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Cancer in Pregnancy: Lung Cancer and Pregnancy
Lung cancer during pregnancy is rare. However, the number of cases may be growing due to the combined effects of increased cigarette consumption in young women and delayed child bearing.
The incidence of lung cancer complicating pregnancy is unknown. The presenting signs and symptoms associated with lung cancer and pregnancy are similar to the non pregnant state and depend mainly on the stage of the lung cancer. Symptoms related to the growth of the tumor, such as blood-streaked sputum, persistent cough or change in cough pattern, wheesing, decreased appetite with poor weight gain during pregnancy, along with other loco-regional symptoms (with or without a detectable pleural effusion) are commonly seen. Delays in the diagnosis may occur due to reasons such as low index of suspicion, tendency to attribute symptoms such as fatigue and dyspnea on the pregnant state and physician reluctance to order a chest radiograph during pregnancy.
A detailed history and accurate physical examination remain the most important steps in the evaluation of these patients, including assessment of risk factors. Plain anteroposterior and lateral chest radiographs are the most valuable tools in the diagnosis of lung cancer 1. Ultrasound and MRI studies are probably appropriate for metastatic work-up, especially in subdiaphragmatic sites 2.
Diagnostic evaluation consists of histologic confirmation and staging. The former can be achieved by sputum cytology, percutaneous fine needle aspiration, bronchoscopy with biopsy or by bronchoalveolar lavage. In patients with metastatic disease, biopsy of other readily accessible sites (i.e. palpable nodes) is also a reliable and relatively non-invasive procedure.
Lung cancer staging consists of physical examination in combination with surgical and radiologic investigations. Staging investigations must focus on the determination of the local extent of the disease if surgery is considered and possible sites of metastatic disease. Decisions regarding the use of radiological investigations must take into account the age of the fetus and the estimated dose of radiation delivered with the respective imaging study.
The metastatic workup is determined by the presenting signs and symptoms as well as the histological subtype (small cell vs non-smallcell).
There is no evidence that therapeutic abortion offers a survival advantage. The need for chemotherapy or radiotherapy during the early stages of pregnancy for rapidly progressive disease (i.e. small cell lung cancer) may lead to consideration of termination of pregnancy.
Pathology and Biology
Little is known about the effect of pregnancy on the course of lung cancer. The published experience with non-small cell lung cancer is limited to nine case reports 3-12. The histologies recorded include: large cell (2 cases), adenocarcinoma (4 cases), squamous cell (2 case) and bronchoalveolar (1 case). The median age was 35.5 (range 29-44). With the exception of 2 patients, all the patients presented with metastatic disease. Maternal data is insufficient to comment on association with smoking.
Data on small cell lung cancer and pregnancy is also scarce.
Five case reports have been published . All 5 cases had involvement of the placenta by the tumor, suggesting extensive disease.5, 11, 13-15
Stage I and II (T1-2, N0-1, M0)
The treatment of choice in early stage non-small cell lung cancer is curative surgical resection. Despite primary control, combined-modality treatments are being investigated, since micrometastatic disease is probably present at the time of initial treatment. There is no contraindication to surgery during pregnancy, but appreciation of altered maternal physiology due to the pregnancy, teratogenicity of medications and rates of fetal loss according to stage of pregnancy is mandatory for the anesthetist. Treatment delay until after delivery is an option in patients late in the pregnancy. There is a single case report dealing with early stage lung cancer5. A 34 year old patient presented with a symptomatic left lower lobe mass in the seventh month of pregnancy. She delivered a healthy baby and postpartum underwent a left lower lobectomy. The pathology was consistent with squamous cell carcinoma; she died of metastatic disease 3.5 years later.
Stage III A ((T1-3, N2, M0 or T3, N0-2, M0)
The treatment of patients with this stage of non-small cell lung cancer depends on the size and location of the primary tumor and the extent of nodal involvement. Treatment options in non-pregnant patients may include different combinations of surgery, chemotherapy and radiotherapy.
Stage IIIB (any T, N3, M0 or T4, any N, M0)
Patients with this stage of lung cancer have a poor prognosis and generally receive radiation with or without chemotherapy.
Stage IV (any T, any N, M1)
This stage of lung cancer has a poor prognosis and treatment is palliative. Treatment options include chemotherapy, radiotherapy to symptomatic areas and palliative surgery for situations such as impending fracture of the femur. In light of the limited success of chemotherapy in treatment of metastatic non-small cell lung cancer, delay in treatment until after delivery is a reasonable option.Supportive care, to maximize maternal oxygenation and nutrition is mandatory in all stages of lung cancer.
With respect to non-small cell lung cancer, experience with treatment during pregnancy is limited to 2 cases; both were in the later stages of pregnancy. One patient presented at 23 weeks with symptoms of a poorly differentiated adenocarcinoma of the lung 4. Treatment consisted of chest radiation (2800 rads) and resection of a metastatic right mandibular node followed by radiation to that area (2000 rads). Aggressive supportive treatment including TPN, oxygen and steroids was carried out. Delivery at 30 weeks by emergency cesarean section was prompted by maternal respiratory failure. A male infant with Apgar scores of 3 and 7 was delivered. Birth weight was 1300 g (appropriate for gestational age). Mild respiratory distress syndrome was the only complication of the neonatal course.
The other case involved intramedullary nailing and palliative radiotherapy (with fetal shielding) to the left femur in a 36 year old patient who presented with metastatic adenocarcinoma at 29 weeks gestation 8. Delivery of a healthy male infant occurred at 32 weeks after spontaneous membrane rupture. At 8 months follow-up, the infant was healthy. In the remainder of the cases, patients who presented with metastatic disease received postpartum treatment or supportive care only.
Small Cell Carcinoma
Small cell lung cancer is characterized by an aggressive clinical course and relatively good (although short lived) response to chemo/radiotherapy compared to other types of lung cancer. Treatment during pregnancy must balance the toxicity of treatment to mother and fetus against the morbidity of untreated disease. None of the case reports of small cell lung cancer involved treatment during pregnancy 5,11,13-15. Patients received postpartum chemotherapy or radiotherapy or supportive treatment only.
Most drugs have, at best, moderate activity in non-small cell lung cancer. Cisplatin is considered by many investigators to be the most active single agent 2. Combination chemotherapy was investigated in an attempt to increase response rates. Cisplatin and vinorelbine are considered a standard regimen against which future investigational regimens should be measured, since this combination proved superior to the single agent 2.
Antineoplastic drugs are very potent teratogens. Currently, there is very little information on the effect of cancer chemotherapy on the fetus 16. The risk of malformations when chemotherapy is administered in the first trimester has been estimated to be around 10% for single agent chemotherapy 17 and 25% for combination chemotherapy 18. It is generally suggested that chemotherapy be avoided during first trimester, when cells are actively dividing. Use of these agents in the second and third trimesters has been associated with an increased risk of stillbirth, intrauterine growth retardation and low birth weight 16,19,20. When chemotherapy is administered during pregnancy, timing of delivery of the infant should take into account the expected bone marrow depression and potential problems such as bleeding or infections. Self limiting fetal haematopoetic depression has been described and the neonate should be monitored for complications of this 21. Long term neurodevelopmental complications of in utero chemotherapy exposure have not been extensively studied. Limited data exist to suggest that this may be normal in the offspring of patients with haematologic malignancies treated during various stages of the pregnancy 22.
There is no evidence that pregnancy alters the prognosis of lung cancer. Maternal outcome for both small cell and non-small cell lung cancer has been poor and is a reflection of the advanced stage at diagnosis. This may be due in part, to misinterpretation of respiratory symptoms and physician's reluctance to perform radiologic imaging studies during pregnancy 23.
There is no evidence that fetal outcome is adversely affected by maternal lung cancer, provided that adequate supportive treatment is provided to the mother. Metastatic involvement of the placenta has been reported in the majority of the reported cases. In contrast, there were no reports of fetal involvement 11.
Cytotoxic agents administered systemically may reach significant levels in breast milk and thus breast feeding while on chemotherapy is contraindicated.
There is no evidence that fertility is adversely affected by lung cancer itself. However, some chemotherapeutic agents can cause sterility which may be age dependent.
- Nicklas A, Baker M. Imaging strategies in the pregnant cancer patient. Seminars in Oncology:Vol 27, No 6, December, 2000.
- Vincent T, Devita JR, Hellman S, Rosenberg SA. Cancer. Principles & Practice of Oncology. 5th Ed. Lippincott-Raven Publishers. 1997.
- Read E. J. J. and Platzer P. B. Placental metastasis from maternal carcinoma of the lung. Obstet Gynaecol., 58: 387-391, 1981.
- Reiter A. A., Carpenter R. J., Dudrick S. J. and Hinkley C. M. Pregnancy associated with advanced adenocarcinoma of the lung. Int J Gynaecol Obstet., 23: 75-78, 1985.
- Stark P., Greene R. E., Morgan G. and Hildebrandt-Stark H. E. Lung cancer and pregnancy. Radiologe., 25: 30-32, 1985.
- Suda R., Repke J. T., Steer R. and Niebyl J. R. Metastatic adenocarcinoma of the lung complicating pregnancy: a case report. J Reprod Med., 31: 1113-1116, 1986.
- Dildy III G. A., Moise K. J. J., Carpenter R. J. J. and Klima T. Maternal malignancy metastatic to the products of conception: a review. Obstet Gynecol Surv., 44: 535-540, 1989.
- Van Winter J. T., Wilkowske M. A., Shaw E. G., Ogburn P. L. and Pritchard D. J. Lung cancer complicating pregnancy: case report and review of literature. Mayo Clin Proc., 70: 384-387, 1995.
- Bitar R. J., Melillo N. and Pesin J. L. Lung cancer during pregnancy. (Letter). Mayo Clin Proc., 70: 1130, 1995.
- Cone L. A., Dawson A. C. and Mata A. M. Lung cancer during pregnancy. (Letter). Mayo Clin Proc., 70: 1130, 1995.
- Barr J. S. Placental metastases from a bronchial carcinoma. J Obstet Gynaecol Br Emp., 60: 895-897, 1953.
- Watanabe M, Tomita K, Burioka N, Yajima H et al. Mucoepidermoid carcinoma of the trachea with airway hyperresponsiveness. Anticancer Research 20:1995-1998, 2000.
- Hesketh J. A case of carcinoma of the lung with secondary deposits in the placenta. J Obstet Gynaecol Br Comm., 69: 514, 1962.
- Jones E. M. Placental metastases from bronchial carcinoma. BMJ., 2: 491-492, 1969.
- Delerive C., Locquet F., Mallart A., Janin A. and Goselin B. Placental metastasis from maternal bronchial oat cell carcinoma. Arch Pathol Lab Med., 113: 556-558, 1989.
- Zemlickis D., Lishner M. and Koren G. Review of fetal effects of cancer chemotherapeutic agents. In: Koren G, Lishner M, Farine D (eds.), Cancer in pregnancy. 1 ed. pp. 168. Cambridge: Press Syndicate of the University of Cambridge, 1996.
- Nicholson H. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynecol Br Commonwealth., 75: 307, 1968.
- Doll D. C., Ringenberg S. and Yarbro D. W. Management of cancer during pregnancy. Arch Intern Med., 148: 2058, 1988.
- Zemlickis D., Lishner M., Degendorfer P. and et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol., 166: 781-787, 1992.
- Zemlickis D., Lishner M., Degendrofer P. and et al. Fetal outcome following in utero exposure to cancer chemotherapy: the Toronto study. Arch Inter Med., 15: 573, 1992.
- Blatt J., Milvihill J. J., Ziegler J. L. and et al. Pregnancy outcome following cancer chemotherapy. Am J Med., 39: 828, 1980.
- Aviles A., Diaz-Maqueo J. C., Talavera A. and et al. Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am J Hematol., 36: 243, 1991.
- Chen Ky, Wang HC, Shih Jy, Yang Pc. Lung cancer in pregnancy: report of 2 cases. J. Formos Med. Assoc. 97: 573-6, 1998.