Low Dose Total Body Irradiation for Relapsed Low Grade Non-Hodgkin’s Lymphoma: Experience of National Cancer Institute, Cairo

Abstract

Background and Purpose: The relapsed low grade non-Hodgkin’s lymphoma (LG-NHL) is currently incurable disease and the optimal treatment regimen has not determined yet. Low dose total body irradiation (LTBI) provides an alternative mechanism of action against cancer cells rather than direct cell kill. The mode of action of LTBI is immune-modulatory effect, induction of apoptosis and hypersensitivity to low radiation doses. The aim of our study is to evaluate the effect of LTBI on relapsed LG-NHL and reporting our experience at National Cancer Institute, Cairo (NCI, Cairo). Material and Methods: Fifty eight patients with relapsed LG-NHL and received LTBI studied retrospectively. LTBI dose was 1.6 Gy/8 fractions divided on 2 courses; each course 4 fractions treated over 4 days with 2 weeks rest between the 2 courses. Results: The median age is 54 years; 65% of the patients are men. Forty (69%) patients had performance status of 2 or more. Twenty seven patients were stage II/III and 31 patients (53%) had stage IV disease. Twenty six (45%) patients had bulky disease more than 10 cm and 22 (38%) patients had B symptoms at the time of relapse. The extranodal disease was present in 17 patients (29%) and 78% of the patients received >3 regimens of chemotherapy before referral to LTBI. Twenty three patients received IFRT (mean dose 32 ± 4 Gy) to initially bulky sites after LTBI. Fourteen patients (24%) achieved complete remission (CR) while 45%, 21% and 10% had partial remission (PR), stable disease (SD) and progressive disease (PD) respectively. The median PFS duration was 14 months and the median OS duration was 39 months. Stage VI, >3 regimen of chemotherapy and bad response to LTBI (SD) affected progression duration adversely (0.03, 0.05 and 0.01 respectively). The response to LTBI is the only factor affected the OS duration significantly. The 3-year PFS was 19% ± 9%, and 3-year OS was 45% ± 8%. Stage IV was the only factor affected the 3-year PFS significantly with p value 0.03. The hematological toxicity was the main side effect of LTBI. Eleven patients developed G3/4 anemia while 8 patients only developed G3/4 thrombocytopenia and 13 patients developed G3/4 leucopenia. Conclusion: The use of LTBI in patients with relapsed low grade NHL is a feasible, effective and tolerable treatment that is worthy of testing in a future with chemotherapy and Rituximab maintenance.

Share and Cite:

Bayoumi, Y. and Radwan, A. (2015) Low Dose Total Body Irradiation for Relapsed Low Grade Non-Hodgkin’s Lymphoma: Experience of National Cancer Institute, Cairo. Journal of Cancer Therapy, 6, 25-33. doi: 10.4236/jct.2015.61004.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] American Cancer Society (2014) Cancer Facts and Figures 2014. American Cancer Society, Atlanta.
[2] Klasa, R.J., Meyer, R.M., Shustik, C., et al. (2002) Randomized Phase III Study of Fludarabine Phosphate versus Cyclophosphamide, Vincristine, and Prednisone in Patients with Recurrent Low-Grade Non-Hodgkin’s Lymphoma Previously Treated with an Alkylating Agent or Alkylator-Containing Regimen. Journal of Clinical Oncology, 20, 4649-4654. http://dx.doi.org/10.1200/JCO.2002.11.068
[3] Thomson, K.J., Morris, E.C., Milligan, D., et al. (2010) T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients with Multiply Relapsed Follicular Lymphoma. Journal of Clinical Oncology, 28, 3695-3700. http://dx.doi.org/10.1200/JCO.2009.26.9100
[4] Delic, J., Magdelenat, H., Barbaroux, C., et al. (1995) In-Vivo Induction of Apoptosis in Human Lymphocyes by Therapeutic Fractionated Total Body Irradiation. British Journal of Radiology, 68, 997-1003. http://dx.doi.org/10.1259/0007-1285-68-813-997
[5] Marples, B., Lambin, P., Skov, K.A., et al. (1997) Low-Dose Hypersensitivity and Induced Radioresistance in Mammalian Cells. International Journal Radiation Biology, 71, 721-735.
http://dx.doi.org/10.1080/095530097143725
[6] Hashimoto, S. (1997) Effects of Low-Dose Total Body Irradiation on Tumour Bearing Rats. Nippon Igaku Hoshasen Gakkai Zasshi, 57, 418-424.
[7] Rees, G.J., Bullimore, J.A. and Lever, J.V. (1980) Total Body Irradiation as a Secondary Therapy in Non-Hodgkin’s Lymphoma. Clinical Radiology, 31, 437-439. http://dx.doi.org/10.1016/S0009-9260(80)80185-1
[8] van Dijk-Miatz, A. (1979) Total Body Irradiation in Advanced Lymphosarcoma. British Journal of Radiology, 52, 568-570. http://dx.doi.org/10.1259/0007-1285-52-619-568
[9] Chaffey, J.T., Rosenthal, D.S., Pinkus, G., et al. (1975) Advanced Lymphosarcoma Treated by Total Body Irradiation. British Journal of Cancer, 31, 441-449.
[10] Quast, U. (1985) Physical Treatment Planning of Total Body Irradiation: Patient Translation and Beam Zone Method. Medical Physics, 12, 567-573. http://dx.doi.org/10.1118/1.595677
[11] Quast, U. (1987) Total Body Irradiation—Review of Treatment Techniques in Europe. Radiotherapy & Oncology, 9, 91-106. http://dx.doi.org/10.1016/S0167-8140(87)80197-4
[12] (1979) WHO Handbook for Reporting Results of Cancer Treatment. WHO off Set Publication, Geneva.
[13] Hochster, H.S., Kim, K.M., Green, M.D., et al. (1992) Activity of Fludarabine in Previously Treated Non-Hodgkin’s Low-Grade Lymphoma: Results of an Eastern Cooperative Oncology Group Study. Journal of Clinical Oncology, 10, 28-32.
[14] Kay, A.C., Saven, A., Carrera, C.J., et al. (1992) 2-Chlorodeoxyadenosine Treatment of Low-Grade Lymphomas. Journal of Clinical Oncology, 10, 371-377.
[15] Redman, J.R., Cabanillas, F., Velasquez, W.S., et al. (1992) Phase II Trial of Fludarabine Phosphate in Lymphoma: An Effective New Agent in Low-Grade Lymphoma. Journal of Clinical Oncology, 10, 790-794.
[16] Yonkosky, D.M., Feldman, M.I., Cathcart, E.S. and Kim, S. (1978) Improvement of in Vitro Mitogen Proliferative Reponses in Non-Hodgkin’s Lymphoma Patients Exposed to Fractionated Total Body Irradiation. Cancer, 42, 1204-1210. http://dx.doi.org/10.1002/1097-0142(197809)42:3<1204::AID-CNCR2820420325>3.0.CO;2-S
[17] Jacobs, P. and King, H.S. (1987) A Randomised Prospective Comparison of Chemotherapy to Total Body Irradiation as Initial Treatment for the Indolent Lymphoproliferative Diseases. Blood, 69, 1642-1646.
[18] Carabell, S.C., Chaffey, J.T., Rosenthal, D.S., et al. (1979) Results of Total Body Irradiation in the Treatment of Advanced Non-Hodgkin’s Lymphoma. Cancer, 43, 994-1000.
http://dx.doi.org/10.1002/1097-0142(197903)43:3<994::AID-CNCR2820430331>3.0.CO;2-0
[19] Meerwaldt, J.H., Carde, P., Burgers, J.M.V., et al. (1991) Low-Dose Total Body Irradiation versus Combination Chemotherapy for Lymphomas with Follicular Growth Pattern. International Journal of Radiation Oncology Biology Physics, 21, 1167-1172. http://dx.doi.org/10.1016/0360-3016(91)90272-6
[20] Lybeert, M.L.M., Meerwaldt, J.H. and Deneve, W. (1987) Long Term Results of Low Dose Total Body Irradiation for Advanced Non-Hodgkin’s Lymphoma. International Journal of Radiation Oncology Biology Physics, 13, 1845-1852.
[21] Roncadin, M., Arcicasa, M., Bortolus, R., et al. (1991) Feasibility of Total Body Irradiation in Chronic Lymphocytic Leukemia and Low Grade Non-Hodgkin’s Lymphomas. Cancer Investigation, 9, 403-407. http://dx.doi.org/10.3109/07357909109084637
[22] Safwat, A. (2000) The Role of Low-Dose Total Body Irradiation in Treatment of NHL: A New Look at an Old Method. Radiotherapy & Oncology, 56, 1-8. http://dx.doi.org/10.1016/S0167-8140(00)00167-5
[23] Piro, L.D., White, C.A., Grillo-López, A.J., et al. (1999) Extended Rituximab (Anti-CD20 Monoclonal Antibody) Therapy for Relapsed or Refractory Low-Grade or Follicular Non-Hodgkin’s Lymphoma. Annals of Oncology, 10, 655-661. http://dx.doi.org/10.1023/A:1008389119525
[24] Davis, T.A., Grillo-López, A.J., White, C.A., et al. (2000) Rituximab Anti-CD20 Monoclonal Antibody Therapy in Non-Hodgkin’s Lymphoma: Safety and Efficacy of Re-Treatment. Journal of Clinical Oncology, 18, 3135-3143.
[25] van Oers, M.H., Van Glabbeke, M., Giurgea, L., et al. (2010) Rituximab Maintenance Treatment of Relapsed/Resistant Follicular Non-Hodgkin’s Lymphoma: Long-Term Outcome of the EORTC 20981 Phase III Randomized Intergroup Study. Journal of Clinical Oncology, 28, 2853-2858.
http://dx.doi.org/10.1200/JCO.2009.26.5827
[26] Martinelli, G., Schmitz, S.F., Utiger, U., et al. (2010) Long-Term Follow-Up of Patients with Follicular Lymphoma Receiving Single-Agent Rituximab at Two Different Schedules in Trial SAKK 35/98. Journal of Clinical Oncology, 28, 4480-4484. http://dx.doi.org/10.1200/JCO.2010.28.4786
[27] van Oers, M.H., Klasa, R., Marcus, R.E., et al. (2006) Rituximab Maintenance Improves Clinical Outcome of Relapsed/Resistant Follicular Non-Hodgkin Lymphoma in Patients Both with and without Rituximab during Induction: Results of a Prospective Randomized Phase 3 Intergroup Trial. Blood, 108, 3295-3301. http://dx.doi.org/10.1182/blood-2006-05-021113
[28] Young, R.C., Johnson, R.E., Canellos, G.P., et al. (1977) Advanced Lymphocytic Lymphoma: Randomized Comparisons of Chemotherapy and Radiotherapy, Alone or in Combination. Cancer Treatment Reports, 61, 1153-1159.
[29] Roncadin, M., Arcicasa, M. and Zagonel, V. (1994) Total Body Irradiation and Prednimustine in Chronic Lymphocytic Leukemia and Low Grade Non-Hodgkin’s Lymphoma: A 9-Year Experience in a Single Institution. Cancer, 74, 978-984. http://dx.doi.org/10.1002/1097-0142(19940801)74:3<978::AID-CNCR2820740330>3.0.CO;2-B
[30] Bayoumi, Y., Radwan, A. and El Sharkawi, N. (2008) Low Dose Total Body Irradiation in Patients with Metastatic Renal Cell Carcinoma: A Feasibility Study and Immunomodulatory Effect. Medical Journal of Cairo University, 76, 261-266.
[31] Safwat, A., Bayoumi, Y., El-Sharkawy, N., Shaaban, K., et al. (2003) The Potential Palliative Role and Possible Immune Modulatory Effects of Low-Dose Total Body Irradiation in Relapsed or Chemo-Resistant NHL. Radiotherapy and Oncology, 69, 33-36. http://dx.doi.org/10.1016/S0167-8140(03)00247-0
[32] Safwat, A., Bayoumi, Y., Akkoush, H. and Mahmoud, H.K. (2004) A Phase II Trial of Adjuvant Low-Dose Total Body Irradiation in Non-Hodgkin’s Lymphoma Patients Following Standard CHOP. Acta Oncologica, 43, 480-485.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.