Conventional and Conformal Radiotherapy with and without Beam Intensity Modulation in Patients with Stage II Hodgkin’s Lymphoma with Supradiaphragmal Lesions

LYMPHOID TUMORS , , ,

YuN Vinogradova1, EI Ivanova1, AI Chumachenko1, EV Smirnova2, GI Andreev2, AM Kalesnik2, NA Vorob’ev2, NV Il’in1

1 AM Granov Russian Research Centre of Radiology and Surgery Technologies, 70 Leningradskaya str., Pesochnyi, Saint Petersburg, Russian Federation, 197758

2 Nuclear Medicine Centre of SM Berezin International Institute of Biological Systems, 43 Karl Marx str., Pesochnyi, Saint Petersburg, Russian Federation, 197758

For correspondence: Nikolai Vasil’evich Il’in, PhD, Professor, 70 Leningradskaya str., Pesochnyi, Saint Petersburg, Russian Federation, 197758; Tel.: +7(812)596-90-35; e-mail: ilyin_prof@mail.ru.

For citation: Vinogradova YuN, Ivanova EI, Chumachenko AI, et al. Conventional and Conformal Radiotherapy with and without Beam Intensity Modulation in Patients with Stage II Hodgkin’s Lymphoma with Supradiaphragmal Lesions. Clinical oncohematology. 2018;11(1):70-7.

DOI: 10.21320/2500-2139-2018-11-1-70-77

ABSTRACT

Aim. To increase the efficacy of chemo-radiotherapy in patients with stage II Hodgkin’s lymphoma (HL) with supradiaphragmal lesions by different fractionation (conventional fractionation [CF] and multi-fractionation [MF]) and various radiation volume (mantle radiotherapy, involved field radiotherapy [IFRT] or involved site radiotherapy [ISRT]).

Materials & Methods. The clinical trial included 317 patients with stage II classical HL with supradiaphragmal lesions who have received chemo-radiotherapy in AM Granov Russian Scientific Centre of Radiology and Surgery Technologies from 1986 to 2015 (n = 301) and in SM Berezin International Institute of Biological Systems from 2014 to 2016 (n = 16). The mean age was 30.9 years (range 18–65); the study group included 107 men and 210 women. The diagnosis in all the cases was confirmed by immunomorphologic analysis. The treatment program included 2 to 6 cycles of ABVD regimen followed by CF (n = 153) or MF (n = 148) radiation therapy. The patients received mantle radiotherapy or IFRT with the cumulative dose of 30 to 40 Gy (2D planning, 237 patients) or ISRT with the cumulative dose of 30 to 40 Gy (3D planning, n = 80, CF only). The MF-regimen was administered only with 2D planning, mantle radiotherapy and IFRT. The CF-regimen was administered with 2D-planning (n = 89) with the same volume of radiation and 3D planning using conformal RT (3D-CRT) as ISRT with the cumulative dose of 30 to 36 Gy (n = 80). From the total of 80 patients 16 patients were treated with beam intensity modulation (IMRT) and 64 patients were treated without IMRT.

Results. The treatment response (both complete and partial remission) was reported in 235 (99.2 %) of 237 patients of 2D planning group. In 2 cases (0.8 %) a progression of disease was diagnosed. Out of 235 patients with remission 222 (94.5 %) had a complete remission and 13 (5.5 %) had a partial remission. Within the group treated with the conventional RT 19 (8.1 %) patients had recurrent disease. Overall 5- and 10-year survival (OS) was equal and accounted for 98.0 ± 1.4 %, the disease-free survival (DFS) was also equal between groups and accounted for 85.9 ± 1.3 %. The rate of 5- and 10-year OS in patients who received CF was 97.8 ± 1.7 %; the DFS rate for the same period was 85.0 ± 1.5 % with standard fractionation and 86.2 ± 1.6 % with MF (p > 0.1). The total number of local radiation reactions and the number of radiation pulmonitis were significantly smaller with the exposure twice daily compared to CF at 2D planning and mantle irradiation. Decreasing the radiation volume from the mantle type to IFRT was shown to reduce the incidence of pulmonitis. The incidence of esophagitis remained the same with different fractionation and the irradiation volumes specified above. The results of the analysis proved the total absence of radiation pericarditis with both types of conformal RT with or without IMRT. No pulmonitis cases were observed with IMRT; the use of 3D-CRT and 2D-RT significantly increased the incidence of pulmonitis. The incidence of esophagitis within the CRT-group (n = 80) was 2 times lower compared to the conventional RT (22.5 % and 43.9 %; p < 0.01).

Conclusion. The innovative technologies of radiation therapy allowed to reduce the incidence of early local radiation reactions. These technologies will be the basis for preventing severe late radiation complications that reduce the life expectancy and quality of life of patients with HL.

Keywords: Hodgkin’s lymphoma, radiotherapy, fractionation, 2D and 3D planning.

Received: September 16, 2017

Accepted: December 5, 2017

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REFERENCES

  1. Yahalom J, Hoppe RT. Principles of Radiation Techniques in Hodgkin Lymphoma. In: Engert A, Horning SJ, eds. Hodgkin Lymphoma. A Comprehensive Update on Diagnostics and Clinics. Berlin, Heidelberg: Springer; 2011. pp. 117–39. doi: 10.1007/978-3-642-12780-9.
  2. Даниленко А.А., Шахтарина С.В. Лучевая терапия лимфомы Ходжкина: от «радикальной программы» лечения до современных технологий. Медицинская радиология и радиационная безопасность. 2015;60(4):71–9. [Danilenko AA, Shakhtarina Radiation therapy of Hodgkin’s lymphoma: from the “radical radiation therapy” to the actual technology. Meditsinskaya radiologiya i radiatsionnaya bezopasnost’. 2015;60(4):71–9. (In Russ)]
  3. Lugtenburg E, Hagenbeek A. Treatment of Early Favorable Hodgkin Lymphoma. In: Engert A, Horning SJ, eds. Hodgkin Lymphoma. A Comprehensive Update on Diagnostics and Clinics. Berlin, Heidelberg: Springer; 2011. pp. 163–81. doi: 10.1007/978-3-642-12780-9.
  4. Hoppe R. Radiotherapy Planning for the Lymphomas: Expanding Roles for Biologic Imaging. In: Meyer JL, ed. IMRT, IGRT, SBRT: Advances in the Treatment Planning and Delivery of Radiotherapy, 2nd, revised and extended edition. Basel: Karger; 2011. 487 p.
  5. Pavlovsky S, Maschio M, Santarelli MT, et al. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I–II Hodgkin’s disease. J Natl Cancer Inst. 1988;80(18):1466–73. doi: 10.1093/jnci/80.18.1466.
  6. Laskar S, Gupta T, Vimal S, et al. Consolidation radiation after complete remission in Hodgkin’s disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need? J Clin Oncol. 2004;22(1):62–8. doi: 10.1200/jco.2004.01.021.
  7. Straus DJ, Portlock CS, Qin J, et al. Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages III, and IIIA non bulky Hodgkin disease. Blood. 2004;104(12):3483–9. doi: 10.1182/blood-2004-04-1311.
  8. Meyer RM, Gospodarowicz MK, Connors JM, et al. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin’s lymphoma: National Cancer Institute of Canada Clinical Trial Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005;23(21):4634–42. doi: 10.1200/JCO.2005.09.085.
  9. Engert A, Shiller P, Josting A, et al. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin’s lymphoma: results of the HD8 trial of the German Hodgkin’s Study Group. J Clin Oncol. 2003;21(19):3601–8. doi: 10.1200/jco.2003.03.023.
  10. Bonadonna G, Bonfante V, Viviani S, et al. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin’s disease: long-term results. J Clin Oncol. 2004;22(14):2835–41. doi: 10.1200/jco.2004.12.170.
  11. Ferme C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin’s disease. N Engl J Med. 2007;357(19):1916–27. doi: 10.1056/NEJMoa064601.
  12. Von Treskow B, Gorgen H, Plutschow A, et al. Infradiaphragmatic Hodgkin lymphoma in patients treated with state-of-the-art therapies: a risk factors analysis from the German Hodgkin Study Group (GHSG) HD13 and HD14 trials. Haematologica. 2013;98(2):12–3. (abstr. P036).
  13. Акимов А.А., Ильин Н.В. Роль фракционирования дозы в повышении эффективности лучевой терапии опухолей. СПб.: Берсерк, 2005. 29 с.[Akimov AA, Il’in NV. Rol’ fraktsionirovaniya dozy v povyshenii effektivnosti luchevoi terapii opukholei. (Significance of dose fractionation in increasing of efficacy of tumor radiation therapy.) Saint Petersburg: Berserk Publ.; 2005. 29 p. (In Russ)]
  14. Yahalom J. Principles, Indications, and Techniques of Radiation Therapy of Lymphomas. In: Canellos G, Lister TA, Young B, eds. The Lymphomas, 2nd edition. Elsevier; 2006. pp. 203–24. doi: 10.1016/b978-0-7216-0081-9.50016-9.
  15. Крутилина Н.И. Эффективность нетрадиционной лучевой терапии больных лимфогранулематозом IIA-IIIA стадий. Медицинская радиология. 1990;9:44. [Krutilina NI. Efficacy of non-traditional radiotherapy of stages IIA/IIIA Hodgkin’s lymphoma. Meditsinskaya radiologiya. 1990;9:44. (In Russ)]
  16. Ильин Н.В. Оптимизация методов лучевой терапии лимфогранулематоза: Автореф. дис. … д-ра мед. наук. СПб., 1993. 42 с.[Il’in NV. Optimizatsiya metodov luchevoi terapii limfogranulematoza. (Optimization of methods of radiation treatment of Hodgkin’s disease.) [dissertation] Saint Petersburg; 1993. 42 p. (In Russ)]
  17. Акимов А.А. Анализ дозно-временных зависимостей при лучевой терапии злокачественных опухолей: Автореф. дис. … д-ра мед. наук. СПб., 2000. 48 с. [Akimov AA. Analiz dozno-vremennykh zavisimostei pri luchevoi terapii zlokachestvennykh opukholei. (Analysis of dose and time correlations in radiation treatment of malignant tumors.) [dissertation] Saint Petersburg; 2000. 48 p. (In Russ)]
  18. Ильин Н.В., Виноградова Ю.Н., Николаева Е.Н., Смирнова Е.В. Значение мультифракционирования дозы радиации при первичном лучевом лечении больных лимфомой Ходжкина. Онкогематология. 2007;4:47–53. [Il’in NV, Vinogradova YuN, Nikolaeva EN, Smirnova EV. Value of accelerated hyperfraction doses of radiation in primary radiation treatment for Hodgkin’s lymphoma. Onkogematologiya. 2007;4:47–53. (In Russ)]
  19. Изотов Б.М. Исходные прогностические факторы и оптимизация терапии больных лимфогранулематозом IIIA стадии: Автореф. дис. … канд. мед. наук. СПб., 2000. 24 с. [Izotov BM. Iskhodnye prognosticheskie faktory i optimizatsiya terapii bol’nykh limfogranulematozom IIIA stadii. (Background prognostic factors and optimization of treatment of stage IIIA Hodgkin’s lymphoma.) [dissertation] Saint Petersburg; 2000. 24 p. (In Russ)]
  20. Николаева Е.Н. Оценка эффективности режима ускоренного мультифракционирования дозы в лучевом и комбинированном лечении больных лимфомой Ходжкина II–III стадий: Автореф. дис. … канд. мед. наук. СПб., 2005. 23 с. [Nikolaeva EN. Otsenka effektivnosti rezhima uskorennogo mul’tifraktsionirovaniya dozy v luchevom i kombinirovannom lechenii bol’nykh limfomoi Khodzhkina II–III stadii. (Efficacy evaluation of the accelerated dose multifranctionation in radiation and combined treatment of stages II/III Hodgkin’s lymphoma.) [dissertation] Saint Petersburg; 2005. 23 p. (In Russ)]
  21. Specht L, Yahalom J, Illidge T, et al. Modern Radiation Therapy for Hodgkin’s lymphoma: Field and Dose Guidelines from the International Lymphoma Radiation Oncology Group (ILROG). Int J Rad Oncol Biol Phys. 2014;89(4):854–62. doi: 10.1016/j.ijrobp.2013.05.005.
  22. Carbone PP, Kaplan HS, Musshoff K, et al. Report of the Committee on Hodgkin’s disease staging classification. Cancer Res. 1971;31:1860–1.
  1. Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol. 1989;7(11):1630–6. doi: 10.1200/jco.1989.7.11.1630.
  2. Симбирцева Л.П., Синицын Р.В., Виноградов В.М., Ватницкий С.М. Планирование и проведение лучевой терапии больных лимфогранулематозом по радикальной программе с помощью крупных полей сложных конфигураций: Методические рекомендации. Ленинград, 1979. 27 с. [Simbirtseva LP, Sinitsyn RV, Vinogradov VM, Vatnitskii SM. Planirovanie i provedenie luchevoi terapii bol’nykh limfogranulematozom po radikal’noi programme s pomoshch’yu krupnykh polei slozhnykh konfiguratsii. Metodicheskie rekomendatsii. (Radiotherapy planning and realization in patients with Hodgkin’s disease according to the radical program using large fields with complicated configuration. Methodological guidelines.) Leningrad; 1979. 27 p. (In Russ)]
  3. Kaplan H. The radical radiotherapy of regionally localized Hodgkin’s disease. Radiology. 1962;78(4):553–61. doi: 10.1148/78.4.553.
  4. Yahalom J, Mauch P. The involved field is back: issues in delineating the radiation field in Hodgkin’s disease. Ann Oncol. 2002;13(Suppl 1):79–83. doi: 10.1093/annonc/13.s1.79.
  5. Girinsky T, van der Maazen, Specht L, et al. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol. 2006;79(3):270–7. doi: 10.1016/j.radonc.2006.05.015.
  6. World health statistics annual. Volume II. Infectious diseases: Cases and deaths 228 World Health Organization Geneva 1978 Sw. fr. 32 EW. Public Health. 1979;93(3):199–200. doi: 10.1016/s0033-3506(79)80127-4.
  7. Cox J, Stetz J, Pajak T. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6. doi: 10.1016/0360-3016(95)00060-c.
  8. Cheson BD, Horning SJ, Coiffer B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol. 1999:17(4):1244–53. doi: 10.1200/jco.1999.17.4.1244.
  9. Cheson BD, Pfisther B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86. doi: 10.1200/jco.2006.09.2403.
  10. Волчков В.А. Краткое практическое руководство по биометрии для врачей, 2-е издание. СПб., 2004. 60 с. [Volchkov VA. Kratkoe prakticheskoe rukovodstvo po biometrii dlya vrachei. (Quick practical guide on biometry for medical doctors.) 2nd edition. Saint Petersburg; 2004. 60 p. (In Russ)]
  11. Macdonald DA, DingK, Gospodarowicz MK, et al. Patterns of disease progression and outcomes in a randomized trial testing ABVD alone for patients with limited-stage Hodgkin lymphoma. Ann Oncol. 2007;18(10):1680–4. doi: 10.1093/annonc/mdm
  12. Количественный анализ повреждений здоровых органов и тканей при проведении лучевой терапии злокачественных новообразований (Проект QUANTEC). Обзор толерантности нормальных тканей: Пер. с англ. под ред. С.И. Ткачева. М., 2015. 250 c. [Quantitative analysis of normal organ and tissue injuries in radiotherapy of malignant neoplasms (QUANTEC project). Quantitative Analyses of Normal Tissue Effects in the Clinic. (Russ. ed.: Tkachev SI. Kolichestvennyi analiz povrezhdenii zdorovykh organov i tkanei pri provedenii luchevoi terapii zlokachestvennykh novoobrazovanii (Proekt QUANTEC). Obzor tolerantnosti normal’nykh tkanei. Moscow; 2015. 250 p.)]
  13. Terezakis SA, Hunt M, Specht L, Yahalom J. Traditional and Modern Techniques for Radiation Treatment Planning. In: Specht L, Yahalom J, eds. Radiotherapy for Hodgkin Lymphoma. Berlin, Heidelberg: Springer; 2011. pp. 123–51. doi: 10.1007/978-3-540-78944-4_10.