Critical appraisal:Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, et al 2003

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Critical Appraisal

Article being appraised

Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, et al. Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003 Feb 15;21(4):716-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12586811.


Applicable clinical question

Key Facts

Study Design

cohort study

Study aims:

to determine the effect, if any, on pregnancy loss, live births, and birthweight of treatment for cancer diagnosed during childhood or adolescence.

Number of Patients:

8405

[[Appraisal number of patients comments::-Cancer group: 4,106 male Childhood Cancer Survivor Study (CCSS) participants (a cohort of 20,319 <21years at Dx b/w 1970-1986 across 25 institutions) -14,008 members of the cohort or their proxy (if the cohort member was deceased) completed a baseline questionnaire and returned it by February 3, 2000.

-Control group: Permission was requested from a random sample of 50% of the cohort to contact their nearest-age male sibling. 7039 patients were selected, of which 5,903 indicated that they had a full sibling who was alive. Permission to contact was given by 4,283. [unclear how many siblings responded so in the number above I have assumed all] -7514 males completed the baseline questionnaire - 4,122 (59%) who answered the question indicated that they had been sexually active. Medical record extraction was completed for 3,472 (84.2%).|-Cancer group: 4,106 male Childhood Cancer Survivor Study (CCSS) participants (a cohort of 20,319 <21years at Dx b/w 1970-1986 across 25 institutions) -14,008 members of the cohort or their proxy (if the cohort member was deceased) completed a baseline questionnaire and returned it by February 3, 2000.
-Control group: Permission was requested from a random sample of 50% of the cohort to contact their nearest-age male sibling. 7039 patients were selected, of which 5,903 indicated that they had a full sibling who was alive. Permission to contact was given by 4,283. [unclear how many siblings responded so in the number above I have assumed all]

-7514 males completed the baseline questionnaire - 4,122 (59%) who answered the question indicated that they had been sexually active. Medical record extraction was completed for 3,472 (84.2%).]]
Reported outcome(s):

pregnancy outcome (incl preganncy, miscariage, live birth) among sexually active males

Results of outcome(s):

-1,227 reported they sired 2,323 pregnancies (69% live births, 1% stillbirths, 13% miscarriages, 13% abortions, 5% unknown or in gestation)
-The proportion of pregnancies of the partners of male survivors was significantly less than siblings (RR = 0.79; 95%CI, 0.65 to 0.96, P =� .016).
-significantly more medical abortions reported by Wilms tumor patients (RR �= 2.43; 95% CI, 1.35 to 4.38; P �= .003).
-Bone cancer patients reported significantly lower rates of live births (RR �=0.59; 95% CI, 0.44 to 0.78; P =� .0003), and significantly higher rates of miscarriage (RR �= 1.58; 95% CI, 1.10 to 2.26; P �=.012) and medical abortion (RR �= 1.56; 95% CI, 1.04 to 2.33; P =� .031), when compared with the partners of sibling controls
-There were no significant differences in pregnancy outcome by treatment
- live birth was significantly lower in survivors than for siblings (RR �= 0.77, P =� .007).
- Only survivors treated with dactinomycin have a lower rate of live births (compared to siblings) (RR=0.68; 95% CI, 0.49 to 0.94; P �= .02). Other chemos/ doses no difference.
-miscarriage higher for survivors Tx with >5,000 mg/m2 of procarbazine than for those treated with 0-5,000 mg/m2 (RR=2.44, 95% CI , 1.28 to 4.67, P �= .007). No difference with cyclophosphamide.

Comments on results:

-male-to-female ratio of the offspring of the partners of the male survivors was significantly different from that of the offspring of the partners of the male siblings of the survivors (1.0:1.03 v 1.24:1.0; P=�.016) --> ration varied according to Tx: surgery only, 1.19:1.0; radiotherapy only, 1.75:1.0; chemotherapy only, 1.0:1.13; surgery and radiotherapy, 1.0:1.08; surgery and chemotherapy, 1.14:1.0; radiotherapy and chemotherapy, 1.07:1.04; surgery,
radiotherapy, and chemotherapy, 1.0:1.22; and unknown 1.05:1.0 [Note that some of these groups were small samples]
-no difference in the distribution of birthweights of offspring when comparing use of alkylating agent, smoking or pelvic irradiaiton (vs not).
-offspring of survivors Tx with nonalkylating agent chemotherapy were more likely to weigh <2,500 g (RR =� 3.03; 95% CI, 1.15 to 7.98; P �= .025).

Includes an economic evaluation

no

Evidence ratings

Level of evidence

III-3

Risk of bias
Moderate risk of bias Comments: Although sources from a large cohort - this relied on returned questionnaires - so some self-selection bais, recall biases etc.

Using teh chonort as a numerator, the response rate (i.e. follow-up rate) was <80%

Result of appraisal

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Completed by

Dr Jessica Harris

Jutta's tick icon.png This appraisal has been completed.


Article
Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, et al. Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003 Feb 15;21(4):716-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12586811.
Assigned to
User:Michelle.peate
Topic area
Guidelines:Cancer fertility preservation guidelines/Impact of cancer on fertility
Clinical question
Form
Form:Critical appraisal


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