OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

BACKGROUND: Pulmonary deportation of hydatidiform mole is an exceedingly rare entity. The underlying mechanisms and proper management strategies remain unclear based on sporadic case reports over the past six decades. This study aimed to investigate the clinical features and rational treatment of patients with benign molar pregnancies with pulmonary deportation based on our experience. METHODS: Medical records of 20 cases of hydatidiform mole with pulmonary deportation were retrospectively reviewed at Peking Union Medical College Hospital from November 2006 to May 2019. The detailed information of all patients was recorded and analyzed. Patients were divided into different groups according to their characteristics and Mann-Whitney U test was used to compare the duration to achieve a normal β-human chorionic gonadotrophin (β-hCG) level after the first evacuation among groups. RESULTS: Initial pulmonary computed tomography scans showed suspected bilateral, left and right chest deportation of hydatidiform mole in 12, four, and four patients, respectively, with the maximum nodular diameter ranging from 0.6 to 1.2 cm. Ten patients achieved lesion resolution while the remaining ten patients achieved decreases in the size of their pulmonary lesions. The median duration to achieve a normal β-hCG level after the first evacuation was 15.5 (13.0, 21.9) weeks. There was no significant difference in the duration to achieve a normal β-hCG level after the first evacuation between two groups based on age (≥40 years vs. < 40 years: 15.8 [12.2, 21.5] weeks vs. 15.5 [12.9, 23.0] weeks, Z = 0.094, P = 0.925), type of antecedent mole (partial mole vs. complete mole: 15.2 [12.5, 27.4] weeks vs. 15.9 [12.9, 21.5] weeks, Z = 0.165, P = 0.869), distribution of pulmonary nodules (bilateral lungs vs. unilateral lung: 15.2 [12.8, 22.5] weeks vs. 15.9 [13.2, 22.2] weeks, Z = 0.386, P = 0.700), maximum size of pulmonary nodules (>0.5 cm vs. ≤0.5 cm: 13.0 [11.3, 17.2] weeks vs. 16.0 [14.5, 23.8] weeks, Z = 1.815, P = 0.070), and number of uterine evacuations (once vs. twice or three times: 15.0 [13.0, 16.3] weeks vs. 16.0 [12.8, 23.9] weeks, Z = 0.832, P = 0.405). The post-molar cohort was followed up for 17 to 139 months, and no gestational trophoblastic neoplasia was observed. CONCLUSIONS No surgeries other than uterine evacuation and no chemotherapy regimens are recommended for such patients if they achieve satisfactory decreases in the level of hCG and gradual decrease or disappearance of pulmonary deportation nodules. Patients should be informed about the necessity of long-term follow-up. More collaborative international studies on this exceedingly rare condition may guide decisions regarding optimal management strategies.

Objective To investigate the application of laparoscopy and /or hysteroscopy in differential di-agnosis and treatment of suspected gestational trophoblastic neoplasia (GTN), and its potential impact on out-come.Methods From January 2005 to December 2013, 160 patients with a suspected diagnosis of GTN were admitted to Peking Union Medical College Hospital and underwent laparoscopy and /or hysteroscopy for it .The clinical data , diagnosis , and outcome of these patients were retrospectively analyzed .Results Among the 160 eligible patients , 26 were confirmed with GTN , including choriocarcinoma in 15 cases , invasive mole in 6 cases , and placental site trophoblastic tumor (PSTT) in 5 cases.The diagnosis of GTN was ruled out in the other 134 ca-ses, including intrauterine gestational residues in 106 (51 cases of incomplete abortion , 52 cases of residues of cor-nual pregnancy , 2 cases of placental remnants , 1 case of residual hydatidiform mole ) , cesarean scar pregnancy in 23, cornual pregnancy in 3, intramural pregnancy in 2.There was no significant difference in most of the clini-cal data between GTN patients and non-GTN patients except for the type of last pregnancy ( P<0.001 ) .All of the GTN and the non-GTN patients achieved complete remission or cure by subsequent chemotherapy or surgical therapy except one patient lost to follow-up during the course of the treatment .Conclusions Laparoscopy and/or hysteroscopy could be an effective strategy to facilitate diagnosis when it is difficult to differentiate GTN from non -GTN diseases by clinical data .Furthermore, that technique would not affect the outcome for GTN patients , while for non-GTN patients they could offer effective treatment .

Objective To investigate the clinical characteristics and significance of diagnosis and treat -ment associated with persistent real low-level elevation of human chorionic gonadotropin ( hCG) .Methods Six patients diagnosed with persistent real low-level hCG elevation at Peking Union Medical College Hospital in the period from August 2011 to March 2015 were collected .Clinical records of the 6 patients were reviewed to retro-spectively analyze clinical features , diagnosis and treatment approaches , and follow-up results.Results Among the 6 patients , 3 were secondary to uterine curettage for hydatidiform moles , and the other 3 had received chemo-therapy for invasive moles , in whom the median chemotherapy cycle number was 8 and all experienced failure of at least one chemotherapy regimen .The median follow-up time was 24 months.The median period between the termination of treatment and the initial low-level hCG elevation was 5.5 months.The median duration of low-level hCG elevation was 16.5 months.Four patients had no evidence of progression , 1 patient progressed to choriocar-cinoma, and 1 presented with the hCG level decreasing to the normal range after spontaneous delivery .Conclu-sion Persistent real low-level hCG elevation may persist for a long time and not respond to chemotherapy .Long-term close monitoring is necessary , but treatment is not recommended .

OBJECTIVETo evaluate the combination chemotherapy regimen with floxuridine, dactinomycin, etoposide, and vincristine (FAEV) as primary treatment for gestational trophoblastic neoplasia (GTN).

METHODSClinical data and outcome of the patients with GTN from 1 January 2004 to 31 December 2009 were retrospectively reviewed. Totally 38 eligible patients had received at least one cycle of FAEV chemotherapy as primary treatment. The primary end points were response rate and toxicity of FAEV regimen.

RESULTSTotally 38 patients and 205 cycles of FAEV chemotherapy were included. Twenty-eight of these patients (73.6%) achieved serologic complete remission (SCR). Regimens were changed in 10 patients because of 5 with no response and 5 with intolerable toxicity. The most serious adverse events were greater than or equal to grade 3 neutropenia (31.6%), febrile neutropenia (7.9%), and greater than or equal to grade 3 thrombocytopenia (5.3%). During the follow-up, none relapsed.

CONCLUSIONFAEV is an effective regimen with manageable toxicity for patients with GTN as primary treatment, especially for patients with non-metastatic low or high risk GTN.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Dactinomycin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Floxuridine ; administration & dosage ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Middle Aged ; Pregnancy ; Retrospective Studies ; Treatment Outcome ; Vincristine ; administration & dosage ; Young Adult

BACKGROUNDRespiratory failure caused by metastatic pulmonary choriocarcinoma usually develops rapidly and is associated with a high mortality. The clinical management strategy is important in choriocarcinoma patients with acute respiratory failure. The objective of this study was to evaluate the clinical characteristics, treatment outcome and potential risk factors in patients with acute respiratory failure from metastatic pulmonary choriocarcinoma.

METHODSSixteen patients with acute respiratory failure from pulmonary metastases choriocarcinoma were enrolled and treated at Peking Union Medical College Hospital from 1995 to 2010. Clinical characteristics, causes of pulmonary failure, treatment profiles and outcomes were analyzed retrospectively.

RESULTSThe presence of respiratory infection or hemorrhage was associated with acute respiratory failure in patients with metastatic choriocarcinoma. Fifteen (93.8%) patients presented with pulmonary infection, 8 (50.0%) patients with pulmonary hemorrhage. All patients were treated with face mask or mechanical ventilation. Fourteen (87.5%) patients received initial chemotherapy at a low dosage or with modified regimens, with a median of 2 cycles (range 1 to 4). Seven patients achieved a complete remission (CR), two had a partial remission. Six CR patients remained alive with a median follow-up of 59 months (range 16 to 120). Seven patients developed progressive diseases and subsequently died.

CONCLUSIONSRespiratory infection and hemorrhage were associated with acute respiratory failure in metastatic pulmonary choriocarcinoma. The initial administration of gentle chemotherapy regimens, accompanied with mechanical ventilation, is feasible and effective in attenuating respiratory failure in patients with metastatic pulmonary choriocarcinoma.

Adolescent ; Adult ; China ; Choriocarcinoma ; complications ; secondary ; surgery ; Female ; Humans ; Lung Neoplasms ; complications ; secondary ; surgery ; Male ; Middle Aged ; Respiratory Insufficiency ; drug therapy ; etiology ; surgery ; Retrospective Studies ; Treatment Outcome ; Young Adult

Background Respiratory failure caused by metastatic pulmonary chodocarcinoma usually develops rapidly and is associated with a high mortality.The clinical management strategy is important in choriocarcinoma patients with acute respiratory failure.The objective of this study was to evaluate the clinical characteristics,treatment outcome and potential risk factors in patients with acute respiratory failure from metastatic pulmonary choriocarcinoma.@@Methods Sixteen patients with acute respiratory failure from pulmonary metastases choriocarcinoma were enrolled and treated at Peking Union Medical College Hospital from 1995 to 2010.Clinical characteristics,causes of pulmonary failure,treatment profiles and outcomes were analyzed retrospectively.@@Results The presence of respiratory infection or hemorrhage was associated with acute respiratory failure in patients with metastatic choriocarcinoma.Fifteen (93.8％) patients presented with pulmonary infection,8 (50.0％) patients with pulmonary hemorrhage.All patients were treated with face mask or mechanical ventilation.Fourteen (87.5％) patients received initial chemotherapy at a low dosage or with modified regimens,with a median of 2 cycles (range 1 to 4).Seven patients achieved a complete remission (CR),two had a partial remission.Six CR patients remained alive with a median follow-up of 59 months (range 16 to 120).Seven patients developed progressive diseases and subsequently died.@@Conclusions Respiratory infection and hemorrhage were associated with acute respiratory failure in metastatic pulmonary choriocarcinoma.The initial administration of gentle chemotherapy regimens,accompanied with mechanical ventilation,is feasible andeffective in attenuating respiratory failure in patients with metastatic pulmonary chodocarcinoma.

OBJECTIVETo investigate the clinicopathologic features, diagnosis, treatment and prognosis of uterine mullerian adenosarcoma.

METHODSThe clinicopathological data of 9 cases of uterine mullerian adenosarcoma in PUMC hospital from January 2003 to February 2009 were retrospectively analyzed.

RESULTSThere were 6 uterine endometrial adenosarcomas and 3 cervical adenosarcomas. The main clinical manifestations were abnormal vaginal bleeding and pelvic pain. Physical examination showed cervical/vaginal mass, enlarged uterus or pelvic mass. The adenosarcoma was characterized by benign or atypical-appearing neoplastic glands within a sarcomatous stroma. This stroma could appear as periglandular cuffs or intraglandular polypoid projections of increased cellular structure. The primary diagnostic rate was 66.7% and the most common clinical stage was stage I (7/9). All patients received surgical treatment and seven had postoperative chemotherapy, radiotherapy or hormone therapy. Conservation of unilateral ovary or bilateral ovaries was performed in 5 cases. Three patients underwent local excision, which resulted in the preservation of reproductive function. During the follow-up, 2 cases of uterine endometrial adenosarcoma recurred. One patient of clinical stage III containing sarcomatous overgrowth died from recurrence 13 months after surgery. The other one recurred 2 years after local excision of the tumor in the uterine cavity and she remained healthy since hysterectomy.

CONCLUSIONUterine mullerian adenosarcoma is a rare tumor without specific clinical symptoms and signs. The diagnosis depends on pathomorphologic examination. The tumors show low malignant potential and the vast majority are at early stage. Surgical excision is the main treatment strategy with a good prognosis in the early stage disease with complete removal of tumors. The prognosis is poor in advanced adenosarcoma with sarcomatous overgrowth. Due to the relatively high rate of recurrence, long-term follow-up is recommended.

Adenosarcoma ; drug therapy ; pathology ; surgery ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemotherapy, Adjuvant ; Cisplatin ; therapeutic use ; Endometrial Neoplasms ; drug therapy ; pathology ; surgery ; Etoposide ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Ifosfamide ; therapeutic use ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; surgery ; Uterine Neoplasms ; drug therapy ; pathology ; surgery ; Young Adult

Adenosarcoma ; mortality ; pathology ; therapy ; Adolescent ; Adult ; Female ; Humans ; Middle Aged ; Mixed Tumor, Mullerian ; mortality ; pathology ; therapy ; Prognosis ; Uterine Neoplasms ; mortality ; pathology ; therapy