Demographic data
A total of 37 NGC patients were recruited, all of Chinese origin. The mean age at onset of disease was 22.8 (9.6, range 9-44) years. As in March 2020, the follow-up period of this cohort amounted to 87.5 (82.4, range 1-269) months. Twenty-three patients had no pregnancy history, including 7 premenarchal girls. Twenty of them declared no previous sex life history. (Table 1)
Clinical presentations
For 37 NGC patients, ovary was the most commonly affected location with an 11:22:1 ratio of left/right/bilateral. Two patients had NGC in pituitary, another one had NGC in stomach. Twenty-one (56.8%) patients had metastatic lesions of which lungs were the most commonly observed (40.5%) locations. Brain and liver metastasis were found in two patients. Another 4 patient had extensive lesions in abdomen cavity.
Symptoms of these NGC patients were relatively not specific. Abdominal pain was reported by 24 patients. Six of them had acute abdomen and were underwent emergency surgery. Sixteen postpuberal patients had abnormal uterine bleeding, such as irregular menstruation and amenorrhea. Two pituitary patients were affected with insipidus. Other tumor-related manifestations, such as fever, pregnancy symptoms, palpable mass, headache, cough, hemoptysis, and melena were only rare conditions. No choriocarcinoma or any other type of tumor history of primary relatives were reported by these 37 NGC patients.
Serum β-hcg levels of each patient was regularly measured. The mean of each patient’s highest value of serum β-hcg during the whole disease course was 77278 (121363, range 89.1-386274) mIU/ml. AFP was tested in 13 patients. Only one mixed germ cell tumor NGC with dysgerminoma and embryonal carcinoma patient had elevated AFP.
Seven patients had histopathologically confirmed mixed NGC (1 in pituitary, 5 in ovary, 1 in stomach). Apart from choriocarcinoma, other components include dysgerminoma, embryonal carcinoma, teratoma and adenocarcinoma. A Student's t test shows that mixed NGC and pure NGC had little differences between onset age (p=0.283), choriocarcinoma staging (p=0.245), ovary cancer staging (p=0.507, only for 34 ovary NGC patients), β-hcg level (p=.0.311), having metastasis or not (p=0.523), overall courses of chemotherapy (p=0.836), courses to reach CR (p=0.262), and CR rate (p=0.277). (Table 1 & Figure 1)
Therapeutic modalities
Treatments include chemotherapy, surgery, radiotherapy and intrathecal injection. All patients received multiple-drug combined chemotherapy. The main regimen chosen are EMA/CO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, Vincristine, for 20 patients), FAEV (Floxuridine, Actinomycin-D, Etoposide, Vincristine, for 15 patients), BEP (Bleomycin, Etoposide, Cisplatin, for 7 patients), PVB (Bleomycin, Vincristine, Cisplatin, for 4 patients), and ICE (Ifosfamide, Carboplatin, Etoposide, for 2 patients). Nine patients received chemotherapy before surgery. The overall mean courses and courses to reach CR were 9.9 and 5.8, respectively. For 7 mixed NGC patients, 2 took mainly BEP protocol and another 3 used EMACO protocol, all with a CR response. BEP, EMACO and FAEV protocols were prescribed for another ovary mixed NGC patients but was unable to control her disease. The stomach mixed NGC patient obtained CR after FAEV therapy but had disease relapse after 2 years.
Myelosuppression was commonly observed adverse effect of chemotherapy, but only one patient had life-threatening myelosuppression. Other conditions such as liver injury, dental ulcer, anorexia were rarely reported by sporadic patients.
All 37 patients underwent surgery and thus had a histopathological confirmation of choriocarcinoma. For 34 ovary NGC patients, 16 underwent cytoreductive surgery and 18 received fertility-preserving surgery. For 16 cytoreductive surgery patients, 6 was initially underwent fertility-preserving procedures. However, a debulking surgery was performed in our medical center because of unsatisfactory drop of β-hcg or disease relapse. Even though 15 patients had lung metastases, only three of them received pulmonary lobectomy.
Assisting chemotherapy, one pituitary NGC patients completed 25 times of radiotherapy treatments (total 45 Gray). Another patient with cerebral metastasis received 3 methotrexate intrathecal injections. (Table 2)
Outcomes
For all 37 NGC patients, 30 (81.1%) achieved CR, 4 (10.8%) achieved PR. Three (8.1%) patients had PD and were died. One patient was diagnosed in 1980s and received nonstandard multi-drug combined chemotherapy. She gave up treatment after 44 months of unsuccessful decline of hCG. Another subject had mixed NGC with teratoma and dysgerminoma components. She underwent debulking surgery and received FAEV, BEP and EMACO chemotherapy for 23 months. The last patient died of chemoresistance. Succession regimen of FAEV, PVB, ICE and EMAEP (Etoposide, Methotrexate, Actinomycin D, Cisplatin) were unable to decline β-hcg to nomality.
For 34 CR and PR patients, 8 patients were lost of follow-up, including 4 CR and 4 PR patients. With a mean of 87.5 months of follow-up, the overall 1-year, 3-year and 5-year survival rates are 86.2%, 80.0% and 75.5%.
Five (16.7%) of the CR patients had disease relapse during follow-up. Four were affected by ovary NGC and initially received fertility-preserving procedures. After disease relapse, three underwent another debulking surgery and subsequent chemotherapies. One girl only received another 6 courses of EMACO. All of them four obtained CR again. The stomach NGC patient showed multiple metastases in abdomen 2 years after reaching CR and died of chemoresistance.