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. Author manuscript; available in PMC: 2019 Feb 1.
Published in final edited form as: Radiat Res. 2018 May 15;190(2):117–132. doi: 10.1667/RR14888.1

TABLE 4.

Relative risk (rate ratio) for incidence rate of hypothyroidism according to type of treatment with chemotherapy agents in the Childhood Cancer Survivor Study cohort.

Characteristic Cases PYR/10,000 RR (95% CI)a
Any chemotherapy & type of childhood cancer
 No chemotherapyb 190 3.5 1.0
 Any chemotherapy & leukemia 193 6.5 1.1 (0.2–7.1)
 Any chemotherapy & CNS cancer 58 0.4 6.7 (3.0–14.8)
 Any chemotherapy & HL 148 1.2 0.8 (0.0–20.4)
 Any chemotherapy & other cancers 171 6.7 1.8 (0.7–4.5)
Pc =0.14
Any alkylating agentsd
 No 326 9.2  1.0
 Yes 433 9.2 1.8 (1.1–3.0)
Pc =0.04
Any anthracyclinesc
 No 522 11.3 1
 Yes 237 7.1 1.1 (0.6–2.1)
Pc =0.85
Any bleomycin
 No 690 17.6 1
 Yes 69 0.8 3.4 (1.6–7.3)
Pc =0.03
Any platinum-based compounds
 No 725 17.7 1
 Yes 34 0.7  1.1 (0.3–4.8)
Pc = 0.88
Any epipodophyllotoxins
 No 696 17.2 1
 Yes 63 1.3 1.5 (1.0–2.3)
Pc =0.08
 Alkylating Agents   
 CCNU (Lomustine)  
  No 704 18.0 1.0
  Yes 55 0.4 3.0 (1.5–5.3)
Pc <0.01
CCNU, mg/m2  
  0 704 18.0 1.0
 >0- < 411.18 13 0.1 1.0 (0.1–7.4)
 411.18- <800.0 23 0.1 5.0 (2.5–9.9)
 >800.0 12 0.04 8.2 (3.6–18.9)
Pc <0.01
CCNU & type of cancer
 No CCNU 704 18.0 1.0
 CCNU & CNS cancer 35 0.2 3.6 (1.2–7.1)
 CCNU & other cancers 20 0.2 2.6 (0.8–5.6)
Pc =0.03
BCNU (Carmustine)
  No 729 17.7 1.0
  Yes 30 0.7 1.1 (0.5–2.0)
Pc 0.50
Cyclophosphamide
  No 450 10.3 1.0
  Yes 309 8.1 1.3 (1.0–1.8)
Pc =0.05
Cyclophosphamide, mg/m2
0 450 10.4 1.0
 >0- < 5323.1 120 3.0 1.3 (0.9–1.9)
 5323.1- <11,448.3 89 2.4 1.3 (0.9–1.9)
 >11,448.3 74 2.1  1.3 (0.9–2.1)
Pc =0.36
Procarbazine
 No 598 17.1 1.0
 Yes 161 1.3 1.0 (0.4–2.3)
Pc >0.50
Mechlorethamine
No 668 17.6 1.0
 Yes 91 0.9 0.7
Pc >0.50
Melphalan
 No 745 18.2 1.0
 Yes 14 0.2 2.2 (0.7– 5.2)
Pc =0.16
Thiotepa
 No 747 18.4 1.0
 Yes 12 0.05 5.7 (0.2–15.2)
Pc =0.14
a

RRs adjusted for an additive association for categories of the cross-tabulation of radiation dose to the thyroid and and pituitary, with dose categories as in Table 5, and categories of exposure to classes of chemotherapy agents or chemotherapy drugs/doses. Baseline was adjusted for sex, attained age, type of cancer, and calendar year of follow-up. Type of first cancer included to account for possible differential surveillance and shared predisposition. Patients with missing pituitary dose and missing information on the specific class of chemotherapy agent or chemotherapydrugs/doses were excluded from this analysis. Alkylating agents with fewer than 10 cases (busulfan, chlorambucil and ifosfamide) were not included in this analysis.

b

Number of cases who did not receive chemotherapy, by type of cancer: leukemia=1, CNS=69, HL=98 and others=22

c

Likelihood ratio test of homogeneity of risk across categories

Abbreviations: BCNU=bis-chloroethyl-nitrosourea, CCNU=cyclohexyl-chloroethyl-nitrosourea; CI=confidence interval;CNS=central nervous system; HL= Hodgkin lymphoma); PYR=person-years; RR=relative risk (rate ratio); Thiotepa= triethylenethiophosphoramide