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ORIGINAL RESEARCH |
From the *Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine and Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, Canada; Department of Pediatrics, Tel Aviv University, Sackler School of Medicine, Ramat Aviv, Israel; and University Musculoskeletal Oncology Unit, Mount Sinai Hospital and the Sarcoma Site Group, Princess Margaret Hospital, University of Toronto and Department of Surgery, University of Toronto, Toronto, Canada.
Address reprint requests to: Cynthia Maxwell, MD, FRCSC, Department of Obstetrics and Gynecology, Mount Sinai Hospital, OPG 3, 600 University Avenue, Toronto, ON Canada M5G 1X5; e-mail: cmaxwell{at}mtsinai.on.ca.
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ABSTRACT |
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METHODS: Pregnant women diagnosed with bone or soft-tissue tumors during pregnancy or within 3 months after delivery were identified retrospectively for the years 1983–2003 in the University Health Network database, University of Toronto. Relevant maternal and neonatal data were collected on a standardized data form.
RESULTS: In more than 60,000 deliveries during the study period, 17 patients were identified. Gestational age at diagnosis ranged from 11 weeks to 2 months postpartum. Eight cases involved the lower extremity and 6 involved the upper extremity. Osteosarcoma, chondrosarcoma, and giant-cell tumors were the most common histological types. Metastases occurred in 7 cases. Nine cases were treated surgically during the course of pregnancy. The majority of patients were delivered at term. Chemotherapy was deferred until the postpartum period. One patient elected for early termination of pregnancy. Three patients were delivered before 37 weeks of gestation to proceed with therapy. One neonate delivered at 34 weeks developed respiratory distress syndrome and required intubation. Three patients died, all as the result of metastatic disease. There were no perinatal or infant deaths.
CONCLUSION: Most cases of soft-tissue and bone tumors during pregnancy can be successfully managed with surgery during gestation. Therapies with fetal toxicity were more likely to be deferred to the postpartum period.
LEVEL OF EVIDENCE: III
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MATERIALS AND METHODS |
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RESULTS |
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Nine patients underwent operative procedures to remove their tumors and in some cases to reconstruct their limbs during pregnancy. No patients received chemotherapy or radiation while pregnant. Only 1 operative procedure was complicated by transient preterm labor at 29 weeks of gestation. The patient received tocolysis and was ultimately delivered at term. One patient had been treated previously for a malignant peripheral nerve sheath tumor with surgery and radiation. She subsequently developed radiation-induced leiomyosarcoma and presented with a pathological fracture of the right humerus at 22 weeks of gestation. At 28 weeks of gestation she underwent resection and reconstruction with a proximal humeral allograft. She had an uncomplicated vaginal delivery at term. Several years later, she went on to have recurrent disease.
Seven patients presented with metastatic or locally advanced disease. Two of these patients were intentionally delivered before 37 weeks of gestation to expedite maternal therapy. One patient experienced a pathological fracture of the right femur as the result of a primary osteosarcoma at 26 weeks of gestation and underwent en bloc resection and reconstruction with an uncemented proximal femur tumor prosthesis at 28 weeks of gestation. As a result of a chest computed tomography scan showing evidence of pulmonary metastases, she was induced at 34 weeks of gestation to begin urgent postpartum treatment with systemic chemotherapy.
The majority of patients delivered vaginally (76%). One patient delivered dichorionic twins vaginally at 35 weeks of gestation. Indications for cesarean delivery included marginal placenta previa, joint and physical limitations, and elective repeat. One patient elected for early termination of pregnancy to proceed with radiation and chemotherapy for mesenchymal chondrosarcoma complicated by lung metastases. There were 2 maternal deaths related to metastatic disease (patients 3 and 4) both of which occurred within 1 year of delivery. The third death (patient 19) occurred 7 years after delivery, also as the result of metastatic disease.
Three mothers (18%) were delivered before 37 weeks of gestation, resulting in the birth of 4 preterm neonates. All were delivered early to facilitate maternal therapy for their tumors. There were no cases of intrauterine growth restriction. All infants were admitted to the NICU after delivery. Two neonates (a set of twins in a patient with osteosarcoma) were treated for transient tachypnea of the newborn. One infant developed respiratory distress syndrome requiring surfactant therapy and intubation for 48 hours. This infant was also treated for hyperbilirubinemia of prematurity and subsequently did well. The majority of infants (67%) were delivered after 37 weeks of gestation. None of the infants or their placentas showed evidence of metastatic disease on postnatal examination.
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DISCUSSION |
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The counseling of pregnant patients presenting with bone and soft-tissue tumors offers many challenges. A major concern is maternal prognosis and survival, which varies depending on tumor type and grade. Tumors such as chondrosarcoma,9,10 osteosarcoma,11 and angiosarcoma12 carry a worse prognosis when compared with nonmalignant lesions, such as giant-cell tumors, which are locally aggressive but have an excellent long-term prognosis with only rare cases developing metastases.13,14
A major concern for pregnant patients is the potential fetal risks from the presence of maternal tumors, surgery, chemotherapy, and radiation from X-ray studies and radiotherapy. Bone tumors have been shown to metastasize to the placenta, although fetal metastasis has not been reported.15,16 The involvement of the placenta by tumor could lead to a theoretical risk of intrauterine growth restriction, although this remains unlikely and has not been described in the literature.
There is much experience with surgical intervention and general anesthesia in pregnant mothers, and these processes are generally regarded as safe.17 Given concerns with potential airway difficulties in pregnant mothers, particularly at advanced gestational ages, regional anesthetic techniques are preferable.18
Chemotherapy rarely is used during pregnancy, given the potential for teratogenicity in the first trimester and risk of fetal growth restriction throughout gestation.19 In most cases, chemotherapy will be delayed until delivery of the infant can be achieved at an advanced gestational age (32–34 weeks). For some tumors that are responsive to chemotherapy, such as osteosarcoma, a delay in therapy may affect prognosis, and a discussion regarding indicated preterm delivery or termination of pregnancy should take place between the physician and patient. In the case of osteosarcoma, prognosis is dependent on the extent of pathological necrosis resulting from neoadjuvant chemotherapy, in addition to presence of metastases.8 Thus, early delivery, with the possible administration of antenatal corticosteroids depending on gestational age, may be indicated in such cases. Longhi et al20 reported on reproductive function and fertility in patients treated with chemotherapy for osteosarcoma. They found that normal menstrual function returned in the majority of patients, and no congenital anomalies were found in the newborns.
A review of the medical literature reveals several studies describing either case reports or case series of pregnant women with soft-tissue and bone tumors. In a retrospective study by Simon et al,21 33 patients were identified. Nineteen of these patients were diagnosed during pregnancy and 14 within 3 months postpartum. Of the 8 women diagnosed in the first trimester, 3 elected to terminate the pregnancy. Four patients were induced before 37 weeks of gestation, with the earliest induction at 32 weeks of gestation. There were 25 liveborn infants and 2 perinatal deaths, both of which were the result of prematurity. The deliveries resulting in perinatal deaths took place in 1961 and 1968, respectively, and the gestational age at birth was not reported. It is unlikely that the mothers received antenatal corticosteroids during this era. Eight patients underwent surgery during gestation, but all chemotherapy and radiation were reserved for the postpartum period. Four of the patients, all with metastatic osteogenic sarcoma, died within 2 years of their diagnosis. The authors concluded that pregnancy did not affect the mortality and that therapeutic abortion should not be routinely recommended in cases diagnosed early in gestation unless chemotherapy is indicated.
Huvos et al22 performed a case–control study from 1921 to 1981 comparing 18 pregnant women with osteogenic sarcoma with nonpregnant controls. The majority of patients were treated surgically, whereas radiation and chemotherapy were used in selected cases during pregnancy. Because there were no adverse neonatal outcomes, the authors concluded that management of these tumors during pregnancy did not pose excess risk to the mother or fetus. Outcomes in pregnant mothers did not differ significantly from the matched, nonpregnant control subjects.
Merimsky and Le Cesne23 have reported on pregnant patients with bone and soft-tissue sarcomas. In an early publication, the outcomes of 7 pregnant patients were described. In 5 of the cases, the authors state that diagnosis and treatment of malignancy were delayed because of pregnancy. One patient received chemotherapy during the third trimester without fetal toxicity. There was 1 case of prematurity and 1 small-for-gestational-age infant, but otherwise there were no other neonatal complications. In a more recent article, Merimsky et al24 describe 13 patients. Most of these patients did not receive surgery until after delivery, and none received chemotherapy or radiation during gestation. All patients reported disease progression during pregnancy. The 1-year survival rate was 78%, and the 5-year survival rate was 37.5%, comparable with nonpregnant controls as reported by Huvos et al.22 One mother in this cohort died from metastatic Ewing's sarcoma (also published as a separate case report).25
Pregnancy has not been shown to aggravate the progression of these tumors. However, several investigators have identified estrogen and progesterone receptors in giant-cell tumors and chondrosarcomas26 as well as in angiosarcomas.27 The implication of such receptor status in tumors associated with pregnancy is unknown.
Because cumulative radiation greater than 5 rem in pregnancy has been reported to carry a risk of teratogenicity, potential neurological injury, and future myelogenous neoplasm to the fetus, the exposure of pregnant women to X-ray studies should be kept below this level.28 Shielding of the maternal abdomen should be conducted whenever possible to further minimize this exposure. Because radiation therapy involves much higher exposures, it is usually deferred until after delivery.
In summary, pregnant women with bone and soft-tissue tumors tend to have maternal and fetal outcomes similar to their nonpregnant counterparts if they receive appropriate local and systemic treatment. The major difference in management during pregnancy is often a delay in chemotherapy and radiation treatment until after delivery. Surgical resections may be performed safely during all 3 trimesters of pregnancy. Vaginal delivery is possible, unless obstetric factors favor cesarean delivery. A multidisciplinary approach is helpful in managing these complex cases and in providing in-depth counseling. Although a frank discussion regarding maternal and fetal prognosis and mortality presents a challenging situation for the pregnant patient, her family, and health care providers, families need to be well prepared to plan for parenting and social supports. Conversations involving the patient, perinatologist, surgical oncologist, neonatologist, anesthesiologist, and specialists from other disciplines as well as relevant social services can facilitate this process.
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Footnotes |
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10.1097/01.AOG.0000133502.76679.71
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REFERENCES |
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This article has been cited by other articles:
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  A. Longhi, M. Mercuri, G. Bianchi, C. Errani, and G. Bacci Maternal and Neonatal Outcomes in Pregnancies Complicated by Bone and Soft-Tissue Tumors Obstet. Gynecol., February 1, 2005; 105(2): 447 - 447. [Full Text] [PDF]
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