Daily low-dose cisplatin-based concurrent chemoradiotherapy in patients with uterine cervical cancer with emphasis on elderly patients: a phase 2 trial.

OBJECTIVE: We evaluated the usefulness of daily low-dose cisplatin-based concurrent chemoradiotherapy (daily CCRT) in patients with cervical cancer with an emphasis on elderly patients. METHODS: Between January 2003 and December 2008, a total of 65 patients with untreated stage IIA to IIIB cervical cancer were enrolled and 54 were selected for this nonrandomized prospective study. The daily CCRT comprised pelvic external beam radiotherapy (2 Gy/d × 25) with daily low-dose cisplatin (8.0 mg/m(2) per day) and either low- or high-dose rate intracavitary brachytherapy. RESULTS: The median age of the patients was 62 years (range, 29-85 years), and 21 patients (39%) were 70 years or older. The median follow-up period was 47 months (range, 4-107 months). Daily CCRT was successfully completed in 91% (49/54) of the patients. The mean total cisplatin dose was 191 mg/m (range, 128-224 mg/m(2)), and a neutropenia grade higher than 3 was observed in 24% of the patients. Of the 21 patients 70 years or older, 17 (81%) completed daily CCRT with acceptable toxicity. The 3-year overall survival (OS) rate for all the patients was 82.9%. No statistically significant differences in the OS rate and toxicity were observed between patients 70 years or older and those younger than 70 years. CONCLUSIONS: Daily CCRT showed acceptable toxicity and compliance, leading to the use of a high total dosage of cisplatin. The OS rate for daily CCRT was comparable to that for previously reported weekly CCRT. Daily CCRT could be an alternate choice for the CCRT treatment in elderly patients with cervical cancer.

Early growth response-1 mediates downregulation of telomerase in cervical cancer.

Early growth response (Egr)-1 is a transcription factor that triggers transcription of downstream genes within 15-30 min of various stimulations. These genes are expressed rapidly through specific promoter activation and mediate cell growth and angiogenesis. Following the previous computational identification of a site that was thought to be an Egr-1 consensus binding site at -273 to -281 in the human telomerase reverse transcriptase (hTERT) promoter region, the present study was conducted to evaluate the role of Egr-1 in the regulation of hTERT and telomerase in uterine cervical cancer. First, the expression of Egr-1 and hTERT at the mRNA level was examined in cervical cancer tissues. Egr-1 and hTERT were expressed much higher in cervical cancer tissues than in the normal cervix. However, a negative correlation was noted in the expression between Egr-1 and hTERT. By luciferase assay using hTERT promoter constructs, hTERT transcriptional activation was shown to be inhibited when Egr-1 was overexpressed. Furthermore, Egr-1 overexpression decreased hTERT protein production as well as hTERT mRNA as observed by western blotting analysis and real-time reverse transcription-polymerase chain reaction, respectively. The present study suggests that Egr-1 plays an important regulatory role in the transcriptional activation of hTERT.

Serum p53 antibody as a diagnostic marker of high-risk endometrial cancer.

OBJECTIVE: The purpose of this study was to investigate the diagnostic impact of preoperative serum p53 antibody (S-p53 Ab) in patients with endometrial cancer. STUDY DESIGN: A hospital-based series of 67 patients, comprising 58 endometrioid adenocarcinomas (EA) and 9 serous adenocarcinomas (SA) between 1998-2002 were included. First, preoperative pathology was compared with final pathology in terms of histologic classification and tumor grade. Second, S-p53 Ab and CA125 were measured using preoperative serum samples, and immunohistochemical staining for p53 protein was assessed using hysterectomy specimens. RESULTS: There were discrepancies between preoperative and final pathology in terms of histologic classification (7%) and tumor grade in EAs (30%); other objective tests, therefore, were needed to minimize the diagnostic problems. S-p53 Ab titers varied from 0.27-786 (mean, 124) in SAs and from 0.1-7.47 (mean, 0.46) U/mL in EAs, respectively, and were positive in 6 (67%) SAs and in 3 (6%) EAs using 1.3 U/mL as cut-off. S-p53 Ab-positive rate was significantly correlated with SA histology and grade 3 EA tumor (odds ratio, 40; P = .005; 95% confidence interval, 3.04-525.43) with higher sensitivity and higher specificity than p53 staining and CA125, respectively. CONCLUSION: S-p53 Ab could conveniently and specifically identify high-risk endometrial cancer.

Fertility-preserving treatment with progestin, and pathological criteria to predict responses, in young women with endometrial cancer.

BACKGROUND: There are therapeutic dilemmas regarding conservative management of endometrial cancer in young women. METHODS: We planned a prospective study to conservatively treat women aged under 40 years with clinical stage 1A, grade 1 endometrioid adenocarcinoma from 1999 to 2005. There were nine women (aged 28-40) who fulfilled the criteria, and medroxyprogesterone acetate (400 mg/day) was continued for 6 months. Curettage materials were pathologically evaluated according to our criteria including partial response (PR) (a small amount of cancer tissue with remarkable hormonal effects or atypical hyperplasia). To predict complete response (CR) to progestin, immunohistochemical staining for insulin-like growth factor type 1 receptor, phosphatase and tensin homolog deleted on chromosome ten, progesterone receptor (PgR), estrogen receptor and Ki67 were assessed. RESULTS: Seven (78%) and two cases presented complete and PRs, respectively. Two patients developed recurrent disease 10 and 22 months after the last dilatation and curettage, and both had synchronous ovarian cancer. However, all nine patients were alive and disease-free for a mean of 39 months. Of eight married patients, four (50%) conceived and three delivered full-term singletons. CR was related to positive expression of PgR (P=0.008). CONCLUSIONS: Patients with an initial PR can obtain CR after further treatment, and the PgR may be useful in predicting CR to fertility-preserving treatment in young women with endometrial cancer.

Primary synovial sarcoma in fallopian tube: case report and literature review.

Synovial sarcoma, a malignant mesenchymal neoplasm, occurs mostly near the joints of the extremities and occasionally outside the joint such as lung. We report a case of soft tissue sarcoma arising in the fallopian tube origin that showed characteristic pathological appearance of biphasic synovial sarcoma. Molecular analysis detected a fusion gene transcript of synovial sarcoma translocation (SYT) gene from chromosome 18 and synovial sarcoma X chromosome breakpoint 1 (SSX1) gene, which is believed to pathognomonic for synovial sarcoma of joint origin. Recurrent abdominal tumor, observed at 12 month after the initial surgery and following chemotherapy using doxorubicin, cisplatin and ifosfamide, partially responded to chemotherapy using paclitaxel and carboplatin and, then, optimal surgery was performed. This is the first report of a synovial sarcoma arising in the fallopian tube.

Recent changes of the incidence of complete and partial mole in Chiba prefecture.

AIMS: To study the changes of the incidence of complete mole (CM) and partial mole (PM) by 10-year age groups in Chiba Prefecture. METHODS: All women registered as CM and PMs in Chiba Prefecture during these 18 years were included in this study. The diagnosis of CM and PM was based on the macroscopic and/or microscopic findings. The annual numbers of pregnancy were obtained from the Division of Statistics in Chiba Prefecture Government. RESULTS: The incidence of CM at the upper and lower extremes of maternal age is higher than that of PM. The incidence of CM has decreased constantly at all maternal ages and significantly decreased in women of middle reproductive age (20-39 years old) since 1991, while that of PM has stayed constant during these 18 years. CONCLUSIONS: The incidence of CM and PM in Chiba Prefecture has become as low as that in Europe or the USA. These recent changes suggest that Japanese women may have lost the increased risk to ovulate a nuclear or inactive oocytes, or the differential diagnosis between CM and PM may be obscured with the macroscopic and/or microscopic findings.

Tamoxifen and the risk of endometrial cancer in Japanese women with breast cancer.

PURPOSE: There is ongoing debate about whether tamoxifen for breast cancer is associated with a risk of endometrial cancer in Japanese women. We conducted a study to investigate this further. METHODS: We conducted a retrospective hospital-based cohort study. A total of 674 consecutive patients underwent surgery for primary breast cancer between January 1989 and December 1998. By December 2003, endometrial cancers had been diagnosed in six of these patients. Based on medical records, we evaluated the potential risk factors for endometrial cancer, including age, menopausal status, obesity, parity, diabetes mellitus, hypertension, and tamoxifen. The 674 patients were divided into three groups based on the cumulative duration of tamoxifen use (A, <2 years vs B, 2-5 years vs C, >5 years). To examine the relationships between endometrial cancer and tamoxifen (and other factors), the hazards ratio (HR), 95% confidence interval (CI), and two-sided P value for endometrial cancer associated with each variable were calculated by the Cox regression method. RESULTS: Endometrial cancer was found in 1/318 (0.31%) patients in group A, 3/247 in group B, and 2/109 in group C. In a multivariate analysis no variable was significant, but tamoxifen use for longer than 5 years (group C) was closely correlated with endometrial cancer (HR = 7.92, CI = 0.69-90.89, P = 0.096). CONCLUSION: Although our data did not reach significance, they support a link between long-term tamoxifen and the development of endometrial cancer in Japanese women with breast cancer.

Discordance between serum level and tissue immunohistochemical staining of CA125 in endometrioid adenocarcinoma of the uterine corpus.

This study was designed to correlate tissue expression of CA125 with the corresponding serum value in endometrial cancer. The records of 52 endometrioid adenocarcinomas diagnosed were reviewed. Serum CA125 levels were examined before definitive surgery, and 20 U/ml was used as the cutoff value. Immunohistochemical staining for CA125 was assessed according to the ImmunoReactive Score. Statistical analyzes were performed to identify independent factor for high serum CA125 levels, including CA125 staining and the conventional pathologic features. Elevated serum CA125 levels were found in 15 of 52 patients (29%) (range, 0.1-172.1; mean 22.6 U/ml). The frequency of positive CA125 tissue staining (35/52, 67%) tended to be higher than that of elevated serum levels (p = 0.046). Fifteen patients with elevated serum CA125 levels statistically differed from the remaining 37 patients with normal serum CA125 level with respect to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.027) and lymph node metastasis (p = 0.024), and tended to have positive washing cytology (p = 0.052). In multivariate analysis, elevated serum CA125 significantly correlated only with FIGO stage III, but not with tumor size or CA125 tissue staining. Intrauterine tumor may not be the main source of serum CA125 in endometrial cancer, and elevated serum level is closely related to the presence of disseminated cancer cells in the peritoneal cavity.

Relapse rate of patients with low-risk gestational trophoblastic tumor initially treated with single-agent chemotherapy.

OBJECTIVE: To determine the factors for relapse in patients with low-risk gestational trophoblastic tumor (GTT) treated with single-agent chemotherapy. METHODS: Between 1974 and 2000, 272 consecutive patients with low-risk GTT were initially treated with methotrexate (MTX), actinomycin D (Act-D) or etoposide chemotherapy. The primary remission rate, change of chemotherapy because of drug resistance or toxicity, and relapse rate were compared. RESULTS: Overall survival rate and primary remission rate for 272 patients were 100% and 75.7%, respectively. Primary remission rate was significantly higher in patients given etoposide than those given conventional MTX (P < 0.0001) or MTX-folinic acid (MTX-CF) (P = 0.0005). Twenty-four (8.8%) patients required a change of chemotherapy because of drug resistance. The frequency of drug resistance was significantly higher in patients treated with MTX-CF than those treated with etoposide (P = 0.006). Although maternal age, presence of metastasis, high pretreatment hCG titer, and planned hysterectomy did not influence the development of drug resistance, the new FIGO scores were significantly higher in patients who developed drug resistance. Relapse rate increased significantly in patients who had high FIGO scores and who required change of chemotherapy due to drug resistance. CONCLUSIONS: All patients with low-risk GTT eventually attained complete remission, even though some developed drug resistance to the first-line chemotherapy. The relapse rate was significantly higher in patients with drug resistance than those with primary remission. Chemotherapy regimen that induces little drug resistance is desirable from the viewpoint of long-term prognosis.

Postoperative pelvic radiotherapy for cervical cancer patients with positive parametrial invasion.

OBJECTIVE: To evaluate patterns of failure in cervical cancer patients with histopathologic parametrial invasion treated with postoperative pelvic radiation therapy. METHODS: Records of 117 stages IB-IIB cervical cancer patients with parametrial invasion treated with postoperative radiation therapy from 1985 to 2002 were retrospectively reviewed. Patients were divided into two groups based on status of pelvic lymph nodes. Patterns of recurrence and prognosis by status of pelvic lymph nodes were statistically analyzed. RESULTS: Status of pelvic lymph nodes had significant impact on both recurrence and survival. Extrapelvic recurrence was observed in 23 of 66 node-positive patients compared with 6 of 51 node-negative patients (P = 0.005). Of 66 patients with a positive pelvic lymph node, 18 developed visceral metastases, whereas only three visceral metastases were noted in the 51 node-negative patients (P = 0.003). Five-year overall survival in node-positive and -negative patients was 52% and 89%, respectively (P = 0.0005). Corresponding rates for recurrence-free survival were 44% and 83%, respectively (P = 0.0002). The correlation between nodal metastasis and prognosis was enhanced when node-positive patients were stratified into two groups based on number of positive nodes (n = 1 and n > or = 2). Five-year recurrence-free survival rates for patients with negative, one positive, and two or more positive nodes were 83%, 61%, and 31%, respectively (P = 0.0001). CONCLUSIONS: Extrapelvic recurrence was uncommon in node-negative patients with parametrial invasion. These findings do not support use of systemic therapy for cervical cancer patients with parametrial invasion if pelvic lymph node metastasis is negative.

Serum vascular endothelial growth factor (VEGF) and VEGF-C levels as tumor markers in patients with cervical carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) and VEGF-C play a crucial role in the regulation of tumor growth and metastasis. The current study examined the significance of serum VEGF and VEGF-C levels in relation to conventional clinicopathologic parameters, response to treatment, and survival in patients with cervical carcinoma. METHODS: Between December 1999 and March 2004, serum VEGF and VEGF-C levels were analyzed in 78 patients with cervical carcinoma undergoing primary treatment (primary surgery [n=40] and radiotherapy [n=38]), as well as in 30 healthy controls. Serum VEGF and VEGF-C levels were assessed by enzyme-linked immunosorbent assay before and within 2 weeks after treatment. RESULTS: Serum VEGF and VEGF-C levels were higher in patients with cervical carcinoma than in the healthy control (P=0.0002 and P=0.0007, respectively). Both VEGF and VEGF-C concentrations increased significantly in patients with squamous cell carcinoma (SCC vs. normal control: P<0.0001 and P=0.0001, respectively), but not in adenocarcinoma (vs. normal control: P=0.2982 and P=0.7766, respectively). In an analysis of SCC, the pretherapeutic serum levels of VEGF and VEGF-C correlated significantly with advanced International Federation of Gynecology and Obstetrics stage and large tumor size, but not with lymph node metastasis. The pretherapeutic serum level of VEGF-C also correlated significantly with disease recurrence or persistence after treatment. Both serum VEGF and VEGF-C levels decreased significantly after treatment. CONCLUSIONS: The serum levels of both VEGF and VEGF-C have potential usefulness as biologic markers of SCC of the uterine cervix.

Phase I study of daily cisplatin and concurrent radiotherapy in patients with cervical carcinoma.

OBJECTIVE: Chemoradiation based on cisplatin is the standard treatment for locally advanced cervical carcinoma; however, the optimal scheduling and dosing have still not been established. This study was conducted to determine the maximum-tolerated dose (MTD) of cisplatin for daily administration during pelvic radiotherapy (RT). METHODS: Fourteen patients with locally advanced cervical carcinoma and 13 who required postoperative RT were registered. A low dose of cisplatin was given daily concurrently with RT. Cisplatin dosing was started at 6.0 mg/m(2)/day, which was incremented by 0.5 mg/m(2)/day. RT was delivered at 2 Gy/day to a total dose of 50 Gy. The MTD was defined as the dose level immediately below that causing dose-limiting toxicity (DLT) in over one-third of treated patients. RESULTS: Twenty-five patients were treated with a maximum of six escalating dose levels. In 22/25 patients (88%), cisplatin was administered continuously as planned without interruption. The MTD was determined to be 8 mg/m(2) and the DLT was indicated by the onset of neutropenia. CONCLUSION: Daily cisplatin, at 8 mg/m(2)/day, is a well-tolerated radiosensitizer in cervical carcinoma patients.

Clinicopathologic study of 56 patients with endometrial cancer during or after adjuvant tamoxifen use for their breast cancers.

OBJECTIVES: The aim of this study was to describe the clinicopathologic features and prognosis of endometrial cancer patients diagnosed during or after tamoxifen treatment for breast cancer. METHODS: Fifty-six tamoxifen-related endometrial cancers were identified from 10 hospitals in Japan. Past users were defined as endometrial cancer patients diagnosed more than 12 months after the cessation of tamoxifen treatment for breast cancer. All other users were classified as recent users. RESULTS: Age at diagnosis of the endometrial cancer ranged from 29 to 81 years. Sixteen (29%) and 19 (34%) patients were nulliparous and overweight, respectively. When the patients were divided into two groups: 30 recent and 26 past users, the distribution of various clinical characteristics, except for age at the time of diagnosis for endometrial cancer and the interval between the diagnoses of two cancers, was similar for two groups. The daily dose, duration and cumulative dose also showed no significant difference between the two groups. Past users had histopathologically more invasive tumors showing prognostically more unfavorable subtypes than recent users. The background lesions including endometrial polyps and diffuse cystic changes were similar for the two groups. The cumulative 3-year survival was significantly worse for past users than for recent users (74.8% and 96.4%, respectively, P < 0.04). In multivariate analysis including recentness of tamoxifen use and age at diagnosis of endometrial cancer, the significance of past user disappeared. CONCLUSIONS: Past users had a worse prognosis of endometrial cancer with more invasive histologic features than recent users, probably because they included more elderly patients.

Early pregnancy outcomes after chemotherapy for gestational trophoblastic tumor.

OBJECTIVE: To analyze the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). STUDY DESIGN: A total of 393 patients with GTT (87 with high-risk and 306 with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of them, 137 (19 with high-risk and 118 with low-risk GTT) who achieved primary remission and had at least 1 conception following chemotherapy were included in the study. RESULTS: The overall outcomes of the first subsequent pregnancies in the 137 women treated with chemotherapy were comparable to those in the general Japanese population. However, the incidence of abnormal pregnancies (spontaneous abortion, stillbirth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (6 of 16, 37.5%) than in those who conceived after the recommended waiting period, > 12 months (11 of 99, 10.5%) (P=.014). CONCLUSION: Patients who achieved primary remission with various kinds of chemotherapy may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormality, a waiting period of at least 6 months after chemotherapy for GTT is recommended.

Salvage chemotherapy for high-risk gestational trophoblastic tumor.

OBJECTIVE: To evaluate the efficacy and safety of etoposide/methotrexate/actinomycin D (MEA regimen) as initial chemotherapy and 5-fluorouracil/actinomycin D (FA regimen) as salvage chemotherapy for high-risk gestational trophoblastic tumor (GTT). STUDY DESIGN: From 1985 to 2001, 36 patients with World Health Organization (WHO)--defined high-risk GTT were treated with MEA or FA at Chiba University Hospital. Thirty-three patients were initially treated with MEA. FA was administered to 11 patients; 1 had had no previous chemotherapy, 7 had developed drug resistance to MEA, 1 had relapsed following MEA, and 2 had relapsed following etoposide/methotrexate/actinomycin D/ cyclophosphamide/vincristine (EMA/CO) combination chemotherapy. RESULTS: The primary remission rate with MEA was 69.7% (23 of 33). With FA the survival rate was 81.8% (9 of 11) for a mean follow-up period of 11.5 years. Two patients died due to multidrug resistance, and 2 patients relapsed subsequently. The 2 relapse cases were successfully salvaged again with MEA. The toxicity of FA was evaluated in 89 cycles. Myelosuppression seemed to be the dose-limiting toxicity, and the incidence of WHO grade 4 leukocytopenia and thrombocytopenia were 5.6% and 3.4%, respectively. CONCLUSION: Although etoposide-containing chemotherapy is currently the most effective and well tolerated regimen for high-risk GTT, 20-30% of patients develop drug resistance to these regimens. Salvage combination chemotherapy with FA is effective for refractory patients, and the toxicity is predictable and manageable.

Criteria for initiating chemotherapy in patients after evacuation of hydatidiform mole.

OBJECTIVES: To evaluate the spontaneous regression curve of serum human chorionic gonadotropin (hCG) in patients with an uneventful course after evacuation of hydatidiform mole and to compare the criteria for initiating chemotherapy in patients after evacuation of mole. METHODS: From 1986 to 2001, 608 patients were followed at our department after evacuation of mole. The spontaneous regression curves of serum hCG in 432 patients with an uneventful course were established. RESULTS: After evacuation of mole, the titers of serum hCG decreased constantly, and 90% of patients with an uneventful course were within normal range within 16 weeks. In 432 patients with an uneventful course, the upper 95% confidence limit of serum hCG at 5, 8 and 20 weeks was 753.7, 422.9 and 14.8 mIU/ml, respectively. Moreover, 39 (9.0%) and 15 patients (3.5%) with an uneventful course might have been diagnosed with gestational trophoblastic tumor and received needless chemotherapy based on the normal regression curve established by the Japan Society of Obstetrics and Gynecology or the US criteria of 4 consecutive plateauing or rising hCG values, respectively. CONCLUSIONS: Our more selective criteria for initiating chemotherapy in patients after evacuation of mole, i.e. hCG of 10,000 mIU/ml at 5 weeks, 1,000 mIU/ml at 8 weeks and nondetectable levels at 24 weeks after evacuation of mole, may be safe and acceptable in the management of patients after evacuation of mole.

Placental mesenchymal dysplasia initially diagnosed as partial mole.

Placental mesenchymal dysplasia is a rare condition of pregnancy that presents as macroscopic features of molar change in the placenta and normal karyotype fetus. These cases are often misdiagnosed as partial mole. We report a new case of mesenchymal dysplasia. A 27-year-old Japanese primigravida delivered an 820 g female baby (46XX karyotype) without congenital anomalies at 27 weeks gestation due to massive bleeding with placenta previa. The placenta had mimicking partial moles, grape-like vesicles and normal villi that diffusely occupied the area on the maternal surface of the placenta. Pathologically, enlarged stem villi contained loose, moderately cellular connective tissue with focal cistern-like formation, and peripherally located vessels. Abnormal trophoblastic proliferation and trophoblastic inclusions were not observed in any of the sections examined. Some villi contained chorioangiomatoid changes. The mother and child were followed up for more than 5 years and showed no sign of trophoblastic disease or Beckwith-Wiedemann syndrome features.

Significance of perivascular lymphocytic infiltrates on survival of patients with invasive cervical cancer.

The authors retrospectively reviewed the medical records of 129 patients with stage IB and II cervical cancer (93 squamous cell carcinomas, 30 adenocarcinomas, and 6 adenosquamous carcinomas) who underwent primary surgery between 1989 and 2000. Vascular invasion is the predictor of recurrence, and lymphocytic infiltrates within the tumor is associated with favorable outcome in cervical cancer. Hence, 129 patients were divided into three groups according to the presence or absence of vascular invasion (VI) and perivascular lymphocytic infiltrates (PLI); VI- (n = 77), VI+PLI- (n = 26), and VI+PLI+ (n = 26), to evaluate the significance of PLI. Age, clinical stage, histology, tumor grade, depth of stromal invasion, VI and PLI, tumor size, ovarian metastasis, pelvic lymph node metastasis, postoperative irradiation, and chemotherapy were assessed statistically for recurrence of the disease by Cox regression analysis. Disease-free survival was analyzed using Kaplan-Meier survival analysis. Recurrence was observed in 32 (25%) of all 129 cases. In a multivariate analysis, VI ( = 0.003) and histology ( = 0.006) remained significantly associated with recurrence. When divided into three groups, the hazard ratio for recurrence was higher in the absence of PLI (2.95 in VI+PLI- group versus 2.07 in VI+PLI+ group), and value became significant in the absence of PLI (0.008 in VI+PLI- group versus 0.106 in VI+PLI+ group). In Kaplan-Meier survival analysis, only the VI+PLI- group ( = 0.006) was significantly associated with worse survival compared with the VI- group. These results suggest that the coexistence of perivascular lymphocytic infiltrates is associated with a better prognosis in cases with vascular invasion.

Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor.

OBJECTIVE: This study analyzed the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). METHODS: A total of 387 patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of these patients, 130 women (18 with high-risk GTT and 112 with low-risk GTT), who achieved remission and had at least one conception following chemotherapy, were included in the study. RESULTS: The outcomes of all the first subsequent pregnancies in women treated with methotrexate, actinomycin-D, or etoposide (including those switched to other regimens), or combination therapy, were comparable to those in the Japanese general population. However, the incidence of abnormal pregnancies (spontaneous abortion, still birth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (4/15; 40%) than in those who conceived after the recommended waiting period of more than 12 months (10/95; 10.5%) (P = 0.028). CONCLUSION: Patients with GTT who achieved remission after chemotherapy with methotrexate, actinomycin-D, or etoposide, or combination therapy, may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormalities, a waiting period of at least 6 months after chemotherapy for GTT is suggested.