Treatment outcomes and relative dose intensity of chemotherapy in patients with advanced Hodgkin lymphoma

Rožman,Samo; Rožman,Samo; Novaković,Barbara Jezeršek; Novaković,Barbara Jezeršek; Gorenjec,Nina Ružić; Gorenjec,Nina Ružić; Novaković,Srdjan; Novaković,Srdjan

doi:10.3892/ol.2022.13440

Treatment outcomes and relative dose intensity of chemotherapy in patients with advanced Hodgkin lymphoma

Authors:
- Samo Rožman
- Barbara Jezeršek Novaković
- Nina Ružić Gorenjec
- Srdjan Novaković
View Affiliations

Affiliations: Pharmacy Department, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia, The Department of Lymphoma Treatment, Division of Medical Oncology, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia, Institute for Biostatistics and Medical Informatics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia, Department of Molecular Diagnostics, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia
Published online on: July 19, 2022 https://doi.org/10.3892/ol.2022.13440
Article Number: 320
Copyright: © Rožman et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of patients with advanced stage Hodgkin lymphoma (HL) receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimens (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 patients with HL treated between 2004 and 2013 were enrolled for evaluation. The association of variables with overall survival (OS) and progression‑free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, and the majority were male and had stage IV disease. A total of 54 patients received ABVD and 60 received BEACOPP chemotherapy with 24 and four deaths, respectively. Patients in the BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) and better performance status in comparison with the ABVD group, making the comparison of groups not possible. In the ABVD group, RDI was not significantly associated with OS (P=0.590) or PFS (P=0.354) in a multivariate model where age was controlled. The low number of events prevented this analysis in the BEACOPP group. The age of patients was strongly associated with both OS and PFS; all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI, performance status) lost their effect in multivariate analyses where age was controlled. Based on these observations, it was concluded that RDI was not associated with OS or PFS after age is controlled, neither in all patients combined nor in the ABVD group.

View Figures

View References

1	Shanbhag S and Ambinder RF: Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin. 68:116–132. 2018. View Article : Google Scholar : PubMed/NCBI
2	Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, et al: SEER cancer statistics review, 1975–2017, https://seer.cancer.gov/csr/1975_2017/simplehttps://seer.cancer.gov/csr/1975_2017/, based on November 2019 SEER data submission, posted to the SEER web site. National Cancer Institute; Bethesda, MD: 2020
3	Evens AM, Antillón M, Aschebrook-Kilfoy B and Chiu BC: Racial disparities in Hodgkin's lymphoma: A comprehensive population-based analysis. Ann Oncol. 23:2128–2137. 2012. View Article : Google Scholar : PubMed/NCBI
4	Zadnik V, Primic Zakelj M, Lokar K, Jarm K, Ivanus U and Zagar T: Cancer burden in Slovenia with the time trends analysis. Radiol Oncol. 51:47–55. 2017. View Article : Google Scholar : PubMed/NCBI
5	Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group and Eastern Cooperative Oncology Group, ; et al: Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol. 32:3059–3068. 2014. View Article : Google Scholar : PubMed/NCBI
6	Eichenauer DA, Aleman BMP, André M, Federico M, Hutchings M, Illidge T, Engert A and Ladeto M; ESMO Guidelines Committee, : Hodgkin lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 29 (Suppl 4):iv19–iv29. 2018. View Article : Google Scholar
7	Engert A, Plütschow A, Eich HT, Lohri A, Dörken B, Borchmann P, Berger B, Greil R, Willborn KC, Wilhelm M, et al: Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 363:640–652. 2010. View Article : Google Scholar : PubMed/NCBI
8	Specht L, Yahalom J, Illidge T, Berthelsen AK, Constine LS, Eich HT, Girinsky T, Hoppe RT, Mauch P, Mikhaeel NG, et al: Modern radiation therapy for Hodgkin lymphoma: Field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys. 89:854–862. 2014. View Article : Google Scholar : PubMed/NCBI
9	Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, et al: Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 357:1916–1927. 2007. View Article : Google Scholar : PubMed/NCBI
10	Canellos GP, Niedzwiecki D and Johnson JL: Long-term follow-up of survival in Hodgkin's lymphoma. N Engl J Med. 361:2390–2391. 2009. View Article : Google Scholar : PubMed/NCBI
11	Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, Zijlstra J, Král Z, Fuchs M, Hallek M, et al: Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): A randomised, open-label, phase 3 non-inferiority trial. Lancet. 379:1791–1799. 2012. View Article : Google Scholar : PubMed/NCBI
12	Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, Ho A, Dörken B, Rank A, Grosu AL, et al: Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: Final analysis of the German Hodgkin study group HD11 trial. J Clin Oncol. 28:4199–4206. 2010. View Article : Google Scholar : PubMed/NCBI
13	Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A and Peterson BA: Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 327:1478–1484. 1992. View Article : Google Scholar : PubMed/NCBI
14	Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés A, Picardi M, et al: Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med. 378:331–344. 2018. View Article : Google Scholar : PubMed/NCBI
15	Skoetz N, Will A, Monsef I, Brillant C, Engert A and von Tresckow B: Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev. 5:CD0079412017.PubMed/NCBI
16	Hryniuk WM and Goodyear M: The calculation of received dose intensity. J Clin Oncol. 8:1935–1937. 1990. View Article : Google Scholar : PubMed/NCBI
17	Wildiers H and Reiser M: Relative dose intensity of chemotherapy and its impact on outcomes in patients with early breast cancer or aggressive lymphoma. Crit Rev Oncol Hematol. 77:221–240. 2011. View Article : Google Scholar : PubMed/NCBI
18	Charlson ME, Pompei P, Ales KL and MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 40:373–383. 1987. View Article : Google Scholar : PubMed/NCBI
19	Kaplan EL and Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc. 53:457–481. 1958. View Article : Google Scholar
20	Cox DR: Regression models and life tables. J R Stat Soc Ser B (Methodological). 34:187–220. 1972.
21	R Core Team R, . A language and environment for statistical computing. R Foundation for Statistical Computing. (Vienna, Austria). 2021.Available from. https://www.R-project.org/
22	Borchmann P, Goergen H, Kobe C, Lohri A, Greil R, Eichenauer DA, Zijlstra JM, Markova J, Meissner J, Feuring-Buske M, et al: PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): Final results of an open-label, international, randomised phase 3 trial by the German Hodgkin study group. Lancet. 390:2790–2802. 2017. View Article : Google Scholar : PubMed/NCBI
23	Dann EJ, Bar-Shalom R, Tamir A, Haim N, Ben-Shachar M, Avivi I, Zuckerman T, Kirschbaum M, Goor O, Libster D, et al: Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high-risk Hodgkin lymphoma with no impairment of outcome. Blood. 109:905–909. 2007. View Article : Google Scholar : PubMed/NCBI
24	Gregory SA and Trümper L: Chemotherapy dose intensity in non-Hodgkin's lymphoma: Is dose intensity an emerging paradigm for better outcomes? Ann Oncol. 16:1413–1424. 2005. View Article : Google Scholar : PubMed/NCBI
25	Yamaguchi H, Hirakawa T and Inokuchi K: Importance of relative dose intensity in chemotherapy for diffuse large B-cell lymphoma. J Clin Exp Hematop. 51:1–5. 2011. View Article : Google Scholar : PubMed/NCBI
26	Gutiérrez A, Bento L, Bautista-Gili AM, Garcia F, Martinez-Serra J, Sanchez B, Martorell C, Gines J, Garcia L, Gimeno E, et al: Differential impact of relative dose-intensity reductions in diffuse large B-cell lymphoma treated with R-CHOP21 or R-CHOP14. PLoS One. 10:e01239782015. View Article : Google Scholar : PubMed/NCBI
27	Owadally WS, Sydes MR, Radford JA, Hancock BW, Cullen MH, Stenning SP and Johnson PW: Initial dose intensity has limited impact on the outcome of ABVD chemotherapy for advanced Hodgkin lymphoma (HL): Data from UKLG LY09 (ISRCTN97144519). Ann Oncol. 21:568–573. 2010. View Article : Google Scholar : PubMed/NCBI
28	Raida L, Papajik T, Rusinakova Z, Prochazka V, Faber E, Cahova D, Tucek P and Indrak K: Reduced relative dose intensity of primary chemotherapy does not influence prognosis of patients with Hodgkin lymphoma. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 158:428–432. 2014. View Article : Google Scholar : PubMed/NCBI
29	Landgren O, Algernon C, Axdorph U, Nilsson B, Wedelin C, Porwit-MacDonald A, Grimfors G and Björkholm M: Hodgkin's lymphoma in the elderly with special reference to type and intensity of chemotherapy in relation to prognosis. Haematologica. 88:438–444. 2003.PubMed/NCBI