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Jiang C, Qian C, Jiang Q, Zhou H, Jiang Z, Teng Y, Xu B, Li X, Ding C, Tian R. Virtual biopsy for non-invasive identification of follicular lymphoma histologic transformation using radiomics-based imaging biomarker from PET/CT. BMC Med 2025; 23:49. [PMID: 39875864 PMCID: PMC11776338 DOI: 10.1186/s12916-025-03893-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 01/22/2025] [Indexed: 01/30/2025] Open
Abstract
BACKGROUND This study aimed to construct a radiomics-based imaging biomarker for the non-invasive identification of transformed follicular lymphoma (t-FL) using PET/CT images. METHODS A total of 784 follicular lymphoma (FL), diffuse large B-cell lymphoma, and t-FL patients from 5 independent medical centers were included. The unsupervised EMFusion method was applied to fuse PET and CT images. Deep-based radiomic features were extracted from the fusion images using a deep learning model (ResNet18). These features, along with handcrafted radiomics, were utilized to construct a radiomic signature (R-signature) using automatic machine learning in the training and internal validation cohort. The R-signature was then tested for its predictive ability in the t-FL test cohort. Subsequently, this R-signature was combined with clinical parameters and SUVmax to develop a t-FL scoring system. RESULTS The R-signature demonstrated high accuracy, with mean AUC values as 0.994 in the training cohort and 0.976 in the internal validation cohort. In the t-FL test cohort, the R-signature achieved an AUC of 0.749, with an accuracy of 75.2%, sensitivity of 68.0%, and specificity of 77.5%. Furthermore, the t-FL scoring system, incorporating the R-signature along with clinical parameters (age, LDH, and ECOG PS) and SUVmax, achieved an AUC of 0.820, facilitating the stratification of patients into low, medium, and high transformation risk groups. CONCLUSIONS This study offers a promising approach for identifying t-FL non-invasively by radiomics analysis on PET/CT images. The developed t-FL scoring system provides a valuable tool for clinical decision-making, potentially improving patient management and outcomes.
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Affiliation(s)
- Chong Jiang
- Department of Nuclear Medicine, West China Hospital, Sichuan University, Guoxue Alley, Address: No.37, Chengdu City, Sichuan, 610041, China
| | - Chunjun Qian
- School of Electrical and Information Engineering, Changzhou Institute of Technology, Changzhou, Jiangsu, China
- The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, Changzhou, China
- Center of Medical Physics, Nanjing Medical University, Changzhou, China
| | - Qiuhui Jiang
- Department of Hematology, School of Medicine, The First Affiliated Hospital of Xiamen University and Institute of Hematology, Xiamen University, Xiamen, China
| | - Hang Zhou
- Department of Nuclear Medicine, Qilu Hospital of Shandong University, No.107, Wenhua Xilu, Lixia District, Jinan City, Shandong, 250012, China
| | - Zekun Jiang
- Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yue Teng
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Bing Xu
- Department of Hematology, School of Medicine, The First Affiliated Hospital of Xiamen University and Institute of Hematology, Xiamen University, Xiamen, China
| | - Xin Li
- Department of Nuclear Medicine, Qilu Hospital of Shandong University, No.107, Wenhua Xilu, Lixia District, Jinan City, Shandong, 250012, China.
| | - Chongyang Ding
- Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, No.321, Zhongshan Road, Nanjing City, Jiangsu Province, 210008, China.
| | - Rong Tian
- Department of Nuclear Medicine, West China Hospital, Sichuan University, Guoxue Alley, Address: No.37, Chengdu City, Sichuan, 610041, China.
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Wark A, Kim JY, Mavriopoulou E, la Fougère C, Wiegel T, Scholz CW, Baues C, Li M, Gauler T, Combs SE, Herfarth K. PET/CT-based target volume definition in involved-site radiotherapy for treatment of early-stage nodal follicular lymphoma. Strahlenther Onkol 2025:10.1007/s00066-024-02356-x. [PMID: 39808202 DOI: 10.1007/s00066-024-02356-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 12/06/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE Recent advancements in imaging, particularly 18F-fluorodeoxyglucose positron-emission tomography-computed tomography (FDG-PET/CT), have improved the detection of involved lymph nodes, thus influencing staging accuracy and potentially treatment outcomes. This study is a post hoc analysis of the GAZAI trial data to evaluate the impact of FDG-PET/CT versus computed tomography (CT) alone on radiation target volumes for involved-site radiotherapy (IS-RT) in early-stage follicular lymphoma (FL). METHODS All patients in the GAZAI trial underwent pretherapeutic FDG-PET/CT examinations, which were subject to central quality control. Lymph nodes with pathological metabolism were assessed for CT morphology. Differential regional involvement and the impact on radiation target volume for IS-RT were compared between PET/CT-based to solely CT-based staging. RESULTS In 54 patients with PET-positive lymph nodes after initial surgery, 170 involved lymph nodes were identified in total. FDG-PET/CT identified additionally involved lymph nodes not detected by CT in 61% of the patients, leading to a significant change in radiation treatment fields for 30% of the cohort. Only 58% of all involved lymph nodes exhibited pathological CT morphology. The findings were robust across different Deauville score thresholds and CT morphological metrics. CONCLUSION The findings confirm the essential role of FDG-PET/CT in accurately defining the radiation volume for treatment of early-stage follicular lymphomas with radiotherapy. These results support the integration of FDG-PET/CT into the standard diagnostic pathway and its inclusion in the service catalogue of statutory health insurance, emphasizing its importance for optimal treatment planning and the potential impact on patient outcomes.
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Affiliation(s)
- Antje Wark
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - Ji-Young Kim
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - Elena Mavriopoulou
- Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany
| | - Christian la Fougère
- Institute of Nuclear Medicine und Clinical Molecular Imaging, University Hospital Tübingen, Tübingen, Germany
| | - Thomas Wiegel
- Department of Radiation Oncology, Ulm University Hospital, Ulm, Germany
| | - Christian W Scholz
- Department of Hematology and Oncology, Vivantes Klinikum Am Urban, Berlin, Germany
| | - Christian Baues
- Clinic and Polyclinic for Radiation Oncology, Cyberknife and Radiation Therapy, Universitätsklinikum of Cologne, Cologne, Germany
| | - Minglun Li
- Department of Radiation Oncology, University Hospital LMU Munich, Munich, Germany
| | - Thomas Gauler
- Department of Radiation Therapy, University Essen, Essen, Germany
| | - Stephanie E Combs
- Department of Radiation Oncology, Hospital of the Technical University Munich, Munich, Germany
| | - Klaus Herfarth
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
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Kato K, Izutsu K, Nishikori M, Shibayama H, Maeda Y, Yoshimura K, Tateishi U, Miyamoto T, Matsuda Y, Ishikawa J, Rai S, Takahashi T, Yamauchi T, Matsumura I, Akashi K, Kanakura Y, Suzumiya J. End-of-treatment 18[F]-FDG PET can predict early progression in patients receiving bendamustine-rituximab for follicular lymphoma in first relapse: a prospective West Japan hematology Study Group (W-JHS) NHL01 trial. Int J Hematol 2024; 119:677-685. [PMID: 38519820 DOI: 10.1007/s12185-024-03738-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 02/13/2024] [Accepted: 02/22/2024] [Indexed: 03/25/2024]
Abstract
Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8 weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.
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Affiliation(s)
- Koji Kato
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
| | - Koji Izutsu
- Department of Hematology, Toranomon Hospital, Tokyo, Japan
| | - Momoko Nishikori
- Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hirohiko Shibayama
- Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yoshinobu Maeda
- Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan
| | - Kenichi Yoshimura
- Innovative Clinical Research Centre, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
| | - Ukihide Tateishi
- Department of Diagnostic Radiology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshihiro Miyamoto
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yasufumi Matsuda
- Cancer Care Promotion Center, University of Fukui Hospital, Fukui, Japan
| | - Jun Ishikawa
- Department of Hematology, Osaka International Centre Institute, Osaka, Japan
| | - Shinya Rai
- Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Tsutomu Takahashi
- Department of Hematology, Shimane University Hospital, Shimane, Japan
| | - Takahiro Yamauchi
- Department of Hematology and Oncology, University of Fukui, Fukui, Japan
| | - Itaru Matsumura
- Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Koichi Akashi
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yuzuru Kanakura
- Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Junji Suzumiya
- Department of Hematology, Koga Community Hospital, Daikakuji 2-30-1, Yaizu, Shizuoka, 425-0088, Japan.
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Draye-Carbonnier S, Camus V, Becker S, Tonnelet D, Lévêque E, Zduniak A, Jardin F, Tilly H, Vera P, Decazes P. Prognostic value of the combination of volume, massiveness and fragmentation parameters measured on baseline FDG pet in high-burden follicular lymphoma. Sci Rep 2024; 14:8033. [PMID: 38580734 PMCID: PMC10997640 DOI: 10.1038/s41598-024-58412-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 03/28/2024] [Indexed: 04/07/2024] Open
Abstract
The prognostic value of radiomic quantitative features measured on pre-treatment 18F-FDG PET/CT was investigated in patients with follicular lymphoma (FL). We conducted a retrospective study of 126 FL patients (grade 1-3a) diagnosed between 2006 and 2020. A dozen of PET/CT-derived features were extracted via a software (Oncometer3D) from baseline 18F-FDG PET/CT images. The receiver operating characteristic (ROC) curve, Kaplan-Meier method and Cox analysis were used to assess the prognostic factors for progression of disease within 24 months (POD24) and progression-free survival at 24 months. Four different clusters were identified among the twelve PET parameters analyzed: activity, tumor burden, fragmentation-massiveness and dispersion. On ROC analyses, TMTV, the total metabolic tumor volume, had the highest AUC (0.734) followed by medPCD, the median distance between the centroid of the tumors and their periphery (AUC: 0.733). Patients with high TMTV (HR = 4.341; p < 0.001), high Tumor Volume Surface Ratio (TVSR) (HR = 3.204; p < 0.003) and high medPCD (HR = 4.507; p < 0.001) had significantly worse prognosis in both Kaplan-Meier and Cox univariate analyses. Furthermore, a synergistic effect was observed in Kaplan-Meier and Cox analyses combining these three PET/CT-derived parameters (HR = 12.562; p < 0.001). Having two or three high parameters among TMTV, TVSR and medPCD was able to predict POD24 status with a specificity of 68% and a sensitivity of 75%. TMTV, TVSR and baseline medPCD are strong prognostic factors in FL and their combination better predicts disease prognosis.
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Affiliation(s)
| | - V Camus
- Department of Hematology, Centre Henri Becquerel, Rouen, France
- INSERM U1245, Université de Rouen, IRIB, Rouen, France
| | - S Becker
- Department of Nuclear Medicine, Centre Henri Becquerel, Rouen, France
- QuantIF-LITIS (EA 4108-FR CNRS 3638), Faculty of Medicine, University of Rouen, Rouen, France
| | - D Tonnelet
- Department of Nuclear Medicine, Centre Henri Becquerel, Rouen, France
| | - E Lévêque
- Department of Statistics and Clinical Research Unit, Centre Henri Becquerel, Rouen, France
| | - A Zduniak
- Department of Hematology, Centre Henri Becquerel, Rouen, France
| | - F Jardin
- Department of Hematology, Centre Henri Becquerel, Rouen, France
- INSERM U1245, Université de Rouen, IRIB, Rouen, France
| | - H Tilly
- Department of Hematology, Centre Henri Becquerel, Rouen, France
- INSERM U1245, Université de Rouen, IRIB, Rouen, France
| | - P Vera
- Department of Nuclear Medicine, Centre Henri Becquerel, Rouen, France
- QuantIF-LITIS (EA 4108-FR CNRS 3638), Faculty of Medicine, University of Rouen, Rouen, France
| | - P Decazes
- Department of Nuclear Medicine, Centre Henri Becquerel, Rouen, France.
- QuantIF-LITIS (EA 4108-FR CNRS 3638), Faculty of Medicine, University of Rouen, Rouen, France.
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Zheng Y, Liu J, Si J, Xue Q, Chen D, Nuermaimaiti R, Tian C. Positron emission tomography to detect bone marrow involvement for patients with follicular lymphoma: a systematic review and meta-analysis. Ann Hematol 2023; 102:2403-2412. [PMID: 37209118 DOI: 10.1007/s00277-023-05274-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 05/09/2023] [Indexed: 05/22/2023]
Abstract
Detection of bone marrow involvement (BMI) for patients with follicular lymphoma (FL) is of great significance for staging and treatment. The clinical value of positron emission tomography/computed tomography (PET/CT) in assessing BMI is still under debate and investigation. PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify studies evaluating PET/CT in detecting BMI in FL patients. Data extraction and quality evaluation were independently conducted by two reviewers, and nine eligible studies were selected as final quantitative analysis. Nine studies comprising 1119 FL patients were included. The pooled sensitivity was 0.67 (95% CI, 0.38-0.87), and the pooled specificity was 0.82 (95% CI, 0.75-0.87). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 3.7 (95% CI, 2.1-6.3), 0.4 (95% CI, 0.18-0.91), and 9 (95% CI, 2-33), respectively. The area under the curve of PET/CT to detect BMI in FL patients was 0.83 (95% CI, 0.8-0.86). Current evidence suggests that PET/CT cannot replace bone marrow biopsy to detect BMI, but it is still of partial clinical significance for the prognosis of patients with follicular lymphoma.
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Affiliation(s)
- Yaxin Zheng
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Jun Liu
- Sunshine Union Hospital, Weifang, Shandong, China
| | - Junqi Si
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Qiang Xue
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
- Department of Hematology, Hotan District People's Hospital, 848000, Hotan, Xinjiang, China
| | - Dan Chen
- Department of Hematology, Hotan District People's Hospital, 848000, Hotan, Xinjiang, China
| | - Rexidan Nuermaimaiti
- Department of Hematology, Hotan District People's Hospital, 848000, Hotan, Xinjiang, China
| | - Chen Tian
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
- Department of Hematology, Hotan District People's Hospital, 848000, Hotan, Xinjiang, China.
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Hatta S, Fukuhara S, Fujino T, Saito Y, Ito Y, Makita S, Munakata W, Suzuki T, Maruyama D, Kusumoto M, Izutsu K. The role of surveillance computed tomography in patients with follicular lymphoma. Ther Adv Hematol 2022; 13:20406207221095963. [PMID: 35585967 PMCID: PMC9109489 DOI: 10.1177/20406207221095963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 04/04/2022] [Indexed: 11/15/2022] Open
Abstract
Introduction Surveillance computed tomography (CT) is performed during the follow-up of patients with lymphoma who have completed initial therapy. However, studies on the clinical benefit of surveillance CT for patients with incurable subtypes, such as follicular lymphoma (FL), are limited. This study aimed to evaluate the value of surveillance CT for patients with FL after achieving the first complete response (CR) or CR unconfirmed in the rituximab era. Methods We retrospectively reviewed the medical records of patients with FL who achieved CR with first-line treatment between 2000 and 2016 at our institution. In patients who experienced first relapse, we examined the patient's clinical characteristics at the time of relapse, subsequent therapies, and post-relapse survival, based on the method of relapse detection. Results Of the 248 patients who achieved CR after initial therapy, 109 had a relapse, with a median follow-up of 11 years; 100 were enrolled into this study. Relapse was detected by surveillance CT in 61 patients (surveillance CT group) and by means other than surveillance CT, such as the presence of patient-reported symptoms, physical findings, and blood work-up abnormalities (non-surveillance CT group), in 39 patients. There was no significant difference in the patients' characteristics at the time of relapse between the two groups, except for a higher incidence of extranodal involvement in the non-surveillance CT group. The method of relapse detection did not affect therapeutic selection after relapse and post-relapse survival. In this study, 86.8% of the 38 patients who relapsed with only deep lesions, such as mesenteric or retroperitoneal lymph nodes, had surveillance CT-detected relapse. Conclusion Surveillance CT did not show any clinical benefit for patients with FL in CR; however, it might lead to early detection of relapse in cases of deep lesions that cannot be identified without imaging.
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Affiliation(s)
- Shunsuke Hatta
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Suguru Fukuhara
- Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - Takahiro Fujino
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Yo Saito
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Yuta Ito
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Shinichi Makita
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Wataru Munakata
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Tatsuya Suzuki
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Dai Maruyama
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Masahiko Kusumoto
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
| | - Koji Izutsu
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
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7
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Zhang X, Jiang H, Wu S, Wang J, Zhou R, He X, Qian S, Zhao S, Zhang H, Civelek AC, Tian M. Positron Emission Tomography Molecular Imaging for Phenotyping and Management of Lymphoma. PHENOMICS (CHAM, SWITZERLAND) 2022; 2:102-118. [PMID: 36939797 PMCID: PMC9590515 DOI: 10.1007/s43657-021-00042-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 12/18/2021] [Accepted: 12/21/2021] [Indexed: 10/19/2022]
Abstract
Positron emission tomography (PET) represents molecular imaging for non-invasive phenotyping of physiological and biochemical processes in various oncological diseases. PET imaging with 18F-fluorodeoxyglucose (18F-FDG) for glucose metabolism evaluation is the standard imaging modality for the clinical management of lymphoma. One of the 18F-FDG PET applications is the detection and pre-treatment staging of lymphoma, which is highly sensitive. 18F-FDG PET is also applied during treatment to evaluate the individual chemo-sensitivity and accordingly guide the response-adapted therapy. At the end of the therapy regiment, a negative PET scan is indicative of a good prognosis in patients with advanced Hodgkin's lymphoma and diffuse large B-cell lymphoma. Thus, adjuvant radiotherapy may be alleviated. Future PET studies using non-18F-FDG radiotracers, such as 68Ga-labeled pentixafor (a cyclic pentapeptide that enables sensitive and high-contrast imaging of C-X-C motif chemokine receptor 4), 68Ga-labeled fibroblast activation protein inhibitor (FAPI) that reflects the tumor microenvironment, and 89Zr-labeled atezolizumab that targets the programmed cell death-ligand 1 (PD-L1), may complement 18F-FDG and offer essential tools to decode lymphoma phenotypes further and identify the mechanisms of lymphoma therapy.
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Affiliation(s)
- Xiaohui Zhang
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Han Jiang
- grid.411176.40000 0004 1758 0478PET-CT Center, Fujian Medical University Union Hospital, Fuzhou, 350001 Fujian China
| | - Shuang Wu
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Jing Wang
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Rui Zhou
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Xuexin He
- grid.412465.0Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
| | - Shufang Qian
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Shuilin Zhao
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Hong Zhang
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XKey Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 310027 Zhejiang China
- grid.13402.340000 0004 1759 700XCollege of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310027 Zhejiang China
| | - Ali Cahid Civelek
- grid.469474.c0000 0000 8617 4175Department of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, MD 21287 USA
| | - Mei Tian
- grid.8547.e0000 0001 0125 2443Human Phenome Institute, Fudan University, Shanghai, 201203 China
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8
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Diagnostic value of baseline 18FDG PET/CT skeletal textural features in follicular lymphoma. Sci Rep 2021; 11:23812. [PMID: 34893676 PMCID: PMC8664828 DOI: 10.1038/s41598-021-03278-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 11/17/2021] [Indexed: 01/06/2023] Open
Abstract
At present, 18F-fluorodesoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) cannot be used to omit a bone marrow biopsy (BMB) among initial staging procedures in follicular lymphoma (FL). The additional diagnostic value of skeletal textural features on baseline 18FDG-PET/CT in diffuse large B-cell lymphoma (DLBCL) patients has given promising results. The aim of this study is to evaluate the value of 18FDG-PET/CT radiomics for the diagnosis of bone marrow involvement (BMI) in FL patients. This retrospective bicentric study enrolled newly diagnosed FL patients addressed for baseline 18FDG PET/CT. For visual assessment, examinations were considered positive in cases of obvious bone focal uptakes. For textural analysis, the skeleton volumes of interest (VOIs) were automatically extracted from segmented CT images and analysed using LifeX software. BMB and visual assessment were taken as the gold standard: BMB −/PET − patients were considered as bone-NEGATIVE patients, whereas BMB +/PET −, BMB −/PET + and BMB +/PET + patients were considered bone-POSITIVE patients. A LASSO regression algorithm was used to select features of interest and to build a prediction model. Sixty-six consecutive patients were included: 36 bone-NEGATIVE (54.5%) and 30 bone-POSITIVE (45.5%). The LASSO regression found variance_GLCM, correlation_GLCM, joint entropy_GLCM and busyness_NGLDM to have nonzero regression coefficients. Based on ROC analysis, a cut-off equal to − 0.190 was found to be optimal for the diagnosis of BMI using PET pred.score. The corresponding sensitivity, specificity, PPV and NPV values were equal to 70.0%, 83.3%, 77.8% and 76.9%, respectively. When comparing the ROC AUCs with using BMB alone, visual PET assessment or PET pred.score, a significant difference was found between BMB versus visual PET assessments (p = 0.010) but not between BMB and PET pred.score assessments (p = 0.097). Skeleton texture analysis is worth exploring to improve the performance of 18FDG-PET/CT for the diagnosis of BMI at baseline in FL patients.
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Limited benefit of additional contrast-enhanced CT to end-of-treatment PET/CT evaluation in patients with follicular lymphoma. Sci Rep 2021; 11:18496. [PMID: 34531504 PMCID: PMC8445966 DOI: 10.1038/s41598-021-98081-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 09/02/2021] [Indexed: 11/17/2022] Open
Abstract
Despite follicular lymphoma (FL) is frequently characterized by a moderate increase of glucose metabolism, PET/CT examinations provides valuable information for staging and response assessment of the disease. The aim of the study was to assess and compare the diagnostic performance of PET/ldCT and PET/ceCT, respectively, in evaluating FL patients at the end of treatment. Fifty FL consecutive patients who underwent end-of-therapy PET/CT with both ldCT and ceCT were analyzed. Two blinded observers independently assessed PET/ldCT and PET/ceCT applying the Deauville score (DS) and Lugano classification criteria. PET imaging obtained after the end-of-treatment (EoT) was classified as showing PET and ce-CT matched response (concordant imaging group, CIG) or PET and ce-CT unmatched response (discordant imaging group, DIG). Relapse rate and Event-Free Survival (EFS) were compared between CIG and DIG patients. Overall, no differences in metabolic response classification were observed between PET/ldCT and PET/ceCT. In 13 (26%) patients PET/ceCT identified additional FDG-negative nodal lesions in mesenteric, retroperitoneal and iliac regions. However, in all cases, final DS remained unchanged and the additional results did not modify the following therapeutic decision. Among patients, who obtained complete metabolic response a comparable rate of relapse was registered in DIG 3/13 (23%) and CIG subgroups 5/20 (25%) [p = 0.899]. In all 3 DIG cohort patients who relapsed the recurrent disease involved also, but not exclusively, PET negative lymph nodes detected by ceCT. In overall population metabolic response defined by PET/ldCT predicted EFS [76% (group of patients with metabolic response) vs 35% (group of patients with residual disease), p = 0.0013] significantly better than ceCT-Based response assessment [75% (group of patients with complete response) vs 53% (group of patients with residual disease), p = 0.06]. Our study demonstrates a negligible diagnostic and predictive value of ceCT performed in addition to standard 18FDG PET/ldCT for EoT response evaluation in FLs. PET/ldCT should be performed as first-line imaging procedure, also in patients with prevalent abdominal and pelvic involvement, limiting the acquisition of ceCT in selected cases. This tailored approach would contribute to avoid useless radiation exposure and preserve renal function of patients.
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Lo AC, James LP, Prica A, Raymakers A, Peacock S, Qu M, Louie AV, Savage KJ, Sehn L, Hodgson D, Yang JC, Eich HTT, Wirth A, Hunink MGM. Positron-emission tomography-based staging is cost-effective in early-stage follicular lymphoma. J Nucl Med 2021; 63:543-548. [PMID: 34413148 PMCID: PMC8973292 DOI: 10.2967/jnumed.121.262324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 07/15/2021] [Indexed: 11/17/2022] Open
Abstract
The objective was to assess the cost-effectiveness of staging PET/CT in early-stage follicular lymphoma (FL) from the Canadian health-care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding staging PET/CT versus using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a noncurative approach, or no change in RT treatment as planned. The subsequent disease course was described using a state-transition cohort model over a 30-y time horizon. Diagnostic characteristics, probabilities, utilities, and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars), and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs) and was cost-effective in 89% of simulations (i.e., either saved costs or had an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis showed that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT before curative-intent RT.
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Affiliation(s)
| | | | | | | | | | - Melody Qu
- London Health Sciences Centre, Canada
| | | | | | | | | | - Joanna C Yang
- University of California, San Francisco, United States
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Assanto GM, Ciotti G, Brescini M, De Luca ML, Annechini G, D’Elia GM, Agrippino R, Del Giudice I, Martelli M, Chiaravalloti A, Pulsoni A. High Basal Maximal Standardized Uptake Value (SUV max) in Follicular Lymphoma Identifies Patients with a Low Risk of Long-Term Relapse. Cancers (Basel) 2021; 13:cancers13122876. [PMID: 34207518 PMCID: PMC8227030 DOI: 10.3390/cancers13122876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/03/2021] [Accepted: 06/07/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUVmax alone at baseline PET/CT could have a different prognostic role. PATIENTS AND METHODS We performed a retrospective observational monocentric cohort study. All patients affected by FL who underwent a basal PET/CT were included. Two subgroups were identified and compared in terms of PFS and OS: (A) Basal SUVmax ≤ 6; and (B) Basal SUVmax > 6. RESULTS Ninety-four patients were included, 34 in group A (36.2%) and 60 in group B (63.8%). The PFS at two years was comparable in the two groups (97%). The five-year PFS was 73.5% for group A and 95% for group B (p 0.005). The five-year PFS in the whole cohort was 87.5%. A clear advantage was confirmed in group A in the absence of other risk factors. Patients with SUVmax ≤ 6 and no risk factors showed a 5-year PFS of 73% against 83% for patients with SUVmax > 6 and at least two risk factors. CONCLUSION A high FDG uptake favorably correlated with PFS. A low basal SUVmax reflected a higher rate of late relapse requiring a prolonged follow-up. The basal SUVmax is an approachable parameter with prognostic implications.
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Affiliation(s)
- Giovanni Manfredi Assanto
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Giulia Ciotti
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Mattia Brescini
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Maria Lucia De Luca
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Giorgia Annechini
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Gianna Maria D’Elia
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Roberta Agrippino
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Ilaria Del Giudice
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Maurizio Martelli
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
| | - Agostino Chiaravalloti
- Nuclear Medicine, Department of Biomedicine and Prevention, University Tor Vergata, 00133 Rome, Italy;
- Nuclear Medicine, Istituto Neurologico Mediterraneo IRCCS Neuromed, 86077 Pozzilli, Italy
| | - Alessandro Pulsoni
- Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Via Benevento 6, 00161 Rome, Italy; (G.M.A.); (G.C.); (M.B.); (M.L.D.L.); (G.A.); (G.M.D.); (R.A.); (I.D.G.); (M.M.)
- Correspondence:
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Zanoni L, Mattana F, Calabrò D, Paccagnella A, Broccoli A, Nanni C, Fanti S. Overview and recent advances in PET/CT imaging in lymphoma and multiple myeloma. Eur J Radiol 2021; 141:109793. [PMID: 34148014 DOI: 10.1016/j.ejrad.2021.109793] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 03/18/2021] [Accepted: 05/21/2021] [Indexed: 02/07/2023]
Abstract
Imaging in hematological diseases has evolved extensively over the past several decades. Positron emission tomography/computed tomography (PET/CT) with of 2-[18 F]-fluoro-2-deoxy-d-glucose ([18 F] FDG) is currently essential for accurate staging and for early and late therapy response assessment for all FDG-avid lymphoproliferative histologies. The widely adopted visual Deauville 5-point scale and Lugano Classification recommendations have recently standardized PET scans interpretation and improved lymphoma patient management. In addition [18 F] FDG-PET is routinely recommended for initial evaluation and treatment response assessment of Multiple Myeloma (MM) with significant contribution in risk-stratification and prognostication, although magnetic resonance imaging remains the Gold Standard for the assessment of bone marrow involvement. In this review, an overview of the role of [18 F] FDG-PET, in hematological malignancies is provided, particularly focusing on Hodgkin lymphoma (HL) and Diffuse Large B Cell Lymphoma (DLBCL), both in adult and pediatric populations, and MM, at each point of patient management. Potential alternative molecular imaging applications in this field, such as non-[18 F] FDG-tracers, whole body magnetic resonance imaging (WB-MRI), hybrid PET/MRI and emerging radiomics research are briefly presented.
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Affiliation(s)
- Lucia Zanoni
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Nuclear Medicine, via Massarenti 9, 40138, Bologna, Italy.
| | - Francesco Mattana
- Nuclear Medicine, DIMES, Alma Mater studiorum, Università di Bologna, Bologna, Italy.
| | - Diletta Calabrò
- Nuclear Medicine, DIMES, Alma Mater studiorum, Università di Bologna, Bologna, Italy.
| | - Andrea Paccagnella
- Nuclear Medicine, DIMES, Alma Mater studiorum, Università di Bologna, Bologna, Italy.
| | - Alessandro Broccoli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
| | - Cristina Nanni
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Nuclear Medicine, via Massarenti 9, 40138, Bologna, Italy.
| | - Stefano Fanti
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Nuclear Medicine, via Massarenti 9, 40138, Bologna, Italy; Nuclear Medicine, DIMES, Alma Mater studiorum, Università di Bologna, Bologna, Italy.
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Baseline FDG-PET/CT detects bone marrow involvement in follicular lymphoma and provides relevant prognostic information. Blood Adv 2021; 4:1812-1823. [PMID: 32343798 DOI: 10.1182/bloodadvances.2020001579] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 03/20/2020] [Indexed: 01/16/2023] Open
Abstract
In follicular lymphoma (FL), detection of bone marrow (BM) involvement (BMI) by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) improves the accuracy of staging vs BM biopsy (BMB) alone. Our objective was to determine the diagnostic utility of PET for BMI FL and the prognostic value of BMI by PET (positive PET result [PET+]). Records of patients (2002-2016) with PET and BMB at the time of initial treatment were reviewed. BMI was identified by positive BMB result (BMB+) and/or unifocal or multifocal BM FDG uptake on blindly reviewed PET scans with no corresponding CT abnormality (PET+). Among 261 patients, BMI was diagnosed in 78 patients (29.9%) by PET+, in 81 patients (31.0%) by BMB+, and in 113 patients (43.3%) by either PET+ or BMB+. PET+ upstaged 24 patients to stage IV, including 10 from stages I or II to stage IV. Median duration of follow-up was 6.0 years (range, 0-16.6 years). In univariate analysis, a high Follicular Lymphoma International Prognosis Index (FLIPI) score, PET+, and BMB+ correlated with shorter progression-free survival (PFS; all P ≤ .03), and high FLIPI, PET+, and combined PET+ and BMB+ with shorter overall survival (OS; all P ≤ .01). In multivariate analysis, PET+ was the only independent predictor of PFS, whereas high FLIPI score and PET+ predicted OS (P ≤ .03). Combined PET and BMB identify BMI more accurately than either BMB or PET alone, but BMB rarely adds critical information. For patients initiating treatment of FL, identification of BMI by PET is predictive of PFS and OS.
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Zoellner A, Herfarth K, Herold M, Klapper W, Skoetz N, Hiddemann W. Clinical Practice Guideline: Follicular Lymphoma—Diagnosis, Treatment, and Follow-up. DEUTSCHES ARZTEBLATT INTERNATIONAL 2021; 118:320-325. [PMID: 33632384 PMCID: PMC8295529 DOI: 10.3238/arztebl.m2021.0022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 11/09/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND Follicular lymphoma (FL) occurs predominantly at advanced age, with an annual incidence of 3-5 cases per 100 000 inhabitants in Western countries. The clinical course is heterogeneous. METHODS For this new guideline, systematic literature searches were conducted in medical databases (MEDLINE, PubMed Central) (up to November 2017) and in the Guidelines International Network (G-I-N), and recent publications were added. RESULTS The results of 21 systematic reviews with meta-analyses, 75 randomized controlled trials, and 58 prospective and retrospective studies were evaluated. Lymph-node biopsy is necessary for initial diagnosis of FL. CT scanning of the neck, thorax, and abdomen should be performed to assess how far the disease has spread, together with bone marrow biopsy and, if required, PET/CT. In early FL (stages I and II; 10-15 %), potentially curative radiotherapy combined with an anti-CD 20 antibody is recommended. In advanced disease (stages III and IV), watchful waiting is indicated for patients who have no clinical symptoms and a low tumor burden. Patients with clinical symptoms and/or high tumor burden should receive chemotherapy in combination with an anti-CD 20 antibody, followed by 2 years' maintenance treatment with an anti-CD 20 antibody. CONCLUSION Given the good long-term prognosis of FL, the treatment must be chosen with care and thorough follow-up is necessary to ensure detection of late sequelae such as second malignancies or organ damage.
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Affiliation(s)
- Anna Zoellner
- Department of Medicine III, Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany
| | - Klaus Herfarth
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
| | - Michael Herold
- Department of Medicine III, Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany
| | - Wolfram Klapper
- Department of Pathology, Lymph Node Registry, Hematopathology Section, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Nicole Skoetz
- Evidence-based Oncology Research Group, Department of Medicine I, University of Cologne, Cologne, Germany
| | - Wolfgang Hiddemann
- Department of Medicine III, Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany
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15
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St‐Pierre F, Broski SM, LaPlant BR, Maurer MJ, Ristow K, Thanarajasingam G, Macon WR, Habermann TM, Witzig TE. Fluorodeoxyglucose-Positron Emission Tomography Predicts Bone Marrow Involvement in the Staging of Follicular Lymphoma. Oncologist 2020; 25:689-695. [PMID: 32319706 PMCID: PMC7418364 DOI: 10.1634/theoncologist.2019-0952] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 03/30/2020] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Standard bone marrow biopsy (BMB) and bone involvement with follicular lymphoma (FL) on positron emission tomography (PET)/computed tomography (CT) both predict early clinical failure in FL. The key clinical question is whether PET/CT findings can obviate the need for BMB. The goal of this study was to determine the value of PET/CT in determining bone involvement in FL, using posterior iliac crest BMB as the gold standard. MATERIALS AND METHODS A total of 548 patients with newly diagnosed grade 1-3A FL were included. The presence, pattern, and location of bone involvement, spleen involvement, and standardized uptake values (SUVs) in the L3 vertebral body were recorded for all patients and compared with the BMB report. RESULTS Excluding patients with focal bone lesions on PET/CT, the sensitivity and specificity of PET/CT in detecting bone or marrow involvement, compared with BMB, were 53% and 88%, respectively. The sensitivity and specificity of spleen involvement on PET/CT in predicting a positive BMB were 55% and 86%, respectively. An L3 SUVmax of less than 2.0 resulted in a negative predictive value (NPV) of 96% for marrow involvement on BMB; an L3 SUVmean below 1.4 resulted in an NPV of 100%. CONCLUSION In newly diagnosed FL, PET/CT-detected bone and splenic involvement is highly specific for a positive BMB, and very low SUV values (<2.0 SUVmax and < 1.4 SUVmean ) in the lumbar spine have a high NPV for a negative BMB. Routine BMB may be obviated in these patients. BMB remains necessary to definitively exclude bone marrow involvement in a large majority of patients with a negative PET. IMPLICATIONS FOR PRACTICE Predicting early clinical failure in follicular lymphoma (FL) is important but difficult. Bone marrow involvement by FL is associated with early clinical failure, and determining this involvement is a key component of the initial staging. This study highlights that in certain patients, positron emission tomography/computed tomography is sufficient in determining bone or marrow involvement, without the need for a confirmatory bone marrow biopsy (BMB). An algorithm is provided based on these findings to help clinicians determine which patients would benefit from BMB and when it can be avoided.
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Affiliation(s)
| | - Stephen M. Broski
- Department of Radiology, Division of Nuclear Radiology, Mayo ClinicRochesterMinnesotaUSA
| | - Betsy R. LaPlant
- Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo ClinicRochesterMinnesotaUSA
| | - Matthew J. Maurer
- Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo ClinicRochesterMinnesotaUSA
| | - Kay Ristow
- Department of Medicine, Division of Hematology, Mayo ClinicRochesterMinnesotaUSA
| | - Gita Thanarajasingam
- Department of Medicine, Division of Hematology, Mayo ClinicRochesterMinnesotaUSA
| | - William R. Macon
- Department of Laboratory Medicine, Mayo ClinicRochesterMinnesotaUSA
| | - Thomas M. Habermann
- Department of Medicine, Division of Hematology, Mayo ClinicRochesterMinnesotaUSA
| | - Thomas E. Witzig
- Department of Medicine, Division of Hematology, Mayo ClinicRochesterMinnesotaUSA
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McNamara C, Montoto S, Eyre TA, Ardeshna K, Burton C, Illidge T, Linton K, Rule S, Townsend W, Wong WL, McKay P. The investigation and management of follicular lymphoma. Br J Haematol 2020; 191:363-381. [PMID: 32579717 DOI: 10.1111/bjh.16872] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
| | - Silvia Montoto
- St Bartholomew’s and The Royal London NHS Trust London UK
| | - Toby A. Eyre
- Department of Clinical Haematology Oxford University Hospitals NHS Foundation Trust Oxford UK
| | - Kirit Ardeshna
- Department of Haematology University College London Hospital LondonUK
| | - Cathy Burton
- Department of Haematology Leeds Cancer Centre Leeds UK
| | - Tim Illidge
- Institute of Cancer Sciences the Christie NHS Foundation Trust University of Manchester Manchester UK
| | - Kim Linton
- Department of Medical Oncology The Christie Hospital NHS Trust Manchester UK
| | - Simon Rule
- Department of Haematology University of Plymouth Medical School Plymouth UK
| | - William Townsend
- Department of Haematology University College London Hospital LondonUK
| | - Wai L. Wong
- Paul Strickland Scanner Centre Mount Vernon Hospital Northwood UK
| | - Pam McKay
- Department of Haematology Beatson West of Scotland Cancer Centre Glasgow Scotland UK
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König L, Herfarth K, Hörner-Rieber J, Dietrich S, Wiegel T, Debus J, Viardot A. Oncological outcome and recurrence pattern analysis after involved-field irradiation in combination with rituximab for early-stage nodal and extranodal follicular lymphoma. Strahlenther Onkol 2020; 196:705-714. [PMID: 32377821 PMCID: PMC7385027 DOI: 10.1007/s00066-020-01624-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 04/15/2020] [Indexed: 11/25/2022]
Abstract
Purpose Combined radioimmunotherapy (RIT) in follicular lymphomas (FL) has shown promising treatment efficacy in the Mabthera® and Involved field Radiation (MIR) study. Aim of this study was to analyze treatment efficacy and recurrence patterns after RIT in early-stage nodal and extranodal FL. Methods We reviewed 107 patients who were treated with combined RIT in two centers. Treatment consisted of 4 × rituximab followed by RIT with 4 × rituximab and involved field (IF) radiotherapy with 30/40 Gy. Median follow-up period was 71 months. In contrast to the MIR study, extranodal involvement and grade 3A histology were included in the analysis. Results Extranodal involvement and grade 3A histology were present in 21.8% and 13.1%, respectively. Overall response rate (ORR) after 4 × rituximab, after completion of RIT, and after 6 months was 78.1%, 98.8%, and 98.8%, respectively, with increasing rates of complete remissions (CR). Predictive factors associated with superior PFS were tumor size, completely excised lymphomas, and response to first 4 × rituximab. 5‑year PFS rate was 87.3%, with mostly outfield recurrences (94.1%). Second-line treatment was effective, with 53.3% CR and 46.7% partial remissions (PR). 5‑year OS was 98.1%. RIT was tolerated well, with mainly grade 1–2 acute side effects. Conclusion The real-world efficacy of RIT is comparable with the results of the MIR study. Additionally, this analysis shows that extranodal involvement and grade 3A histology are not associated with inferior PFS.
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Affiliation(s)
- Laila König
- Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
- National Center for Tumor diseases (NCT), Heidelberg, Germany.
| | - Klaus Herfarth
- Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
- National Center for Tumor diseases (NCT), Heidelberg, Germany
| | - Juliane Hörner-Rieber
- Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
- National Center for Tumor diseases (NCT), Heidelberg, Germany
| | - Sascha Dietrich
- Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Wiegel
- Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany
| | - Jürgen Debus
- Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
- National Center for Tumor diseases (NCT), Heidelberg, Germany
| | - Andreas Viardot
- Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany
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18
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Batlevi CL, Sha F, Alperovich A, Ni A, Smith K, Ying Z, Gerecitano JF, Hamlin PA, Horwitz SM, Joffe E, Kumar A, Matasar MJ, Moskowitz AJ, Moskowitz CH, Noy A, Owens C, Palomba LM, Straus D, von Keudell G, Zelenetz AD, Seshan VE, Luminari S, Marcheselli L, Federico M, Younes A. Positron-emission tomography-based staging reduces the prognostic impact of early disease progression in patients with follicular lymphoma. Eur J Cancer 2020; 126:78-90. [PMID: 31927165 PMCID: PMC7331469 DOI: 10.1016/j.ejca.2019.12.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 11/14/2019] [Accepted: 12/02/2019] [Indexed: 11/12/2022]
Abstract
BACKGROUND Previous studies reported that early progression of disease (POD) after initial therapy predicted poor overall survival (OS) in patients with follicular lymphoma (FL). Here, we investigated whether pre-treatment imaging modality had an impact on prognostic significance of POD. METHODS In this retrospective study, we identified 1088 patients with grade I-IIIA FL; of whom, 238 patients with stage II-IV disease were initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), and 346 patients were treated with rituximab-based chemotherapy. Patients (N = 484) from the FOLL05 study served as an independent validation cohort. We risk-stratified patients based on pre-treatment radiographic imaging (positron-emission tomography [PET] versus computed tomography [CT]) and early POD status using event-defining and landmark analyses. A competing risk analysis evaluated the association between early POD and histologic transformation. RESULTS In the discovery cohort, patients with POD within 24 months (PFS24) of initiating R-CHOP therapy had a 5-year OS of 57.6% for CT-staged patients compared with 70.6% for PET-staged patients. In the validation cohort, the 5-year OS for patients with early POD was 53.9% and 100% in CT- and PET-staged patients, respectively. The risk of histologic transformation in patients whose disease progressed within one year of initiating therapy was higher in CT-staged patients than in PET-staged patients (16.7% versus 6.3%, respectively), which was associated with a 9.7-fold higher risk of death. CONCLUSION In FL, pre-treatment PET staging reduced the prognostic impact of early POD compared with CT staging. Patients with early POD and no histologic transformation have an extended OS with standard therapy.
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Affiliation(s)
- Connie L Batlevi
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Fushen Sha
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Anna Alperovich
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ai Ni
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Katy Smith
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Zhitao Ying
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - John F Gerecitano
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Paul A Hamlin
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Steve M Horwitz
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Erel Joffe
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Anita Kumar
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Matthew J Matasar
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alison J Moskowitz
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Craig H Moskowitz
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ariela Noy
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Colette Owens
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Lia M Palomba
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - David Straus
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Gottfried von Keudell
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrew D Zelenetz
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Venkatraman E Seshan
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Stefano Luminari
- Department of Surgical, Medical, Dental and Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Italy; Hematology Unit, AUSL IRCCS Reggio Emilia, Reggio Emilia, Italy
| | - Luigi Marcheselli
- Department of Medical and Surgical Sciences, FIL Trial Office, University of Modena and Reggio Emilia, Italy
| | - Massimo Federico
- Department of Surgical, Medical, Dental and Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Italy
| | - Anas Younes
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Major A, Hammes A, Schmidt MQ, Morgan R, Abbott D, Kamdar M. Evaluating Novel PET-CT Functional Parameters TLG and TMTV in Differentiating Low-grade Versus Grade 3A Follicular Lymphoma. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2020; 20:39-46. [PMID: 31761712 PMCID: PMC9040515 DOI: 10.1016/j.clml.2019.09.609] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 08/02/2019] [Accepted: 09/21/2019] [Indexed: 10/25/2022]
Abstract
BACKGROUND Follicular lymphoma (FL) grading, low-grade 1-2 (LG) versus grade 3A (3A), informs management. However, accurate grading is challenging owing to disease heterogeneity and inter-reader variability. The [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) parameter maximum standardized uptake value (SUVmax) has utility in differentiating LG from 3A FL, but the utility of novel parameters total lesion glycolysis (TLG) and total metabolic tumor volume (TMTV) is unknown. PATIENTS AND METHODS Retrospective review of diagnostic pre-treatment PET-CTs of patients aged > 18 years with FL grades 1-3A from 2009-2017 was performed. PET-CT parameters SUVmax, TLG, and TMTV values were generated using manual (MW) and semi-automated workflows (SW). Poisson regression and receiver operating characteristic curves were used to compare PET-CT parameters between LG and 3A. RESULTS A total of 49 patients with FL were identified: 38 LG and 11 3A. PET-CT parameters were significantly higher in 3A as compared with LG in both workflows. The cutoff values, sensitivities, and specificities were as follows: SUVmax: 10.4, 64%, and 74% in MW and 11.9, 73%, and 76% in SW; TLG: 543, 82%, and 74% in MW and 371, 73%, and 74% in SW; and TMTV: 141, 73%, and 76% in MW and 93, 64%, and 76% in SW. SUVmax had identical cutoff, sensitivity, and specificity across all 3 SWs, whereas TLG and TMTV had considerable variance across all 3 SWs. CONCLUSIONS TLG and TMTV are comparable to SUVmax in differentiating LG versus 3A FL. Cutoffs, sensitivities, and specificities varied in MW versus SW. Novel PET-CT parameters serve as reproducible adjuncts but not replacements for biopsy in differentiating grades of FL.
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Affiliation(s)
- Ajay Major
- Department of Medicine, Internal Medicine Residency Training Program, University of Colorado School of Medicine, Aurora, CO.
| | - Andrew Hammes
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO
| | | | - Rustain Morgan
- Department of Radiology, University of Colorado School of Medicine, Aurora, CO
| | - Diana Abbott
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO
| | - Manali Kamdar
- Department of Medicine, Division of Hematology, University of Colorado School of Medicine, Aurora, CO
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Strati P, Ahmed MA, Fowler NH, Nastoupil LJ, Samaniego F, Fayad LE, Hagemeister FB, Romaguera JE, Rodriguez A, Wang M, Westin JR, Cheah C, Noorani M, Feng L, Davis RE, Neelapu SS. Pre-treatment maximum standardized uptake value predicts outcome after frontline therapy in patients with advanced stage follicular lymphoma. Haematologica 2019; 105:1907-1913. [PMID: 31601688 PMCID: PMC7327641 DOI: 10.3324/haematol.2019.230649] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 10/04/2019] [Indexed: 01/26/2023] Open
Abstract
The impact of pre-treatment maximum standardized uptake value (SUVmax) on the outcome of follicular lymphoma (FL) following specific frontline regimens has not been explored. We performed a retrospective analysis of 346 patients with advanced stage follicular lymphoma (FL) without histological evidence of transformation, and analyzed the impact of SUVmax on outcome after frontline therapy. Fifty-two (15%) patients had a SUVmax >18, and a large lymph node ≥6 cm was the only factor associating with SUVmax >18 on multivariate analysis (odds ratio 2.7, 95% confidence interval [CI]: 1.3-5.3, P=0.006). The complete response rate was significantly lower among patients treated with non-anthracycline-based regimens if SUVmax was >18 (45% vs. 92%, P<0.001), but not among patients treated with R-CHOP (P=1). SUVmax >18 was associated with significantly shorter progression-free survival among patients treated with non-anthracycline-based regimens (77 months vs. not reached, P=0.02), but not among patients treated with R-CHOP (P=0.73). SUVmax >18 associated with shorter overall survival (OS) both in patients treated with R-CHOP (8-year OS 70% vs. 90%, P=0.02) and non-anthracycline-based frontline regimens (8-year OS 50% vs. 85%, P=0.001). In conclusion, pre-treatment PET scan has prognostic and predictive value in patients with advanced stage FL receiving frontline treatment.
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Affiliation(s)
- Paolo Strati
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Mohamed Amin Ahmed
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Nathan H Fowler
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Loretta J Nastoupil
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Felipe Samaniego
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Luis E Fayad
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | | | - Jorge E Romaguera
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Alma Rodriguez
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Michael Wang
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Jason R Westin
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Chan Cheah
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Mansoor Noorani
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Lei Feng
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Richard E Davis
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
| | - Sattva S Neelapu
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
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König L, Dreyling M, Dürig J, Engelhard M, Hohloch K, Viardot A, Witzens-Harig M, Kieser M, Klapper W, Pott C, Herfarth K. Therapy of nodal Follicular Lymphoma (WHO grade 1/2) in clinical stage I/II using response adapted Involved Site Radiotherapy in combination with Obinutuzumab (Gazyvaro) - GAZAI Trial (GAZyvaro and response adapted Involved-site Radiotherapy): a study protocol for a single-arm, non-randomized, open, national, multi-center phase II trial. Trials 2019; 20:544. [PMID: 31470902 PMCID: PMC6717383 DOI: 10.1186/s13063-019-3614-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 07/24/2019] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Large field irradiation had been standard for early-stage follicular lymphoma (FL) for a long time. Although involved field radiotherapy (IF-RT) was recently favored because of the toxicity of large field irradiation, smaller irradiation fields have been accompanied with an increased risk of out-of-field recurrence. The MIR (MabThera® and Involved field Radiation) trial has shown that the combination of IF-RT at a dose of 30-40 Gy with the anti-CD20 antibody rituximab has led to similar efficacy compared with large field irradiation but with markedly reduced side effects. Immune modulating radiation therapy alone using low-dose radiotherapy (LDRT) of 2 × 2 Gy has been shown to be effective in FL. The GAZAI (GAZyvaro and response Adapted Involved-site Radiotherapy) trial aims to prove the efficacy of LDRT in combination with a novel anti-CD20 therapy. METHODS/DESIGN The GAZAI trial is a non-randomized, open, non-controlled, German, multi-center phase II trial that includes patients with early-stage (I and II) nodular FL (grades 1 and 2) confirmed by central histological review. A maximum of 93 patients will be included in the trial. Patients will receive a combined approach of immunotherapy with the fully humanized anti-CD20 antibody obinutuzumab (Gazyvaro®) and involved site radiotherapy (IS-RT) with 2 × 2 Gy. The primary endpoint of the trial is the rate of metabolic complete response (CR), based on fludeoxyglucose positron emission tomography/computed tomography, after obinutuzumab and 2 × 2 Gy IS-RT in week 18. Secondary endpoints are morphologic CR rate in weeks 7 and 18 and month 6, progression-free survival, toxicity, recurrence patterns, overall survival, and quality of life. Additionally, minimal residual disease response is assessed. The risk for a potentially higher recurrence rate after LDRT will be minimized by additional salvage radiation up to the "full dose" of 40 Gy for patients who have less than a metabolic CR and morphologic partial response/CR, which will be evaluated in week 18, offering a response-adapted approach. DISCUSSION The goal of this trial is a further reduction of the radiation dose in patients with nodal early-stage FL showing a good response to a combination of LDRT and anti-CD20 immunotherapy and a comparison with the currently published MIR trial. TRIAL REGISTRATION EudraCT number: 2016-002059-89. ClinicalTrials.gov identifier: NCT03341520 .
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Affiliation(s)
- Laila König
- Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 280, Heidelberg, 69120 Germany
| | - Martin Dreyling
- Department of Medicine III, University Hospital, Ludwig-Maximilians-University, Munich, Germany
| | - Jan Dürig
- Department of Hematology, University of Essen, Essen, Germany
| | - Marianne Engelhard
- Department of Radiotherapy, University Hospital of Essen, Essen, Germany
| | - Karin Hohloch
- Department of Hematology and Oncology, Kantonspital Graubünden, CH-7000 Chur, Switzerland
- Department of Hematology and Oncology, Georg August University, Göttingen, Germany
| | - Andreas Viardot
- Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany
| | - Mathias Witzens-Harig
- Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Meinhard Kieser
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Wolfram Klapper
- Department of Pathology, Hematopathology Section and Lymph Node Registry, University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
| | - Christiane Pott
- Department of Medicine 2, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Klaus Herfarth
- Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 280, Heidelberg, 69120 Germany
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22
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Outcome of patients with early-stage follicular lymphoma staged with 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) and treated with radiotherapy alone. Eur J Nucl Med Mol Imaging 2018; 46:80-86. [PMID: 30083824 DOI: 10.1007/s00259-018-4112-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 07/26/2018] [Indexed: 01/02/2023]
Abstract
PURPOSE/OBJECTIVE(S) To evaluate the impact of positron emission tomography (PET) staging on overall survival (OS) and progression-free survival (PFS) in patients with early-stage (stages I and II) follicular lymphoma (ESFL) treated with radiation therapy alone. MATERIALS/METHODS Eighty-five patients with ESFL treated with curative-intent radiation therapy (RT) between December 2000 and May 2011 were identified. Of those, 13 who had no PET staging and 25 who received additional systemic therapy were excluded from the analysis. Thus, we analyzed 47 patients with PET-staged ESFL treated with definitive radiation therapy alone (dose > 23Gy). Tumour features, pre-treatment computed tomography (CT) and PET stage, dose fractionation, and radiation therapy field extent were recorded. The Kaplan-Meier method was used to estimate the OS and PFS. Patterns of failure were assessed as cumulative incidences assuming competing risks. RESULTS Median age was 57 years (range 24-83); 43% were females. Most were PET stage 1 (76.6%). Median maximum nodal diameter was 3 cm. Median pre-treatment lactate dehydrogenase (LDH) was 327.5 (range 123-607, upper normal limit = 220). Twenty-six patients (55.3%) had infra-diaphragmatic disease. All received 30-36Gy in 15-24 fractions, with 59.6% treated with involved-field radiation therapy (IFRT) techniques. There was no significant difference in PFS between CT stage I and stage II (HR 1.30 95% CI [0.25-6.72], p = 0.75) with a 5-year PFS of 77% and 78% respectively. However, stage I on PET staging had a significantly better PFS than stage II (HR 4.66 95% CI [1.15-18.8], p = 0.038), with 5-year PFS of 84% and 60% respectively. Ten patients had recurrent disease, with distant disease being the first site of failure in seven patients. Seven-year OS was 91% (95% CI 79-100) for the whole cohort. CONCLUSION FDG-PET should be considered an essential element in the evaluation of patients with ESFL being considered for RT.
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Pulsoni A, Cappelli LV, Ballotta L, Canichella M, Serrao A, Annechini G, D'Elia GM, Foà R. Current and future therapeutic approaches for the treatment of follicular lymphoma. Expert Rev Anticancer Ther 2018; 18:931-941. [PMID: 29972084 DOI: 10.1080/14737140.2018.1493926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
INTRODUCTION Recent advances in prognostication as well as management of Follicular Lymphoma (FL) are moving to personalized approach. Areas covered: Prognostic scores as well as consolidated and innovative therapeutic approaches are evaluated according to the various presentation modalities. For asymptomatic, low-tumor burden FL, a 'watch and wait' policy is currently the first-choice approach, although possible alternatives are discussed. Early stage FL may be treated with local radiotherapy although the role of minimal residual disease in possible additional agents should be determined. The first line treatment for symptomatic FL is chemo-immunotherapy followed by two years maintenance therapy with anti-CD20 monoclonal antibodies. A deeper knowledge of FL biology has opened new perspectives regarding the timing of therapy and has offered new targets for the development of novel agents that aim to change the therapeutic scenario of FL management. Expert commentary: The introduction of novel agents could question the incurability of FL and change the therapeutic goal from prolonging the complete remission state to eradicating the disease in young/fit patients, as well as improving quality of life in elderly/unfit patients. In the near future, combining new biologic agents and adoptive cell therapies could help in achieving these aims.
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Affiliation(s)
- Alessandro Pulsoni
- a Hematology, Department of Cellular Biotechnologies and Hematology , Sapienza University , Rome , Italy
| | - Luca Vincenzo Cappelli
- a Hematology, Department of Cellular Biotechnologies and Hematology , Sapienza University , Rome , Italy
| | - Laura Ballotta
- a Hematology, Department of Cellular Biotechnologies and Hematology , Sapienza University , Rome , Italy
| | - Martina Canichella
- a Hematology, Department of Cellular Biotechnologies and Hematology , Sapienza University , Rome , Italy
| | - Alessandra Serrao
- a Hematology, Department of Cellular Biotechnologies and Hematology , Sapienza University , Rome , Italy
| | - Giorgia Annechini
- a Hematology, Department of Cellular Biotechnologies and Hematology , Sapienza University , Rome , Italy
| | - Gianna Maria D'Elia
- a Hematology, Department of Cellular Biotechnologies and Hematology , Sapienza University , Rome , Italy
| | - Robin Foà
- a Hematology, Department of Cellular Biotechnologies and Hematology , Sapienza University , Rome , Italy
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Adams HJA, Kwee TC. Assessing complete remission status in incurable follicular lymphomas, to what purpose? Br J Haematol 2018; 184:467-469. [PMID: 29363739 DOI: 10.1111/bjh.15114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Hugo J A Adams
- Department of Radiology and Nuclear Imaging, Deventer Hospital, Deventer, The Netherlands
| | - Thomas C Kwee
- Department of Radiology, Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Strati P, Fowler N, Pina-Oviedo S, Medeiros LJ, Overman MJ, Romaguera JE, Nastoupil L, Wang M, Hagemeister FB, Rodriguez A, Oki Y, Westin J, Turturro F, Neelapu SS, Fayad L. Long-Term Remissions of Patients With Follicular Lymphoma Grade 3 Treated With R-CHOP. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2018; 18:e103-e108. [DOI: 10.1016/j.clml.2017.11.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 10/09/2017] [Accepted: 11/08/2017] [Indexed: 11/27/2022]
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27
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Bentur OS, Gurion R, Gafter-Gvili A, Gatt M, Shvidel L, Horowitz NA, Ram R, Herishanu Y, Sarid N, Paltiel O, Ganzel C, Kreiniz N, Dally N, Gutwein O, Raanani P, Avivi I, Perry C. Treatment and prognosis of stage I follicular lymphoma in the modern era - does PET matter? Leuk Lymphoma 2017; 59:1163-1171. [PMID: 28901817 DOI: 10.1080/10428194.2017.1375102] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. Patients with stage I disease are usually treated with radiotherapy (RT). In previous studies, mostly from the pre positron emission tomography-computed tomography (PET-CT) era, the 5 year progression-free survival (PFS) and overall survival (OS) rates of stage I disease were 60-80% and 80-93%, respectively. This study retrospectively evaluated the outcome of stage I FL which was treated with involved field RT in the PET-CT era between 2002 and 2015. Ninety-one patients were enrolled. Five year PFS and OS rates were 73% and 97%, respectively. Relapse occurred in 19 (21%) patients, 74% occurring outside the radiation field. In conclusion, PET-CT staging of clinical stage I FL may contribute to the improved prognosis in patients treated with RT compared to historical cohorts, possibly due to better identification of "genuine" stage I disease.
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Affiliation(s)
- Ohad S Bentur
- a Department of Hematology , Tel Aviv Sourasky Medical Center , Tel Aviv , Israel
| | - Ronit Gurion
- b Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.,c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel
| | - Anat Gafter-Gvili
- b Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.,c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.,d Department of Medicine A , Rabin Medical Center , Petah-Tikva , Israel
| | - Moshe Gatt
- e Hadassah Medical Center , Jerusalem , Israel.,f Faculty of Medicine , Hebrew University of Jerusalem , Jerusalem , Israel
| | - Lev Shvidel
- f Faculty of Medicine , Hebrew University of Jerusalem , Jerusalem , Israel.,g Kaplan Medical Center , Rehovot , Israel
| | - Netanel A Horowitz
- h Rambam Medical Center and Rappaport Faculty of Medicine - Technion , Israel
| | - Ron Ram
- a Department of Hematology , Tel Aviv Sourasky Medical Center , Tel Aviv , Israel.,c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel
| | - Yair Herishanu
- a Department of Hematology , Tel Aviv Sourasky Medical Center , Tel Aviv , Israel.,c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel
| | - Nadav Sarid
- a Department of Hematology , Tel Aviv Sourasky Medical Center , Tel Aviv , Israel
| | - Ora Paltiel
- e Hadassah Medical Center , Jerusalem , Israel.,f Faculty of Medicine , Hebrew University of Jerusalem , Jerusalem , Israel
| | - Chezi Ganzel
- f Faculty of Medicine , Hebrew University of Jerusalem , Jerusalem , Israel.,i Shaare Zedek Medical Center , Jerusalem , Israel
| | | | - Najib Dally
- k Faculty of Medicine, Ziv Medical Center and Bar Ilan University , Safed , Israel
| | - Odit Gutwein
- c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.,l Assaf Harofe Medical Center , Tel Aviv , Israel
| | - Pia Raanani
- b Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.,c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel
| | - Irit Avivi
- a Department of Hematology , Tel Aviv Sourasky Medical Center , Tel Aviv , Israel.,c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel
| | - Chava Perry
- a Department of Hematology , Tel Aviv Sourasky Medical Center , Tel Aviv , Israel.,c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel
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Rai A, Nastoupil LJ, Williams JN, Lipscomb J, Ward KC, Howard DH, Lee D, Flowers CR. Patterns of use and survival outcomes of positron emission tomography for initial staging in elderly follicular lymphoma patients. Leuk Lymphoma 2017; 58:1570-1580. [PMID: 27830968 PMCID: PMC5726977 DOI: 10.1080/10428194.2016.1253836] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The role of positron emission tomography (PET) in the initial assessment of follicular lymphoma (FL) has been a topic of debate. We examined the patterns of utilization of PET staging in FL and assessed the association of PET with survival. Using the SEER-Medicare database, we identified 5712 patients diagnosed with first primary FL between 2000 and 2009. Older age, African-American race, poor performance status, B-symptoms and history of anemia were negatively associated with PET staging. Receipt of PET staging was positively associated with treatment at institutions affiliated with research networks and with residence in areas with higher concentrations of nuclear medicine specialists. PET was associated with improved lymphoma-related (HR 0.69, 95% CI: 0.58-0.82) and overall (HR 0.75, 95% CI: 0.68-0.83) survival. Our findings substantiate the use of PET as the standard of care for imaging in FL patients. Further investigation is warranted to identify mechanisms underlying the apparent survival advantage associated with PET staging in FL.
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Affiliation(s)
- Ashish Rai
- Surveillance & Health Services Research Program, American Cancer Society, Atlanta, GA, USA
- Department of Health Policy and Management, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | | | | | - Joseph Lipscomb
- Department of Health Policy and Management, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Kevin C. Ward
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - David H. Howard
- Department of Health Policy and Management, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Daniel Lee
- Emory University School of Medicine, Atlanta, GA, USA
| | - Christopher R. Flowers
- Emory University School of Medicine, Atlanta, GA, USA
- Winship Cancer Institute, Emory University, Atlanta, GA, USA
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FDG-PET Scan: a new Paradigm for Follicular Lymphoma Management. Mediterr J Hematol Infect Dis 2017; 9:e2017029. [PMID: 28512558 PMCID: PMC5419199 DOI: 10.4084/mjhid.2017.029] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 03/03/2017] [Indexed: 01/16/2023] Open
Abstract
In the present review, the reader will be led to the most relevant observations that prompted oncologists and haematologist to consider FDG-PET/CT as a new paradigm for FL management in clinical practice. The role of functional imaging in lymphoma staging, restaging, prognostication, and metabolic tumour volume computing will be reviewed in detail. Moreover, a special focus will be addressed to technical and practical aspects of PET scan reporting, which have been set during the last decade to ensure the reproducibility of the therapeutic results. Finally, the predictive role of PET/CT on long-term treatment outcome will be compared with another well-known prognosticator as minimal residual disease (MRD) detection by Immunoglobulin gene rearrangement assessment.
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Systemic Front Line Therapy of Follicular Lymphoma: When, to Whom and How. Mediterr J Hematol Infect Dis 2016; 8:e2016062. [PMID: 27872742 PMCID: PMC5111519 DOI: 10.4084/mjhid.2016.062] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Accepted: 11/04/2016] [Indexed: 02/06/2023] Open
Abstract
The natural history of follicular lymphoma is usually characterized by an indolent course with a high response rate to the first line therapy followed by recurrent relapses, with a time to next treatment becoming shorter after each subsequent treatment line. More than 80% of patients have advanced stage disease at diagnosis. The time of initiation and the nature of the treatment is mainly conditioned by symptoms, tumor burden, lymphoma grading, co-morbidities and patients preference. A number of clinical and biological factors have been determined to be prognostic in this disease, but the majority of them could not show to be predictive of response to treatment, and therefore can’t be used to guide the treatment choice. CD20 expression is the only predictive factor recognized in the treatment of FL and justifies the use of “naked” or “conjugated” anti-CD20 monoclonal antibodies as a single agent or in combination with chemo- or targeted therapy. Nevertheless, as this marker is almost universally found in FL, it has little role in the choice of treatment. The outcome of patients with FL improved significantly in the last years, mainly due to the widespread use of rituximab, autologous and allogeneic transplantation in young and fit relapsed patients, the introduction of new drugs and the improvement in diagnostic accuracy and management of side effects. Agents as new monoclonal antibodies, immuno-modulating drugs, and target therapy have recently been developed and approved for the relapsed setting, while studies to evaluate their role in first line treatment are still ongoing. Here we report our considerations on first line treatment approach and on the potential factors which could help in the choice of therapy.
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Jiménez Londoño G, García Vicente A, Poblete García V, Amo-Salas M, Calle Primo C, Ibañez García Á, Martínez Sanchís B, López-Fidalgo J, Solano Ramos F, Martínez Hellín A, Díaz Morfa M, Soriano Castrejón Á. Basal 18 F-FDG PET/CT in follicular lymphoma: A comparison of metabolic and clinical variables in the prognostic assessment. Rev Esp Med Nucl Imagen Mol 2016. [DOI: 10.1016/j.remnie.2016.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Jiménez Londoño GA, García Vicente AM, Poblete García VM, Amo-Salas M, Calle Primo C, Ibañez García Á, Martínez Sanchís B, López-Fidalgo JF, Solano Ramos F, Martínez Hellín A, Díaz Morfa M, Soriano Castrejón Á. Basal (18)F-FDG PET/CT in follicular lymphoma: A comparison of metabolic and clinical variables in the prognostic assessment. Rev Esp Med Nucl Imagen Mol 2016; 35:298-305. [PMID: 27312693 DOI: 10.1016/j.remn.2016.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Revised: 03/31/2016] [Accepted: 04/01/2016] [Indexed: 10/21/2022]
Abstract
AIM To analyze the relationship of clinical variables related to prognosis and tumor burden, with metabolic variables obtained in the staging (18)F-FDG PET/CT, and their value in the prognosis in follicular lymphoma (FL). METHODS 82 patients with FL, a (18)F-FDG PET/CT at diagnosis and a follow-up for a minimum of 12 months, were retrospectively enrolled in the present study. Clinical variables (Tumor grade, Follicular Lymphoma International Prognostic Index (FLIPI) and Tumor burden) were evaluated. Metabolic variables such as SUVmax in the highest hypermetabolic lesion, extralymphatic locations, number of involved lymph node locations, bone marrow (BM) involvement, PET stage and diameter of the biggest hypermetabolic lesion, were analyzed in order to establish a PET score and classify the studies in low, intermediate and high metabolic risk. Clinical and metabolic variables (included metabolic risk) were compared. The relation among all variables and disease-free survival (DFS) was studied. RESULTS The 28% of patients had a high-grade tumor. The 30.5% had FLIPI risk low, 29.3% intermediate y 40.2% high. The 42.7% presented a high tumor burden. The PET/CT was positive in 94% of patients. The tumor grade did not show significant relation with metabolic variable. FLIPI risk and tumor burden showed statistical relations with the SUV max and the PET score (p<0.008 and p=0.003 respectively). With respect to DFS, significant differences were detected for the PET stage and FLIPI risk (p=0.015 and p=0.047 respectively). FLIPI risk was the only significant predictor in Cox regression analysis, with a Hazard Ratio of 5.13 between high risk and low risk. CONCLUSION The present research highlights the significant relation between metabolic variables obtained with FDG PET/CT and clinical variables although their goal as an independent factor of prognosis was not demonstrated in the present work.
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Affiliation(s)
- G A Jiménez Londoño
- Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Spain.
| | - A M García Vicente
- Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Spain
| | - V M Poblete García
- Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Spain
| | - M Amo-Salas
- Department of Mathematics, University of Castilla La Mancha, Ciudad Real, Spain
| | - C Calle Primo
- Department of Hematology, Hospital General Universitario de Ciudad Real, Spain
| | - Á Ibañez García
- Department of Hematology, Complejo Hospitalario Universitario de Albacete, Spain
| | - B Martínez Sanchís
- Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Spain
| | - J F López-Fidalgo
- Department of Mathematics, University of Castilla La Mancha, Ciudad Real, Spain
| | - F Solano Ramos
- Department of Hematology, Hospital Ntra. Sra. del Prado, Talavera de la Reina, Toledo, Spain
| | - A Martínez Hellín
- Department of Hematology, Complejo Hospitalario Universitario de Albacete, Spain
| | - M Díaz Morfa
- Department of Hematology, Hospital Universitario de Guadalajara, Spain
| | - Á Soriano Castrejón
- Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Spain
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Ujjani CS, Hill EM, Wang H, Nassif S, Esposito G, Ozdemirli M, Cordova C, Cheson BD. (18) F-FDG PET-CT and trephine biopsy assessment of bone marrow involvement in lymphoma. Br J Haematol 2016; 174:410-6. [PMID: 27098364 DOI: 10.1111/bjh.14071] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Accepted: 01/26/2016] [Indexed: 11/29/2022]
Abstract
The ability of positron emission tomography-computerized tomography (PET-CT) to accurately detect bone marrow involvement (BMI) has been suggested in Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL), but its abilities in other histologies is less established. The aim of this retrospective study was to confirm the role of PET-CT in detecting BMI in DLBCL and HL, and to explore its usefulness in other subtypes. Of the 149 newly diagnosed patients, common subtypes included DLBCL, follicular lymphoma (FL) and HL. In DLBCL, the sensitivity and specificity of PET-CT at diagnosis were 75% and 92%. In FL, the sensitivity and specificity of PET-CT were 67% and 85% at diagnosis, and 73% and 89% at relapse. In HL, the sensitivity and specificity were 100% and 74%. PET-CT was able to detect BMI in patients with negative biopsies. Most of the patients in which PET-CT failed to identify BMI were already advanced stage by imaging. In this analysis, PET-CT was highly accurate for detecting BMI at diagnosis in DLBCL and HL and highly specific in FL at diagnosis and relapse. Results also suggested the diagnostic advantage of PET-CT over bone marrow biopsy in detecting BMI. Prospective evaluation is necessary and may eliminate biopsies in future patients.
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Affiliation(s)
- Chaitra S Ujjani
- Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Elizabeth M Hill
- Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Hongkun Wang
- Department of Biostatistics, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Samer Nassif
- Department of Pathology, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Giuseppe Esposito
- Department of Nuclear Medicine, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Metin Ozdemirli
- Department of Pathology, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Christine Cordova
- Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Bruce D Cheson
- Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA
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Perry C, Lerman H, Joffe E, Sarid N, Amit O, Avivi I, Kesler M, Ben-Ezra J, Even-Sapir E, Herishanu Y. The Value of PET/CT in Detecting Bone Marrow Involvement in Patients With Follicular Lymphoma. Medicine (Baltimore) 2016; 95:e2910. [PMID: 26945387 PMCID: PMC4782871 DOI: 10.1097/md.0000000000002910] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Follicular lymphoma (FL) is the 2nd most common type of lymphoma diagnosed in the Western World. Bone marrow (BM) involvement is an adverse prognostic factor in FL, routinely assessed by an arbitrary biopsy of the iliac crest. This study was aimed to investigate the role of positron emission tomography/computed tomography (PET/CT) in identifying BM involvement by FL. In this retrospective, single-center study we reviewed the records of consecutive patients with FL at diagnosis or relapse who underwent staging/restaging workup visual assessment of BM uptake was categorized as either normal, diffusely increased, or focally increased. Quantitative BM fluorine-18-fluro-deoxyglucose (FDG) uptake was measured using mean standardized uptake value (BM-SUVmean). The diagnosis of BM involvement was based on either BM histological findings or disappearance of increased uptake at end-treatment PET/CT in patients who responded to treatment. Sixty eight cases with FL were included. Sixteen (23.5%) had BM involvement, 13 (19.1%) had a biopsy proven involvement, and 3 (4.4%) had a negative BM biopsy, but increased medullary uptake that normalized post-treatment. BM FDG uptake in these patients was diffuse in 8 (50%) and focal in 8 (50%). Focal increased uptake was indicative of BM involvement; however, diffuse uptake was associated with 17 false positive cases (32.7%). Overall, visual assessment of BM involvement had a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 48.5%. On a quantitative assessment, BM-SUVmean was significantly higher in patients with BM involvement (SUVmean of 3.7 [1.7-6] vs 1.4 [0.4-2.65], P < 0.001). On receiver operator curve (ROC) analysis, BM-SUVmean > 2.7 had a PPV of 100% for BM involvement (sensitivity of 68%), while BM-SUVmean < 1.7 had an NPV of 100% (specificity of 73%). Visual assessment of PET/CT is appropriate for ruling out BM involvement by FL. Although focal increased uptake indicates marrow involvement, diffuse uptake is nonspecific. SUV measurement improves PET/CT diagnostic accuracy, identifying additional 19% of patients with BM involvement that would have been otherwise missed.
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Affiliation(s)
- Chava Perry
- From the Department of Hematology (CP, EJ, NS, OA, IA, YH); Department of Nuclear Medicine (HL, MK, EES); Department of Pathology, Tel Aviv Sourasky Medical Center (B-E); and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (B-E, EES, IA, YH)
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Iwamuro M, Kondo E, Takata K, Yoshino T, Okada H. Diagnosis of follicular lymphoma of the gastrointestinal tract: A better initial diagnostic workup. World J Gastroenterol 2016; 22:1674-1683. [PMID: 26819532 PMCID: PMC4721998 DOI: 10.3748/wjg.v22.i4.1674] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 09/28/2015] [Accepted: 10/12/2015] [Indexed: 02/06/2023] Open
Abstract
Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease's endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis.
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36
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Discordant bone marrow involvement in non-Hodgkin lymphoma. Blood 2015; 127:965-70. [PMID: 26679865 DOI: 10.1182/blood-2015-06-651968] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 12/14/2015] [Indexed: 12/14/2022] Open
Abstract
A discordant lymphoma occurs where 2 distinct histologic subtypes coexist in at least 2 separate anatomic sites. Histologic discordance is most commonly observed between the bone marrow (BM) and lymph nodes (LNs), where typically aggressive lymphoma is found in a LN biopsy with indolent lymphoma in a BM biopsy. Although the diagnosis of discordance relied heavily on histopathology alone in the past, the availability of flow cytometry and molecular studies have aided the identification of this entity. The true prevalence and clinical ramifications of discordance remain controversial as available data are principally retrospective, and there is therefore little consensus to guide optimal management strategies. In this review, we examine the available literature on discordant lymphoma and its outcome, and discuss current therapeutic approaches. Future studies in discordant lymphoma should ideally focus on a large series of patients with adequate tissue samples and incorporate molecular analyses.
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FDG PET/CT Imaging of an Isolated Recurrence in the Eyelid of a Patient With Follicular Lymphoma. Clin Nucl Med 2015; 40:871-2. [DOI: 10.1097/rlu.0000000000000938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Bone marrow uptake of indolent non-Hodgkin lymphoma on PET/CT with histopathological correlation. Nucl Med Commun 2015. [PMID: 26225940 DOI: 10.1097/mnm.0000000000000361] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Adams HJA, Nievelstein RAJ, Kwee TC. Opportunities and limitations of bone marrow biopsy and bone marrow FDG-PET in lymphoma. Blood Rev 2015; 29:417-25. [PMID: 26113144 DOI: 10.1016/j.blre.2015.06.003] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 06/10/2015] [Accepted: 06/12/2015] [Indexed: 12/17/2022]
Abstract
Bone marrow involvement in lymphoma may have prognostic and therapeutic consequences. Bone marrow biopsy (BMB) is the established method for the evaluation of the bone marrow. (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) plays an important role in lymphoma staging, but its value in the assessment of the bone marrow and whether it can replace BMB is still a topic of debate and investigation. The purpose of this scientific communication is to provide an evidence-based overview about the opportunities and limitations of BMB and FDG-PET in the evaluation of the bone marrow in patients with lymphoma. This article first reviews the basic properties, opportunities and limitations of BMB and bone marrow FDG-PET, and then focuses on the clinical utility of BMB and bone marrow FDG-PET in three major lymphoma subtypes including Hodgkin lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma.
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Affiliation(s)
- Hugo J A Adams
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
| | - Rutger A J Nievelstein
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Thomas C Kwee
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
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FDG-PET/CT and FLT-PET/CT for differentiating between lipid-poor benign and malignant adrenal tumours. Eur Radiol 2015; 25:3696-705. [PMID: 25925356 DOI: 10.1007/s00330-015-3787-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 03/31/2015] [Accepted: 04/08/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To compare F-18-fluorodeoxyglucose (FDG) and F-18-fluorothymidine (FLT) PET/CT examinations for differentiating between benign and malignant adrenal tumours. METHODS Thirty lipid-poor benign and 11 malignant tumours of 40 patients were included. FDG- and FLT-based indices including visual score, maximum standardized uptake value (SUVmax) and FDG adrenal lesion/liver SUVmax (A/L SUVmax) or FLT adrenal lesion/back muscle SUVmax (A/B SUVmax) ratio were compared between benign and malignant tumours using the Mann-Whitney's U or Wilcoxon signed-rank test, and their diagnostic performances were evaluated by means of the area under the curve (AUC) values derived from the receiver operating characteristic analysis. RESULTS All indices were significantly higher in malignant than benign tumours on both images (p < 0.05 each). On FDG-PET/CT, the sensitivity, specificity, and accuracy were 91 %, 63 % and 71 % for visual score, 91 %, 67 % and 73 % for SUVmax, and 100 %, 70 % and 78 % for A/L SUVmax ratio, respectively. On FLT-PET/CT, they were 100 %, 97 % and 98 % for visual score, SUVmax and A/B SUVmax ratio, respectively. All FLT indices were significantly higher than those of FDG in AUC (p < 0.05 each). CONCLUSION FLT-PET/CT may be superior to FDG-PET/CT in differentiating lipid-poor benign from malignant adrenal tumours because of higher specificity and accuracy. KEY POINTS • All FDG indices were significantly higher in malignant than in benign tumours. • All FLT indices were significantly higher in malignant than in benign tumours. • All FLT indices were significantly higher than those of FDG in AUC.
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Alcantara M, Dupuis J, Mareschal S, Julian A, Cottereau AS, Becker S, Dubois S, Oberic L, Huynh A, Meignan M, Laurent G, Tilly H, Haioun C, Ysebaert L. PET/CT before autologous stem cell transplantation predicts outcome in refractory/relapsed follicular lymphoma. Eur J Nucl Med Mol Imaging 2014; 42:215-21. [PMID: 25239490 DOI: 10.1007/s00259-014-2896-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Accepted: 08/13/2014] [Indexed: 12/17/2022]
Abstract
PURPOSE Salvage of young patients with follicular lymphoma (FL) after R-CHOP includes salvage immunochemotherapy followed by autologous stem cell transplantation (ASCT). Previous studies dealing with relapsed Hodgkin lymphoma have shown the prognostic value of PET/CT prior to ASCT. METHODS We retrospectively analysed 59 patients with refractory/relapsed FL after first-line R-CHOP who were chemosensitive (as evaluated by CT) to the salvage treatment and who proceeded to ASCT. The role of PET/CT in this setting to define chemosensitivity is not definitely established. So we focused on the prognostic value of PET/CT performed after salvage treatment, before ASCT. RESULTS The estimated 3-year progression-free survival (PFS) and overall survival were 63.1% (50.9-78.3%) and 90.5% (82.8 - 98.8%), respectively, and did not differ significantly according to their Follicular Lymphoma International Prognostic Index at relapse, conditioning regimen, or type of salvage. PFS was significantly lower in PET/CT-positive patients, according to the International Harmonization Project revised response criteria, with a 3-year PFS of 45.5% (26.6 - 77.8%) versus 72.6% (58.5 - 90.0%; p = 0.039). To better refine prognosis, we applied two types of throsholds: a Deauville five-point scale positive threshold of ≥3 (3-year PFS of 74.9%, range 61.0 - 92.1% %, versus 42.8%, range 24.7 - 74.4%; p = 0.02), and a ≥70% ∆SUVmax threshold between presalvage and pre-ASCT PET/CT (3-year PFS of 72.4%, range 57.5 - 91.3% versus 13.3%, 2.2 - 81.7%; p < 10(-3)). The PET/CT findings before ASCT were independently correlated with PFS in our series. CONCLUSION PET/CT negativity before ASCT is a desirable and achievable goal in the management of chemosensitive FL relapsing after first-line R-CHOP.
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Affiliation(s)
- Marion Alcantara
- Service d'Hématologie, Centre Henri Becquerel, Université de Rouen, rue d'Amiens, Rouen, Cedex 760381, France
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The prognostic value of mid- and post-treatment [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in indolent follicular lymphoma. Ann Nucl Med 2014; 28:805-11. [DOI: 10.1007/s12149-014-0874-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2014] [Accepted: 06/20/2014] [Indexed: 10/25/2022]
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45
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Mayerhoefer ME, Karanikas G, Kletter K, Prosch H, Kiesewetter B, Skrabs C, Porpaczy E, Weber M, Pinker-Domenig K, Berzaczy D, Hoffmann M, Sillaber C, Jaeger U, Müllauer L, Simonitsch-Klupp I, Dolak W, Gaiger A, Ubl P, Lukas J, Raderer M. Evaluation of Diffusion-Weighted MRI for Pretherapeutic Assessment and Staging of Lymphoma: Results of a Prospective Study in 140 Patients. Clin Cancer Res 2014; 20:2984-93. [DOI: 10.1158/1078-0432.ccr-13-3355] [Citation(s) in RCA: 83] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Kostakoglu L, Cheson BD. Current role of FDG PET/CT in lymphoma. Eur J Nucl Med Mol Imaging 2014; 41:1004-27. [PMID: 24519556 DOI: 10.1007/s00259-013-2686-2] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Accepted: 12/27/2013] [Indexed: 01/08/2023]
Abstract
The management approach in Hodgkin's (HL) and high-grade non-Hodgkin's lymphomas (NHL) has shifted towards reducing the toxicity and long-term adverse effects associated with treatment while maintaining favorable outcomes in low-risk patients. The success of an individualized treatment strategy depends largely on accurate diagnostic tests both at staging and during therapy. In this regard, positron emission tomography (PET) using fluorodeoxyglucose (FDG) with computed tomography (CT) has proved effective as a metabolic imaging tool with compelling evidence supporting its superiority over conventional modalities, particularly in staging and early evaluation of response. Eventually, this modality was integrated into the routine staging and restaging algorithm of lymphomas. This review will summarize the data on the proven and potential utility of PET/CT imaging for staging, response assessment, and restaging, describing current limitations of this imaging modality.
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Affiliation(s)
- Lale Kostakoglu
- Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1141, New York, NY, 10029, USA,
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Tychyj-Pinel C, Ricard F, Fulham M, Fournier M, Meignan M, Lamy T, Vera P, Salles G, Trotman J. PET/CT assessment in follicular lymphoma using standardized criteria: central review in the PRIMA study. Eur J Nucl Med Mol Imaging 2014; 41:408-15. [DOI: 10.1007/s00259-013-2441-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 04/22/2013] [Indexed: 12/20/2022]
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Pyo J, Won Kim K, Jacene HA, Sakellis CG, Brown JR, Van den Abbeele AD. End-Therapy Positron Emission Tomography for Treatment Response Assessment in Follicular Lymphoma: A Systematic Review and Meta-analysis. Clin Cancer Res 2013; 19:6566-77. [DOI: 10.1158/1078-0432.ccr-13-1511] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Kostakoglu L, Cheson BD. State-of-the-Art Research on "Lymphomas: Role of Molecular Imaging for Staging, Prognostic Evaluation, and Treatment Response". Front Oncol 2013; 3:212. [PMID: 24027671 PMCID: PMC3762124 DOI: 10.3389/fonc.2013.00212] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Accepted: 08/02/2013] [Indexed: 12/11/2022] Open
Abstract
Lymphomas are heterogeneous but potentially curable group of neoplasms. Treatment of lymphomas has rapidly evolved overtime with significant improvement in the cure rate and reductions in treatment-related toxicities. Despite excellent results, treatment programs are continued to be developed to achieve better curative and safety profiles. In these patients individualized therapy schemes can be devised based on a well-defined risk categorization. The therapy efficacy can be increased early during therapy in non-responding patients with escalated therapy protocols or with the addition of radiation therapy, particularly, in advanced-stage or unfavorable risk patients. The increasing availability of positron emission tomography using 18F-fluorodeoxyglucose, particularly fused with computed tomography (FDG-PET/CT) has lead to the integration of this modality into the routine staging and restaging for lymphoma with convincing evidence that it is a more accurate imaging modality compared with conventional imaging techniques. FDG-PET/CT is also is a promising surrogate for tumor chemosensitivity early during therapy. This review will summarize published data on the utility of FDG-PET/CT imaging in the staging, restaging, and predicting therapy response in patients with lymphoma.
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Affiliation(s)
- Lale Kostakoglu
- Department of Radiology, Mount Sinai Medical Center , New York, NY , USA
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Luminari S, Biasoli I, Arcaini L, Versari A, Rusconi C, Merli F, Spina M, Ferreri A, Zinzani P, Gallamini A, Mastronardi S, Boccomini C, Gaidano G, D'Arco A, Di Raimondo F, Carella A, Santoro A, Musto P, Federico M. The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi. Ann Oncol 2013; 24:2108-12. [DOI: 10.1093/annonc/mdt137] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
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