- Email: [email protected]
Lung cancer and pregnancy
G Model LUNG-4205; No. of Pages 3
ARTICLE IN PRESS Lung Cancer xxx (2012) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
Lung cancer and pregnancy Nesrin Sarıman a,∗,1 , Ender Levent a,1 , Nes¸e Arzu Yener b,1 , Alpay Örki c,1 , Attila Saygı a,1 a
Pulmonology Department, Maltepe University Hospital, Istanbul, Turkey Pathology Department, Maltepe University Hospital, Istanbul, Turkey c Thoracic Surgery Department, Maltepe University Hospital, Istanbul, Turkey b
a r t i c l e
i n f o
Article history: Received 6 October 2012 Received in revised form 15 November 2012 Accepted 19 November 2012 Keywords: Lung cancer in pregnancy Adenocarcinoma Diagnosis Smoking
a b s t r a c t Lung cancer in the pregnant woman is a very rare and dramatic coincidence with poor prognosis. Treatment depends on the gestational week of the pregnancy, patient’s medical status, social, personal, familial, and even religious beliefs. We present a case of adenocarcinoma of the lung in a 34-year-old pregnant patient whose initial complaints were cough, dyspnea, fever and fatigue. She was diagnosed with pneumonia at another hospital, and antibiotic therapy was administered. Meanwhile, at 28 weeks she delivered a preterm low-birth-weight baby. Chest X-ray and thorax CT revealed a mass lesion in the upper left lung lobe. After admission to our clinic, needle aspiration of left supraclavicular lymph node and bronchoscopic biopsy from upper lobe bronchus showed a non-small lung cancer; adenocarcinoma. Brain MRI was normal. PET CT revealed multiple bone metastases. Multidisciplinary Tumor Committee at our hospital referred her to the Oncology Department as an advanced stage IV disease. Chemotherapy was administered with paclitaxel and carboplatin for a total of 12 weeks. Reassessment of the patient revealed new bone metastases and crizotinib was administered since her tumor was found positive for EML4-ALK mutations. The treatment was well tolerated. During a follow up period of 6 months her clinical condition was stable and no adverse events were encountered. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
this case since lung cancer accompanying pregnancy is a very rare coincidence.
Cancer during pregnancy is rare and occurs in one of every 1000 gestations. The most common types of cancer diagnosed during pregnancy are breast and cervical cancer, lymphoma, melanoma, and leukemia [1–4]. In one of the latest reviews in the literature, only 44 cases were identified who were diagnosed and/or treated for lung cancer during the course of pregnancy [1]. The prevalence of lung cancer in women has increased over the last decades, partly due to the increase in the prevalence of smoking among women [2]. Smoking during pregnancy is associated with various pathological conditions such as fetal growth retardation, stillbirth, preterm birth, placental abruption, spontaneous abortions, and sudden infant death syndrome [5]. Despite these facts some pregnant women still do not quit smoking during pregnancy. Herein, we present a 34-year-old patient with advanced lung cancer during pregnancy who received standard chemotherapy and ALK-targeted therapy after delivering a preterm baby. We report
∗ Corresponding author at: Maltepe Üniversitesi Tıp Fakültesi Hastanesi, Gö˘güs Hastalıkları Anabilim Dalı, Feyzullah Cad. No: 39 Maltepe, I˙ stanbul 34843, Turkey. Tel.: +90 216 4440620x2119; fax: +90 216 3830270. E-mail address: [email protected] (N. Sarıman). 1 All the authors have contributed substantially to the design, performance, and reporting of the work.
2. Case report A 34 year-old, current smoker, female patient was admitted to Maltepe University Hospital complaining of dyspnea, cough, sputum production, and frequent sweating. In her story, she delivered a preterm low birth weight baby (1130 g) at 28 weeks of gestation, 2 weeks ago, when she was diagnosed with pneumonia at another hospital. The baby was transferred to the pediatric intensive care unit and was discharged home in good condition 6 weeks later. There was not any gynecological pathology that could be a cause of the pre-term delivery. So it was assessed that pre-term delivery happened because of the intercurrent “pneumonia” and her current smoking. She had a smoking history of 7 pack/year, and she did not quit smoking although she was pregnant. She described morning cough and phlegm for about 6 months. But she ignored them since she considered that these symptoms were related to her smoking habit. Physical examination showed a palpable supraclavicular lymph node. On auscultation, diminished breath sounds on her left upper hemithorax and expiratory rhonchi on bilateral basal lung fields were heard. Complete blood count and blood chemistry revealed leukocytosis: 10,110 ml/mm3 (N: 3.5–10.0 103 /mm3 ), elevated C-reactive protein: 7.5 mg/dl (N: 0–0.5 mg/dl), and
0169-5002/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.lungcan.2012.11.014
Please cite this article in press as: http://dx.doi.org/10.1016/j.lungcan.2012.11.014
Sarıman
N,
et
al.
Lung
cancer
and
pregnancy.
Lung
Cancer
(2012),
G Model LUNG-4205; No. of Pages 3
ARTICLE IN PRESS N. Sarıman et al. / Lung Cancer xxx (2012) xxx–xxx
2
Fig. 3. Malignant neoplastic epithelial tumor of the lung, non-small cell type. H&E, 200×.
Fig. 1. Chest X-ray showing a consolidation in the left lung apical region.
erithrocyte sedimentation rate: 61 mm/h (0–15 mm/h). Serum LDH was elevated: 194 U/l (N: 100–190 U/l) consistent with the tumor burden. ALP was also elevated: 163 U/l (N: 50–136 U/l), suggesting bone metastases. Serum albumin level was decreased: 2.7 g/dl (N: 3.4–5 g/dl), partly due to cancer related protein catabolism. Chest X-ray showed a consolidation in the upper left lung lobe (Fig. 1). CT of the thorax demonstrated a mass lesion obstructing left upper lobe bronchus, extending from apical region to the left hilus (Fig. 2). Needle aspiration biopsy of the left-supraclavicular lymph node was performed, and histopathological examination showed poorly differentiated adenocarcinoma of the lung. Bronchoscopy revealed edema of the bronchial mucous membranes, and left upper lobe bronchus was totally obstructed with the tumor. Bronchoscopic punch biopsies were obtained from the lesion and bronchoscopic lavage fluid was collected. Histopathological diagnosis was given as invasive adenocarcinoma in a small bronchial fragment. Then, excision of the left supraclavicular lymph node was planned in order to
do immunphenotyping and also to detect any genetic alterations in the cancerous tissue (Fig. 3). The neoplastic cells were positive for TTF-1 and cytokeratin 7 immunostains confirming the metastasis from the lung (Fig. 4a and b). Genetic study done from the paraffin blocks revealed that EGFR mutations were negative and EML4/ALK mutations were (+). Brain MRI was normal. Staging study was completed with PET CT revealing multiple bone metastases. She had
Fig. 2. Thorax CT revealing a mass lesion in the left upper lobe, extending from apical region to the left hilus.
Please cite this article in press as: http://dx.doi.org/10.1016/j.lungcan.2012.11.014
Sarıman
N,
et
Fig. 4. (a and b) Neoplastic cells are positive for TTF-1 and cytokeratin 7.
al.
Lung
cancer
and
pregnancy.
Lung
Cancer
(2012),
G Model LUNG-4205; No. of Pages 3
ARTICLE IN PRESS N. Sarıman et al. / Lung Cancer xxx (2012) xxx–xxx
been referred to the Oncology Department with an advanced stage IV disease. Chemotherapy was administered with paclitaxel (65 mg/m2 ) and carboplatin (AUC 2) for a total of 12 weeks. Reassessment of the patient after chemotherapy revealed new bone metastases. Since tests showed that her tumor was positive (+) for EML4/ALK mutations, crizotinib was administered 250 mg (p.o.) twice daily. At the end of 6 months after diagnosis, she was stable and the treatment was well tolerated without any side effects. 3. Discussion Lung cancer is one of the most common forms of cancer with high mortality rates in developed countries [5]. This cancer group is still a rare tumor during pregnancy. We learn from the reported lung cancer cases during the pregnancy, that almost 60% of these smoker pregnant mothers are unfortunately still smoking during pregnancy. The most frequent diagnosed lung cancer type is nonsmall cell lung cancer (NSCLC) accounting for 72% of all cases. Adenocarcinoma and large cell undifferentiated carcinomas are the most predominant histological types of NSCLC. More than 80% of these patients have been diagnosed in advanced III and IV disease stages [2,3]. The median age of pregnant women with lung cancer was 36 years, and the median gestational age at diagnosis was 29 weeks. All reported cases of pregnancy-associated lung cancers were diagnosed during the second and third trimesters [3]. Limited number of patients received therapy during pregnancy, as radiotherapy and chemotherapy with cisplatin/vinorelbine or etoposide. Most patients were treated after delivery with surgery, chemotherapy or radiotherapy according to the stage of their disease [4]. There is no evidence that therapeutic abortion provides a survival advantage [6]. In case of the need for chemotherapy or radiotherapy during the early stages of pregnancy, termination of pregnancy can be considered. Decision about the pregnancy termination should be made regarding probability for cure, drugs to be used and wishes of the patient [4,6]. Some pregnant women prefer to postpone the treatment until delivery, despite increasing risk of their own health, to protect their babies from the possible adverse effects of chemotheuropetics. Patients with early stage I and II tumors can undergo curative thoracotomy which does not necessitate termination of pregnancy. Stage IIIA/IIIB NSCLC cases have poor prognosis. These women should be informed about the course of the disease so they can prefer either abortion or neoadjuvant combination chemotherapy which is safe after the first trimester [4]. Combinations of cisplatin and vinorelbine or etoposide have been administered in pregnant women with lung cancer without detrimental fetal effects in the second and third trimesters [7]. Radiation therapy can be applied after delivery. Pregnant women with metastatic NSCLC have poor prognosis which makes pregnancy termination advisable in the first or second trimesters. A detailed history and physical examination are the most important steps in the evaluation of these patients. The diagnostic work-up of the pregnant woman with cancer should limit exposure to ionizing radiation and be restricted to procedures that do not endanger health of the fetus [1]. Thorough physical examination should be performed, palpable lymph nodes should be searched, skin lesions, breast abnormalities, hepato/splenomegaly should be palpated [7]. If detected, fine needle aspiration biopsy of lymph nodes at readily accessible sites, can be safely and practically performed as noninvasive diagnostic procedures [8]. In the pregnant women with cancer, decisions about the use of radiological investigations must take into account at the age of the fetus and the estimated dose of radiation delivered with the imaging study. Staging imaging tests should be limited to
Please cite this article in press as: http://dx.doi.org/10.1016/j.lungcan.2012.11.014
Sarıman
N,
et
3
those associated with the lowest exposure to ionizing radiation. No major effect has been observed when the radiation dose of <0.1 Gy (<10 rad) is applied [6]. Anteroposterior and lateral chest X-rays are the mostly used tools in the diagnosis of lung cancer. Ultrasound and MRI studies are appropriate for metastatic work-up which limit exposure of the pregnant woman to ionizing radiation [1]. Our patient was a 34 year-old, current smoker female who gave birth to a preterm low birth weight baby at 28 weeks of gestation. Her symptoms such as dyspnea, cough, and sputum production have been evaluated as a respiratory tract infection without any suspect of a lung carcinoma. After the delivery diagnostic work up revealed an advanced stage IV adenocarcinoma of the lung. EGFR and ALK mutation analysis of her tumor cells revealed that EGFR mutations were negative and EML4/ALK mutations were (+). We immediately referred the patient to the Oncology Department. It was a dramatic and difficult event to handle for the patient and her family and also for the medical team. Furthermore, she had 2 more young children. Patients with advanced metastatic disease may achieve improved survival and palliation of symptoms with chemotherapy, targeted agents, and other supportive measures [7]. Treatment options for patients are determined by histology, stage, and general health and comorbidities of the patient. EML4-ALK is an oncoprotein reported in NSCLC. Crizotinib, an oral ALK inhibitor, is demonstrated to provide dramatic clinical benefit with little toxicity in patients having advanced NSCLC [9,10]. Our patient received ALK- targeted therapy with crizotinib after standard chemotherapy when new bone matastases appeared. No adverse events were encountered. At the present time, her clinical condition is stable and her baby is 9 months old. Baby’s physical and mental development are normal, but we are informed that he is scheduled for “undescended testis” surgery. The coincidence of lung cancer and pregnancy is probably increasing due to childbearing is shifted toward later reproductive ages as third or fourth decades in the modern world as well as smoking is becoming increasingly common among young women [3,7]. Preventive measures through the campaigns against smoking are very important in young women at childbearing ages [5]. Conflict of interest statement All authors declare that they have no conflict of interest. References [1] Azim HA, Peccatori FA, Pavlidis N. Lung cancer in the pregnant woman: to treat or not to treat, that is the question. Lung Cancer 2010;67:251–6. [2] Garridoa M, Claverob J, Huetec A, S’ancheza C, Solar A, Alvareza M, Orellanaa E. Prolonged survival of a woman with lung cancer diagnosed and treated with chemotherapy during pregnancy: review of cases reported. Lung Cancer 2008;60:285–90. [3] Pavlidis N. Lung cancer during pregnancy: an emerging issue. Lung Cancer 2008;59:279–81. [4] Pentheroudakis G, Pavlidis N. Cancer and pregnancy: poena magna, not anymore. Eur J Cancer 2006;42:126–40. [5] Cnattingius S. The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine Tobacco Res 2004;6(Suppl. 2):125–40. [6] Pavlidis NA. Coexistence of pregnancy and malignancy. Oncologist 2002;7:279–87. [7] Pentheroudakis G, Orrechia R, Hoekstra HJ, Pavlidis N. Cancer, fertility and pregnancy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21(Suppl. 5):v266–73. [8] Yener NA, Midi A, Cubuk R, Orki A, Onar C, Ersev A, Arman B. Palpable lesions as a diagnostic tool in patients with thoracic pathology. Diagn Cytopathol 2011;16, http://dx.doi.org/10.1002/dc.21755 [Epub ahead of print]. [9] Gerber DE, Minna JD. ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Cancer Cell 2010;18(6):548–51. [10] Azim HA, Pavlidis N, Peccatori FA. Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Cancer Treat Rev 2010;36: 110–21.
al.
Lung
cancer
and
pregnancy.
Lung
Cancer
(2012),
ARTICLE IN PRESS Lung Cancer xxx (2012) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
Lung cancer and pregnancy Nesrin Sarıman a,∗,1 , Ender Levent a,1 , Nes¸e Arzu Yener b,1 , Alpay Örki c,1 , Attila Saygı a,1 a
Pulmonology Department, Maltepe University Hospital, Istanbul, Turkey Pathology Department, Maltepe University Hospital, Istanbul, Turkey c Thoracic Surgery Department, Maltepe University Hospital, Istanbul, Turkey b
a r t i c l e
i n f o
Article history: Received 6 October 2012 Received in revised form 15 November 2012 Accepted 19 November 2012 Keywords: Lung cancer in pregnancy Adenocarcinoma Diagnosis Smoking
a b s t r a c t Lung cancer in the pregnant woman is a very rare and dramatic coincidence with poor prognosis. Treatment depends on the gestational week of the pregnancy, patient’s medical status, social, personal, familial, and even religious beliefs. We present a case of adenocarcinoma of the lung in a 34-year-old pregnant patient whose initial complaints were cough, dyspnea, fever and fatigue. She was diagnosed with pneumonia at another hospital, and antibiotic therapy was administered. Meanwhile, at 28 weeks she delivered a preterm low-birth-weight baby. Chest X-ray and thorax CT revealed a mass lesion in the upper left lung lobe. After admission to our clinic, needle aspiration of left supraclavicular lymph node and bronchoscopic biopsy from upper lobe bronchus showed a non-small lung cancer; adenocarcinoma. Brain MRI was normal. PET CT revealed multiple bone metastases. Multidisciplinary Tumor Committee at our hospital referred her to the Oncology Department as an advanced stage IV disease. Chemotherapy was administered with paclitaxel and carboplatin for a total of 12 weeks. Reassessment of the patient revealed new bone metastases and crizotinib was administered since her tumor was found positive for EML4-ALK mutations. The treatment was well tolerated. During a follow up period of 6 months her clinical condition was stable and no adverse events were encountered. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
this case since lung cancer accompanying pregnancy is a very rare coincidence.
Cancer during pregnancy is rare and occurs in one of every 1000 gestations. The most common types of cancer diagnosed during pregnancy are breast and cervical cancer, lymphoma, melanoma, and leukemia [1–4]. In one of the latest reviews in the literature, only 44 cases were identified who were diagnosed and/or treated for lung cancer during the course of pregnancy [1]. The prevalence of lung cancer in women has increased over the last decades, partly due to the increase in the prevalence of smoking among women [2]. Smoking during pregnancy is associated with various pathological conditions such as fetal growth retardation, stillbirth, preterm birth, placental abruption, spontaneous abortions, and sudden infant death syndrome [5]. Despite these facts some pregnant women still do not quit smoking during pregnancy. Herein, we present a 34-year-old patient with advanced lung cancer during pregnancy who received standard chemotherapy and ALK-targeted therapy after delivering a preterm baby. We report
∗ Corresponding author at: Maltepe Üniversitesi Tıp Fakültesi Hastanesi, Gö˘güs Hastalıkları Anabilim Dalı, Feyzullah Cad. No: 39 Maltepe, I˙ stanbul 34843, Turkey. Tel.: +90 216 4440620x2119; fax: +90 216 3830270. E-mail address: [email protected] (N. Sarıman). 1 All the authors have contributed substantially to the design, performance, and reporting of the work.
2. Case report A 34 year-old, current smoker, female patient was admitted to Maltepe University Hospital complaining of dyspnea, cough, sputum production, and frequent sweating. In her story, she delivered a preterm low birth weight baby (1130 g) at 28 weeks of gestation, 2 weeks ago, when she was diagnosed with pneumonia at another hospital. The baby was transferred to the pediatric intensive care unit and was discharged home in good condition 6 weeks later. There was not any gynecological pathology that could be a cause of the pre-term delivery. So it was assessed that pre-term delivery happened because of the intercurrent “pneumonia” and her current smoking. She had a smoking history of 7 pack/year, and she did not quit smoking although she was pregnant. She described morning cough and phlegm for about 6 months. But she ignored them since she considered that these symptoms were related to her smoking habit. Physical examination showed a palpable supraclavicular lymph node. On auscultation, diminished breath sounds on her left upper hemithorax and expiratory rhonchi on bilateral basal lung fields were heard. Complete blood count and blood chemistry revealed leukocytosis: 10,110 ml/mm3 (N: 3.5–10.0 103 /mm3 ), elevated C-reactive protein: 7.5 mg/dl (N: 0–0.5 mg/dl), and
0169-5002/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.lungcan.2012.11.014
Please cite this article in press as: http://dx.doi.org/10.1016/j.lungcan.2012.11.014
Sarıman
N,
et
al.
Lung
cancer
and
pregnancy.
Lung
Cancer
(2012),
G Model LUNG-4205; No. of Pages 3
ARTICLE IN PRESS N. Sarıman et al. / Lung Cancer xxx (2012) xxx–xxx
2
Fig. 3. Malignant neoplastic epithelial tumor of the lung, non-small cell type. H&E, 200×.
Fig. 1. Chest X-ray showing a consolidation in the left lung apical region.
erithrocyte sedimentation rate: 61 mm/h (0–15 mm/h). Serum LDH was elevated: 194 U/l (N: 100–190 U/l) consistent with the tumor burden. ALP was also elevated: 163 U/l (N: 50–136 U/l), suggesting bone metastases. Serum albumin level was decreased: 2.7 g/dl (N: 3.4–5 g/dl), partly due to cancer related protein catabolism. Chest X-ray showed a consolidation in the upper left lung lobe (Fig. 1). CT of the thorax demonstrated a mass lesion obstructing left upper lobe bronchus, extending from apical region to the left hilus (Fig. 2). Needle aspiration biopsy of the left-supraclavicular lymph node was performed, and histopathological examination showed poorly differentiated adenocarcinoma of the lung. Bronchoscopy revealed edema of the bronchial mucous membranes, and left upper lobe bronchus was totally obstructed with the tumor. Bronchoscopic punch biopsies were obtained from the lesion and bronchoscopic lavage fluid was collected. Histopathological diagnosis was given as invasive adenocarcinoma in a small bronchial fragment. Then, excision of the left supraclavicular lymph node was planned in order to
do immunphenotyping and also to detect any genetic alterations in the cancerous tissue (Fig. 3). The neoplastic cells were positive for TTF-1 and cytokeratin 7 immunostains confirming the metastasis from the lung (Fig. 4a and b). Genetic study done from the paraffin blocks revealed that EGFR mutations were negative and EML4/ALK mutations were (+). Brain MRI was normal. Staging study was completed with PET CT revealing multiple bone metastases. She had
Fig. 2. Thorax CT revealing a mass lesion in the left upper lobe, extending from apical region to the left hilus.
Please cite this article in press as: http://dx.doi.org/10.1016/j.lungcan.2012.11.014
Sarıman
N,
et
Fig. 4. (a and b) Neoplastic cells are positive for TTF-1 and cytokeratin 7.
al.
Lung
cancer
and
pregnancy.
Lung
Cancer
(2012),
G Model LUNG-4205; No. of Pages 3
ARTICLE IN PRESS N. Sarıman et al. / Lung Cancer xxx (2012) xxx–xxx
been referred to the Oncology Department with an advanced stage IV disease. Chemotherapy was administered with paclitaxel (65 mg/m2 ) and carboplatin (AUC 2) for a total of 12 weeks. Reassessment of the patient after chemotherapy revealed new bone metastases. Since tests showed that her tumor was positive (+) for EML4/ALK mutations, crizotinib was administered 250 mg (p.o.) twice daily. At the end of 6 months after diagnosis, she was stable and the treatment was well tolerated without any side effects. 3. Discussion Lung cancer is one of the most common forms of cancer with high mortality rates in developed countries [5]. This cancer group is still a rare tumor during pregnancy. We learn from the reported lung cancer cases during the pregnancy, that almost 60% of these smoker pregnant mothers are unfortunately still smoking during pregnancy. The most frequent diagnosed lung cancer type is nonsmall cell lung cancer (NSCLC) accounting for 72% of all cases. Adenocarcinoma and large cell undifferentiated carcinomas are the most predominant histological types of NSCLC. More than 80% of these patients have been diagnosed in advanced III and IV disease stages [2,3]. The median age of pregnant women with lung cancer was 36 years, and the median gestational age at diagnosis was 29 weeks. All reported cases of pregnancy-associated lung cancers were diagnosed during the second and third trimesters [3]. Limited number of patients received therapy during pregnancy, as radiotherapy and chemotherapy with cisplatin/vinorelbine or etoposide. Most patients were treated after delivery with surgery, chemotherapy or radiotherapy according to the stage of their disease [4]. There is no evidence that therapeutic abortion provides a survival advantage [6]. In case of the need for chemotherapy or radiotherapy during the early stages of pregnancy, termination of pregnancy can be considered. Decision about the pregnancy termination should be made regarding probability for cure, drugs to be used and wishes of the patient [4,6]. Some pregnant women prefer to postpone the treatment until delivery, despite increasing risk of their own health, to protect their babies from the possible adverse effects of chemotheuropetics. Patients with early stage I and II tumors can undergo curative thoracotomy which does not necessitate termination of pregnancy. Stage IIIA/IIIB NSCLC cases have poor prognosis. These women should be informed about the course of the disease so they can prefer either abortion or neoadjuvant combination chemotherapy which is safe after the first trimester [4]. Combinations of cisplatin and vinorelbine or etoposide have been administered in pregnant women with lung cancer without detrimental fetal effects in the second and third trimesters [7]. Radiation therapy can be applied after delivery. Pregnant women with metastatic NSCLC have poor prognosis which makes pregnancy termination advisable in the first or second trimesters. A detailed history and physical examination are the most important steps in the evaluation of these patients. The diagnostic work-up of the pregnant woman with cancer should limit exposure to ionizing radiation and be restricted to procedures that do not endanger health of the fetus [1]. Thorough physical examination should be performed, palpable lymph nodes should be searched, skin lesions, breast abnormalities, hepato/splenomegaly should be palpated [7]. If detected, fine needle aspiration biopsy of lymph nodes at readily accessible sites, can be safely and practically performed as noninvasive diagnostic procedures [8]. In the pregnant women with cancer, decisions about the use of radiological investigations must take into account at the age of the fetus and the estimated dose of radiation delivered with the imaging study. Staging imaging tests should be limited to
Please cite this article in press as: http://dx.doi.org/10.1016/j.lungcan.2012.11.014
Sarıman
N,
et
3
those associated with the lowest exposure to ionizing radiation. No major effect has been observed when the radiation dose of <0.1 Gy (<10 rad) is applied [6]. Anteroposterior and lateral chest X-rays are the mostly used tools in the diagnosis of lung cancer. Ultrasound and MRI studies are appropriate for metastatic work-up which limit exposure of the pregnant woman to ionizing radiation [1]. Our patient was a 34 year-old, current smoker female who gave birth to a preterm low birth weight baby at 28 weeks of gestation. Her symptoms such as dyspnea, cough, and sputum production have been evaluated as a respiratory tract infection without any suspect of a lung carcinoma. After the delivery diagnostic work up revealed an advanced stage IV adenocarcinoma of the lung. EGFR and ALK mutation analysis of her tumor cells revealed that EGFR mutations were negative and EML4/ALK mutations were (+). We immediately referred the patient to the Oncology Department. It was a dramatic and difficult event to handle for the patient and her family and also for the medical team. Furthermore, she had 2 more young children. Patients with advanced metastatic disease may achieve improved survival and palliation of symptoms with chemotherapy, targeted agents, and other supportive measures [7]. Treatment options for patients are determined by histology, stage, and general health and comorbidities of the patient. EML4-ALK is an oncoprotein reported in NSCLC. Crizotinib, an oral ALK inhibitor, is demonstrated to provide dramatic clinical benefit with little toxicity in patients having advanced NSCLC [9,10]. Our patient received ALK- targeted therapy with crizotinib after standard chemotherapy when new bone matastases appeared. No adverse events were encountered. At the present time, her clinical condition is stable and her baby is 9 months old. Baby’s physical and mental development are normal, but we are informed that he is scheduled for “undescended testis” surgery. The coincidence of lung cancer and pregnancy is probably increasing due to childbearing is shifted toward later reproductive ages as third or fourth decades in the modern world as well as smoking is becoming increasingly common among young women [3,7]. Preventive measures through the campaigns against smoking are very important in young women at childbearing ages [5]. Conflict of interest statement All authors declare that they have no conflict of interest. References [1] Azim HA, Peccatori FA, Pavlidis N. Lung cancer in the pregnant woman: to treat or not to treat, that is the question. Lung Cancer 2010;67:251–6. [2] Garridoa M, Claverob J, Huetec A, S’ancheza C, Solar A, Alvareza M, Orellanaa E. Prolonged survival of a woman with lung cancer diagnosed and treated with chemotherapy during pregnancy: review of cases reported. Lung Cancer 2008;60:285–90. [3] Pavlidis N. Lung cancer during pregnancy: an emerging issue. Lung Cancer 2008;59:279–81. [4] Pentheroudakis G, Pavlidis N. Cancer and pregnancy: poena magna, not anymore. Eur J Cancer 2006;42:126–40. [5] Cnattingius S. The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine Tobacco Res 2004;6(Suppl. 2):125–40. [6] Pavlidis NA. Coexistence of pregnancy and malignancy. Oncologist 2002;7:279–87. [7] Pentheroudakis G, Orrechia R, Hoekstra HJ, Pavlidis N. Cancer, fertility and pregnancy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21(Suppl. 5):v266–73. [8] Yener NA, Midi A, Cubuk R, Orki A, Onar C, Ersev A, Arman B. Palpable lesions as a diagnostic tool in patients with thoracic pathology. Diagn Cytopathol 2011;16, http://dx.doi.org/10.1002/dc.21755 [Epub ahead of print]. [9] Gerber DE, Minna JD. ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Cancer Cell 2010;18(6):548–51. [10] Azim HA, Pavlidis N, Peccatori FA. Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Cancer Treat Rev 2010;36: 110–21.
al.
Lung
cancer
and
pregnancy.
Lung
Cancer
(2012),