Critical appraisal:Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al 2010

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Critical Appraisal

Article being appraised

Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2010 Jan 10;28(2):332-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19949008.


Applicable clinical question

Key Facts

Study Design

cohort study

Study aims:

to determine the effect of treatment for childhood cancer on male fertility

Number of Patients:

7516

-Male Childhood Cancer Survivor Study survivor (cohort of 20,720 pt <21yrs at Dx between 1970-1986 who survived >5years from 26 insitutions) and sibling cohorts who completed a questionnaire - analysis was restricted to pts 15-40 years at completion of the baseline questionnaire. --> 6,224 survivors age 15 to 44 years who were not surgically sterile

-Permission was requestedfromarandomsample of the cohort to contact their nearest age sibling - not designed

for matched pair analyses but rather as a socio-demographically similar comparison population.Among 4,782 eligible siblings selected, 3,048 (80.5%) participated, of whom 1,449 were males between the ages of 15 and 44 years --> 1,292 male (not sterile) siblings included
Reported outcome(s):

pregnancy outcomes (pregnancy, miscarriage, terminations, still births and live births)

Results of outcome(s):

-Survivors: 941 indicated that they had ever sired a pregnancy 5 years or more after the date of the primary cancer diagnosis.
-Hazard ratio (HR) for ever siring a pregnancy was 0.56 (95% CI, 0.49 to 0.63; P � .001) compared with siblings (adjusted for marital status, race/ethnicity, and educational attainment)
-The HR for ever siring a pregnancy (adj for marital status, race/ethnicity, and educational attainment) for Survivors who had an AAD score of 0, a hypothalamic/pituitary radiation dose of 0 Gy, and a testes radiation dose of 0 Gy was 0.91 (95% CI, 0.73 to 1.14; P �= .41)
-Dx of Hodgkin’s lymphoma were least likely to sire a pregnancy (HR, 0.34; 95% CI, 0.28 to 0.41; P =� .001)
-No effect of pituitary irradiation on fertility was observed after adjusting for other risk factors and confounders
- multivariable models: In survivors, the HR of siring a pregnancy was decreased by radiation therapy of more than 7.5 Gy to the testes (HR, 0.12; 95% CI, �0.02 to 0.64), higher cumulative alkylating agent dose (AAD) score or treatment with cyclophosphamide (third tertile HR, 0.42; 95% CI, �0.31 to 0.57) or procarbazine (second tertile HR, 0.48; 95% CI, �0.26 to 0.87; third tertile HR, 0.17; 95% CI, �0.07 to 0.41).
-multivariable models: Compared with siblings, the HR for ever siring a pregnancy for survivors who had an AAD score � 0, a hypothalamic/pituitary radiation dose � 0 Gy, and a testes radiation dose � 0 Gy was 0.91 (95% CI, 0.73 to 1.14; P � .41).
-In both models: receiving cytarabine = more likely to ever sire a pregnancy. In addition, those who were 0-4yrs of age at Dx were more likely to ever sire a pregnancy than those 15-20 yrs. Did not observe differences in the likelihood
of siring a pregnancy for those 5-9 or 10-14 yrs of age, relative to the 15-20yr group.

Comments on results:

-Survivors were younger (P � .001), more likely to be of minority race/ethnicity (P � .001), less likely to have a bachelor’s degree or higher (P � .001), and more likely to have never been married (P � .001)
-alkylating agent dose (AAD) score was calculated by adding the tertile score (1, 2, or 3)11 for each of the alkylating agents given to a particular patient. An AAD score of zero was assigned to nonexposed patients.
-Both models yielded qualitatively identical results whether constructed with or without the inclusion of those for whom age at first pregnancy was imputed.


Evidence ratings

Level of evidence

III-3

Risk of bias
Moderate risk of bias Comments: Querstionnaire based (self-selection bias, recall bias) and <80% uptake.
Result of appraisal

Jutta's tick icon.png Included




Completed by

Dr Jessica Harris

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Article
Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2010 Jan 10;28(2):332-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19949008.
Assigned to
User:Michelle.peate
Topic area
Guidelines:COSA:Cancer fertility preservation guidelines/Impact of cancer on fertility
Clinical question
Form
Form:Critical appraisal


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