Skip to main content
SpringerLink
Log in

Radiation Therapy in Follicular Lymphoma

  • Living reference work entry
  • First Online:
Radiation Oncology

  • 213 Accesses

Abstract

Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphomas and arises from the germinal center B cells with a follicular (nodular) pattern, for which reason it was previously called follicle center lymphoma. Grades 1–3a normally show an indolent behavior, whereas grade 3b shows a more aggressive behavior. Most patients present with painless lymphadenopathy in advanced stages (III–IV).

For the approximately 15–30% of FL with limited stages I–II and low grade, primary radiotherapy remains the gold standard with long-lasting remissions and the potential chance for cure. However, regarding radiation dose, field size, and a combination with a CD20 antibody, different treatment approaches are possible.

Patients with advanced (stage III/IV) disease are not cured with conventional therapies, and therefore different strategies are used, depending on the extent of the disease. Most patients do not require immediate treatment unless they suffer from symptomatic disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Advani R, Rosenberg SA, Horning SJ. Stage I and II follicular non-Hodgkin’s lymphoma: long-term follow-up of no initial therapy. J Clin Oncol. 2004;22(8): 1454–9.

    Article  Google Scholar 

  • Al Khabori M, et al. Autologous stem cell transplantation in follicular lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2012;104(1):18–28.

    Article  Google Scholar 

  • Ardeshna KM, et al. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003;362(9383): 516–22.

    Article  CAS  Google Scholar 

  • Barrington SF, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27): 3048–58.

    Article  Google Scholar 

  • Brice P, et al. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d’Etude des Lymphomes Folliculaires. Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 1997;15(3):1110–7.

    Article  CAS  Google Scholar 

  • Buske C, et al. The follicular lymphoma international prognostic index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome. Blood. 2006;108(5):1504–8.

    Article  CAS  Google Scholar 

  • Czuczman MS, et al. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin’s lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004;22(23):4711–6.

    Article  CAS  Google Scholar 

  • de Jong D. Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors. J Clin Oncol. 2005;23(26):6358–63.

    Article  Google Scholar 

  • Dreyling M, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii83–92.

    Article  Google Scholar 

  • Eich HT, et al. Long-term outcome and prognostic factors in early-stage nodal low-grade non-Hodgkin’s lymphomas treated with radiation therapy. Strahlenther Onkol. 2009;185(5):288–95. https://doi.org/10.1007/s00066-009-1937-4.

    Article  PubMed  Google Scholar 

  • Engelhard M, et al. Follicular lymphoma: curability by radiotherapy in limited stage nodal disease ? updated results of a randomized trial. Ann Oncol. 2011;22(Suppl 4):iv90–1.

    Google Scholar 

  • Federico M, et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009;27(27):4555–62.

    Article  Google Scholar 

  • Flinn IW, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014;123(19):2944–52.

    Article  CAS  Google Scholar 

  • Freedman AS. Biology and management of histologic transformation of indolent lymphoma. Hematology Am Soc Hematol Educ Program. 2005;2005(1):314–20.

    Article  Google Scholar 

  • Ganem G, et al. Potential role for low dose limited-field radiation therapy (2 × 2 grays) in advanced low-grade non-Hodgkin’s lymphomas. Hematol Oncol. 1994;12(1):1–8.

    Article  CAS  Google Scholar 

  • Ganem G, et al. Localized low-dose radiotherapy for follicular lymphoma: history, clinical results, mechanisms of action, and future outlooks. Int J Radiat Oncol Biol Phys. 2010;78(4):975–82.

    Article  Google Scholar 

  • Girinsky T, et al. A high and sustained response rate in refractory or relapsing low-grade lymphoma masses after low-dose radiation: analysis of predictive parameters of response to treatment. Int J Radiat Oncol Biol Phys. 2001;51(1):148–55.

    Article  CAS  Google Scholar 

  • Haas RL, et al. High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas. J Clin Oncol. 2003;21(13):2474–80.

    Article  CAS  Google Scholar 

  • Haas RL, et al. In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients. Int J Radiat Oncol Biol Phys. 2004;59(3):782–7.

    Article  Google Scholar 

  • Herfarth K, Konig L. Radiation therapy (4 Gy vs. 24 Gy) in patients with indolent non-Hodgkins lymphoma: results of the FORT Study. Strahlenther Onkol. 2014;190(11):1084–5.

    Article  Google Scholar 

  • Herfarth K, et al. PD-0518: early stage nodal follicular lymphoma using IF radiotherapy and rituximab: results of the MIR trial of the GLSG and ARO. Radiother Oncol. 2014;111:S204.

    Article  Google Scholar 

  • Herold M, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007;25(15): 1986–92.

    Article  CAS  Google Scholar 

  • Hiddemann W, Cheson BD. How we manage follicular lymphoma. Leukemia. 2014;28(7):1388–95.

    Article  CAS  Google Scholar 

  • Hiddemann W, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106(12):3725–32.

    Article  CAS  Google Scholar 

  • Hoskin PJ, et al. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. Lancet Oncol. 2014;15(4):457–63. https://doi.org/10.1016/S1470-2045(14)70036-1. S1470-2045(14)70036-1 [pii].

    Article  PubMed  Google Scholar 

  • Illidge T, et al. Modern radiation therapy for nodal non-Hodgkin lymphoma-target definition and dose guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2014;89(1):49–58.

    Article  Google Scholar 

  • Kahl BS, et al. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: eastern cooperative oncology group protocol e4402. J Clin Oncol. 2014;32(28):3096–102.

    Article  CAS  Google Scholar 

  • Kelsey SM, et al. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19–25.

    Article  CAS  Google Scholar 

  • Knoops L, et al. In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma. Blood. 2007;110(4):1116–22.

    Article  CAS  Google Scholar 

  • Konig L, et al. Response rates and recurrence patterns after low-dose radiotherapy with 4Gy in patients with low-grade lymphomas. Strahlenther Onkol. 2018;194: 454. https://doi.org/10.1007/s00066-018-1277-3.

    Article  PubMed  Google Scholar 

  • Landberg TG, et al. CVP-remission-maintenance in stage I or II non-Hodgkin’s lymphomas: preliminary results of a randomized study. Cancer. 1979;44(3):831–8.

    Article  CAS  Google Scholar 

  • Lawrence TS, et al. Retrospective analysis of stage I and II indolent lymphomas at the National Cancer Institute. Int J Radiat Oncol Biol Phys. 1988;14(3):417–24.

    Article  CAS  Google Scholar 

  • Lowry L, et al. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol. 2011;100(1):86–92.

    Article  Google Scholar 

  • Mac Manus MP, Hoppe RT. Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. J Clin Oncol. 1996;14(4): 1282–90. https://doi.org/10.1200/jco.1996.14.4.1282.

    Article  CAS  PubMed  Google Scholar 

  • Maloney DG, et al. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin’s lymphoma. J Clin Oncol. 1997;15(10):3266–74.

    Article  CAS  Google Scholar 

  • Marcus R, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008;26(28):4579–86.

    Article  CAS  Google Scholar 

  • Marcus R, et al. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017;377(14): 1331–44.

    Article  CAS  Google Scholar 

  • Martin AR, et al. Prognostic value of cellular proliferation and histologic grade in follicular lymphoma. Blood. 1995;85(12):3671–8.

    CAS  PubMed  Google Scholar 

  • McLaughlin P, et al. Stage I–II low-grade lymphomas: a prospective trial of combination chemotherapy and radiotherapy. Ann Oncol. 1991;2(Suppl 2):137–40.

    Article  Google Scholar 

  • McNamara C, et al. Guidelines on the investigation and management of follicular lymphoma. Br J Haematol. 2012;156(4):446–67.

    Article  Google Scholar 

  • Monfardini S, et al. Improved five year survival after combined radiotherapy-chemotherapy for stage I–II non-Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys. 1980;6(2):125–34.

    Article  CAS  Google Scholar 

  • Morton LM, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood. 2006;107(1):265–76.

    Article  CAS  Google Scholar 

  • Neumann H, et al. Follicle centre lymphoma: treatment results for stage I and II. Strahlenther Onkol. 2003;179(12):840–6.

    Article  Google Scholar 

  • Nooka AK, et al. Examination of the follicular lymphoma international prognostic index (FLIPI) in the National LymphoCare study (NLCS): a prospective US patient cohort treated predominantly in community practices. Ann Oncol. 2013;24(2):441–8.

    Article  CAS  Google Scholar 

  • Ott OJ, et al. Radiotherapy for stage I–III nodal low-grade non-Hodgkin’s lymphoma. Strahlenther Onkol. 2003;179(10):694–701. https://doi.org/10.1007/s00066-003-1062-8.

    Article  PubMed  Google Scholar 

  • Rowley JD. Chromosome studies in the non-Hodgkin’s lymphomas: the role of the 14;18 translocation. J Clin Oncol. 1988;6(5):919–25.

    Article  CAS  Google Scholar 

  • Salles G, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008;112(13):4824–31.

    Article  CAS  Google Scholar 

  • Salles G, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377(9759):42–51.

    Article  CAS  Google Scholar 

  • Sant M, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116(19): 3724–34.

    Article  CAS  Google Scholar 

  • Sawyer EJ, Timothy AR. Low dose palliative radiotherapy in low grade non-Hodgkin’s lymphoma. Radiother Oncol. 1997;42(1):49–51.

    Article  CAS  Google Scholar 

  • Seymour JF, et al. Long-term follow-up of a prospective study of combined modality therapy for stage I–II indolent non-Hodgkin’s lymphoma. J Clin Oncol. 2003;21(11):2115–22.

    Article  CAS  Google Scholar 

  • Skvortsova I, et al. Rituximab enhances radiation-triggered apoptosis in non-Hodgkin’s lymphoma cells via caspase-dependent and – independent mechanisms. J Radiat Res. 2006;47(2):183–96.

    Article  CAS  Google Scholar 

  • Solal-Celigny P, et al. Follicular lymphoma international prognostic index. Blood. 2004;104(5):1258–65.

    Article  CAS  Google Scholar 

  • Soubeyran P, et al. Localized follicular lymphomas: prognosis and survival of stages I and II in a retrospective series of 103 patients. Radiother Oncol. 1988;13(2): 91–8.

    Article  CAS  Google Scholar 

  • Stuschke M, et al. Extended field and total central lymphatic radiotherapy in the treatment of early stage lymph node centroblastic-centrocytic lymphomas: results of a prospective multicenter study. Study Group NHL-fruhe Stadien. Cancer. 1997;80(12): 2273–84.

    Article  CAS  Google Scholar 

  • Swerdlow SH, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.

    Article  CAS  Google Scholar 

  • Tsukamoto N, et al. The usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and a comparison of (18)F-FDG-pet with (67)gallium scintigraphy in the evaluation of lymphoma: relation to histologic subtypes based on the World Health Organization classification. Cancer. 2007;110(3):652–9.

    Article  Google Scholar 

  • van de Schans SA, et al. Validation, revision and extension of the follicular lymphoma international prognostic index (FLIPI) in a population-based setting. Ann Oncol. 2009;20(10):1697–702.

    Article  Google Scholar 

  • Wilder RB, et al. Long-term results with radiotherapy for stage I–II follicular lymphomas. Int J Radiat Oncol Biol Phys. 2001;51(5):1219–27.

    Article  CAS  Google Scholar 

  • Yahalom J, et al. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study. Cancer. 1993;71(7):2342–50.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Laila König & Klaus Herfarth

Authors
  1. Laila König
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Herfarth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laila König .

Editor information

Editors and Affiliations

  1. Department of Radiation Oncology, University Hospital Mannheim, Mannheim, Germany

    Frederik Wenz

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

König, L., Herfarth, K. (2018). Radiation Therapy in Follicular Lymphoma. In: Wenz, F. (eds) Radiation Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-52619-5_21-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-52619-5_21-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-52619-5

  • Online ISBN: 978-3-319-52619-5

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation