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Small Cell Carcinoma of the Cervix Complicated by Pregnancy
Clinical Oncology
Clinical Oncology (1999)11:123–125 # The Royal College of Radiologists
Case Report Small Cell Carcinoma of the Cervix Complicated by Pregnancy T. W. Leung, S. H. Lo, S. F. Wong, M. K. Yuen, F. C. S. Wong, S. Y. Tung, W. K. Sze and S. K. O Tuen Mun Hospital, Hong Kong Abstract. We report the results of treatment in a 26-year old patient with stage IB2 small cell carcinoma of the cervix complicated by pregnancy. A pathological complete remission was achieved following sandwich chemotherapy and radiotherapy. The patient remains in clinical remission 14 months after presentation. Keywords: Cervix; Chemotherapy; Pregnancy; Radiotherapy; Small cell carcinoma
Introduction Small cell carcinoma of the cervix (SCCC) complicated by pregnancy is rare, and there is no consensus regarding treatment. Perrin et al. identified a total of five patients with SCCC in association with pregnancy [1]. They concluded that the outcome had been universally poor, with the longest survival being 32 months after initial diagnosis. We report a patient achieving a pathological complete remission following sandwich chemotherapy and radiotherapy.
Case Report A 26-year-old primigravida presented in April 1997 with vaginal bleeding at estimated 31 weeks gestation. On examination, the cervix was replaced by a hard nodular growth measuring 7 6 7 cm. The fornices and the parametria were clear. There were no other abnormalities. Blood biochemistry test results were normal and the chest radiograph was clear. A punch biopsy of the cervix confirmed the diagnosis of small cell carcinoma (Fig. 1). Immunohistochemistry showed positive staining for neurone specific enolase and chromogranin. Magnetic resonance imaging (MRI) of the abdomen and pelvis showed abnormal T2 hyperintensity and thickening at the anterior and posterior lips of the cervix. The whole cervical canal was enlarged and measured 7 6 6 6 7 cm (Fig. 2). Left parametrial involvement was suggested. The liver, kidney and spleen were normal. No lymphadenopathy was identified. Trephine biopsy was refused. The patient was Correspondence and offprint requests to: Dr T. W. Leung, Department of Clinical Oncology, Tuen Mun Hospital, Tsing Chung Koon Road, Hong Kong.
jointly assessed by a clinical oncologist and a gynaecologist. The recommendation was for chemoradiation after the delivery of the baby. Examination under anaesthesia was performed at 34 weeks estimated gestational age, which showed a stage IB2 carcinoma of the cervix (FIGO). The baby was delivered by classical caesarean section at the same time. The patient was scheduled to be treated with six 3weekly cycles of chemotherapy with cisplatin 100 mg/m2 intravenously (i.v.) on day 1 and etoposide 100 mg/m2 i.v. on days 1–3 (EP). The first cycle of EP was given on the eighth day after the caesarean section. We believed that a radical dose of radiotherapy together with the chemotherapy would have a good chance of eradicating the disease locally. The second and third cycles of EP were given at weekends without any overlap with radiotherapy. The tumour showed an initial response and measured 3 6 3 cm prior to the commencement of the second cycle of EP.
Fig. 1. Infiltrative tumour composed of small, uniform cells with a high nuclear/cytoplasmic ratio, prominent karyorrhexis and frequent mitosis (H&E 6 100).
Fig. 2. Sagittal T2-weighted image showing a large tumour in the cervix. Cephalic presentation of the foetus is observed.
Radiotherapy was started on day 21 after the caesarean section. She was treated with posterior–anterior opposing pelvic fields giving 40 Gy to the mid-plane in 20 fractions over 28 days. This was followed by parametrial irradiation, giving 10 Gy in five fractions over 6 days. The primary site was irradiated further with high dose rate intracavitary brachytherapy, delivering 18 Gy in three fractions over 2 weeks to point A. The patient developed grade 4 neutropenia after the second cycle of EP and required colony stimulating factors for support. The third cycle of EP was delayed for a week as planned to allow for recovery from the chemoradiation. The last (fourth) scheduled intracavitary treatment was withheld because of severe thrombocytopenia (platelet count 22 6 109/l). Vaginal examination then showed a 2.5 6 2.5 cm growth replacing the anterior lip of the cervix. MRI of the pelvis showed a T1 isointense, T2 hypointense mass measuring 2.0 6 1.5 6 1.0 cm at the anterior lip of the cervix (Fig. 3) and residual disruption of the cervical stromal stripe at the left parametrium. We decided to proceed to surgery in view of the apparent persistent disease, the poor marrow tolerance, and the likelihood that this tumour had developed resistance to chemotherapy and radiotherapy. The last planned intracavitary treatment was therefore not given, in order to minimize the late morbidity of radiotherapy. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Pathological examination, however, showed no evidence of malignancy. The treatment was completed in August 1997. Chest radiography in December 1997 was normal. The patient and her baby remain well 14 months after presentation.
Discussion
Fig. 3. Sagittal T2-weighted fat-suppressed image after intravenous gadolinium DTPA, showing residual non-enhanced changes at the anterior lip of the cervix (arrow).
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Small cell carcinoma of the cervix is rare, and accounts for 0.5% of all cervical cancers in Hong Kong. There is no consensus regarding its optimal management. Chemoradiation regimens extrapolated from protocols used in small cell lung cancer are commonly employed in the treatment of SCCC [2,3]. The situation becomes even more complex if it is complicated by pregnancy. The timing and modalities of treatment, the anticipated morbidity to the mother and the baby, and the family’s preference, should be taken into account in formulating the treatment plan. Small cell carcinoma is believed to be both chemotherapy and radiotherapy sensitive. We advocate first line systemic chemotherapy to eradicate the potential micrometastases, because most patients die of distant failure [4]. Hoskins et al. advocated a multimodality regimen of four cycles of EP given every 2 weeks, with concurrent radiotherapy starting at the time of the second cycle of EP [2]. The total dose given to point A was 95% of their standard dose for squamous cell carcinoma of the cervix. This 5% reduction was used because concurrent chemotherapy was given. The toxicity was significant, with two of 11 patients dying of toxicity; one died of radiation-induced bowel complications. They reported a 3-year survival of 42% for six patients with FIGO Stage I disease. We adopted a slightly different approach. To minimize the toxicity of concurrent chemoradiation, we decided to give sandwich chemotherapy and radiotherapy, with the
same radiation dose to point A as if we were treating squamous cell carcinoma of the cervix. Despite the clinical suggestion of persistent local disease, this tumour was confirmed to have a pathological complete remission after three cycles of EP and 89% of the standard dose of radiation. Further chemotherapy was not given as we were unconvinced of the benefit in the face of the associated potential toxicity: (1) it was doubtful whether further chemotherapy with a major dose reduction would be beneficial; (2) the treatment break between the third and the fourth cycles would be at least 6 weeks to allow for optimal wound healing; (3) there was no evidence of metastatic disease; (4) the patient ran a high risk of chemotherapy-induced toxicity. If we have to face a similar situation in the future, we will be more confident in continuing with the planned chemoradiation and will monitor the response by biopsy. Surgery can be reserved as salvage therapy for those with residual or recurrent disease at the primary site after the completion of the chemoradiation. Another two patients with SCCC in pregnancy were identified in a search of the literature [5,6]. They remained disease free 51 and 54 months, respectively. The prognosis for patients with SCCC complicated by pregnancy appears to be not so dismal as has been suggested in the past.
Acknowledgements. The authors wish to thank S. K. Lau, S. K. Wan and Mark Lowes for their assistance.
References 1. Perrin L, Bell J, Ward B. Small cell carcinoma of the cervix of neuroendocrine origin causing obstructed labour. Aust NZ J Obstet Gynaecol 1996;1:85–7. 2. Hoskins PJ, Wong F, Swenerton KD, et al. Small cell carcinoma of the cervix treated with concurrent radiotherapy, cisplatin, and etoposide. Gynecol Oncol 1995;56:218–25. 3. Pazdur R, Bonomi P, Slayton R, et al. Neuroendocrine carcinoma of the cervix: implications for staging and therapy. Gynecol Oncol 1981;12:120–8. 4. Sheets EE, Berman ML, Hrountas CK, et al. Surgically treated, early-stage neuroendocrine small cell cervical carcinoma. Obstet Gynecol 1988;71:10–4. 5. Abeler VM, Holm R, Nesland JM, et al. Small cell carcinoma of the cervix. Cancer 1994;73:672–7. 6. Lewandowski GS, Copeland LJ. A potential role for intensive chemotherapy in the treatment of small cell neuroendocrine tumors of the cervix. Gynecol Oncol 1993;48:127–31. Received for publication May 1998 Accepted following revision July 1998
Small Cell Carcinoma of the Cervix Complicated by Pregnancy
125
Clinical Oncology (1999)11:123–125 # The Royal College of Radiologists
Case Report Small Cell Carcinoma of the Cervix Complicated by Pregnancy T. W. Leung, S. H. Lo, S. F. Wong, M. K. Yuen, F. C. S. Wong, S. Y. Tung, W. K. Sze and S. K. O Tuen Mun Hospital, Hong Kong Abstract. We report the results of treatment in a 26-year old patient with stage IB2 small cell carcinoma of the cervix complicated by pregnancy. A pathological complete remission was achieved following sandwich chemotherapy and radiotherapy. The patient remains in clinical remission 14 months after presentation. Keywords: Cervix; Chemotherapy; Pregnancy; Radiotherapy; Small cell carcinoma
Introduction Small cell carcinoma of the cervix (SCCC) complicated by pregnancy is rare, and there is no consensus regarding treatment. Perrin et al. identified a total of five patients with SCCC in association with pregnancy [1]. They concluded that the outcome had been universally poor, with the longest survival being 32 months after initial diagnosis. We report a patient achieving a pathological complete remission following sandwich chemotherapy and radiotherapy.
Case Report A 26-year-old primigravida presented in April 1997 with vaginal bleeding at estimated 31 weeks gestation. On examination, the cervix was replaced by a hard nodular growth measuring 7 6 7 cm. The fornices and the parametria were clear. There were no other abnormalities. Blood biochemistry test results were normal and the chest radiograph was clear. A punch biopsy of the cervix confirmed the diagnosis of small cell carcinoma (Fig. 1). Immunohistochemistry showed positive staining for neurone specific enolase and chromogranin. Magnetic resonance imaging (MRI) of the abdomen and pelvis showed abnormal T2 hyperintensity and thickening at the anterior and posterior lips of the cervix. The whole cervical canal was enlarged and measured 7 6 6 6 7 cm (Fig. 2). Left parametrial involvement was suggested. The liver, kidney and spleen were normal. No lymphadenopathy was identified. Trephine biopsy was refused. The patient was Correspondence and offprint requests to: Dr T. W. Leung, Department of Clinical Oncology, Tuen Mun Hospital, Tsing Chung Koon Road, Hong Kong.
jointly assessed by a clinical oncologist and a gynaecologist. The recommendation was for chemoradiation after the delivery of the baby. Examination under anaesthesia was performed at 34 weeks estimated gestational age, which showed a stage IB2 carcinoma of the cervix (FIGO). The baby was delivered by classical caesarean section at the same time. The patient was scheduled to be treated with six 3weekly cycles of chemotherapy with cisplatin 100 mg/m2 intravenously (i.v.) on day 1 and etoposide 100 mg/m2 i.v. on days 1–3 (EP). The first cycle of EP was given on the eighth day after the caesarean section. We believed that a radical dose of radiotherapy together with the chemotherapy would have a good chance of eradicating the disease locally. The second and third cycles of EP were given at weekends without any overlap with radiotherapy. The tumour showed an initial response and measured 3 6 3 cm prior to the commencement of the second cycle of EP.
Fig. 1. Infiltrative tumour composed of small, uniform cells with a high nuclear/cytoplasmic ratio, prominent karyorrhexis and frequent mitosis (H&E 6 100).
Fig. 2. Sagittal T2-weighted image showing a large tumour in the cervix. Cephalic presentation of the foetus is observed.
Radiotherapy was started on day 21 after the caesarean section. She was treated with posterior–anterior opposing pelvic fields giving 40 Gy to the mid-plane in 20 fractions over 28 days. This was followed by parametrial irradiation, giving 10 Gy in five fractions over 6 days. The primary site was irradiated further with high dose rate intracavitary brachytherapy, delivering 18 Gy in three fractions over 2 weeks to point A. The patient developed grade 4 neutropenia after the second cycle of EP and required colony stimulating factors for support. The third cycle of EP was delayed for a week as planned to allow for recovery from the chemoradiation. The last (fourth) scheduled intracavitary treatment was withheld because of severe thrombocytopenia (platelet count 22 6 109/l). Vaginal examination then showed a 2.5 6 2.5 cm growth replacing the anterior lip of the cervix. MRI of the pelvis showed a T1 isointense, T2 hypointense mass measuring 2.0 6 1.5 6 1.0 cm at the anterior lip of the cervix (Fig. 3) and residual disruption of the cervical stromal stripe at the left parametrium. We decided to proceed to surgery in view of the apparent persistent disease, the poor marrow tolerance, and the likelihood that this tumour had developed resistance to chemotherapy and radiotherapy. The last planned intracavitary treatment was therefore not given, in order to minimize the late morbidity of radiotherapy. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Pathological examination, however, showed no evidence of malignancy. The treatment was completed in August 1997. Chest radiography in December 1997 was normal. The patient and her baby remain well 14 months after presentation.
Discussion
Fig. 3. Sagittal T2-weighted fat-suppressed image after intravenous gadolinium DTPA, showing residual non-enhanced changes at the anterior lip of the cervix (arrow).
124
T. W. Leung et al.
Small cell carcinoma of the cervix is rare, and accounts for 0.5% of all cervical cancers in Hong Kong. There is no consensus regarding its optimal management. Chemoradiation regimens extrapolated from protocols used in small cell lung cancer are commonly employed in the treatment of SCCC [2,3]. The situation becomes even more complex if it is complicated by pregnancy. The timing and modalities of treatment, the anticipated morbidity to the mother and the baby, and the family’s preference, should be taken into account in formulating the treatment plan. Small cell carcinoma is believed to be both chemotherapy and radiotherapy sensitive. We advocate first line systemic chemotherapy to eradicate the potential micrometastases, because most patients die of distant failure [4]. Hoskins et al. advocated a multimodality regimen of four cycles of EP given every 2 weeks, with concurrent radiotherapy starting at the time of the second cycle of EP [2]. The total dose given to point A was 95% of their standard dose for squamous cell carcinoma of the cervix. This 5% reduction was used because concurrent chemotherapy was given. The toxicity was significant, with two of 11 patients dying of toxicity; one died of radiation-induced bowel complications. They reported a 3-year survival of 42% for six patients with FIGO Stage I disease. We adopted a slightly different approach. To minimize the toxicity of concurrent chemoradiation, we decided to give sandwich chemotherapy and radiotherapy, with the
same radiation dose to point A as if we were treating squamous cell carcinoma of the cervix. Despite the clinical suggestion of persistent local disease, this tumour was confirmed to have a pathological complete remission after three cycles of EP and 89% of the standard dose of radiation. Further chemotherapy was not given as we were unconvinced of the benefit in the face of the associated potential toxicity: (1) it was doubtful whether further chemotherapy with a major dose reduction would be beneficial; (2) the treatment break between the third and the fourth cycles would be at least 6 weeks to allow for optimal wound healing; (3) there was no evidence of metastatic disease; (4) the patient ran a high risk of chemotherapy-induced toxicity. If we have to face a similar situation in the future, we will be more confident in continuing with the planned chemoradiation and will monitor the response by biopsy. Surgery can be reserved as salvage therapy for those with residual or recurrent disease at the primary site after the completion of the chemoradiation. Another two patients with SCCC in pregnancy were identified in a search of the literature [5,6]. They remained disease free 51 and 54 months, respectively. The prognosis for patients with SCCC complicated by pregnancy appears to be not so dismal as has been suggested in the past.
Acknowledgements. The authors wish to thank S. K. Lau, S. K. Wan and Mark Lowes for their assistance.
References 1. Perrin L, Bell J, Ward B. Small cell carcinoma of the cervix of neuroendocrine origin causing obstructed labour. Aust NZ J Obstet Gynaecol 1996;1:85–7. 2. Hoskins PJ, Wong F, Swenerton KD, et al. Small cell carcinoma of the cervix treated with concurrent radiotherapy, cisplatin, and etoposide. Gynecol Oncol 1995;56:218–25. 3. Pazdur R, Bonomi P, Slayton R, et al. Neuroendocrine carcinoma of the cervix: implications for staging and therapy. Gynecol Oncol 1981;12:120–8. 4. Sheets EE, Berman ML, Hrountas CK, et al. Surgically treated, early-stage neuroendocrine small cell cervical carcinoma. Obstet Gynecol 1988;71:10–4. 5. Abeler VM, Holm R, Nesland JM, et al. Small cell carcinoma of the cervix. Cancer 1994;73:672–7. 6. Lewandowski GS, Copeland LJ. A potential role for intensive chemotherapy in the treatment of small cell neuroendocrine tumors of the cervix. Gynecol Oncol 1993;48:127–31. Received for publication May 1998 Accepted following revision July 1998
Small Cell Carcinoma of the Cervix Complicated by Pregnancy
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