Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma

PurposeThe presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study.MethodsFrom 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease.ResultsMedian TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % (p = 0.001) and 44 % vs. 79 % (p < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 (p = 0.0005, RR 6.3) and TMTV0 (p < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml (n = 37, 63 %), ΔSUVmaxPET0-2 = <71 % or TMTV0 >225 ml (n = 17, 29 %), and ΔSUVmaxPET0-2 = <71 % and TMTV0 >225 ml (n = 5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively.ConclusionTMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may guide clinicians in their choice of therapeutic strategy.

[1]  F. Brunotte,et al.  Interim 18F-FDG PET SUVmax Reduction Is Superior to Visual Analysis in Predicting Outcome Early in Hodgkin Lymphoma Patients , 2014, The Journal of Nuclear Medicine.

[2]  J. Connors Positron emission tomography in the management of Hodgkin lymphoma. , 2011, Hematology. American Society of Hematology. Education Program.

[3]  Seong-Jang Kim,et al.  Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement , 2011, Annals of Hematology.

[4]  S. Hyun,et al.  Volume-Based Parameters of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Outcome Prediction in Early-Stage Non–Small Cell Lung Cancer After Surgical Resection , 2013, Annals of surgery.

[5]  Cyrill Burger,et al.  Radiation treatment planning with an integrated positron emission and computer tomography (PET/CT): a feasibility study. , 2003, International journal of radiation oncology, biology, physics.

[6]  Martin Hutchings,et al.  PET/CT for Therapy Response Assessment in Lymphoma , 2009, Journal of Nuclear Medicine.

[7]  Bruce D Cheson,et al.  Role of functional imaging in the management of lymphoma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  F. Angrilli,et al.  Chemoresistance as a function of the pretherapy tumor burden and the chemotherapy regimen administered: differences observed with 2 current chemotherapy regimens for advanced Hodgkin lymphoma. , 2011, Clinical lymphoma, myeloma & leukemia.

[9]  J. Armitage,et al.  A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. , 1998, The New England journal of medicine.

[10]  Olker,et al.  A PROGNOSTIC SCORE FOR ADVANCED HODGKIN ’ S DISEASE , 2000 .

[11]  R. Advani,et al.  Interim-treatment quantitative PET parameters predict progression and death among patients with hodgkin's disease , 2012, Radiation oncology.

[12]  E. Merkle,et al.  Extranodal malignant lymphoma: detection with FDG PET versus CT. , 1998, Radiology.

[13]  Seong-Jang Kim,et al.  Metabolic tumor volume by positron emission tomography/computed tomography as a clinical parameter to determine therapeutic modality for early stage Hodgkin's lymphoma , 2013, Cancer science.

[14]  Federica Fioroni,et al.  Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients , 2014, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  Emmanuel Itti,et al.  Early 18F-FDG PET for Prediction of Prognosis in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment Versus Visual Analysis , 2007, Journal of Nuclear Medicine.

[16]  A. Alavi,et al.  Utility of fluorodeoxyglucose-PET imaging in the management of patients with Hodgkin's and non-Hodgkin's lymphomas. , 2004, Radiologic clinics of North America.

[17]  P. Gobbi,et al.  Tumour burden predicts treatment resistance in patients with early unfavourable or advanced stage Hodgkin lymphoma treated with ABVD and radiotherapy , 2012, Hematological oncology.

[18]  Jacob Cohen A Coefficient of Agreement for Nominal Scales , 1960 .

[19]  Stage IA to IIB mediastinal Hodgkin's disease: three-dimensional volumetric assessment of response to treatment. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  S. Pileri,et al.  Early positron emission tomography (PET) restaging: a predictive final response in Hodgkin's disease patients. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  P. Gobbi,et al.  The clinical value of tumor burden at diagnosis in Hodgkin lymphoma , 2004, Cancer.

[22]  M. Dreyling,et al.  Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[23]  W. Youden,et al.  Index for rating diagnostic tests , 1950, Cancer.

[24]  W. Oyen,et al.  FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0 , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[25]  T. D. Hamilton,et al.  Classification of Tumours , 1930, Edinburgh medical journal.

[26]  Quynh-Thu Le,et al.  Metabolic tumor burden predicts for disease progression and death in lung cancer. , 2007, International journal of radiation oncology, biology, physics.

[27]  Ho-Jin Shin,et al.  Prognostic value of metabolic tumor volume on PET / CT in primary gastrointestinal diffuse large B cell lymphoma , 2012, Cancer science.

[28]  F. d'Amore,et al.  Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: a report from a joint Italian-Danish study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  A. Levis,et al.  The predictive value of positron emission tomography scanning performed after two courses of standard therapy on treatment outcome in advanced stage Hodgkin's disease. , 2006, Haematologica.

[30]  P. Gobbi,et al.  Image-aided estimate of tumor burden in Hodgkin's disease: evidence of its primary prognostic importance. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Martin Hutchings,et al.  FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. , 2006, Blood.

[32]  B. C. Penney,et al.  Prognostic value of metabolic tumor burden from (18)F-FDG PET in surgical patients with non-small-cell lung cancer. , 2013, Academic radiology.

[33]  J. R. Landis,et al.  The measurement of observer agreement for categorical data. , 1977, Biometrics.

[34]  Shang-Wen Chen,et al.  Use of pretreatment metabolic tumor volumes on PET-CT to predict the survival of patients with squamous cell carcinoma of esophagus treated by curative surgery. , 2012, Anticancer research.

[35]  R L Wahl,et al.  Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. , 1999, Radiographics : a review publication of the Radiological Society of North America, Inc.

[36]  C. Rübe,et al.  Comparison of different methods for delineation of 18F-FDG PET-positive tissue for target volume definition in radiotherapy of patients with non-Small cell lung cancer. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[37]  Sigrid Stroobants,et al.  Revised response criteria for malignant lymphoma. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  N. Nissen,et al.  Tumor burden as the most important prognostic factor in early stage Hodgkin's disease. Relations to other prognostic factors and implications for choice of treatment , 1988, Cancer.

[39]  M. Bøgsted,et al.  Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography-staged treatment-naive patients with Hodgkin lymphoma. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  J. Roh,et al.  Prognostic value of metabolic tumor volume measured by 18F-FDG PET/CT in advanced-stage squamous cell carcinoma of the larynx and hypopharynx. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[41]  D Visvikis,et al.  [Metabolically active volumes automatic delineation methodologies in PET imaging: review and perspectives]. , 2012, Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique.