Skip to main content
Top
Published in: Clinical and Translational Oncology 8/2015

01-08-2015 | Research Article

On the prediction of Hodgkin lymphoma treatment response

Authors: E. J. deAndrés-Galiana, J. L. Fernández-Martínez, O. Luaces, J. J. del Coz, R. Fernández, J. Solano, E. A. Nogués, Y. Zanabilli, J. M. Alonso, A. R. Payer, J. M. Vicente, J. Medina, F. Taboada, M. Vargas, C. Alarcón, M. Morán, A. González-Ordóñez, M. A. Palicio, S. Ortiz, C. Chamorro, S. Gonzalez, A. P. González-Rodríguez

Published in: Clinical and Translational Oncology | Issue 8/2015

Login to get access

Abstract

Purpose

The cure rate in Hodgkin lymphoma is high, but the response along with treatment is still unpredictable and highly variable among patients. Detecting those patients who do not respond to treatment at early stages could bring improvements in their treatment. This research tries to identify the main biological prognostic variables currently gathered at diagnosis and design a simple machine learning methodology to help physicians improve the treatment response assessment.

Methods

We carried out a retrospective analysis of the response to treatment of a cohort of 263 Caucasians who were diagnosed with Hodgkin lymphoma in Asturias (Spain). For that purpose, we used a list of 35 clinical and biological variables that are currently measured at diagnosis before any treatment begins. To establish the list of most discriminatory prognostic variables for treatment response, we designed a machine learning approach based on two different feature selection methods (Fisher’s ratio and maximum percentile distance) and backwards recursive feature elimination using a nearest-neighbor classifier (k-NN). The weights of the k-NN classifier were optimized using different terms of the confusion matrix (true- and false-positive rates) to minimize risk in the decisions.

Results and conclusions

We found that the optimum strategy to predict treatment response in Hodgkin lymphoma consists in solving two different binary classification problems, discriminating first if the patient is in progressive disease; if not, then discerning among complete and partial remission. Serum ferritin turned to be the most discriminatory variable in predicting treatment response, followed by alanine aminotransferase and alkaline phosphatase. The importance of these prognostic variables suggests a close relationship between inflammation, iron overload, liver damage and the extension of the disease.
Appendix
Available only for authorised users
Literature
1.
go back to reference Alvaro-Naranjo T, Lejeune M, Salvado-Usach MT, Bosch-Princep R, Reverter-Branchat G, Jaen-Martinez J, et al. Tumor-infiltrating cells as a prognostic factor in Hodgkin’s lymphoma: a quantitative tissue microarray study in a large retrospective cohort of 267 patients. Leuk Lymphoma. 2005;46(11):1581–91.PubMedCrossRef Alvaro-Naranjo T, Lejeune M, Salvado-Usach MT, Bosch-Princep R, Reverter-Branchat G, Jaen-Martinez J, et al. Tumor-infiltrating cells as a prognostic factor in Hodgkin’s lymphoma: a quantitative tissue microarray study in a large retrospective cohort of 267 patients. Leuk Lymphoma. 2005;46(11):1581–91.PubMedCrossRef
2.
go back to reference Schreck S, Friebel D, Buettner M, Distel L, Grabenbauer G, Young LS, et al. Prognostic impact of tumour-infiltrating th2 and regulatory t cells in classical Hodgkin lymphoma. Hematol Oncol. 2009;27(1):31–9.PubMedCrossRef Schreck S, Friebel D, Buettner M, Distel L, Grabenbauer G, Young LS, et al. Prognostic impact of tumour-infiltrating th2 and regulatory t cells in classical Hodgkin lymphoma. Hematol Oncol. 2009;27(1):31–9.PubMedCrossRef
3.
go back to reference Hasenclever D, Diehl V, Armitage JO, Assouline D, Björkholm M, Brusamolino E, et al. A prognostic score for advanced Hodgkin’s disease. New Eng J Med. 1998;339(21):1506–14.PubMedCrossRef Hasenclever D, Diehl V, Armitage JO, Assouline D, Björkholm M, Brusamolino E, et al. A prognostic score for advanced Hodgkin’s disease. New Eng J Med. 1998;339(21):1506–14.PubMedCrossRef
4.
go back to reference Friedman S, Henry-Amar M, Cosset JM, Carde P, Hayat M, Dupouy N, et al. Evolution of erythrocyte sedimentation rate as predictor of early relapse in posttherapy early-stage Hodgkin’s disease. J Clin Oncol. 1988;6(4):596–602.PubMed Friedman S, Henry-Amar M, Cosset JM, Carde P, Hayat M, Dupouy N, et al. Evolution of erythrocyte sedimentation rate as predictor of early relapse in posttherapy early-stage Hodgkin’s disease. J Clin Oncol. 1988;6(4):596–602.PubMed
5.
go back to reference Mauch P, Larson D, Osteen R, Silver B, Yeap B, Canellos G, et al. Prognostic factors for positive surgical staging in patients with Hodgkin’s disease. J Clin Oncol. 1990;8(2):257–65.PubMed Mauch P, Larson D, Osteen R, Silver B, Yeap B, Canellos G, et al. Prognostic factors for positive surgical staging in patients with Hodgkin’s disease. J Clin Oncol. 1990;8(2):257–65.PubMed
6.
go back to reference Cheson BD. New staging and response criteria for non-Hodgkin lymphoma and Hodgkin lymphoma. Radiol Clin North Am. 2008;46(2):213–23.PubMedCrossRef Cheson BD. New staging and response criteria for non-Hodgkin lymphoma and Hodgkin lymphoma. Radiol Clin North Am. 2008;46(2):213–23.PubMedCrossRef
7.
go back to reference Biggi A, Gallamini A, Chauvie S, Hutchings M, Kostakoglu L, Gregianin M, et al. International validation study for interim pet in abvd-treated, advanced-stage Hodgkin lymphoma: interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013;54(5):683–90.PubMedCrossRef Biggi A, Gallamini A, Chauvie S, Hutchings M, Kostakoglu L, Gregianin M, et al. International validation study for interim pet in abvd-treated, advanced-stage Hodgkin lymphoma: interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013;54(5):683–90.PubMedCrossRef
8.
go back to reference Smolewski P, Robak T, Krykowski E, Blasinska-Morawiec M, Niewiadomska H, Pluzanska A, et al. Prognostic factors in Hodgkin’s disease: multivariate analysis of 327 patients from a single institution. Clin Cancer Res. 2000;6(3):1150–60.PubMed Smolewski P, Robak T, Krykowski E, Blasinska-Morawiec M, Niewiadomska H, Pluzanska A, et al. Prognostic factors in Hodgkin’s disease: multivariate analysis of 327 patients from a single institution. Clin Cancer Res. 2000;6(3):1150–60.PubMed
9.
go back to reference Zander T, Wiedenmann S, Wolf J. Prognostic factors in Hodgkin’s lymphoma. Ann Oncol. 2002;13(Suppl 1):67–74.PubMedCrossRef Zander T, Wiedenmann S, Wolf J. Prognostic factors in Hodgkin’s lymphoma. Ann Oncol. 2002;13(Suppl 1):67–74.PubMedCrossRef
10.
11.
go back to reference Provencio M, Espana P, Millan I, Yebra M, Sanchez AC, de la Torre A, et al. Prognostic factors in Hodgkin’s disease. Leuk Lymphoma. 2004;45(6):1133–9.PubMedCrossRef Provencio M, Espana P, Millan I, Yebra M, Sanchez AC, de la Torre A, et al. Prognostic factors in Hodgkin’s disease. Leuk Lymphoma. 2004;45(6):1133–9.PubMedCrossRef
12.
go back to reference Ong DST, Wang L, Zhu Y, Ho B, Ding JL. The response of ferritin to lps and acute phase of pseudomonas infection. J Endotoxin Res. 2005;11(5):267–80.PubMedCrossRef Ong DST, Wang L, Zhu Y, Ho B, Ding JL. The response of ferritin to lps and acute phase of pseudomonas infection. J Endotoxin Res. 2005;11(5):267–80.PubMedCrossRef
13.
go back to reference Cheson BD. The international harmonization project for response criteria in lymphoma clinical trials. Hematol Oncol Clin North Am. 2007;21(5):841–54.PubMedCrossRef Cheson BD. The international harmonization project for response criteria in lymphoma clinical trials. Hematol Oncol Clin North Am. 2007;21(5):841–54.PubMedCrossRef
14.
go back to reference Saligan L, Fernández-Martínez JL, deAndrés-Galiana EJ, Sonis S. Supervised classification by filter methods and recursive feature elimination predicts risk of radiotherapy-related fatigue in patients with prostate cancer. Cancer Inform. 2014;13(141–152):12. Saligan L, Fernández-Martínez JL, deAndrés-Galiana EJ, Sonis S. Supervised classification by filter methods and recursive feature elimination predicts risk of radiotherapy-related fatigue in patients with prostate cancer. Cancer Inform. 2014;13(141–152):12.
15.
go back to reference Gandhi MK, Lambley E, Burrows J, Dua U, Elliott S, Shaw PJ, et al. Plasma epstein-barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin’s lymphoma. Clin Cancer Res. 2006;12(2):460–4.PubMedCrossRef Gandhi MK, Lambley E, Burrows J, Dua U, Elliott S, Shaw PJ, et al. Plasma epstein-barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin’s lymphoma. Clin Cancer Res. 2006;12(2):460–4.PubMedCrossRef
16.
go back to reference Bezwoda WR, Derman DP, Bothwell TH, Baynes R, Hesdorffer C, MacPhail AP. Serum ferritin and Hodgkin’s disease. Scand J Haematol. 1985;35:505–10.PubMedCrossRef Bezwoda WR, Derman DP, Bothwell TH, Baynes R, Hesdorffer C, MacPhail AP. Serum ferritin and Hodgkin’s disease. Scand J Haematol. 1985;35:505–10.PubMedCrossRef
17.
go back to reference Dörner MH, Abel U, Fritze D, Manke HG, Drings P. Serum ferritin in relation to the course of Hodgkin’s disease. Cancer. 1983;52:2308–12.PubMedCrossRef Dörner MH, Abel U, Fritze D, Manke HG, Drings P. Serum ferritin in relation to the course of Hodgkin’s disease. Cancer. 1983;52:2308–12.PubMedCrossRef
18.
go back to reference Hohaus S, Massini G, Giachelia M, Vannata B, Bozzoli V, Cuccaro A, et al. Anemia in Hodgkin’s lymphoma: the role of interleukin-6 and hepcidin. J Clin Oncol. 2010;28(15):2538–43.PubMedCrossRef Hohaus S, Massini G, Giachelia M, Vannata B, Bozzoli V, Cuccaro A, et al. Anemia in Hodgkin’s lymphoma: the role of interleukin-6 and hepcidin. J Clin Oncol. 2010;28(15):2538–43.PubMedCrossRef
19.
go back to reference Hohaus S, Giachelia M, Cuccaro A, Voso MT, Leone G. Iron in Hodgkin’s lymphoma. Crit Rev Oncog. 2013;18(5):463–9.PubMedCrossRef Hohaus S, Giachelia M, Cuccaro A, Voso MT, Leone G. Iron in Hodgkin’s lymphoma. Crit Rev Oncog. 2013;18(5):463–9.PubMedCrossRef
20.
go back to reference Aulbert E, Steffens O. Serum ferritin–a tumor marker in malignant lym-phomas? Onkologie. 1990;13(2):102–8.PubMedCrossRef Aulbert E, Steffens O. Serum ferritin–a tumor marker in malignant lym-phomas? Onkologie. 1990;13(2):102–8.PubMedCrossRef
21.
go back to reference Yoh KA, Lee HS, Park LC, Lee EM, Shin SH, Park DJ, et al. The prognostic significance of elevated levels of serum ferritin before chemotherapy in patients with non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2014;14(1):43–9.PubMedCrossRef Yoh KA, Lee HS, Park LC, Lee EM, Shin SH, Park DJ, et al. The prognostic significance of elevated levels of serum ferritin before chemotherapy in patients with non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2014;14(1):43–9.PubMedCrossRef
22.
23.
go back to reference Kittivorapart J, Chinthammitr Y. Incidence and risk factors of bone marrow involvement by non-Hodgkin lymphoma. J Med Assoc Thai. 2011;94(Suppl 1):S239–45.PubMed Kittivorapart J, Chinthammitr Y. Incidence and risk factors of bone marrow involvement by non-Hodgkin lymphoma. J Med Assoc Thai. 2011;94(Suppl 1):S239–45.PubMed
24.
go back to reference Jamakovic M, Baljic R. Significance of copper level in serum and routine laboratory parameters in estimation of outspreading of Hodgkin’s lymphoma. Med Arch. 2013;67(3):185–7.PubMedCrossRef Jamakovic M, Baljic R. Significance of copper level in serum and routine laboratory parameters in estimation of outspreading of Hodgkin’s lymphoma. Med Arch. 2013;67(3):185–7.PubMedCrossRef
25.
go back to reference El-Galaly TC, Hutchings M, Mylam KJ, Brown Pde N, Bukh A, Johnsen HE, et al. Impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography staging in newly diagnosed classical Hodgkin lymphoma: fewer cases with stage I disease and more with skeletal involvement. Leuk Lymphoma. 2014;55(10):2349–55.PubMedCrossRef El-Galaly TC, Hutchings M, Mylam KJ, Brown Pde N, Bukh A, Johnsen HE, et al. Impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography staging in newly diagnosed classical Hodgkin lymphoma: fewer cases with stage I disease and more with skeletal involvement. Leuk Lymphoma. 2014;55(10):2349–55.PubMedCrossRef
26.
go back to reference Brensilver HL, Kaplan MM. Significance of elevated liver alkaline phosphatase in serum. Gastroenterology. 1975;68(6):1556–62.PubMed Brensilver HL, Kaplan MM. Significance of elevated liver alkaline phosphatase in serum. Gastroenterology. 1975;68(6):1556–62.PubMed
27.
go back to reference Brinckmeyer LM, Skovsgaard T, Thiede T, Vesterager L, Nissen NI. The liver in Hodgkin’s disease. Clinico-pathological relations. Eur J Cancer Clin Oncol. 1982;18(5):421–8.PubMedCrossRef Brinckmeyer LM, Skovsgaard T, Thiede T, Vesterager L, Nissen NI. The liver in Hodgkin’s disease. Clinico-pathological relations. Eur J Cancer Clin Oncol. 1982;18(5):421–8.PubMedCrossRef
28.
go back to reference Cunha BA. Fever of unknown origin (FUO): diagnostic importance of serum ferritin levels. Scand J Infect Dis. 2007;39(6–7):651–2.PubMedCrossRef Cunha BA. Fever of unknown origin (FUO): diagnostic importance of serum ferritin levels. Scand J Infect Dis. 2007;39(6–7):651–2.PubMedCrossRef
Metadata
Title
On the prediction of Hodgkin lymphoma treatment response
Authors
E. J. deAndrés-Galiana
J. L. Fernández-Martínez
O. Luaces
J. J. del Coz
R. Fernández
J. Solano
E. A. Nogués
Y. Zanabilli
J. M. Alonso
A. R. Payer
J. M. Vicente
J. Medina
F. Taboada
M. Vargas
C. Alarcón
M. Morán
A. González-Ordóñez
M. A. Palicio
S. Ortiz
C. Chamorro
S. Gonzalez
A. P. González-Rodríguez
Publication date
01-08-2015
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 8/2015
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1285-z

Other articles of this Issue 8/2015

Clinical and Translational Oncology 8/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine