Table 1.
Summary of Prior Studies Describing Pregnancy-Related Outcomes in Cancer Survivors
| First Author, Year (Ref. #) | Participants | Recruited Population | Study Design | Median Age at Cancer Diagnosis (yrs) | Median Age at First Pregnancy (yrs) | Median Follow-Up Duration (yrs) | Distribution of Cancers | Cancer Therapy Details | Anthracycline Dose (Median or Mean) |
Prior Cardiomyopathy/Abnormal LV Function Pre-Pregnancy | CTRCD Definition |
Pregnancy-Related Cardiac Outcome Definition | Pregnancy-Related Cardiac Outcomes | Predictors of Pregnancy-Related Cardiac Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bar et al. 2003, (12) |
72 pregnancies (37 women) | Schneider Children’s Medical Centre (Israel). Inclusion: childhood cancer, doxorubicin treatment; exclusions: none |
Prospective cohort study | 12 (range, 3-18) | 24 (range, 18-32) | 17 (range, 6-29) | Leukemia, 35%; lymphoma, 27%; sarcoma, 32%; Wilms’ tumor 6% |
All received anthracyclines, no information on RT | 400 mg/m2 (range, 150-500 mg/m2) | 8 of 37 (22%)/8 of 37 (22%)∗ | FS <30% on TTEs or RNV-EF <50% on 2 sequential tests 1 month apart | ICU admission for HF during or after delivery | 2 of 37 (5%) | Pre-pregnancy LV function |
| van Dalen et al. 2006, (13) |
100 pregnancies (53 women) | Emma Children’s’ Hospital (the Netherlands). Inclusion: age ≥17 yrs; childhood cancer survival ≥5 yrs post-cancer; anthracycline treated; exclusions: none |
Retrospective cohort study | 11.2 (range, 1.5–17.8) | Not stated | Mean 20.3 (range, 5.8-28) | Leukemia 26%; lymphoma 30%; osteosarcoma, 10%; Ewing’s sarcoma, 19%; Wilms’ tumor, 2%; others, 13% |
All received anthracyclines; 10 patients received RT | 267 mg/m2 (range, 60-552 mg/m2) | 2 of 53 (4%)/NA | Clinical HF (signs + symptoms treated with diuretics during or after chemotherapy | Clinical HF (signs + symptoms treated with diuretics, during pregnancy or <5 months after delivery) | No clinical HF events; no routine cardiac imaging performed | No events |
| Hines et al. 2016, (14) |
1,554 pregnancies (847 women) | St. Jude Children’s Hospital (U.S.). Inclusions: childhood cancer, survival ≥5 yrs after cancer, >13 yrs of age at follow-up; had at least 1 delivery; exclusions: none |
Retrospective cohort study | 10.3 (range, 0.02-22.6) | 22.4 (range, 13.8-40.1) | 26.5 (range, 6.0-48.4) | Leukemia, 38%; lymphoma, 23%; sarcoma, 14%; embryonic tumors, 10% others 15% |
484 patients received anthracyclines (248 also received RT); 363 patients received nonanthracycline therapy (140 received RT) | 200 mg/m2 (39-721 mg/m2) | 26 of 847 (3%)/8 of 847 (1%) | EF <50% or FS <28% by TTE or treatment for HF | LVEF <50% or FS <28% by TTE or treatment for HF within 5 months of delivery (outcomes were self-reported) | 8 of 26 (31%) inpatients with previous CTRCD; 3 of 821 (4%) had new diagnoses during pregnancy (2 asymptomatic LV dysfunction, 1 HF) |
Higher anthracycline dose |
| Thompson et al., 2017 (15)† |
86 pregnancies (58 women) | MD Anderson Cancer Center (U.S.). Inclusions: age 16-55 yrs; cancer diagnosis before age 20 yrs; treated with anthracyclines or chest irradiation. Exclusions: history of abortion or miscarriage; Down syndrome; death without adequate follow-up |
Retrospective cohort study | 11.8 (range, 0.5-19.5)† | 23.0 (range, 16-37)† | 20.2 (range, 5.2-48.2)† | Childhood cancer survivors (no details) | All received anthracycline and/or XRT (numbers in each group not provided) | 292.5 mg/m2 (0-480 mg/m2)† | 3 of 58 (5%)/NA | EF <50% on 2 TTEs or CAD | LVEF <50% on 2 TTEs or CAD within 12 months of delivery | 11 of 58 (19%; all asymptomatic LV dysfunction; 2 of 3 in patients with previous CTRCD; 9 of 55 had new diagnoses during pregnancy.† | High anthracycline dose; younger age at cancer diagnosis; longer time from cancer therapy to first pregnancy |
| Liu, et al., 2018 (16) | 94 pregnancies (78 women) | Mt. Sinai Hospital (Canada). Inclusions: Female; potentially cardiotoxic treatment; exclusions: unknown cancer or treatment; familial cardiomyopathies |
Retrospective cohort study | 28 (range, 2-41) | 34 (range, 22-43) | During pregnancy and peripartum period | Lymphoma, 33%; leukemia, 10%; breast cancer, 32%; Wilms' tumor, 8%; osteosarcoma, 7%; others, 10% |
55 patients received anthracyclines; 16 received nonanthracycline (33 among this 71 received RT); 7 received RT only | 290 mg/m2 (90-500) mg/m2‡ | 13 of 78 (17%); 7 of 78; (10%) |
LVEF to <50% with or without HF symptoms | Composite of cardiac death, clinical HF (signs + symptoms + diuresis escalation or admission), ACS, arrhythmia up to 16 weeks after delivery | 5 HF events in 4 patients; all in patients with previous CTRCD | History of CTRCD; LVEF <53% at the start of pregnancy; cardiac medications |
| Chait-Rubinek, et al., 2019 (17) | 110 pregnancies (64 women) | Peter MacCallum Cancer Centre (Australia). Inclusions: age <30 yrs at cancer diagnosis; ≥5 yrs since cancer treatment; or ≥2 yrs after allogeneic stem cell transplantation. Exclusions: pregnancies prior to 5-yr timepoint since cancer treatment |
Retrospective cohort study | 18 (range, 2-29) | 31 (range, 19-42) | NA | Leukemia, 13%; lymphoma, 66%; Ewing sarcoma, 8%; Wilms’ tumor, 6%; osteosarcoma (1.5%); hepatoblastoma (1.5%); others, 5% |
55 patients received anthracyclines (28 received RT); 9 received nonanthracycline (4 received RT); 5 had RT only | 270 mg/m2 (150–600 mg/m2) | 1/64 (2%); 1/64 (2%) |
Treatment-induced cardiotoxicity (as diagnosed by a cardiologist) prior to pregnancy | Symptomatic cardiac dysfunction defined (clinical signs of HF requiring diuresis therapy with LVEF <50% or FS <28%). Subclinical dysfunction was defined as the absence of clinical features with LVEF <50% or FS <28% during pregnancy or <5 months after delivery |
3 symptomatic cardiac dysfunction events (0 in patients with prior CTRCD) 2 subclinical cardiac dysfunction events (1 in a patient with prior CTRCD) |
Younger age at time of cancer diagnosis; higher cumulative anthracycline dose; diagnosis of solid tumor |
CTRCD = cancer therapy-related cardiac dysfunction; ACS = acute coronary syndrome; CAD = coronary artery disease; FS = fractional shortening; HF = heart failure; ICU = intensive care unit; LVEF = left ventricular ejection fraction; RNV-EF = Radionuclide Ventriculography; TTE = transthoracic echocardiogram; XRT/RT = radiation involving the chest.
∗
Based on a fractional shortening of <30%.
†
Data were obtained through personal communication with the author. All outcomes were EF <50%; none of the patients experienced coronary artery disease.
‡
Data were available only in 23 of 55 patients who received anthracyclines.