Онкопедиатрия. 2018; 5: 24-31
Дисфункция щитовидной железы после лучевой терапии у детей с лимфомой Ходжкина
https://doi.org/10.15690/onco.v5i1.1863Аннотация
Основным подходом к лечению лимфомы Ходжкина является применение цитостатической и консолидирующей лучевой терапии. Сочетание этих методов лечения как улучшает противоопухолевый эффект, так и оказывает выраженное повреждающее действие на железы внутренней секреции. При этом наиболее частыми осложнениями являются различные заболевания щитовидной железы. Цель исследования — определить связь нарушений со стороны щитовидной железы и критической дозой облучения области шеи у пациентов с лимфомой Ходжкина. Методы. В исследование были включены 143 пациента в возрасте от 2 до 17 лет, страдающие лимфомой Ходжкина. В лечении всех пациентов применялась риск-адаптированная терапия: 42 пациента были пролечены согласно протоколу DAL-HD, терапия 86 пациентов осу- ществлялась согласно оригинальному риск-адаптированному протоколу СПбЛХ; 15 пациентов, вошедших в группу неблагоприятного прогноза, пролечены с использованием 6 курсов полихимиотерапии по схеме BEACOPP-базовый. Следующим этапом лечения была консолидирующая лучевая терапия. По завершении лечебной программы пациенты находились под динамическим наблюдением онколога и эндокринолога. В ходе обследования у ряда больных были диагностированы структурные и/или функциональные изменения щитовидной железы. Результаты. Большинству пациентов (n=126) проводилась консолидирующая лучевая терапия на область шейно-надключичных и медиастинальных лимфатических узлов в суммарной очаговой дозе (СОД) 15–46 Гр. Средний период наблюдения за данной группой больных составил 7,5 лет (диапазон 0–22). С помощью ROC-анализа удалось определить критическую дозу облучения, приводящую к развитию дисфункции щитовидной железы — более 39 Гр; площадь под кривой составила 0,717±0,108 (доверительный интервал 0,590–0,822; р=0,0445). Индекс Юдена для этого показателя составил 0,3929. Заключение. Облучение области шеи и щитовидной железы в СОД 39 Гр и выше сопряжено с высоким риском развития дисфункции щитовидной железы.
Список литературы
1. Кулева С.А., Анишкин М.Ю., Колыгин Б.А. Сравнительный анализ двух риск-адаптированных программ, используемых в терапии лимфомы Ходжкина у детей и подростков // Вопросы онкологии. — 2008. — Т.54. — №1 — С. 53–58. [Kuleva SA, Anishkin MYu, Kolygin BA. A comparison of two risk-adapted regimens of therapy of Hodgkin’s disease in children and adolescents. Vopr Onkol. 2008;54(1):53–58. (In Russ).]
2. Chow EJ, Friedman DL, Stovall M, et al. Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer. 2009;53(3):432–437. doi: 10.1002/pbc.22082.
3. Acharya S, Sarafoglou K, LaQuaglia M, et al. Thyriod neoplasms after therapeutic radiation for malignancies during childhood or adolescence. Cancer. 2003;97;2397–2403. doi: 10.1002/cncr.11362.
4. Ziora K, Bubala H, Glowacki J, et al. [Thyroid function after external irradiation of the neck in patients with Hodgkin’s disease long term observation. (In Polish).] Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 2006;12(4):261–267.
5. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993;39(4):561–577.
6. van Leeuwen FE, Klokman WJ, Stovall M, et al. Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin’s disease. J Natl Cancer Inst. 2003;95(13):971–980. doi: 10.1093/jnci/95.13.971.
7. Zaletel LZ, Bratanic N, Jereb B. Gonadal function in patients treated for Hodgkin’s disease in childhood. Radiol Oncol. 2010;44(3):187–193. doi: 10.2478/v10019-010-0034-8.
8. Chang ET, Smedby KE, Hjalgrim H, et al. Family history of hematopoietic malignancy and risk of lymphoma. J Natl Cancer Inst. 2005;97(19):1466–1474. doi: 10.1093/jnci/ dji293.
9. Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization Classification of Tumours: pathology and genetics of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. 352 p.
10. Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the childhood cancer survivor study. J Clin Endocrinol Metab. 2000;85(9):3227–3232. doi: 10.1210/jc.85.9.3227.
11. Au WY, Lie AK, Kung AW, et al. Autoimmune thyroid dysfunction after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2005;35(4):383–388. doi: 10.1038/ sj.bmt.1704766.
12. Taylor AJ, Croft AP, Palace AM, et al. Risk of thyroid cancer in survivors of childhood cancer: results from the British Childhood Cancer Survivor Study. Int J Cancer. 2009;125(10):2400–2405. doi: 10.1002/ijc.24581.
13. Tubiana M. Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol. 2009;91(1):4–15. doi: 10.1016/j. radonc.2008.12.016.
14. Collini P, Massimino M, Leite SF, et al. Papillary thyroid carcinoma of childhood and adolescence: a 30-year experience at the Istituto Nazionale Tumori in Milan. Pediatr Blood Cancer. 2006;46(3):300–306. doi: 10.1002/pbc.20474.
15. Prosnitz LR. Consolidation radiotherapy in the treatment of advanced Hodgkin’s disease: is it dead? Int J Radiat Oncol Biol Phys. 2003;56(3):605–608.
16. Diehl V. Chemotherapy or combined modality treatment: the optimal treatment for Hodgkin’s disease. J Clin Oncol. 2004;22(1):15–18. doi: 10.1200/JCO.2004.10.910.
17. Remonnay R, Morelle M, Giammarile F, et al. Impact of FDGPET on radiation therapy: economic results of a STIC study. Cancer Radiother. 2009;13(4):313–317. doi: 10.1016/j. canrad.2009.03.002.
18. Schaefer NG, Taverna C, Strobel K, et al. Hodgkin disease: diagnostic value of FDG PET/CT after first-line therapy — is biopsy of FDG-avid lesions still needed? Radiology. 2007;244(1):257–262. doi: 10.1148/radiol.2441060810.
19. Koh ES, Tran TH, Heydarian M, et al. A comparison of mantle versus involved-field radiotherapy for Hodgkin’s lymphoma: reduction in normal tissue dose and second cancer risk. Radiat Oncol. 2007;2:13. doi: 10.1186/1748- 717X-2-13.
20. 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):62–68. doi: 10.1200/Jco.2004.01.021.
Oncopediatrics. 2018; 5: 24-31
Thyroid Dysfunction After Radiotherapy in Children with Hodgkin’s Lymphoma
https://doi.org/10.15690/onco.v5i1.1863Abstract
Background. The main approach to Hodgkin’s lymphoma (HL) treatment is the use of cytostatic and consolidation radiation therapy. The combination of both treatment techniques undoubtedly improves the antitumor effect, but also negatively influence on the functioning of the endocrine glands. The most frequent complications are various diseases of the thyroid gland. Objective. Our aim was to determine the relationship between the thyroid disorders and critical dose of neck irradiation in patients with Hodgkin’s lymphoma. Methods. The study included 143 patients aged 2–17 years with HL. In the treatment of all patients, risk-adapted therapy was used: 42 patients were treated according to the DAL-HD protocol, 86 patients — according to the original risk-adjusted SPbHL protocol, and 15 patients included in the unfavorable prognosis group underwent 6 courses of BEACOPP-basic. The next treatment step was consolidation radiation therapy. When the therapy course was completed, patients were diagnosed with structural and/or functional changes in the thyroid gland. Results. The majority of the patients (n =126) received concomitant cervico-supraclavicular radiotherapy involving mediastinal lymph nodes in the total focal dose (SOD) of 15–46 Gy. The mean follow-up period was 7.5 years (range: 0–22). Having performed ROC analysis, we determined the critical dose of radiation leading to the development of thyroid dysfunction — more than 39 Gy; the area under the curve was 0.717±0.108 (CI 0.590–0.822; p =0.0445). The Youden’s Index was 0.3929. Conclusion. Irradiation of the neck and thyroid in total dose of 39 Gy and above is associated with a high risk of developing thyroid dysfunction.
References
1. Kuleva S.A., Anishkin M.Yu., Kolygin B.A. Sravnitel'nyi analiz dvukh risk-adaptirovannykh programm, ispol'zuemykh v terapii limfomy Khodzhkina u detei i podrostkov // Voprosy onkologii. — 2008. — T.54. — №1 — S. 53–58. [Kuleva SA, Anishkin MYu, Kolygin BA. A comparison of two risk-adapted regimens of therapy of Hodgkin’s disease in children and adolescents. Vopr Onkol. 2008;54(1):53–58. (In Russ).]
2. Chow EJ, Friedman DL, Stovall M, et al. Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer. 2009;53(3):432–437. doi: 10.1002/pbc.22082.
3. Acharya S, Sarafoglou K, LaQuaglia M, et al. Thyriod neoplasms after therapeutic radiation for malignancies during childhood or adolescence. Cancer. 2003;97;2397–2403. doi: 10.1002/cncr.11362.
4. Ziora K, Bubala H, Glowacki J, et al. [Thyroid function after external irradiation of the neck in patients with Hodgkin’s disease long term observation. (In Polish).] Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 2006;12(4):261–267.
5. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993;39(4):561–577.
6. van Leeuwen FE, Klokman WJ, Stovall M, et al. Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin’s disease. J Natl Cancer Inst. 2003;95(13):971–980. doi: 10.1093/jnci/95.13.971.
7. Zaletel LZ, Bratanic N, Jereb B. Gonadal function in patients treated for Hodgkin’s disease in childhood. Radiol Oncol. 2010;44(3):187–193. doi: 10.2478/v10019-010-0034-8.
8. Chang ET, Smedby KE, Hjalgrim H, et al. Family history of hematopoietic malignancy and risk of lymphoma. J Natl Cancer Inst. 2005;97(19):1466–1474. doi: 10.1093/jnci/ dji293.
9. Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization Classification of Tumours: pathology and genetics of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. 352 p.
10. Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the childhood cancer survivor study. J Clin Endocrinol Metab. 2000;85(9):3227–3232. doi: 10.1210/jc.85.9.3227.
11. Au WY, Lie AK, Kung AW, et al. Autoimmune thyroid dysfunction after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2005;35(4):383–388. doi: 10.1038/ sj.bmt.1704766.
12. Taylor AJ, Croft AP, Palace AM, et al. Risk of thyroid cancer in survivors of childhood cancer: results from the British Childhood Cancer Survivor Study. Int J Cancer. 2009;125(10):2400–2405. doi: 10.1002/ijc.24581.
13. Tubiana M. Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol. 2009;91(1):4–15. doi: 10.1016/j. radonc.2008.12.016.
14. Collini P, Massimino M, Leite SF, et al. Papillary thyroid carcinoma of childhood and adolescence: a 30-year experience at the Istituto Nazionale Tumori in Milan. Pediatr Blood Cancer. 2006;46(3):300–306. doi: 10.1002/pbc.20474.
15. Prosnitz LR. Consolidation radiotherapy in the treatment of advanced Hodgkin’s disease: is it dead? Int J Radiat Oncol Biol Phys. 2003;56(3):605–608.
16. Diehl V. Chemotherapy or combined modality treatment: the optimal treatment for Hodgkin’s disease. J Clin Oncol. 2004;22(1):15–18. doi: 10.1200/JCO.2004.10.910.
17. Remonnay R, Morelle M, Giammarile F, et al. Impact of FDGPET on radiation therapy: economic results of a STIC study. Cancer Radiother. 2009;13(4):313–317. doi: 10.1016/j. canrad.2009.03.002.
18. Schaefer NG, Taverna C, Strobel K, et al. Hodgkin disease: diagnostic value of FDG PET/CT after first-line therapy — is biopsy of FDG-avid lesions still needed? Radiology. 2007;244(1):257–262. doi: 10.1148/radiol.2441060810.
19. Koh ES, Tran TH, Heydarian M, et al. A comparison of mantle versus involved-field radiotherapy for Hodgkin’s lymphoma: reduction in normal tissue dose and second cancer risk. Radiat Oncol. 2007;2:13. doi: 10.1186/1748- 717X-2-13.
20. 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):62–68. doi: 10.1200/Jco.2004.01.021.
