Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidism in medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study

doi:10.1007/s11684-020-0752-2

Front. Med.

2021, Vol. 15

Issue (1) : 101-107 https://doi.org/10.1007/s11684-020-0752-2

RESEARCH ARTICLE

Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidism in medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study

Maura Massimino¹(

), Marta Podda¹, Lorenza Gandola², Emanuele Pignoli³, Ettore Seregni⁴, Carlo Morosi⁵, Filippo Spreafico¹, Andrea Ferrari¹, Emilia Pecori², Monica Terenziani¹

¹. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20146, Italy
². Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20146, Italy
³. Medical Physics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20146, Italy
⁴. Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20146, Italy
⁵. Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20146, Italy

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Abstract

Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels. We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From 1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value<0.3 μIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels ˂ 0.3 μIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60%±15% and 15.6%±8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively (P=0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.

Keywords iatrogenic primary hypothyroidism late effects of radiotherapy long-term follow-up medulloblastoma Hodgkin lymphoma

Corresponding Author(s): Maura Massimino

Just Accepted Date: 10 July 2020 Online First Date: 13 August 2020 Issue Date: 11 February 2021

Cite this article:

Maura Massimino,Marta Podda,Lorenza Gandola, et al. Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidism in medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study[J]. Front. Med., 2021, 15(1): 101-107.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0752-2
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I1/101

Patient ?code	Sex	Diagnosis	Age at ?diagnosis ?(year)	Craniospinal ?and neck/?mediastinumdoses ?in Gy	Myeloablative ?schedule	Adequate TSH ?suppression	Hypothyroidism	Interval since ?starting RT ?(month)	Other endocrine and ?metabolic problems
3	M	MBL-S	12	39	No	Yes	No	213	Growth hormone (GH), vit D deficiency
5	F	MBL-S	11	39	No	Yes	No	215	GH deficiency, dyslipidemia
11	M	S-PNET-S	18	39	No	Yes	No	239	No
14	F	MBL-S	21	39	Yes	Yes	Yes	214	No
17	M	MBL-S	21	39	No	Yes	No	237	No
19	M	MBL-S	13	39	No	Yes	No	223	No
22	M	MBL-S	15	39	No	Yes	No	227	GH deficiency, dyslipidemia
1	M	MBL-NS	1	20.8	Yes	No	Yes	235	GH deficiency
2	F	MBL-NS	6	31.2	Yes	No	Yes	219	Dyslipidemia, hyperinsulinism, ?panhypopituitarism, vit D deficiency, ?liver steatosis
4	M	MBL-NS	8	20.8	No	No	Yes	243	Dyslipidemia, vit D deficiency
6	M	MBL-NS	6	20.8	No	No	Yes	240	No
7	M	MBL-NS	7	31.2	No	No	No	228	GH deficiency
8	F	MBL-NS	16	39	No	No	Yes	213	No
9	M	S-PNET-NS	2	20.8	Yes	No	No	219	Dyslipidemia, hyperinsulinism, liver ?steatosis, second thyroid tumor
10	M	MBL-NS	18	39	No	No	No	239	GH deficiency
12	F	MBL-NS	7	31.2	No	No	No	238	No
13	F	MBL-NS	4	20.8	No	No	No	241	GH deficiency, vit D deficiency
15	M	MBL-NS	3	31.2	Yes	No	No	232	GH deficiency
16	M	MBL-NS	5	20.8	No	No	Yes	240	GH deficiency
18	M	MBL-NS	8	20.8	No	No	Yes	222	No
20	F	MBL-NS	10	39	No	No	Yes	222	Dyslipidemia, vit D deficiency
21	M	MBL-NS	10	39	No	No	Yes	230	Dyslipidemia, hyperinsulinism, ?panhypopituitarism, liver steatosis
23	M	HL-S	12	30	No	Yes	No	212	No
25	F	HL-S	15	25	No	Yes	Yes	238	Dyslipidemia
29	F	HL-S	16	25	No	Yes	No	215	No
30	M	HL-S	9	25	No	Yes	Yes	240	Second thyroid tumor
31	F	HL-S	17	25	No	Yes	No	207	No
33	M	HL-S	10	30	No	Yes	No	212	No
34	F	HL-S	12	30	No	Yes	No	238	No
36	F	HL-S	17	30	No	Yes	No	227	No
24	F	HL-NS	16	25	No	No	Yes	222	No
26	F	HL-NS	13	26	No	No	Yes	238	No
27	M	HL-NS	13	20	No	No	Yes	209	Dyslipidemia
28	M	HL-NS	10	25	No	No	Yes	232	No
32	F	HL-NS	10	25	No	No	Yes	242	Second thyroid tumor
35	M	HL-NS	15	25.2	No	No	Yes	219	Second thyroid tumor

Tab.1 MBL/PNET and HL cohorts

Fig.1 MBL/PNET and HL patients diagram from diagnosis to present status. hypo, hypothyroid patients; euthy, euthyroid patients.

Fig.2 Hypothyroidism-free survival rates for TSH-suppressed and TSH-not-suppressed patients.

1	SG Waguespack. Thyroid sequelae of pediatric cancer therapy. Horm Res Paediatr 2019; 91(2): 104–117 https://doi.org/10.1159/000495040 pmid: 30541010
2	PD Inskip, LHS Veiga, AV Brenner, AJ Sigurdson, E Ostroumova, EJ Chow, M Stovall, SA Smith, RE Weathers, W Leisenring, LL Robison, GT Armstrong, CA Sklar, JH Lubin. Hypothyroidism after radiation therapy for childhood cancer: a report from the Childhood Cancer Survivor Study. Radiat Res 2018; 190(2): 117–132 https://doi.org/10.1667/RR14888.1 pmid: 29763379
3	M Massimino, L Gandola, P Collini, E Seregni, A Marchianò, A Serra, E Pignoli, F Spreafico, F Pallotti, M Terenziani, V Biassoni, E Bombardieri, F Fossati-Bellani. Thyroid-stimulating hormone suppression for protection against hypothyroidism due to craniospinal irradiation for childhood medulloblastoma/primitive neuroectodermal tumor. Int J Radiat Oncol Biol Phys 2007; 69(2): 404–410 https://doi.org/10.1016/j.ijrobp.2007.03.028 pmid: 17601681
4	M Massimino, L Gandola, E Pignoli, E Seregni, A Marchianò, E Pecori, S Catania, G Cefalo. TSH suppression as a possible means of protection against hypothyroidism after irradiation for childhood Hodgkins lymphoma. Pediatr Blood Cancer 2011; 57(1): 166–168 https://doi.org/10.1002/pbc.22915 pmid: 21557462
5	DN Louis, A Perry, G Reifenberger, A von Deimling, D Figarella-Branger, WK Cavenee, H Ohgaki, OD Wiestler, P Kleihues, DW Ellison. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 2016; 131(6): 803–820 https://doi.org/10.1007/s00401-016-1545-1 pmid: 27157931
6	JL Wémeau, P Caron, C Schvartz, JL Schlienger, J Orgiazzi, C Cousty, V Vlaeminck-Guillem. Effects of thyroid-stimulating hormone suppression with levothyroxine in reducing the volume of solitary thyroid nodules and improving extranodular nonpalpable changes: a randomized, double-blind, placebo-controlled trial by the French Thyroid Research Group. J Clin Endocrinol Metab 2002; 87(11): 4928–4934 https://doi.org/10.1210/jc.2002-020365 pmid: 12414852
7	B Biondi, DS Cooper. Thyroid hormone suppression therapy. Endocrinol Metab Clin North Am 2019; 48(1): 227–237 https://doi.org/10.1016/j.ecl.2018.10.008 pmid: 30717904
8	M Massimino, L Gandola, F Mattavelli, N Pizzi, E Seregni, F Pallotti, F Spreafico, A Marchianò, M Terenziani, G Cefalo, V Biassoni, C Meazza, G Trecate, P Collini. Radiation-induced thyroid changes: a retrospective and a prospective view. Eur J Cancer 2009; 45(14): 2546–2551 https://doi.org/10.1016/j.ejca.2009.06.009 pmid: 19608408
9	DM Green, ML Brecher, D Yakar, LE Blumenson, AN Lindsay, ML Voorhess, M MacGillivray, AI Freeman. Thyroid function in pediatric patients after neck irradiation for Hodgkin disease. Med Pediatr Oncol 1980; 8(2): 127–136 https://doi.org/10.1002/mpo.2950080205 pmid: 7421731
10	AL Ogilvy-Stuart, SM Shalet, HR Gattamaneni. Thyroid function after treatment of brain tumors in children. J Pediatr 1991; 119(5): 733–737 https://doi.org/10.1016/S0022-3476(05)80288-4 pmid: 1941379
11	SL Hancock, RS Cox, IR McDougall. Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med 1991; 325(9): 599–605 https://doi.org/10.1056/NEJM199108293250902 pmid: 1861693
12	EL Kaplan, P Meier. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53(282): 457–481 https://doi.org/10.1080/01621459.1958.10501452
13	R Miller, D Siegmund. Maximally selected chi-square statistics. Biometrics 1982; 38(4): 1101–1106 https://doi.org/10.2307/2529881
14	SL Hancock, IR McDougall, LS Constine. Thyroid abnormalities after therapeutic external radiation. Int J Radiat Oncol Biol Phys 1995; 31(5): 1165–1170 https://doi.org/10.1016/0360-3016(95)00019-U pmid: 7713780
15	E Ron, JH Lubin, RE Shore, K Mabuchi, B Modan, LM Pottern, AB Schneider, MA Tucker, JD Boice Jr. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. 1995. Radiat Res 2012; 178(2): AV43–AV60 https://doi.org/10.1667/RRAV05.1 pmid: 22870979
16	CT Clausen Clausen, H Hasle, AS Holmqvist, L Madanat-Harjuoja, L Tryggvadottir, F Wesenberg, A Bautz, JF Winther, S de Fine Licht. Hyperthyroidism as a late effect in childhood cancer survivors — an adult life after childhood cancer in Scandinavia (ALiCCS) study. Acta Oncol 2019; 58(2): 227–231 https://doi.org/10.1080/0284186X.2018.1535187 pmid: 30585514
17	SC Clement, LCM Kremer, FA Verburg, JH Simmons, M Goldfarb, RP Peeters, EK Alexander, E Bardi, E Brignardello, LS Constine, CA Dinauer, VM Drozd, F Felicetti, E Frey, A Heinzel, MM van den Heuvel-Eibrink, SA Huang, TP Links, K Lorenz, RL Mulder, SJ Neggers, EJM Nieveen van Dijkum, KC Oeffinger, RR van Rijn, SA Rivkees, CM Ronckers, AB Schneider, R Skinner, JD Wasserman, T Wynn, MM Hudson, PC Nathan, HM van Santen. Balancing the benefits and harms of thyroid cancer surveillance in survivors of Childhood, adolescent and young adult cancer: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Cancer Treat Rev 2018; 63: 28–39 https://doi.org/10.1016/j.ctrv.2017.11.005 pmid: 29202445
18	HM van Santen, JE van Dijk, H Rodermond, F Vansenne, E Endert, JJ de Vijlder, J Haveman, T Vulsma. Endocrine intervention during irradiation does not prevent damage to the thyroid gland. Thyroid 2006; 16(4): 387–395 https://doi.org/10.1089/thy.2006.16.387 pmid: 16646686
19	JP Bantle, CK Lee, SH Levitt. Thyroxine administration during radiation therapy to the neck does not prevent subsequent thyroid dysfunction. Int J Radiat Oncol Biol Phys 1985; 11(11): 1999–2002 https://doi.org/10.1016/0360-3016(85)90283-4 pmid: 3932271
20	K Nishiyama, E Tanaka, Y Tarui, K Miyauchi, K Okagawa. A prospective analysis of subacute thyroid dysfunction after neck irradiation. Int J Radiat Oncol Biol Phys 1996; 34(2): 439–444 https://doi.org/10.1016/0360-3016(95)02079-9 pmid: 8567346
21	P Bhatti, LH Veiga, CM Ronckers, AJ Sigurdson, M Stovall, SA Smith, R Weathers, W Leisenring, AC Mertens, S Hammond, DL Friedman, JP Neglia, AT Meadows, SS Donaldson, CA Sklar, LL Robison, PD Inskip. Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study. Radiat Res 2010; 174(6): 741–752 https://doi.org/10.1667/RR2240.1 pmid: 21128798
22	M Wijnen, MM van den Heuvel-Eibrink, M Medici, RP Peeters, AJ van der Lely, SJ Neggers. Risk factors for subsequent endocrine-related cancer in childhood cancer survivors. Endocr Relat Cancer 2016; 23(6): R299–R321 https://doi.org/10.1530/ERC-16-0113 pmid: 27229933
23	J Harris, B Barber, H Almarzouki, R Scrimger, J Romney, D O’Connell, M Urken, H Seikaly. Free thyroid transfer: short-term results of a novel procedure to prevent post-radiation hypothyroidism. Head Neck 2017; 39(6): 1234–1238 https://doi.org/10.1002/hed.24590 pmid: 27862538

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