FDG PET in response evaluation of bulky masses in paediatric Hodgkin’s lymphoma (HL) patients enrolled in the Italian AIEOP-LH2004 trial
We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin’s lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial.
We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors.
Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01).
After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.
KeywordsHodgkin’s lymphoma FDG PET Paediatric Bulky masses Interim evaluation Response assessment
AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) is acknowledged for its support of the current research. AIRC (Associazione Italiana per la Ricerca sul Cancro) is acknowledged for the fellowship support provided to Angelo Castello with the grant no. 18923.
Compliance with ethical standards
All procedures performed in the AIEOP-LH 2004 protocol involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
- 7.Oberlin O. Hodgkin’s disease. In: Voûte PA, Kalifa C, Barrett A, editors. Cancer in children. Clinical management. 4th ed. New York: Oxford University; 1998. p. 137–53.Google Scholar
- 8.Lanzkowski P. Hodgkin’s disease. In: Lanzkowski P, editor. Manual of pediatric hematology and oncology. 3rd ed. San Diego: Academic; 1999. p. 413–43.Google Scholar
- 10.Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children’s Oncology Group Study AHOD0031. J Clin Oncol. 2014;32:3651–8.CrossRefGoogle Scholar
- 11.Furth C, Steffen IG, Amthauer H, Ruf J, Misch D, Schönberger S, et al. Early and late therapy response assessment with [18F] fluorodeoxyglucose positron emission tomography in pediatric Hodgkin’s lymphoma: analysis of a prospective multicenter trial. J Clin Oncol. 2009;27(26):4385–91.CrossRefGoogle Scholar
- 12.Bakhshi S, Bhethanabhotla S, Kumar R, Agarwal K, Sharma P, Thulkar S, et al. Posttreatment PET/CT rather than interim PET/CT using Deauville criteria predicts outcome in pediatric Hodgkin lymphoma: a prospective study comparing PET/CT with conventional imaging. J Nucl Med. 2017;58(4):577–83.CrossRefGoogle Scholar
- 20.Spaepen K, Stroobants S, Dupont P, Van Steenweghen S, Thomas J, Vandenberghe P, et al. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non- Hodgkin’s lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol. 2001;19:414–9.CrossRefGoogle Scholar
- 26.Schwartz CL, Chen L, McCarten K, Wolden S, Constine LS, Hutchison RE, et al. Childhood Hodgkin International Prognostic Score (CHIPS) predicts event-free survival in Hodgkin lymphoma: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2017;64(4):10.1002/pbc.26278.CrossRefGoogle Scholar
- 28.Burnelli R, Rinieri S, Todesco A, Locatelli F, Sala A, BuffardiS, et al. Protocollo AIEOP-LH 2004 per la terapia del linfoma di Hodgkin in età pediatrica: analisi ad interim. XXXV Congresso Nazionale AIEOP, Ancona, 26–28 October 2008. Aricó M, editor. Abstract book, P044. Haematologica 2008;93 Suppl 4:S27.Google Scholar
- 33.Cox DR. Regression models and life tables (with discussion). J R Stat Soc Ser B. 1972;34:187–220.Google Scholar
- 36.Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M, 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. J Clin Oncol. 2007;25:3746–52.CrossRefGoogle Scholar