion criteria
• All patients had histopathological diagnosis of NHL diagnosed by biopsy whatever surgically or image guided. • Staging of patients were assessed according to the Ann Arbor staging criteria [10]. • All the patients had complete physical examination and laboratory
2.9. PET technique
testing including (LDH, ESR, CBC, LFTs and RFTs) for good estimation and evaluation before the start of treatment as well as before imaging the patients for more diagnosis.
PET was done following the CT study in the same patient position. Three dimensional acquisition mode are planned with six to seven bed positions (3–5 min at each bed position) for entire patient scanning.
2.3. Exclusion criteria
• Pregnant woman. • Patients with chronic renal impairment (high serum creatinine).
2.10. PET/CT fusion Axial PET and CT images were initially developed, then reformatted into coronal and sagittal images to facilitate image interpretation. Fusion images were generated for PET and CT sets of images. The estimated acquisition time for fused scan was approximately 20–35 min. Reconstruction for attenuation correction of PET image data sets using CT data were done and images were displayed using special software.
2.4. Imaging Exams were done and data were obtained using Siemens Bio-graph true point PET/CT scanner. These dedicated systems integrate a PET scanner with a 64 multi-section helical CT scanners permit the acquisition of co-registered CT and PET images in one session.
2.11. Timing of exam
2.5. Imaging protocol
CECT and PET/CT scan were performed at 10 days after the 3rd cycle of chemotherapy. CECT and PET/CT were underwent within less than one week apart of each other.
2.5.1. Patient preparation
• All patients were asked to fast for six hours prior to scan. All metallic items were removed from the patients. • Patients were asked to empty the urinary bladder before the procedure. • An I.V. cannulation for administration of 18F-FDG. • The patients were instructed to stay out of any kind of hard activity • • •
2.12. PET/CT interpretation All images were interpretated by a consensus of nuclear medicine physicians and radiologists. The PET and CT images were interpreted for the presence and degree of 18F-FDG uptake in nodal and extranodal organs in the initial studies and follow up during/after therapy. SUVmax values for 18-FDG uptake were estimated for each group of enlarged nodes or mass lesion. Diffuse pattern of bone marrow 18-FDG uptake considered reactive bone marrow hyperplasia after chemotherapy. While bone marrow multifocal uptake was considered as PET positive.
before the examination and after injection of the radioisotope to avoid physiologic muscle uptake of FDG. The patient was instructed to void prior to scan. Serum glucose was routinely measured prior to 18F-FDG injection, and fasting levels were 70–170 ng/dl. The strategies for decreasing brown fat were; providing a controlledtemperature (warm) environment for patients before 18F-FDG
2
The Egyptian Journal of Radiology and Nuclear Medicine xxx (xxxx) xxx–xxx
R.A. Elshafey et al.
Fig. 1. (a) Axial CECT. (b) Axial fused PET-CT. (c) PET MIP (maximum intensity projection) A 33 years male with NHL stage IIA for follow up after end of chemotherapy treatment. The patient reveal complete remission by CECT (stage 0) [18F]fluorodeoxyglucose positron emission tomography/computed tomography scan correctly identified the presence of pathological tracer uptake (max. SUV 5.2) in a solitary lymph node in the cardio-phrenic recess of the left side and so upstage the disease to stage I.
2.13. Treatment
• •
Patients in this study received chemotherapy as the treatment protocol varies from (ABVD, CHOP, RCHOP, MINE) or other according to the oncology decision. Patients were carefully prepared before each cycle as regarding blood picture, liver function and kidney function. Proper evaluation was done after 3 cycles of treatment to categorize the patient response which defined as:
multiplying the maximum long diameter by the longest perpendicular diameter which mean regressive disease. Progressive Disease (PD) was expressed as more than 25% target lesion increase or new lesion appearance. Stable or stationary Disease (SD) was expressed as 50% decrease or less than 25% increase of the measurable lesion.
2.14. Data analysis Statistical results were explained in terms of range, mean ± standard deviation ( ± SD), median, frequencies (number of cases) and percentages when appropriate. Kruskal Wallis analysis of variance
• Complete Cure (CC) if there was disappearance of known disease. • Partial Response (PR) (≥50% decrease in tumor area) calculated by 3
The Egyptian Journal of Radiology and Nuclear Medicine xxx (xxxx) xxx–xxx
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Fig. 2. (A) Axial CECT (b and c) Coronal and axial fused PET-CT A 19 years male with NHL for restaging and treatment assessment. CECT reveal amalgamated lymphamatous adenopathies involving the left inguinal and left femoral lymph node stations (arrows) (stage II). Restaging by PET-CT revealed the CECT detected lymph nodes with additional pathological tracer uptake at right supraclavicular lymph node (max SUV 4.7) and so upstage the disease to stage III.
(ANOVA) test was used for comparison of quantitative variables between the study groups. Statistical calculations were done using Microsoft Excel 2013 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 16 for Microsoft Windows.
revealed solitary lymph node FDG uptake by PET-CT and upstaged them to stage I and one case upstaged to stage II (Fig. 1). PET-CT upstaged 2 cases from stage II to stage IV by detecting metastatic FDG avid osseous deposits confirmed by MRI especially in bone marrow involvement, another 3 cases upstaged from stage II to stage IIE, III & IIIS by detecting extranodal extension & splenic involvement (confirmed by US) (Fig. 2). In contrast, one case downstaged from stage IV to stage II, false positive bone marrow FDG-PET pathological uptake at biopsy (mastocytosis bone uptake). One case was downstaged by PET scan from stage IIE to stage II due to false positive residual mass results by CT (fibrosis). Otherwise PET-CT agreed with CECT which were mainly stage III and IV (Fig. 3). Differences between FDGPET/CT and CECT were statistically significant (P < 0.001) (Table 2).
3. Results Patient characteristics: The study included 45 patients with NHL, with their age ranging from 19 to 78 years at the time of diagnosis (median 48.2 years). Most of their tumors were of diffuse large B-cell type. Most of cases were stage II or greater, and male sex, (Table 1). The 45 patients included in this study underwent CECT & PET/CT scanning to monitor treatment response after 4 cycles of chemotherapy with 12 months follow up as standard of reference. 19 cases revealed complete remission by CECT while 2 of them
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3.1. Change of treatment after PET-CT
accuracy over CT or MRI standard imaging. They found that true positive value of FDG-PET was 90%, with an upstaging percentage from 8% to 17% while downstaging from 2% to 23%. Our Results agree with these studies, as the true positive results of PET/CT is 95% with an upstaging percentage is 17.7%, and downstage percentage is 2.2%. Freudenberg et al. [14] who found an improvement in sensitivity and specificity of combined FDG-PET/CT over each imaging modality alone in the restaging of lymphoma patients. The accuracy of FDG-PET was expressed to be 95% and CT accuracy was 84%. Their study is coinciding with our results as the accuracy of CT in our study is 86% while slightly different as we report higher accuracy of combined PET/ CT. The similarity in staging between 18F-FDG-PET and CT was reported to be 80–90% [15–17]. This is agreeing with our results and found mainly in stage III and IV. The study of Isohashi et al. [12] demonstrated that positive findings in both 18F-FDG-PET and CT/MRI was especially low in relation to the treatment response, and most of the different findings were perfectly diagnosed by 18FFDG-PET as changes in glucose metabolism occur before morphologic alterations [18–21]. The results of our study reveal also that PET/CT reveal no tumor activity in a case of residual soft tissue mass revealed by CECT and downstage it as its SUV equal to 1.9. The limitation of this study is the systemic nature of the disease and difficulty of Detecting and validating lesions in lymphoma. Also, very small lesions can be missed by PET scan. Difficulty in proper interpretation of abdominal FDG uptake because of bowel physiological
The oncological treatment was modified according to PET-CT results. In two patients upstaged to stage IV with bone involvement, involved-field radiation of the bone lesions was added to chemotherapy. In three patients (two with iliac nodes and splenic infiltration and one with liver infiltration), reinforced chemotherapy protocol was done in two cases and stem cell implantation was added in the third case due to disease relapse. The course of the disease was divided into three groups according to PET-CT results which was done after CECT (Table 3). PET-CT improve The sensitivity, specificity, Positive predictive value, negative predictive value and overall accuracy of restaging of NHL and detection response to therapy (Table 4). 4. Discussion A significant progress in treatment and diagnosis of malignant lymphomas in the last few years due to the rapid evolution of recent imaging techniques as well as medical oncology [11]. 18F-FDG-PET is expected to play an important role in the diagnosis and treatment of malignant lymphoma patients [12]. FDG-PET has a high diagnostic accuracy in staging and restaging in lymphoma patients [13]. In the study of Isasi et al. [13] who evaluated the diagnostic accuracy of FDG-PET in the staging of patients with lymphoma using a meta-analysis of 20 studies, concluding its high
Fig. 3. (a) Axial CECT (b–f) axial fused PET-CT, (g) PET MIP 54 years male with NHL stage IV for restaging and treatment assessment. CECT revealed multiple enlarged groups of abdominal LNs. PET-CT in accordance with CECT (max SUV 10) in the abdominal LNs (stage IV). Also, pathological FDG tracer uptake in Metastatic osseous deposits are seen in right femoral mid shaft (max SUV 19), outer aspect of right iliac crest max SUV 11), medial and lateral ends of left clavicle (max SUV 9) and left humeral head (max SUV 12).
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Fig. 3. (continued) Table 2 Comparison between CECT and PET-CT in restaging of 45 patients with NHL after 4 cycles of chemotherapy. Stage (0) (I) (II) (III) (IV)
I II IIE III IIIE IIIS
CECT
PET-CT
19 2 cases 7 cases 3cases 4 cases 2 cases 2 cases 6case
16 4 cases 5 cases 3 cases 5 cases 2cases 3 cases 7 cases
Table 3 Chart of comparison between CT and PET-CT in assessment of treatment response.
uptake of FDG combined with mobility of the bowel during examination. The points of strength in our study as we focused on NHL type and restrict the study on Egypt as Non-Hodgkin lymphoma was among the 5 most common cancers in Lower Egypt. 5. Conclusion FDG-PET/CT improved the sensitivity and accuracy in restaging of NHL after initial treatment and prediction of response to therapy. Therefore, FDGPET/CT imaging is a promising technique for better management of the patient after treatment.
Chart (1): comparison between CECT & PET-CT as regarding response to treatment.
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Table 4 Analysis of PET/CT results in the studied cases.
Sensitivity Specificity Positive predictive value Negative predictive value Overall accuracy
PET-CT
CT
97.7% 66.6% 97.7% 66.6% 100%
82.2% 66.6% 97.7% 20% 86.6%
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