Saturday 3 March 2012

Cancer Treatment OK During Pregnancy

Cancer in pregnant women can usually be treated without terminating the pregnancy and with little impact on infants carried to full term, according to a series of reports.

Children exposed to chemotherapy in utero showed no delay in growth or increase in problems with their central nervous system, heart, or hearing compared with the general population, Frederic Amant, PhD, of University Hospitals Leuven in Leuven, Belgium, and colleagues reported online in The Lancet Oncology.

Pregnancy should be preserved whenever possible with breast and gynecologic cancers, although hematologic cancers can be a problem in the first trimester, separate reviews in the Feb. 11 issue of The Lancet concluded.

"True oncological emergencies in pregnant patients are rare (except for leukemia)," Philippe Morice, MD, of Institut Gustave Roussy in Villejuif, France, and colleagues wrote in a commentary accompanying the Lancet series.
That makes timing the big question in cancer treatment during pregnancy, they noted.
"The crux of the dilemma is finding a balance between the need to delay treatment while the fetus develops and the need to induce a premature delivery," the commentary said.

Prematurity was the one risk identified among 70 children exposed to chemotherapy as part of their mothers' treatment for cancer during pregnancy in a multicenter observational study by Amant's group.
Two-thirds of the children were born before 37 weeks gestation. Their cognitive development scores, although still in the normal range, were lower than those carried to term.
Each additional month of gestation was associated with a statistically significant 11.6-point mean increase in IQ (100 is average).

Other assessments, including behavior, overall health, hearing, and growth, came up normal for the children exposed in utero to chemotherapy who were followed to about age 2.
Some subtle differences in cardiac and neurocognitive measures, though, might warrant further monitoring, Amant's group suggested.

"This study can reassure pregnant women, and their physicians, that the benefits of maternal treatment do not seem to be outweighed by any long-term consequences for the exposed fetus with regards to cardiac or neurological function," Elyce Cardonick, MD, of Cooper University Hospital in Camden, N.J., wrote in an accompanying commentary.

For the mothers, available evidence also suggests that these women don't face higher mortality risk from their cancers than nonpregnant cancer patients, Morice noted.

Gynecologic Cancers
That's the case in cervical and ovarian cancer, for which European guidelines recommend preserving pregnancy, Morice and other researchers noted in one of the Lancet papers.
Tips for treatment of gynecologic cancers in their review included:
  • Early-stage cervical cancer during the first and at the beginning of the second trimester: MRI and laparoscopic lymphadenectomy can help plan a potentially conservative approach
  • Small tumors and tumors without nodal spread: intentionally postponing treatment until fetal maturity and delivery is an option, with careful clinical and radiological follow-up, however radical trachelectomy and neoadjuvant chemotherapy might be appropriate
  • Locally advanced cervical disease: treatment with neoadjuvant chemotherapy and preservation of the pregnancy or chemotherapy and radiotherapy is controversial and should be decided case by case based on tumor size, radiological findings, term of pregnancy, and patient wishes
  • Tumors with peritoneal spread or high-risk early-stage disease: neoadjuvant chemotherapy with pregnancy preservation might be possible, holding completion surgery until after delivery
For various histological types of malignant ovarian diseases, management should depend on the diagnostic characteristics, tumour stage, and term of the pregnancy.

Targeted therapies may have a negative impact on fetal development and should be avoided in pregnancy.

Breast Cancer
A review led by Amant on breast cancer in pregnancy suggested no reason to terminate the pregnancy, since it doesn't improve prognosis for the mother.

Treatment is not only possible during pregnancy but can actually improve the outlook for the baby by preventing medically-induced preterm birth, Amant's group reported.

Chemotherapy is supported by evidence for use after fetal organs form, from 14 weeks' gestation on, while surgery can be done during any trimester.

Radiation, depending on the dose received by the fetus, can result in poor fetal outcomes, so that decision should be made on an individual basis, the researchers noted.

The diagnostic strategy should also be discussed with multidisciplinary help to reduce fetal radiation exposure, they added.

Again, targeted and hormonal therapies like bevacizumab (Avastin) and trastuzumab (Herceptin) were noted as contraindicated in pregnancy for women with breast cancer.

Hematologic Cancers
Things are a little more complicated in hematologic cancer in pregnancy, Benjamin Brenner, MD, of the Israel Institute of Technology in Haifa, Israel, and colleagues reported in a third review.

These cancers, although rare, aren't easy to diagnose because of an overlap between symptoms of disease and of gestation and because of limitations of imaging in pregnancy, they noted.

"The primary goal of treatment is to preserve the mother's health; hence, pregnancy termination is often advisable at early stages, allowing delivery of adequate therapy," Brenner's group wrote. "However, at later gestational stages treatment is often feasible."

Medication to prevent blood clots is often necessary to prevent vascular complications in mother and fetus because the hypercoagulability induced by pregnancy is worsened by cancer.
Further study is needed across cancer types in pregnancy, as occurrence is likely to increase, all the groups agreed.

"As women in developed societies defer childbearing, and because the incidence of most malignancies rises with increasing age, the situation in which cancer complicates pregnancy is expected to become more common," Amant's review noted.

Amant reported being a senior clinical investigator for the Research Fund-Flanders.
Morice's group reported having no conflicts of interest to disclose.
Brenner's group reported having no conflicts of interest to disclose.
None of the commentators reported having conflicts of interest to disclose.

Primary source: 
The Lancet Source reference: Morice P, et al "Gynaecological cancers in pregnancy" Lancet 2012; 379: 558–69.Additional source: The Lancet OncologySource reference: Amant F, et al "Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: an observational study" Lancet Oncol 2012.Additional source: Amant F, et al "Breast cancer in pregnancy" Lancet 2012; 379: 570–79. Source reference: Amant F, et al "Breast cancer in pregnancy" Lancet 2012; 379: 570–79.

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