Top

Published in:

01-04-2023 | Radiotherapy | Radiotherapy

Efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients: a single-centre experience

Authors: Lea Galunic Bilic, Fedor Santek, Josip J. Grah, Sandra Basic-Kinda, Inga Mandac Smoljanovic, Slobodanka Ostojic Kolonic, Zdravko Mitrovic, Marijo Vodanovic, Dino Dujmovic, Igor Aurer

Published in: La radiologia medica | Issue 4/2023

Abstract

Purpose

Data on efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients are scarce. We therefore performed this retrospective study to analyse our experience with radiotherapy exclusively to infradiaphragmal fields.

Materials and methods

we retrospectively evaluated 101 patients treated between 2003 and 2014. Median dose was 36 Gy, range 4 to 54 Gy. Medium dose per fraction was 2 Gy, range 1.5 to 7 Gy.

Results

After a median follow-up of 66 months (range 1–211 months), we observed lymphoma recurrence in 38 patients (38%), five in the RT field and 33 out-of-field. Recurrences were significantly more frequent in the salvage group (17 out-of-field and 4 in-field in 31 patients) than in adjuvant group (16 out-of-field and 1 in-field in 70 patients; p < 0.001).

The 2-, 5- and 10-year event-free survival (EFS) rates were 62%, 56% and 54%. The 2-, 5- and 10-year overall survival (OS) rates for the entire group of patients are 73%, 60% and 54%, respectively. Acute side effects occurred in 43 (43%) patients, most frequent gastrointestinal in 26 (26%) patients. Late side effects occurred in 12 (12%) of all patients, 6 of 23 (26%) followed up for more than 10 years. Six patients developed secondary cancers, four gastrointestinal disturbances, two diabetes mellitus and three renal failure.

Conclusion

Radiotherapy is an effective and safe treatment option for patients with infradiaphragmatic lymphoma providing excellent local disease control with minimal late toxicity. Infradiaphragmatic lymphoma localization should not be regarded as a contraindication for use of radiotherapy. However, patients should be monitored for a secondary malignancy.

Joiner M, Kogel A (2009) Basic clinical radiobiology, 4th edn. CRC Press, Abingdon, OxonCrossRef

Shi Z, Das S, Okwan-Doudu D, Esiashvili N, Flowers C, Chen Z, Wang X, Jiang K, Nastoupil JL, Khan KM (2013) Patterns of failure in advanced stage diffuse large B cell lymphoma after complete response to R-CHOP immunochemotherapy and the emerging role of consolidative radiation therapy. Int J Radiat Oncol Biol Phys 86:569–577CrossRefPubMed

Held G, Murawski N, Ziepert M, Fleckenstein J, Pochel V, Zwick C et al (2014) Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol 32(11):1112–1118. https://doi.org/10.1200/JCO.2013.51.4505CrossRefPubMed

Longo DL (1989) Combined modality therapy for localized aggressive lymphoma: enough or too much? J Clin Oncol 7(9):1179–1181. https://doi.org/10.1200/JCO.1989.7.9.1179CrossRefPubMed

Specht L (2016) Does radiation have a role in advanced stage hodgkin’s or Non-Hodgkin lymphoma? Curr Treat Options Oncol 17(1):4. https://doi.org/10.1007/s11864-015-0377-xCrossRefPubMed

Milgrom SA, Bakst RL, Campbell BA (2021) Clinical outcomes confirm conjecture: modern radiation therapy reduces the risk of late toxicity in survivors of Hodgkin lymphoma. Int J Radiat Oncol Biol Phys 111(4):841–850. https://doi.org/10.1016/j.ijrobp.2021.06.030CrossRefPubMed

Conway JL, Connors JM, Tyldesley S et al (2017) Secondary breast cancer risk by radiation volume in women with Hodgkin lymphoma. Int J Radiat Oncol Biol Phys 97(1):35–41. https://doi.org/10.1016/j.ijrobp.2016.10.004CrossRefPubMed

van Nimwegen FA, Schaapveld M, Cutter DJ et al (2016) Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. J Clin Oncol 34(3):235–243. https://doi.org/10.1200/JCO.2015.63.4444CrossRefPubMed

Ricardi U, Maraldo MV, Levis M, Parkih RR (2019) Proton therapy For lymphomas: current state of the art. Onco Targets Ther 12:8033–8046. https://doi.org/10.2147/OTT.S220730CrossRefPubMedPubMedCentral

10.

Iorio GC, Salvestrini V, Borghetti P et al (2021) The impact of modern radiotherapy on radiation-induced late sequelae: focus on early-stage mediastinal classical Hodgkin lymphoma a critical review by the young group of the italian association of radiotherapy and clinical oncology (AIRO). Crit Rev Oncol Hematol. 161:103326. https://doi.org/10.1016/j.critrevonc.2021.103326CrossRefPubMed

11.

Dorth JA, Prosnitz LR, Broadwater G, Diehl LF, Beaven AW, Coleman RE, Kelsay CR (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 84:762–767CrossRefPubMed

12.

Illidge T, Specht L, Yahalom J, Aleman B, Berthelsen AK, Constine L, Dabaja B et al (2014) Modern radiation therapy for nodal non-Hodgkin lymphoma- target definition and dose guidelines from the international lymphoma oncology group. Int J Radiat Oncol Biol Phys 98:49–58CrossRef

13.

Specht L, Nissen NI (1988) Hodgkin’s disease stages I and II with infradiaphragmatic presentation: a rare and prognostically unfavorable combination. Eur J Haematol 40:396–402CrossRefPubMed

14.

Hull MC, Mendenhall NP, Colgan ME (2002) Subdiaphragmatic hodgkin’s disease: the University of Florida experiance. Int J Rad Oncol Biol Phys 52:161–166CrossRef

15.

Akoum R, Brihi E, Saade M, Hanna T, Chahine G (2007) Salvage abdominal irradiation for refractory non-Hodgkin’s lymphoma. J Can Res Ther 3:143–149. https://doi.org/10.4103/0973-1482.37406CrossRef

16.

Brihi E, Akoum R, Saade M, Chanine G (2003) Abdominal irradiation after chemotherapy in non-Hodgkin’s lymphoma: review of 32 patients. Mol Immunol 39:1121–1128CrossRefPubMed

17.

Glick JH, Kim K, Earle J et al (1995) An ECOG randomized phase III trial of CHOP vs CHOP plus radiotherapy for intermediate grade early stage NHL. Proc Am Soc Clin Oncol. 14:391

18.

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 339:21–26CrossRefPubMed

19.

Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H (2005) Groupe d’Etude des lymphomes de l’Adulte (GELA) ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 352(12):1197–205. https://doi.org/10.1056/NEJMoa042040CrossRefPubMed

20.

Miller T, Leblanc M, Spier C et al (2001) CHOP alone compared with CHOP plus radiotherapy for early stage aggressive non-Hodgkin’s lymphomas: update of the Southwest Oncology Group (SWOG) Randomized trial. Blood. 98:a724

21.

Aviles A, Delgado S, Nambo MJ, Alatriste S, Dias-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 30:799–803CrossRefPubMed

22.

Ferreri AJ, Dell’Oro S, Reni M, Ceresoli GL, Cozzarini C, Ponzoni M, Villa E (2000) Consolidation radiotherapy to bulky or semibulky lesions in the management of stage III-IV diffuse large B cell lymphomas. Oncology 58:219–226. https://doi.org/10.1159/000012104CrossRefPubMed

23.

Vargo JA, Gill BS, Balasubramani GK, Beriwal S (2015) Treatment selection and survival outcomes in early-stage diffuse-large B-cell lymphoma: do we still need consolidative radiotherapy? J Clin Oncol 33:3710–3717. https://doi.org/10.1200/JCO.2015.61.7654CrossRefPubMed

24.

Phan J, Mazloom A, Medeiros LJ, Zreik TG, Wogan C, Shihadeh F et al (2010) Benefit of consolidative radiation therapy in patients with diffuse large B-cell lymphoma treated with R-CHOP chemotherapy. J Clin Oncol 28:4170–4176. https://doi.org/10.1200/JCO.2009.27.3441CrossRefPubMed

25.

Follows GA, Ardeshna KM, Barrington SF et al (2014) Guidelines for the first line management of classical Hodgkin lymphoma. Br J Haematol. 166:34–39. https://doi.org/10.1111/bjh.12878CrossRefPubMed

26.

Delclos L, Braun E J, Raul Herrera J (1963) Whole Abdominal irradiation by Cobalt-60Moving-Strip Technic. Radiology 81(4):632–641CrossRefPubMed

27.

Surbone A, Longo DL, DeVita VT Jr, Ihde DC, Duffey PL et al (1988) Residual abdominal masses in aggressive non-Hodgkin’s lymphoma after combination chemotherapy: significance and management. J Clin Oncol 6:1832–1837. https://doi.org/10.1200/JCO.1988.6.12.1832CrossRefPubMed

28.

Elsayad K, Eich HT (2015) Survival benefit by consolidating Radiotherapy in patients with diffuse large B-Cell lymphoma in early stages. Strahlenther Oncol 192:502–504. https://doi.org/10.1007/s00066-016-0992-xCrossRef

29.

Horning SJ, Weller E, Kim K, Earle JD, O’Connell MJ, Habermann TM, Glick JH (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. https://doi.org/10.1200/JCO.2004.06.088CrossRefPubMed

30.

Imber BS, Yahalom J (2020) Radiotherapy for non-Hodgkin lymphomas. Cancer J 26(3):217–230. https://doi.org/10.1097/PPO.0000000000000453CrossRefPubMedPubMedCentral

31.

Levis M, Piva C, Filippi AR et al (2017) Potential benefit of involved-field radiotherapy for patients with relapsed-refractory Hodgkin’s lymphoma with incomplete response before autologous stem cell transplantation. Clin Lymphoma Myeloma Leuk 17(1):14–22. https://doi.org/10.1016/j.clml.2016.09.008CrossRefPubMed

32.

Wirth A, Corry J, Laidlaw C, Matthews J, Liew KH (1997) Salvage radiotherapy for Hodgkin’s disease following chemotherapy failure. Int J Radiat Oncol Biol Phys 39:599–607. https://doi.org/10.1016/s0360-3016(97)00352-0CrossRefPubMed

33.

Constine LS, Yahalom J, Ng AK, Hodgson DC, Wirth A, Milgrom SA, Mikhaeel MG et al (2018) The role of radiation therapy in patients with relapsed or refractory Hodgkin lymphoma: guidelines from the international lymphoma radiation oncology group. Int J Radiat Oncol Biol Phys 100(5):1100–1118. https://doi.org/10.1016/j.ijrobp.2018.01.011CrossRefPubMed

34.

Kahn S, Flowers C, Xu Z, Esiashvili N (2011) Does the addition of involved field radiotherapy to high-dose chemotherapy and stem cell transplantation improve outcomes for patients with relapsed/refractory Hodgkin lymphoma? Int J Radat Oncol Biol Phys 81(1):175–180. https://doi.org/10.1016/j.ijrobp.2010.05.010CrossRef

35.

Campbell BA, Voss N, Woods R, Gascoyne RD, Morris R, Pickles T et al (2010) Long-term outcomes for patients with limited stage follicular lymphoma: involved regional radiotherapy versus involved node radiotherapy. Cancer. 116:3797–806. https://doi.org/10.1002/cncr.25117CrossRefPubMed

36.

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

37.

Brady JL, Binkley MS, Hajj C, Chelius M, Chau K, Balogh A 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-2018-04-843540CrossRefPubMed

38.

Pugh TJ, Ballonoff P, Newman F, Rabinovitch R (2010) Improved survival with patients with early stage low-grade follicular lymohoma treated with radiation: a surveilance, epidemiology and end results database analysis. Cancer. 116:3843–51. https://doi.org/10.1002/cncr.25149CrossRefPubMed

39.

Haas RL, Girinsky T (2003) HOVON 47/EORTC 20013: chlorambucil vs 2x2 Gy involved field radiotherapy in stage III/IV previously untreated follicular lymphoma patients. Ann Hematol 82:458–462CrossRefPubMed

40.

Hoskin P, Popova B, Schofield O, Brammer C, Robinson M, Brunt AM, Madhavan K, Illidge T, Gallop-Evans E, Syndikus I, Clifton-Hadley L, Kirkwood AA (2021) 4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol 22(3):332–340. https://doi.org/10.1016/S1470-2045(20)30686-0. (Epub 2021 Feb 1 PMID: 33539729)CrossRefPubMed

41.

Russo AL, Chen YH, Martin NE, Vinjamoori A, Luthky SK, Freedman A et al (2013) Low-dose involved-field radiation in the treatment of non-Hodgkin lymphoma: predictors of response and treatment failure. Int J Radiat Oncol Biol Phys. 86:121–7. https://doi.org/10.1016/j.ijrobp.2012.12.024CrossRefPubMed

42.

Haas RL, Poortmans P, de Jong D, Aleman BM, Dewit LG, Verheij M et al (2003) High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas. J Clin Oncol 21:2474–2480. https://doi.org/10.1200/JCO.2003.09.542CrossRefPubMed

43.

Valicenti RK, Wasserman TH, Monyak DJ, Kucik NA (1994) Non-hodgkin’s lymphoma: whole-abdomen irradiation as an adjuvant to chemotherapy. Radiology 192:571–576. https://doi.org/10.1148/radiology.192.2.8029434CrossRefPubMed

44.

Goffinet R, Glatstein E, Fuks Z, Kaplan HS (1976) Abdominal irradiation in non-Hodgkin’s lymphoma. Cancer 37:2797–2806CrossRefPubMed

45.

Coia LR, Hanks GE (1987) Complications from large field intermediate dose infradiaphragmatic radiation: an analysis of the patterns of care outcome studies for Hodgkin’s disease and seminoma. Int J Rad Oncol Biol Phys 15:29–35CrossRef

46.

Niemierko A, Goitein M (1993) Modeling of normal tissue response to radiation: the critical volume model. Int J Radiot Oncol Biol Phys 25:134–145CrossRef

47.

Galunić Bilić L, Šantek F (2018) Infradiaphragmal radiotherapy in patients with Lymphoma volume definition and side effects. Acta clinica Croatica. 57:554–560PubMedPubMedCentral

48.

Gallez-Marchal D, Fayolle M, Henry-Amar M, LeBourgeois JP, Rougier P, Cosset JM (1984) Radiation injuries of the gastrointestinal tract in Hodgkin’s disease: The role of exploratory laparotomy and fractionation. Radiother Oncol 2:93–99CrossRefPubMed

49.

Langlios D, LeBourgeois JP, Leung S, Keuentz M (1985) Intestinal complications of wide field abdominal irradiation for lymphoma. Radiother Onkol 3:293–298CrossRef

50.

Mahé MA, Bourdin S, Le Mevel A, Moreau P, Moreau A, Hamidou M, Gaillard F, Rapp MJ, Milpied N, Harousseau JL (1998) Long-term results of total abdominopelvic irradiation in non-Hodgkin’s lymphomas after failure of chemotherapy. Int J Radiat Oncol Biol Phys 41:117–121. https://doi.org/10.1016/s0360-3016(98)00034-0CrossRefPubMed

51.

Kaplan HS (1980) Hodgkin’s Disease, 2nd edn. MA, Harvard University Press, Boston

52.

Dawson LA, Kavanagh BD, Paulino AC et al (2010) Radiation-Associated Kidney Injury. Int J Radiat Oncol Biol Phys 76:108–115CrossRef

53.

Parikh RR, Grossbard ML, Harrison LB, Yahalom J (2016) Association of intensity-modulated radiation therapy on overall survival for patients with Hodgkin lymphoma. Radiother Oncol. 118:52–59CrossRefPubMed

54.

Choi WH, Cho J (2016) Evolving clinical cancer radiotherapy: concerns regarding normal tissue protection and quality assurance. J Korean Med Sci 31(Suppl 1):S75–S87CrossRefPubMedPubMedCentral

55.

Conway JL, Connors JM, Tyldesley S, Savage KJ, Campbell BA, Zheng YY, Hamm J, Pickles T (2017) Secondary breast cancer risk by Radiation volume in women with Hodgkin Lymphoma. Int J Radiat Oncol Biol Phys 97(1):35–41. https://doi.org/10.1016/j.ijrobp.2016.10.004CrossRefPubMed

56.

Oeffinger KC, Stratton KL, Hudson MM, Leisenring WM, Henderson TO et al (2021) Impact of risk-adapted therapy for pediatric Hodgkin Lymphoma on risk of long-term morbidity: a report from the childhood cancer Survivor study. J Clin Oncol 39(20):2266–2275. https://doi.org/10.1200/JCO.20.01186CrossRefPubMedPubMedCentral

Title: Efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients: a single-centre experience
Authors: Lea Galunic Bilic
Fedor Santek
Josip J. Grah
Sandra Basic-Kinda
Inga Mandac Smoljanovic
Slobodanka Ostojic Kolonic
Zdravko Mitrovic
Marijo Vodanovic
Dino Dujmovic
Igor Aurer
Publication date: 01-04-2023
Publisher: Springer Milan
Keywords: Radiotherapy
Lymphoma
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Published in: La radiologia medica / Issue 4/2023
Print ISSN: 0033-8362
Electronic ISSN: 1826-6983
DOI: https://doi.org/10.1007/s11547-023-01615-8

ERS Congress 2024

Springer Medicine

Efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients: a single-centre experience

Abstract

Purpose

Materials and methods

Results

Conclusion

ERS Congress 2024

Springer Medicine

Abstract

Purpose

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2023

Extreme hypofractionated stereotactic radiotherapy for elderly prostate cancer patients: side effects preliminary analysis of a phase II trial

Delta computed tomography radiomics features-based nomogram predicts long-term efficacy after neoadjuvant chemotherapy in advanced gastric cancer

The association between breast arterial calcification and atherosclerotic cardiovascular disease in an Australian population-based breast cancer case–control study

Utility of virtual stenting in treatment of cerebral aneurysms by flow diverter devices

Accuracy of computed tomography in staging acute appendicitis and its impact on surgical outcome and strategy: a multi-center retrospective case–control study

The added value of the visual analysis of DWI in post-surgery follow-up of soft tissue sarcoma of the extremities: do we really need ADC?