Skip to main content

Advertisement

SpringerLink
Log in

Radiotherapy of extranodal low-grade follicular and marginal zone lymphomas: long-term follow-up of 159 patients

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Objective

To evaluate clinical, histopathologic, and radiation (RT) dose parameters in patients with extranodal low-grade (ENLG) non-Hodgkin lymphoma (NHL) and their possible impact on local control (LC) and survival.

Materials and methods

The medical records of 159 patients with 181 histologically confirmed ENLG-NHL lesions treated at our institution were reviewed retrospectively.

Results

The predominant histological subtype (73%) was marginal zone lymphoma (MZL). Common lesion sites were the gastrointestinal tract (GIT; 33%), skin (26%), and orbit (21%). The majority of patients (88%) presented with stage I/II disease. Thirty-three (20%) lesions were treated with reduced-dose RT (≤30.6 Gy) and 148 lesions (80%) with conventional-dose RT (>30.6 Gy), with an overall median dose of 39.6 Gy (range 4–63). The median follow-up period was 72 months. The 10-year local control (LC), Progression-free survival (PFS), and overall survival (OS) rates were 96, 65, and 82%, respectively. Higher overall response rate (ORR; 98% vs. 94%, p = 0.001) and complete response rate (CRR; 95% vs. 73%, p = 0.001) were observed in patients treated with conventional-dose regimens than in those treated with reduced-dose regimens. Ten-year PFS (p = 0.90) and OS (p = 0.40) was similar between the two dose groups. RT was well tolerated in both dose groups, with no grade 4/5 toxicities. In the multivariate analysis, RT dose and timing (upfront or salvage) were related to LC, whereas age, histology, and complete response (CR) to RT were associated with PFS. Patient age and radiation field size impacted OS.

Conclusion

RT is an effective and curative local treatment for early-stage FL and MZL at conventional and reduced radiation doses. Conventional-doses seems to be associated with local response improvement, without significant differences in PFS rates. Age, histology, and response to RT may influence the PFS.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Yahalom J, Illidge T, Specht L et al (2015) Modern radiation therapy for extranodal lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys 92(1):11–31. https://doi.org/10.1016/j.ijrobp.2015.01.009

    Article  PubMed  Google Scholar 

  2. Casulo C, Barr PM (2019) How I treat early-relapsing follicular lymphoma. Blood 133(14):1540–1547. https://doi.org/10.1182/blood-2018-08-822148

    Article  CAS  PubMed  Google Scholar 

  3. Ricardi U, Filippi AR, Piva C et al (2017) Extranodal marginal zone lymphoma. In: Dabaja BS, Ng AK (eds) Radiation therapy in hematologic malignancies, vol 24. Springer, Cham, pp 55–71

    Chapter  Google Scholar 

  4. Khalil MO, Morton LM, Devesa SS et al (2014) Incidence of marginal zone lymphoma in the United States, 2001–2009 with a focus on primary anatomic site. Br J Haematol 165(1):67–77. https://doi.org/10.1111/bjh.12730

    Article  PubMed  PubMed Central  Google Scholar 

  5. Goda JS, Gospodarowicz M, Pintilie M et al (2010) Long-term outcome in localized extranodal mucosa-associated lymphoid tissue lymphomas treated with radiotherapy. Cancer 116(16):3815–3824. https://doi.org/10.1002/cncr.25226

    Article  PubMed  Google Scholar 

  6. Desai A, Joag MG, Lekakis L et al (2017) Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study. Blood 129(3):324–332. https://doi.org/10.1182/blood-2016-05-714584

    Article  CAS  PubMed  Google Scholar 

  7. Lee G‑I, Oh D, Kim WS et al (2018) Low-dose radiation therapy for primary conjunctival marginal zone B‑cell lymphoma. Cancer Res Treat 50(2):575–581. https://doi.org/10.4143/crt.2017.182

    Article  PubMed  Google Scholar 

  8. Hoppe B (2017) Follicular Lymphoma: treatment for early-stage, grades 1 and 2, and advanced-stage disease. In: Dabaja BS, Ng AK (eds) Radiation therapy in hematologic malignancies, vol 64. Springer, Cham, pp 45–53

    Chapter  Google Scholar 

  9. Neelis KJ, Schimmel EC, Vermeer MH et al (2009) Low-dose palliative radiotherapy for cutaneous B‑ and T‑cell lymphomas. Int J Radiat Oncol Biol Phys 74(1):154–158. https://doi.org/10.1016/j.ijrobp.2008.06.1918

    Article  PubMed  Google Scholar 

  10. Akhtari M, Reddy JP, Pinnix CC et al (2016) Primary cutaneous B‑cell lymphoma (non-leg type) has excellent outcomes even after very low dose radiation as single-modality therapy. Leuk Lymphoma 57(1):34–38. https://doi.org/10.3109/10428194.2015.1040012

    Article  CAS  PubMed  Google Scholar 

  11. Fasola CE, Jones JC, Huang DD et al (2013) Low-dose radiation therapy (2 Gy × 2) in the treatment of orbital lymphoma. Int J Radiat Oncol Biol Phys 86(5):930–935. https://doi.org/10.1016/j.ijrobp.2013.04.035

    Article  PubMed  Google Scholar 

  12. Johannsson J, Specht L, Mejer J et al (2002) Phase II study of palliative low-dose local radiotherapy in disseminated indolent non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Int J Radiat Oncol Biol Phys 54(5):1466–1470

    Article  Google Scholar 

  13. Goyal A, Carter JB, Pashtan I et al (2018) Very low-dose versus standard dose radiation therapy for indolent primary cutaneous B‑cell lymphomas: a retrospective study. J Am Acad Dermatol 78(2):408–410. https://doi.org/10.1016/j.jaad.2017.07.053

    Article  PubMed  PubMed Central  Google Scholar 

  14. Brierley J, Gospodarowicz MK, Wittekind C (eds) (2017) TNM classification of malignant tumours, 8th edn. John Wiley & Sons Inc, Chichester, West Sussex, UK, Hoboken, NJ

    Google Scholar 

  15. Eich HT, Elsayad K (2017) Radiation therapy in peripheral T‑cell and cutaneous lymphomas. In: Wenz F (ed) Radiation oncology, vol 57. Springer, Cham, pp 1–14

    Google Scholar 

  16. Lowry L, Smith P, Qian W et al (2011) Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol 100(1):86–92. https://doi.org/10.1016/j.radonc.2011.05.013

    Article  PubMed  Google Scholar 

  17. Hoskin PJ, Kirkwood AA, Popova B et al (2014) 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. Lancet Oncol 15(4):457–463. https://doi.org/10.1016/S1470-2045(14)70036-1

    Article  PubMed  Google Scholar 

  18. Teckie S, Qi S, Lovie S et al (2015) Long-term outcomes and patterns of relapse of early-stage extranodal marginal zone lymphoma treated with radiation therapy with curative intent. Int J Radiat Oncol Biol Phys 92(1):130–137. https://doi.org/10.1016/j.ijrobp.2015.01.040

    Article  PubMed  Google Scholar 

  19. König L, Hörner-Rieber J, Bernhardt D et al (2018) Response rates and recurrence patterns after low-dose radiotherapy with 4 Gy in patients with low-grade lymphomas. Strahlenther Onkol 194(5):454–461. https://doi.org/10.1007/s00066-018-1277-3

    Article  PubMed  Google Scholar 

  20. Illidge T, Specht L, Yahalom J et al (2014) 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 89(1):49–58. https://doi.org/10.1016/j.ijrobp.2014.01.006

    Article  PubMed  Google Scholar 

  21. Reinartz G, Pyra RP, Lenz G et al (2019) Favorable radiation field decrease in gastric marginal zone lymphoma: Experience of the German Study Group on Gastrointestinal Lymphoma (DSGL). Strahlenther Onkol. https://doi.org/10.1007/s00066-019-01446-5

    Article  PubMed  Google Scholar 

  22. Koch P, Probst A, Berdel WE et al (2005) Treatment results in localized primary gastric lymphoma: data of patients registered within the German multicenter study (GIT NHL 02/96). J Clin Oncol 23(28):7050–7059. https://doi.org/10.1200/JCO.2005.04.031

    Article  PubMed  Google Scholar 

  23. Willich NA, Reinartz G, Horst EJ et al (2000) Operative and conservative management of primary gastric lymphoma: interim results of a German multicenter study. Int J Radiat Oncol Biol Phys 46(4):895–901

    Article  CAS  Google Scholar 

  24. Wirth A, Gospodarowicz M, Aleman BMP et al (2013) Long-term outcome for gastric marginal zone lymphoma treated with radiotherapy: a retrospective, multi-centre, International Extranodal Lymphoma Study Group study. Ann Oncol 24(5):1344–1351. https://doi.org/10.1093/annonc/mds623

    Article  CAS  PubMed  Google Scholar 

  25. Kim S‑W, Lim DH, Ahn YC et al (2013) Clinical outcomes of radiation therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma. WJG 19(36):6062–6068. https://doi.org/10.3748/wjg.v19.i36.6062

    Article  PubMed  Google Scholar 

  26. Herfarth K, Borchmann P, Schnaidt S et al (2018) Rituximab with involved field irradiation for early-stage nodal follicular lymphoma. HemaSphere 2(6):e160. https://doi.org/10.1097/HS9.0000000000000160

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rummel MJ, Niederle N, Maschmeyer G et al (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381(9873):1203–1210. https://doi.org/10.1016/S0140-6736(12)61763-2

    Article  CAS  Google Scholar 

  28. Hill BT, Nastoupil L, Winter AM et al (2019) Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma. Br J Haematol 184(4):524–535. https://doi.org/10.1111/bjh.15720

    Article  CAS  PubMed  Google Scholar 

  29. Morschhauser F, Fowler NH, Feugier P et al (2018) Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med 379(10):934–947. https://doi.org/10.1056/NEJMoa1805104

    Article  CAS  PubMed  Google Scholar 

  30. Brady JL, Binkley MS, Hajj C et al (2019) Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG. Blood 133(3):237–245. https://doi.org/10.1182/blood-2018-04-843540

    Article  CAS  PubMed  Google Scholar 

  31. Morschhauser F, Flinn IW, Advani R et al (2019) Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol 6(5):e254–e265. https://doi.org/10.1016/S2352-3026(19)30026-2

    Article  PubMed  Google Scholar 

  32. Neelapu SS, Locke FL, Bartlett NL et al (2017) Axicabtagene ciloleucel CAR T‑cell therapy in refractory large B‑cell lymphoma. N Engl J Med 377(26):2531–2544. https://doi.org/10.1056/NEJMoa1707447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Qi S, Huang MY, Yang Y et al (2018) Uptake of 18Ffluorodeoxyglucose in initial positron-emission tomography predicts survival in MALT lymphoma. Blood Adv 2(6):649–655. https://doi.org/10.1182/bloodadvances.2017013698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pugh TJ, Ballonoff A, Newman F et al (2010) Improved survival in patients with early stage low-grade follicular lymphoma treated with radiation a surveillance, epidemiology, and end results database analysis. Cancer 116(16):3843–3851. https://doi.org/10.1002/cncr.25149

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Radiation Oncology Department, University Hospital Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Muenster, Germany

    Khaled Elsayad MD,  Gabriele Reinartz MD,  Michael Oertel MD,  Stephan Rehn MD, Jens Eismann,  Sergiu Scobioala MD,  Normann Willich PhD &  Hans Theodor Eich PhD

  2. Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Muenster, Muenster, Germany

    Hendrik Berssenbrügge MD

  3. Department of Ophthalmology, University Hospital Muenster, Muenster, Germany

    Nicole Eter PhD

  4. Department of Dermatology, University Hospital Muenster, Muenster, Germany

    Carsten Weishaupt MD

  5. Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Muenster, Germany

    Hartmut H. Schmidt PhD

  6. Department of Medicine A, University Hospital Muenster, Muenster, Germany

    Birte Friedrichs MD &  Georg Lenz PhD

  7. Gerhard-Domagk-Institute of Pathology, University Hospital Muenster, Muenster, Germany

    Inga Grünewald PhD,  Wolfgang Hartmann PhD &  Eva Wardelmann PhD

Authors
  1. Khaled Elsayad MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriele Reinartz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Oertel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephan Rehn MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jens Eismann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sergiu Scobioala MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hendrik Berssenbrügge MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nicole Eter PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carsten Weishaupt MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hartmut H. Schmidt PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Birte Friedrichs MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Inga Grünewald PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Wolfgang Hartmann PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Georg Lenz PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Eva Wardelmann PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Normann Willich PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hans Theodor Eich PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khaled Elsayad MD.

Ethics declarations

Conflict of interest

K. Elsayad, G. Reinartz, M. Oertel, S. Rehn, J. Eismann, S. Scobioala, H. Berssenbrügge, N. Eter, C. Weishaupt, H.H. Schmidt, B. Friedrichs, I. Grünewald, W. Hartmann, G. Lenz, E. Wardelmann, N. Willich, and H.T. Eich declare that they have no competing interests.

Additional information

KE and GR contributed equally.

This study was presented at the Annual Meeting of the German Society for Radiation Oncology, Muenster, Germany, June 13–16, 2019.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elsayad, K., Reinartz, G., Oertel, M. et al. Radiotherapy of extranodal low-grade follicular and marginal zone lymphomas: long-term follow-up of 159 patients. Strahlenther Onkol 196, 117–125 (2020). https://doi.org/10.1007/s00066-019-01538-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-019-01538-2

Keywords

Search

Navigation