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Lung Cancer Complicating Pregnancy: Case Report and Review of Literature

1995; Elsevier BV; Volume: 70; Issue: 4 Linguagem: Inglês

10.4065/70.4.384

1942-5546

Jo T. Van Winter, Mark A. Wilkowske, Edward G. Shaw, Paul L. Ogburn, Douglas J. Pritchard,

Multiple and Secondary Primary Cancers

Lung cancer during pregnancy is rare. Herein we describe a case of metastatic cancer of the lung in a 36- year-old pregnant patient whose initial complaint was pain in the left thigh. Management of this neoplasm during pregnancy depends on the gestational age of the fetus and the potential operability of the tumor. Surgical, chemotherapeutic, and radiation management considerations are discussed. Lung cancer during pregnancy is rare. Herein we describe a case of metastatic cancer of the lung in a 36- year-old pregnant patient whose initial complaint was pain in the left thigh. Management of this neoplasm during pregnancy depends on the gestational age of the fetus and the potential operability of the tumor. Surgical, chemotherapeutic, and radiation management considerations are discussed. Carcinoma of the lung is now the most common fatal malignant lesion in women. Fortunately, this disease rarely occurs during pregnancy; however, with the recent increase in cigarette smoking among young women, the incidence of lung cancer in women of reproductive age can be expected to increase. Herein we describe the complex maternal and fetal management decisions that must be made after this malignant tumor has been diagnosed during pregnancy. A 36-year-old woman (gravida 2, para 0) was referred to our institution at 29 weeks' gestation because of persistent pain in the left thigh associated with a lesion in the left femur on roentgenography. Initially, the patient noticed some discomfort in her left hip area, which both she and her physician attributed to musculoskeletal discomfort associated with normal changes during pregnancy. The pain, however, persisted and began to extend distally into the region of the thigh. A roentgenogram of the hip and thigh revealed a lesion (2 by 3 cm) that was eroding the diaphysis of the left femur. Ultrasound-guided needle biopsy of this lesion confirmed metastatic adenocarcinoma. Subsequently, mammography showed normal findings, and chest roentgenography disclosed a 3-cm mass in the apical-posterior segment of the upper lobe of the left lung (Fig. 1). These findings, along with the patient's 40-pack-year history of smoking, led to the conclusion that this neoplasm represented metastatic lung carcinoma. Because of concern about the possibility of a spontaneous fracture, intramedullary nailing of the left femur was performed. Subsequently, palliative radiation therapy (with fetal shielding) was initiated to control the patient's left thigh pain. The fetus did well; weekly biophysical profiles and daily nonstress tests were performed. At 322/7 weeks' gestation, premature rupture of membranes occurred. Spontaneous onset of labor ensued, and the patient was delivered (with low forceps) of a vigorous 1,705-g male neonate; Apgar scores were 8 at 1 minute and 9 at 5 minutes of age. After delivery of her infant, the patient had a fever of indeterminate cause that persisted for 5 days despite aggressive antibiotic treatment. The fever resolved on the sixth postpartum day, and the patient and her infant were transported by air ambulance to her hometown hospital. Before dismissal of the patient, we discussed the use of palliative chemotherapy, but she opted for supportive care only because she was concerned about the potential decrease in her quality of life while receiving chemotherapy. The patient died of complications of metastatic disease 8 months after diagnosis. Her infant has remained healthy. Lung cancer is the most common fatal neoplasm in the United States today. Between 1985 and 1988, it surpassed breast cancer as the number one cause of death among women with cancer.1Smith EB Primary cancer of the lung in women.J Natl Med Assoc. 1989; 81: 945-948PubMed Google Scholar, 2Davila DG Williams DE The etiology of lung cancer.Mayo ClinProc. 1993; 68: 170-182Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 3Brownson RC Chang JC Davis JR Gender and histologic type variations in smoking-related risk of lung cancer.Epidemiology. 1992; 3: 61-64Crossref PubMed Scopus (173) Google Scholar Although for many years squamous cell cancer of the lung has been the most common histologic type among smokers, adenocarcinoma has been increasing in incidence in recent years. In fact, the tumor histologic type in all patients younger than age 40 years who have lung cancer is predominantly adenocarcinoma. Today, adenocarcinoma is the most common type of lung cancer in women of all ages.4El-Torky M El-Zeky F Hall JC Significant changes in the distribution of histologic types of cancer: a review of 4928 cases.Cancer. 1990; 65: 2361-2367Crossref PubMed Scopus (95) Google Scholar, 5Antkowiak JG Regal A-M Takita H Bronchogenic carcinoma in patients under age 40.Ann Thorac Surg. 1989; 47: 391-393Abstract Full Text PDF PubMed Scopus (78) Google Scholar Delay in the diagnosis of either localized or metastatic lung cancer during pregnancy is a major problem and occurs because of several reasons. Symptoms such as shortness of breath or blood-tinged sputum are often presumed to be due to infectious causes during pregnancy. Bone pain, which was the first complaint in our patient, is often initially thought by both the patient and the physician to represent musculoskeletal discomfort commonly present during pregnancy. Finally, physicians are often reluctant to use imaging studies that may expose the fetus to radiation. Maternal malignant lesions occur in only 0.1% of of pregnancies, and lung cancer diagnosed during pregnancy has been reported only 12 times, including this case (Table 1).6Barr JS Placental metastases from a bronchial carcinoma.J Obstet Gynaecol Br Emp. 1953; 60: 895-897Crossref PubMed Scopus (22) Google Scholar, 7Hesketh J A case of carcinoma of the lung with secondary deposits in the placenta.J Obstet Gynaecol Br Comm. 1962; 69: 514Crossref Google Scholar, 8Jones EM Placental metastases from bronchial carcinoma.BMJ. 1969; 2: 491-492Crossref PubMed Scopus (21) Google Scholar, 9Read Jr, EJ Platzer PB Placental metastasis from maternal carcinoma of the lung.Obstet Gynecol. 1981; 58: 387-391PubMed Google Scholar, 10Reiter AA Carpenter RJ Dudrick SJ Hinkley CM Pregnancy associated with advanced adenocarcinoma of the lung.Int J Gynaecol Obstet. 1985; 23: 75-78Abstract Full Text PDF PubMed Scopus (13) Google Scholar, 11Stark P Greene RE Morgan G Hildebrandt-Stark HE Lung cancer and pregnancy.Radiologe. 1985; 25: 30-32PubMed Google Scholar, 12Suda R Repke JT Steer R Niebyl JR Metastatic adenocarcinoma of the lung complicating pregnancy: a case report.J Reprod Med. 1986; 31: 1113-1116PubMed Google Scholar, 13Dildy III, GA Moise Jr, KJ Carpenter Jr, RJ Klima T Maternal malignancy metastatic to the products of conception: a review.Obstet Gynecol Surv. 1989; 44: 535-540Crossref PubMed Scopus (164) Google Scholar, 14Delerive C Locquet F Mallart A Janin A Gosselin B Placental metastasis from maternal bronchial oat cell carcinoma.Arch Pathol Lab Med. 1989; 113: 556-558PubMed Google Scholar, 15Wechter DJ Dellinger EH Boehm FH Mandal AK Kramer W Kirshon B et al.Management of lung cancer in a young pregnant woman.Int Correspond Soc Obstet Gynecol Collected Lett. 1993 Jun; 34: 1-7Google Scholar Of the known outcomes, 11 of 11 infants were healthy with no evidence of metastatic disease, placental metastatic involvement occurred in 8 of 11 cases, and maternal death from complications associated with metastatic lung cancer occurred within 9 months after diagnosis in 9 of 10 cases.Table 1Summary of Reported Cases of Lung Cancer During Pregnancy*RDS = respiratory distress syndrome; SCLC = small-cell lung cancer.Metastatic involvementReferenceDiagnosisMaternal age (yr)†G = grávida; P = para.Gestational diagnosis (wk)TreatmentPlacentalFetalInfant outcomeMaternal outcome‡All deaths due to metastatic lung cancer.Barr,6Barr JS Placental metastases from a bronchial carcinoma.J Obstet Gynaecol Br Emp. 1953; 60: 895-897Crossref PubMed Scopus (22) Google Scholar 1953SCLC3922NoneYesNoHealthy at 3yrDied, 4 mo after diagnosisHesketh,7Hesketh J A case of carcinoma of the lung with secondary deposits in the placenta.J Obstet Gynaecol Br Comm. 1962; 69: 514Crossref Google Scholar 1962SCLC16NoneYesNoHealthyDied, 4 mo after diagnosisJones,8Jones EM Placental metastases from bronchial carcinoma.BMJ. 1969; 2: 491-492Crossref PubMed Scopus (21) Google Scholar1969SCLC39 (G5)34RadiotherapyYesNoHealthy at 6 moDied, 9 mo after diagnosisRead & Platzer,9Read Jr, EJ Platzer PB Placental metastasis from maternal carcinoma of the lung.Obstet Gynecol. 1981; 58: 387-391PubMed Google Scholar 1981Large-cell cancer37 (G3,P1)35Radiotherapy, chemotherapy (postpartum)YesNoHealthyDied, 2 mo after diagnosisReiter et al, 198510Reiter AA Carpenter RJ Dudrick SJ Hinkley CM Pregnancy associated with advanced adenocarcinoma of the lung.Int J Gynaecol Obstet. 1985; 23: 75-78Abstract Full Text PDF PubMed Scopus (13) Google ScholarAdenocarcinoma35 (G2, PO)23Radiotherapy (before delivery), chemotherapy (postpartum)NoNoMildRDS, healthy after resolutionDied, 5 mo after referral for therapyStark etal,11Stark P Greene RE Morgan G Hildebrandt-Stark HE Lung cancer and pregnancy.Radiologe. 1985; 25: 30-32PubMed Google Scholar 1985SCLC45 (G6, P5)36Chemotherapy (postpartum)YesNoHealthyLimited follow-upSquamous cell carcinoma34TermLobectomy (postpartum)YesNoHealthyDied, 42 mo after diagnosisSuda et al,12Suda R Repke JT Steer R Niebyl JR Metastatic adenocarcinoma of the lung complicating pregnancy: a case report.J Reprod Med. 1986; 31: 1113-1116PubMed Google Scholar 1986Adenocarcinoma33 (G4, PI)22NoneYesNoHealthyDied, 272 mo after diagnosisDildy et al,13Dildy III, GA Moise Jr, KJ Carpenter Jr, RJ Klima T Maternal malignancy metastatic to the products of conception: a review.Obstet Gynecol Surv. 1989; 44: 535-540Crossref PubMed Scopus (164) Google Scholar 1989Large-cell cancer44 (G5,P1)3472Radiotherapy (postpartum)YesNoHealthyDied, 7 mo after diagnosisDeleriveetal,14Delerive C Locquet F Mallart A Janin A Gosselin B Placental metastasis from maternal bronchial oat cell carcinoma.Arch Pathol Lab Med. 1989; 113: 556-558PubMed Google Scholar 1989SCLC30 (G2.P1)32Palliative radiotherapyNoNoHealthyDied, 8 mo after diagnosisWechteretal,15Wechter DJ Dellinger EH Boehm FH Mandal AK Kramer W Kirshon B et al.Management of lung cancer in a young pregnant woman.Int Correspond Soc Obstet Gynecol Collected Lett. 1993 Jun; 34: 1-7Google Scholar 1993Intraoperative lung cancer with adrenal metastatic involvement28 (twin gestation)20……………Current caseAdenocarcinoma36 (G2, PO)29Palliative radiotherapyNoNoHealthyDied, 8 mo after diagnosis* RDS = respiratory distress syndrome; SCLC = small-cell lung cancer.† G = grávida; P = para.‡ All deaths due to metastatic lung cancer. Open table in a new tab Lung cancer diagnosed during pregnancy potentially involves two patients (mother and fetus) and therefore poses unusual medical and ethical dilemmas. Although information is available on the treatment of several malignant lesions during pregnancy, no information exists for the management of lung cancer. On the basis of the few reported cases, lung cancer diagnosed during pregnancy tends to be an aggressive and usually fatal disease. After lung cancer has been diagnosed, management depends on the gestational age of the fetus, clinical stage or operability of the tumor, and whether the patient elects to continue or terminate her pregnancy. The patient must receive extensive counseling about the clinical stage and prognosis of her lung cancer, including whether her life expectancy will exceed a term pregnancy. Although pregnancy does not seem to alter the course of lung cancer, the diagnosis or treatment (or both) may be delayed. Similarly, lung cancer does not seem to affect the fetus adversely if a gestational age can be achieved that is compatible with survival. In patients who want to continue their pregnancies, a therapeutic course must be established that will optimize the outcome for the patient and fetus. This situation involves a team approach: medical oncologist, thoracic surgeon (if the tumor is resectable), radiation oncologist (if irradiation is indicated), perinatologist, and neonatologist. The timing of an operation for pregnant women with localized or stage I (T1 or T2, NO) non-small-cell lung cancer (adenocarcinoma, large-cell cancer, or squamous cell cancer) is influenced by the gestational age of the fetus. If the cancer is detected during the first trimester, surgical resection may be delayed until the second trimester when organogenesis has been completed and the risk of spontaneous abortion is lower. The risk of delay primarily involves the potential for the tumor to become more advanced. After complete surgical resection of stage I disease, no additional therapy is recommended because adjuvant irradiation or chemotherapy in nonpregnant women has failed to demonstrate any survival benefit. An operation is also the treatment of choice in pregnant patients with stage II (T1 or T2, Nl, M0) non-small-cell cancer. The N1 signifies ipsilateral peribronchial or hilar lymph node involvement. Lymph node involvement can be expected to decrease the 5-year recurrence-free survival rate to about a third to half of that noted when the nodes are free of cancer.16Pairolero PC Williams DE Bergstralh EJ Piehler JM Bernatz PE Payne WS Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease.Ann Thorac Surg. 1984; 38: 331-338Abstract Full Text PDF PubMed Scopus (318) Google Scholar, 17Iascone C DeMeester TR Albertucci M Little AG Golomb HM Local recurrence of resectable non-oat cell carcinoma of the lung: a warning against conservative treatment for NO and Nl disease.Cancer. 1986; 57: 471-476Crossref PubMed Scopus (50) Google Scholar Selected patients with ipsilateral mediastinal or subcarinal lymph node involvement, stage IIIA (T1 or T2, N2, MO), can often undergo surgical resection with curative intent. After complete resection of either stage II or stage IIIA disease, radiation therapy is usually recommended. Previous retrospective studies and a more recent prospective, randomized study have indicated that such treatment decreases the risk of relapse in the chest but does not affect survival in nonpregnant patients.18Shaw EG Bonner JA Foote RL Martenson Jr, JA Frytak S Deschamps C et al.Role of radiation therapy in the management of lung cancer.Mayo Clin Proc. 1993; 68: 593-602Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Recommendations for radiation therapy (with abdominal shielding) for lung cancer during pregnancy are based on the good neonatal outcome in pregnant women who have received irradiation for Hodgkin's disease.19Redman JR Bajorunas DR Lacher MJ Hodgkin's disease: pregnancy and progeny.in: Lacher MJ Redman JR Hodgkin's Disease: The Consequences of Survival. Lea & Febiger, Philadelphia1990: 244-266Google Scholar, 20Friedman E Jones GW Fetal outcome after maternal radiation treatment of supradiaphragmatic Hodgkin' s disease.Can Med Assoc J. 1993; 149: 1281-1283Google Scholar For pregnant patients who refuse to undergo an operation or whose lesions are unresectable (often stage IIIA or stage IIIB [T4 or N3, M0] with supraclavicular or contralateral mediastinal lymph node involvement), treatment usually involves irradiation with or without chemotherapy. The usual dose of irradiation is 6,000 cGy in 30 fractions for 6 weeks. The median survival for nonpregnant patients who receive such therapy is 9 months; the 5-year survival rate is 5%.18Shaw EG Bonner JA Foote RL Martenson Jr, JA Frytak S Deschamps C et al.Role of radiation therapy in the management of lung cancer.Mayo Clin Proc. 1993; 68: 593-602Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Although previous studies that have evaluated the addition of chemotherapy have shown mixed results, a recently published study that used irradiation in combination with cisplatin-based chemotherapy suggested improvement in survival in nonpregnant patients.18Shaw EG Bonner JA Foote RL Martenson Jr, JA Frytak S Deschamps C et al.Role of radiation therapy in the management of lung cancer.Mayo Clin Proc. 1993; 68: 593-602Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Experience with chemotherapy during pregnancy has been primarily based on the assessment of pregnant patients receiving treatment for breast cancer, Hodgkin's lymphoma, and leukemia. If the fetus is exposed to these chemotherapeutic agents during the beginning of the second trimester, neonatal outcome is usually good.21Blatt J Mulvihill JJ Ziegler JL Young RC Poplack DG Pregnancy outcome following cancer chemotherapy.Am J Med. 1980; 69: 828-832Abstract Full Text PDF PubMed Scopus (161) Google Scholar,22van der Zee AG de Bruijn HW Bouma J Aalders JG Oosterhuis JW de Vries EG Endodermal sinus tumor of the ovary during pregnancy: a case report.Am J Obstet Gynecol. 1991; 164: 504-506Abstract Full Text PDF PubMed Scopus (30) Google Scholar The main risk to the fetus seems to be growth retardation or preterm labor associated with poor nutrition, weight loss, anemia, and emotional stress in the mother; however, published experience with the use of cisplatin during pregnancy is meager. In pregnant patients with advanced or metastatic nonsmall-cell cancer of the lung, palliation of symptoms is the primary goal for the mother. Close follow-up is necessary to ensure fetal well-being and to prevent severe complications related to the tumor. Such complications may include superior vena cava syndrome or large airway obstruction and pneumonitis in patients with advanced chest disease. Pathologic fracture, particularly of the femur, is a potential complication in patients with bone involvement. Palliative radiation therapy with abdominal shielding can often be of benefit when painful bony metastatic disease occurs, as was the case with our patient. Recent reviews have also demonstrated that systemic chemotherapy can slightly increase the duration of survival and improve the quality of life by decreasing symptoms such as pain, cough, and shortness of breath.23Souquet PJ Chauvin F Boissel JP Cellerino R Cormier Y Ganz PA et al.Polychemotherapy in advanced non small cell lung cancer: a meta-analysis.Lancet. 1993; 342: 19-21Abstract PubMed Scopus (521) Google Scholar, 24Grilli R Oxman AD Julian JA Chemotherapy for advanced non-small-cell lung cancer: how much benefit is enough?.J Clin Oncol. 1993; 11: 1866-1872Crossref PubMed Scopus (367) Google Scholar In 5 of the 12 reported cases of lung cancer during pregnancy, small-cell cancer was the histologic type (Table 1). Of importance, small-cell cancer of the lung differs from non-small-cell carcinoma in almost every way. Typically, it has an extremely rapid clinical course and tends to be widely disseminated at the time of diagnosis. If treatment is not given, the median survival after diagnosis is only about 2 to 4 months; however, small-cell cancer is often sensitive to chemotherapy and irradiation. Clearly, because of the aggressive nature of this tumor, therapy should not be delayed, even if the diagnosis is made during the first trimester. Obstetric management of the patient with lung carcinoma involves close monitoring of her nutritional status and oxygen requirements. After 20 weeks' gestation, ultrasonography should be performed every 3 weeks to monitor for intrauterine growth retardation. Use of corticosteroids to hasten fetal lung maturity could begin as early as 24 weeks' gestation. No evidence shows that intramuscular administration of corticosteroids or intra-amniotic injections of ine (also used to accelerate fetal lung maturity) adversely affect the malignant tumor.25Romaguera J Reyes G Caiseda D Wallach RC Adamsons K Acceleration of fetal maturation with intra-amniotic thyroxine in the presence of maternal malignancy.Acta Obstet Gynecol Scand. 1990; 69: 229-234Crossref PubMed Scopus (6) Google Scholar Antepartum testing should commence as early as 26 weeks' gestation. In our patient, we used biweekly nonstress testing and evaluated the amniotic fluid volume until delivery to ensure fetal well-being. At 34 to 35 weeks' gestation, amniocentesis should be performed weekly to assess fetal lung maturity, and delivery should occur as soon as a mature profile has been achieved. Any signs of maternal deterioration or fetal compromise, such as intrauterine growth retardation, would prompt an earlier delivery. The mode of delivery depends on obstetric indications. Although the incidence of lung cancer during pregnancy is low, it can be expected to increase. This outcome is due to the unfortunate fact that cigarette use in young women remains high. In addition, the frequency of any cancer, including smoking-related lung cancer, may increase during pregnancy as the number of women becoming pregnant after the age of 40 years increases.