Risk of thyroid disorders in adult and childhood Hodgkin lymphoma survivors 40 years after treatment

Figures & data

Figure 1. Response rate of a questionnaire study.

Table 1. Demographic and treatment characteristics of respondents with Hodgkin lymphoma treated at ages ≤45 years at The Royal Marsden Hospital, 1970–2015.

Characteristic	n (%)
Age at HL diagnosis (years)
0–19	84 (35.4)
20–29	103 (43.5)
30–39	39 (16.5)
40–45	11 (4.6)
Socioeconomic status (ACORN score)*
1 (Highest)	102 (43.0)
2	33 (13.9)
3	60 (25.3)
4	19 (8.0)
5	19 (8.0)
6 (Lowest)	4 (1.7)
Calendar period of first treatment
1970–1974	12 (5.1)
1975–1984	45 (19.0)
1985–1994	70 (29.5)
1995–2004	50 (21.1)
2005–2015	60 (25.3)
Years since treatment: median (range)	24 (2–48)
Age at questionnaire completion (years)
18–29	32 (13.5)
30–39	34 (14.3)
40–49	52 (21.9)
50–59	71 (30.0)
60–79	48 (20.3)
Stage at diagnosis
I	20 (8.4)
II	91 (38.4)
III	26 (11.0)
IV	39 (16.5)
NK	61 (25.7)
B symptoms at diagnosis
Yes	55 (23.2)
No	112 (47.3)
NK	70 (29.5)
Subtype of HL
Nodular sclerosis	153 (64.6)
Mixed cellularity	16 (6.8)
Lymphocyte rich	1 (0.4)
Lymphocyte depleted	2 (0.8)
NLPHL	3 (1.3)
Other	8 (3.4)
NK	54 (22.8)
Treatment modality
Chemotherapy and radiotherapy	117 (49.4)
Radiotherapy only	32 (13.5)
Chemotherapy only	88 (37.1)
Stem cell transplant
No transplant	218 (92.0)
Autologous	19 (8.0)
Allogeneic	0 (0.0)
Radiotherapy
SupraRT ± InfraRT	147 (98.7)
SupraRT only	130 (87.2)
SupraRT + InfraRT	17 (11.4)
InfraRT only	2 (1.3)
SupraRT ± InfraRT	147 (98.7)
Including neck	114 (76.5)
Excluding neck	33 (22.1)
Including axilla(e)	85 (57.0)
Excluding axilla(e)	64 (43.0)
Total radiotherapy dose (Gy)
1–29	12 (8.1)
30–39	74 (49.7)
40–49	32 (21.5)
≥50	17 (11.4)
NK	14 (9.4)
Total radiotherapy	149
Chemotherapy
Total no. chemotherapy cycles
1–4	51 (24.9)
5–6	100 (48.8)
>6	43 (21.0)
NK	11 (5.3)
Chemotherapy regimen containing
Vinca-alkaloid	201 (98.0)
Classic alkylator	97 (47.3)
Anthracycline	149 (72.7)
Platinum	10 (4.9)
MDR	25 (12.2)
Lines of chemotherapy
1	158 (77.1)
2	39 (19.0)
3	4 (2.0)
4	3 (1.5)
Total chemotherapy	205
Total	237

NLPHL: nodular lymphocyte predominant Hodgkin Lymphoma; NK: not known; InfraRT: infradiaphragmatic radiotherapy; SupraRT: supradiaphragmatic radiotherapy; MDR: multi-drug regimen.

*ACORN score is based on socioeconomic characteristics of the postcode of residence [20].

Table 2. Relative risks of thyroid disorders by treatment modality.

Treatment modality	No. with disorder	No. treated	%*	RR	95% CI	p-value
Chemotherapy alone	7	88	8.0	1.0	–	–
Chemotherapy and radiotherapy	51	117	43.6	5.0	2.2–11.3	<0.001
Radiotherapy only	22	32	68.8	6.8	2.6–18.0	<0.001
Any SupraRT	72	147	49.0	5.0	2.2–11.4	<0.001
Including neck	57	114	50.0	5.0	2.1–11.6	<0.001
Excluding neck	15	33	45.5	5.1	2.0–12.6	<0.001
InfraRT	1	2	50.0	4.6	0.5–38.5	0.2
Dose of SupraRT (Gy)
No SupraRT**	8	90	8.9	1.0	–	–
1–29	1	11	9.1	1.0	0.1–7.7	0.97
30–39	41	85	48.2	4.7	2.3–9.8	<0.001
>40	24	37	64.9	6.0	2.8–12.7	<0.001
NK dose SupraRT	6	14	42.9	3.9	1.5–10.1	0.005
Linear trend per Gy^††				1.03	1.02–1.05	<0.001
Total	80	237
Patients treated with chemotherapy alone
Chemotherapy agents
Classic alkylators	3	27	11.1	2.9	0.5–17.6	0.2
Anthracycline	6	79	7.6	0.7	0.08–6.3	0.8
Vinca-alkaloid	6	87	6.9	–^†	–	–
MDR	1	10	10.0	1.4	0.2–12.9	0.7
Platinum	1	5	20.0	3.1	0.4–26.0	0.3
Total no. of chemo cycles
1–4	2	18	11.1	1.0	–	–
5–6	3	51	5.9	0.5	0.09–3.3	0.5
>6	1	17	5.9	0.5	0.04–7.3	0.6
NK no. of cycles	1	2	50.0	4.3	0.4–50.6	0.3
Linear trend per cycle^††				0.88	0.6–1.3	0.5
Total	7	88

HL: Hodgkin Lymphoma; SupraRT: supradiaphragmatic radiotherapy; InfraRT: infradiaphragmatic radiotherapy; Gy: Gray; RR: relative risk; CI: confidence interval.

All analyses adjusted for the duration since the first HL treatment and age at first treatment.

*Proportion of total with risk factor (% by row).

**Includes 2 pts treated with InfraRT only.

^†No events in the comparator group.

^††Excluding NK Gy/no. of cycles.

Table 3. Relative risks of thyroid disorders by demographic and time-related factors.

Risk factor	All patients						SupraRT treated
	No. with any thyroid disorder	No. with risk factor	%*	RR	95% CI	p-value	No. with any thyroid disorder	No. with risk factor	%*	RR	95% CI	p-value
Age at first HL treatment^a (years)
0–19	31	84	36.9	1.0	–	–	27	48	56.3	1.0	–	–
20–29	34	103	33.0	0.9	0.6–1.5	0.7	32	68	47.1	0.9	0.5–1.5	0.7
30–39	14	39	35.9	1.1	0.6–2.0	0.8	12	26	46.2	0.9	0.4–1.8	0.8
40–45	1	11	9.1	0.4	0.05–2.8	0.3	1	5	20.0	0.5	0.1–3.6	0.5
Linear trend per year				1.00	0.98–1.03	0.8				1.00	0.96–1.03	0.9
Age ≤21 at first treatment	37	103	35.9	χ^2 = 0.4		0.5	33	62	53.2	χ^2 = 0.8		0.4
Age >21 at first treatment	43	134	32.1				39	85	45.9
Duration since first HL treatment^b (years)
0–9	5	43	11.6	1.0	–	–	2	9	22.2	1.0	–	–
10–19	7	46	15.2	1.3	0.4–4.1	0.6	5	23	21.7	1.0	0.2–5.0	0.98
20–29	28	70	40.0	3.4	1.3–8.9	0.011	27	47	57.5	2.6	0.6–10.8	0.2
30–39	27	55	49.1	4.2	1.6–11.0	0.003	26	46	56.5	2.5	0.6–10.5	0.2
40–49	13	23	56.5	4.9	1.7–13.6	0.003	12	22	54.6	2.4	0.5–10.8	0.3
Linear trend per year				1.04	1.02–1.06	<0.001				1.02	0.99–1.04	0.1
Treatment decade^†
1970–1974	5	12	41.7	1.0	–	–	5	12	41.7	1.0	–	–
1975–1984	25	45	55.6	1.3	0.5–3.5	0.6	23	39	59.0	1.4	0.5–3.7	0.5
1985–1994	28	70	40.0	1.0	0.4–2.5	0.9	27	47	57.5	1.4	0.5–3.6	0.5
1995–2004	14	50	28.0	0.7	0.2–1.9	0.4	13	30	43.3	1.0	0.4–2.9	0.9
2005–2015	8	60	13.3	0.3	0.1–1.0	0.046	4	19	21.1	0.5	0.1–1.9	0.3
Linear trend per decade				0.7	0.6–0.9	<0.001				0.9	0.7–1.1	0.1
Total	80	237					72	147

HL: Hodgkin lymphoma; RR: relative risk; CI: confidence interval; SupraRT: supradiaphragmatic radiotherapy.

^aAdjusted for time since treatment.

^bAdjusted for age at first treatment.

*Proportion with a thyroid disorder (% by row).

^†Unable to adjust for the duration since treatment due to co-linearity of variables.

Figure 2. Cumulative proportion developing any thyroid disorder by calendar period of treatment.

Figure 3. Cumulative prevalence of thyroid disorders by duration since HL treatment.

Figure 4. Cumulative proportion developing any thyroid disorder by the modality of treatment.

CACI. ACORN. Available from: https://www.caci.co.uk/sites/default/files/resources/Acorn_User_Guide_0.pdf. 2011

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