nach oben

Erschienen in:

26.07.2017 | Original Article

Patterns of failure of diffuse large B‑cell lymphoma patients after involved-site radiotherapy

verfasst von: Eva Holzhäuser, M.D., Maximilian Berlin, Daniel Wollschläger, Thomas Bezold, Arnulf Mayer, Georg Heß, Heinz Schmidberger

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 12/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Radiotherapy (RT) in combination with chemoimmunotherapy is highly efficient in the treatment of diffuse large B‑cell lymphoma (DLBCL). This retrospective analysis evaluated the efficacy of the treatment volume and the dose concept of involved-site RT (ISRT).

Patients and methods

We identified 60 histologically confirmed stage I–IV DLBCL patients treated with multimodal cytotoxic chemoimmunotherapy and followed by consolidative ISRT from 2005–2015. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method. Univariate analyses were performed by log-rank test and Mann–Whitney U‑test.

Results

After initial chemoimmunotherapy (mostly R‑CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), 19 (36%) patients achieved complete response (CR), 34 (64%) partial response (PR) or less. Excluded were 7 (12%) patients with progressive disease after chemoimmunotherapy. All patients underwent ISRT with a dose of 40 Gy. After a median follow-up of 44 months, 79% of the patients remained disease free, while 21% presented with failure, progressive systemic disease, or death. All patients who achieved CR after chemoimmunotherapy remained in CR. Of the patients achieving PR after chemotherapy only 2 failed at the initial site within the ISRT volume. No marginal relapse was observed. Ann Arbor clinical stage I/II showed significantly improved PFS compared to stage III/IV (93% vs 65%; p ≤ 0.021). International Prognostic Index (IPI) score of 0 or 1 compared to 2–5 has been associated with significantly increased PFS (100% vs 70%; p ≤ 0.031). Postchemoimmunotherapy status of CR compared to PR was associated with significantly increased PFS (100% vs 68%; p ≤ 0.004) and OS (100% vs 82%; p ≤ 0.026). Only 3 of 53 patients developed grade II late side effects, whereas grade III or IV side effects have not been observed.

Conclusion

These data suggest that a reduction of the RT treatment volume from involved-field (IF) to involved-site (IS) is sufficient because no marginal failures occurred. The concept of IS will likely reduce the risk for late sequelae of RT.

Bush RS, Gospodarowicz M, Sturgeon J, Alison R (1977) Radiation therapy of localized non-Hodgkin’s lymphoma. Cancer Treat Rep 61(6):1129–1136PubMed

Kaplan HS, Rosenberg SA (1966) The treatment of Hodgkin’s disease. Med Clin North Am 50(6):1591–1610CrossRefPubMed

Lohr F, Georg D, Cozzi L et al (2014) Novel radiotherapy techniques for involved-field and involved-node treatment of mediastinal Hodgkin lymphoma: When should they be considered and which questions remain open? Strahlenther Onkol 190(10):864–866. doi:10.1007/s00066-014-0719-9 (868–871)CrossRefPubMed

Kriz J, Spickermann M, Lehrich P et al (2015) Breath-hold technique in conventional APPA or intensity-modulated radiotherapy for Hodgkin’s lymphoma: comparison of ILROG IS-RT and the GHSG IF-RT. Strahlenther Onkol 191(9):717–725. doi:10.1007/s00066-015-0839-x CrossRefPubMed

Girinsky T, van der Maazen R, Specht L et al (2006) Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol 79(3):270–277. doi:10.1016/j.radonc.2006.05.015 CrossRefPubMed

Girinsky T, Ghalibafian M, Bonniaud G et al (2007) Is FDG-PET scan in patients with early stage Hodgkin lymphoma of any value in the implementation of the involved-node radiotherapy concept and dose painting? Radiother Oncol 85(2):178–186. doi:10.1016/j.radonc.2007.07.003 CrossRefPubMed

Girinsky T, Ghalibafian M (2007) Radiotherapy of hodgkin lymphoma: indications, new fields, and techniques. Semin Radiat Oncol 17(3):206–222. doi:10.1016/j.semradonc.2007.02.007 CrossRefPubMed

Girinsky T, Specht L, Ghalibafian M et al (2008) The conundrum of Hodgkin lymphoma nodes: to be or not to be included in the involved node radiation fields. The EORTC-GELA lymphoma group guidelines. Radiother Oncol 88(2):202–210. doi:10.1016/j.radonc.2008.05.012 CrossRefPubMed

Girinsky T, Aupérin A, Ribrag V et al (2014) Role of FDG-PET in the implementation of involved-node radiation therapy for Hodgkin lymphoma patients. Int J Radiat Oncol Biol Phys 89(5):1047–1052. doi:10.1016/j.ijrobp.2014.04.026 CrossRefPubMed

10.

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. doi:10.1016/j.ijrobp.2014.01.006 CrossRefPubMed

11.

NCCN (2017) Clinical practice guidelines in oncology. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 25 Feb 2017

12.

Kriz J, Baues C, Engenhart-Cabillic R et al (2017) New quality assurance program integrating “modern radiotherapy” within the German Hodgkin Study Group. Strahlenther Onkol 193(2):100–108. doi:10.1007/s00066-016-1048-y CrossRefPubMed

13.

Shi Z, Das S, Okwan-Duodu D et al (2013) Patterns of failure in advanced stage diffuse large B‑cell lymphoma patients after complete response to R‑CHOP immunochemotherapy and the emerging role of consolidative radiation therapy. Int J Radiat Oncol Biol Phys 86(3):569–577. doi:10.1016/j.ijrobp.2013.02.007 CrossRefPubMed

14.

Dorth JA, Prosnitz LR, Broadwater G et al (2012) Impact of consolidation radiation therapy in stage III–IV diffuse large B‑cell lymphoma with negative post-chemotherapy radiologic imaging. Int J Radiat Oncol Biol Phys 84(3):762–767. doi:10.1016/j.ijrobp.2011.12.067 CrossRefPubMed

15.

Ng AK, Dabaja BS, Hoppe RT, Illidge T, Yahalom J (2016) Re-examining the role of radiation therapy for diffuse large B‑cell lymphoma in the modern era. J Clin Oncol 34(13):1443–1447. doi:10.1200/jco.2015.64.9418 CrossRefPubMed

16.

ClinicalTrials.gov (2016) Rituximab and combination chemotherapy with or without radiation therapy in treating patients with B‑cell non-Hodgkin’s Lymphoma – full text view. https://clinicaltrials.gov/ct2/show/study/NCT00278408?term=unfolder&rank=1. Accessed 28 Nov 2016

17.

Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin’s disease staging classification. Cancer Res 31(11):1860–1861PubMed

18.

Cheson BD, Pfistner B, Juweid ME et al (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586. doi:10.1200/jco.2006.09.2403 CrossRefPubMed

19.

Juweid ME, Stroobants S, Hoekstra OS et al (2007) Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 25(5):571–578. doi:10.1200/jco.2006.08.2305 CrossRefPubMed

20.

CTEP (2016) Protocol development. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 25 July 2016

21.

Horning SJ, Weller E, Kim K et al (2004) Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin’s lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol 22(15):3032–3038. doi:10.1200/jco.2004.06.088 CrossRefPubMed

22.

Miller TP, Dahlberg S, Cassady JR et al (1998) Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin’s lymphoma. N Engl J Med 339(1):21–26. doi:10.1056/nejm199807023390104 CrossRefPubMed

23.

Phan J, Mazloom A, Medeiros LJ et al (2010) Benefit of consolidative radiation therapy in patients with diffuse large B‑cell lymphoma treated with R‑CHOP chemotherapy. J Clin Oncol 28(27):4170–4176. doi:10.1200/jco.2009.27.3441 CrossRefPubMed

24.

Marcheselli L, Marcheselli R, Bari A et al (2011) Radiation therapy improves treatment outcome in patients with diffuse large B‑cell lymphoma. Leuk Lymphoma 52(10):1867–1872. doi:10.3109/10428194.2011.585526 CrossRefPubMed

25.

Hu C, Deng C, Zou W, Zhang G, Wang J (2015) The role of consolidative radiotherapy after a complete response to chemotherapy in the treatment of diffuse large B‑cell lymphoma in the rituximab era: results from a systematic review with a meta-analysis. Acta Haematol 134(2):111–118. doi:10.1159/000370096 CrossRefPubMed

26.

Kaplan HS (1980) Hodgkin’s disease: unfolding concepts concerning its nature, management and prognosis. Cancer 45(10):2439–2474CrossRefPubMed

27.

Fuks Z, Kaplan HS (1973) Recurrence rates following radiation therapy of nodular and diffuse malignant lymphomas. Radiology 108(3):675–684. doi:10.1148/108.3.675 CrossRefPubMed

28.

Nickson JJ (1966) Hodgkin’s disease clinical trial. Cancer Res 26(6):1279–1283PubMed

29.

Yahalom J, Mauch P (2002) The involved field is back: issues in delineating the radiation field in Hodgkin’s disease. Ann Oncol 1:79–83CrossRef

30.

Eich HT, Müller R‑P, Engenhart-Cabillic R et al (2008) Involved-node radiotherapy in early-stage Hodgkin’s lymphoma. Definition and guidelines of the German Hodgkin Study Group (GHSG). Strahlenther Onkol 184(8):406–410CrossRefPubMed

31.

Hoskin PJ, Díez P, Williams M, Lucraft H, Bayne M (2013) Participants of the lymphoma radiotherapy group. Recommendations for the use of radiotherapy in nodal lymphoma. Clin Oncol 25(1):49–58. doi:10.1016/j.clon.2012.07.011 CrossRef

32.

Campbell BA, Connors JM, Gascoyne RD, Morris WJ, Pickles T, Sehn LH (2012) Limited-stage diffuse large B‑cell lymphoma treated with abbreviated systemic therapy and consolidation radiotherapy: involved-field versus involved-node radiotherapy. Cancer 118(17):4156–4165. doi:10.1002/cncr.26687 CrossRefPubMed

33.

Verhappen MH, Poortmans PMP, Raaijmakers E, Raemaekers JMM (2013) Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin’s lymphoma. Radiother Oncol 109(1):133–139. doi:10.1016/j.radonc.2013.07.013 CrossRefPubMed

34.

Yu JI, Nam H, Ahn YC, Kim WS, Park K, Kim SJ (2010) Involved-lesion radiation therapy after chemotherapy in limited-stage head-and-neck diffuse large B cell lymphoma. Int J Radiat Oncol Biol Phys 78(2):507–512. doi:10.1016/j.ijrobp.2009.07.1706 CrossRefPubMed

35.

Kwon J, Kim IH, Kim BH, Kim TM, Heo DS (2015) Additional survival benefit of involved-lesion radiation therapy after R‑CHOP chemotherapy in limited stage diffuse large B‑cell lymphoma. Int J Radiat Oncol Biol Phys 92(1):91–98. doi:10.1016/j.ijrobp.2014.12.042 CrossRefPubMed

36.

Elstrom R, Guan L, Baker G et al (2003) Utility of FDG-PET scanning in lymphoma by WHO classification. Blood 101(10):3875–3876. doi:10.1182/blood-2002-09-2778 CrossRefPubMed

37.

Isohashi K, Tatsumi M, Higuchi I et al (2008) 18F-FDG-PET in patients with malignant lymphoma having long-term follow-up: staging and restaging, and evaluation of treatment response and recurrence. Ann Nucl Med 22(9):795–802. doi:10.1007/s12149-008-0186-4 CrossRefPubMed

38.

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. doi:10.1016/j.radonc.2011.05.013 CrossRefPubMed

39.

Avilés A, Delgado S, Nambo MJ, Alatriste S, Díaz-Maqueo JC (1994) Adjuvant radiotherapy to sites of previous bulky disease in patients stage IV diffuse large cell lymphoma. Int J Radiat Oncol Biol Phys 30(4):799–803CrossRefPubMed

40.

Pfreundschuh M, Schubert J, Ziepert M et al (2008) Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B‑cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 9(2):105–116. doi:10.1016/s1470-2045(08)70002-0 CrossRefPubMed

41.

Song M‑K, Chung J‑S, Sung-Yong O et al (2010) Clinical impact of bulky mass in the patient with primary extranodal diffuse large B cell lymphoma treated with R‑CHOP therapy. Ann Hematol 89(10):985–991. doi:10.1007/s00277-010-0964-7 CrossRefPubMed

42.

Held G, Murawski N, Ziepert M et al (2014) Role of radiotherapy to bulky disease in elderly patients with aggressive B‑cell lymphoma. J Clin Oncol 32(11):1112–1118. doi:10.1200/jco.2013.51.4505 CrossRefPubMed

43.

Jegadeesh N, Rajpara R, Esiashvili N et al (2015) Predictors of local recurrence after rituximab-based chemotherapy alone in stage III and IV diffuse large B‑cell lymphoma: guiding decisions for consolidative radiation. Int J Radiat Oncol Biol Phys 92(1):107–112. doi:10.1016/j.ijrobp.2015.01.025 CrossRefPubMedPubMedCentral

44.

Wilder RB, Tucker SL, Ha CS et al (2001) Dose-response analysis for radiotherapy delivered to patients with intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to CHOP-based induction chemotherapy. Int J Radiat Oncol Biol Phys 49(1):17–22CrossRefPubMed

Titel: Patterns of failure of diffuse large B‑cell lymphoma patients after involved-site radiotherapy
verfasst von: Eva Holzhäuser, M.D.
Maximilian Berlin
Daniel Wollschläger
Thomas Bezold
Arnulf Mayer
Georg Heß
Heinz Schmidberger
Publikationsdatum: 26.07.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 12/2017
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-017-1186-x

Springer Medizin

Patterns of failure of diffuse large B‑cell lymphoma patients after involved-site radiotherapy