Tumori, 94: 431-433, 2008
An adolescent with rhabdomyosarcoma during pregnancy Cristina Meazza, Michela Casanova, Elena Zaffignani, Carlo Alfredo Clerici, Francesca Favini, Roberto Vasquez, and Andrea Ferrari Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
ABSTRACT
We report the case of a 15-year-old girl with a large gluteal and perineal rhabdomyosarcoma diagnosed at 24 weeks of pregnancy, whose management posed a great clinical dilemma for us. The patient refused to consider a therapeutic abortion, so we opted for a customized treatment with mild doses of chemotherapy administered weekly to control tumor growth while minimizing fetal and perinatal complications. After the delivery of a healthy female, we adopted a more intensive chemotherapy regimen plus irradiation. Despite an initially good response, the disease unfortunately progressed and the patient died of her disease.
Introduction The case of a 15-year-old girl at 24 weeks of pregnancy with a diagnosis of alveolar rhabdomyosarcoma (RMS) is an exceedingly uncommon event. Cancer in pregnancy is relatively uncommon (1 per 1,000 pregnant women), the most frequently reported being breast cancer, head-neck carcinomas, lymphoma and melanoma1. A diagnosis of cancer in such a young pregnant woman is exceptionally rare, and a very arduous challenge for the pediatric oncologist. Chemotherapy in pregnancy is known to increase the risk of spontaneous abortion, fetal death and major malformations. If chemotherapy cannot be delayed until after delivery and abortion is refused, the clinical dilemma naturally becomes how to treat the mother adequately while minimizing the fetal complications. Such a situation poses very particular ethical issues for the mother and her unborn child as well as for the clinicians.
Case report In September, 2005, a 15-year-old girl 24 weeks into pregnancy was admitted to our institution with a 3-month history of pain and a huge, ulcerated gluteal and perineal mass. Abdominal magnetic resonance imaging (MRI) was performed immediately and revealed a mass 14 x 8 x 7 cm in size, arising in the perineal region and involving the rectum and anal region (Figure 1). The patient underwent chest X-ray and abdominal ultrasound, which ruled out any lung or retroperitoneal metastases; computed tomography (CT) and bone scans were deferred to minimize the radiation exposure risk to the fetus. The patient underwent open biopsy that led to a diagnosis of alveolar RMS. The diagnosis was discussed with the patient and her family and they were informed particularly of the risks and benefits of standard RMS therapy. The patient resolutely refused a therapeutic abortion and asked for a treatment that might adequately control tumor growth, minimizing fetal and perinatal complications. She was evaluated by gynecologists, who suggested reaching 29-30 weeks of gestation before proceeding with a cesarean section.
Key words: rhabdomyosarcoma, pregnancy, chemotherapy. Acknowledgments: This research was partly funded by the Associazione Bianca Garavaglia. The authors wish to thank Dr Davide Scaramuzza for the radiological picture. Correspondence to: Cristina Meazza, MD, Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian, 20133 Milan, Italy. Tel +39-02-23902588; fax +39-02-23902648; e-mail
[email protected] Received July 5, 2007; accepted July 13, 2007.
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size), consistent with post-irradiation inflammation. The patient was given anti-inflammatory and antibiotic therapy, but MRI performed 45 days later unfortunately revealed local and nodal disease progression, associated within a matter of a few days with the onset of multiple subcutaneous breast nodules. Second-line therapy with vinorelbine and oral cyclophosphamide was to no effect and the patient died one month later.
Discussion
Figure 1 - Magnetic resonance image showing the fetus close to the perineal mass.
After much discussion, we chose a customized chemotherapy regimen consisting of weekly treatments alternating cyclophosphamide (500 mg/m2 intravenously) plus doxorubicin (40 mg/m2) with cyclophosphamide plus actinomycin-D (1 mg/m2). This chemotherapy was chosen to avoid myelosuppression and the risk of infection. The patient received 3 cycles of chemotherapy without any complications. Gynecological assessments and fetal ultrasound were performed weekly, revealing only a mild oligohydramnios, while fetal development, activity and growth remained normal. Seventeen days after the third cycle, at 29 + 3 weeks of gestation, the patient underwent a cesarean section and delivered a healthy female weighing 2.8 kg with an Apgar score of 9. The newborn was normal at physical examination and according to blood test findings, and was discharged in good condition after a few days. Three days postpartum the patient had abdominal MRI showing partial tumor remission. A chest CT scan performed at this point was negative, so we decided to start a more intensive chemotherapy regimen using the IVADo schedule (ifosfamide, vincristine, actinomycinD, doxorubicin)2. After 4 cycles, she received hyperfractionated accelerated radiotherapy (total dose 44.8 Gy) simultaneously with 2 cycles of carboplatin and etoposide; after that, 2 further IVA cycles (ifosfamide, vincristine, actinomycin-D) were given. Abdominal MRI performed at the end of these treatments showed complete tumor remission with diffuse contrast enhancement of the pelvic-perineal tissues and enlarged iliac lymph nodes (around 1.5-2 cm in
The overall cure rates for children with RMS have improved over the past decades, and 70-80% of patients with localized disease are currently cured3,4. Nevertheless, the chances of survival depend on different prognostic clinical variables: the patient described in this report presented at diagnosis with very unfavorable features, i.e., age >10 years, tumor size >5 cm, local invasiveness (T2), alveolar subtype, and perineal-pelvic site. According to current treatment protocols, a patient with these characteristics warrants intensive multidrug chemotherapy and appropriate (early) local treatment. The really uncommon characteristic of our patient, however, was that she was pregnant; therefore, it was impossible for us simply to start with chemotherapy according to the patient’s risk group. The clinical and ethical dilemma was whether to give priority to the health of the fetus or the mother, and how to ask such a young patient to make such a difficult decision. The patient’s family situation was also particularly problematic, i.e., the unborn child’s father was unknown, the patient’s father was absent, and her mother (the only adult she could talk to) was pregnant too. We talked for a long time with the patient and her mother about what could be done, considering the potential teratogenicity of cytotoxic drugs and the threat to the future mother’s life related to an “inadequate” treatment. The patient resolutely refused the option of a therapeutic abortion: she wanted her child and she wanted to be cured. The risks of teratogenic effects of drugs generally depend on the timing of exposure, dosage, and the characteristics affecting placental transfer5. While the risk of spontaneous abortion, fetal death, and major malformations is high when chemotherapy is used during the first trimester of pregnancy, exposure during the second and third trimesters may be relatively well tolerated, though it increases the risk of limited intrauterine growth and low birth weight6,7. We therefore recommended a customized treatment strategy using relatively safe drugs such as cyclophosphamide, doxorubicin and actinomycin-D7. To avoid clinical complications, and myelosuppression in particular, chemotherapy was given at mild dosages (but administered weekly). Vincristine was not used because of the risk of fetal lesions8-11. The aim of this therapy was to reach the 29-30 weeks of gestation, perform a cesarean
RHABDOMYOSARCOMA DURING PREGNANCY
section, and then move on to more intensive chemotherapy. This strategy was unfortunately unable to achieve both final goals (cure the patient and enable the birth of her baby): a healthy child was born, but the mother died of tumor progression. It is hard to say whether the changes made to the treatment regimen reduced the mother’s chances of cure. The clinical features of her tumor at presentation were so unfavorable that she was at high risk of failure regardless of the treatment received. On the other hand, the mild initial chemotherapy may have facilitated a subsequent onset of multidrug resistance, despite the initial remission. Similarly, the delay in administering radiotherapy (week 19 instead of weeks 9-12) may be at least partially responsible for our failure to achieve local control. Of course, no standardized treatments are available for patients with cancer during pregnancy, and certainly not for patients with RMS, though there has been one report of an 18-year-old patient with orbital RMS diagnosed at 29 weeks of gestation successfully treated with full-dose chemotherapy with no fetal complications12. The case presented gave us the opportunity to discuss the difficult ethical issues related to the management of such patients, but also suggests that major treatment modifications (i.e., lower chemotherapy dosages) may minimize the risk for the fetus but jeopardize the chances of cure for the mother.
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