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To the Editor: Endometrial cancer (EC) is the sixth most common cancer diagnosed in women, and its prevalence is reportedly increasing worldwide. Endometrial clear cell carcinoma (ECCC) accounts for 2–5% of all EC, and is a rare but ominous subtype of high-risk EC that has a poorer prognosis and exhibits greater chemoresistance. Owing to the rarity of ECCC, few clinical trials have included patients with this disease exclusively, and limited data are available regarding its pathogenesis and clinical progression compared with other more common subtypes of EC. Venous thromboembolism (VTE) has been known to be associated with underlying visceral malignancy since the 19th century, and has been observed at greater incidence rates in patients with cancer. Meanwhile, deep vein thrombosis (DVT) is a significant complication during gynecologic cancer surgery given that the embolus can cause life-threatening conditions, such as pulmonary embolism (PE) and acute cerebral infarction. The potential impact of VTE on survival remains largely unknown with respect to people with ECCC. Therefore, we conducted this retrospective study to investigate the characteristics of patients with ECCC and determine whether VTE has an impact on survival outcomes. Patients with ECCC who underwent primary surgical staging at Peking Union Medical College Hospital (PUMCH) were retrieved, and the study was approved by the Institutional Ethics Review Committee of PUMCH (No. K23C0468), with waived consent as retrospective study. The inclusion criteria were patients with a pathological confirmation of ECCC who underwent primary staging surgery. Electronic medical records of all patients were collected and reviewed. Patients who received post-recurrence treatment without centralized pathology review were excluded. Perioperative VTE was defined as the development of VTE within 30 days pre- or post-surgery. All pathology slides were centralized and assessed by the Pathology Department of PUMCH using the World Health Organization criteria, and miscellaneous carcinoma was defined as one or more pathological entities accompanying the clear cell carcinoma (CCC). The progression-free survival (PFS) was calculated as the interval in months between the date of the primary surgery and that of the detection of any progression or recurrence, including via biopsy pathology or imaging with or without elevated serum CA-125. Overall survival (OS) was calculated as the interval in months between the date of primary surgery and the date of death. Patients lost to follow-up were right-censored. Mann–Whitney, Pearson, and Fisher's exact χ2 (two-tailed) tests were performed for intergroup comparisons. Kaplan–Meier survival curves were analyzed according to VTE status and stage, and the log-rank test was applied to quantify survival differences. Univariate and multivariate Cox regression analyses were conducted on the variates including VTE status, age, comorbidities, stage, surgical completeness, adjuvant therapies, lymphovascular space invasion (LVSI), deep myometrial invasion (DMI), parametrial involvement (PI), and histology; the hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). All statistical analyses were performed using SPSS version 20 (IBM Corp, Armonk, NY, USA); the threshold of statistical significance was set at P <0.05. The records of 137 patients who underwent primary surgery between November 2009 and April 2022 following a histological diagnosis of ECCC were retrieved. The median age at diagnosis and primary surgery was 61 years (range, 31–82 years). Majority had stage I (56.2%, 77/137) or stage III (25.5%, 35/137) ECCC. Among patients with advanced stages, suboptimal cytoreductive surgery was performed in 4 who had a residual mass >1 cm. During the surveillance, the majority of patients received monotherapy or combined adjuvant therapies after primary surgery: 65 patients received mono-adjuvant therapy (either chemotherapy [41.6%, 57/137] or radiotherapy [5.8%, 8/137]); 51 patients (37.2%) were managed by combination chemoradiotherapy; No adjuvant therapy was administered for 15.3% (21/137) of the patients. Patients were screened for VTE under the physician's guidance with or without indications, including elevated d-dimer level, swelling or pain in the lower extremities, or hypoxemia. A total of 22 patients (16.1%) were diagnosed with perioperative VTE during primary treatment. In patients screened positively with VTE, 9 patients were positive for DVT preoperatively; 2 of them were simultaneously diagnosed with PE; 13 patients (including 8 with DVT) had newly diagnosed VTE after surgery; 1 had an isolated PE; and 4 had concomitant DVT and PE [Supplementary Table 1, https://links.lww.com/CM9/B827]. The basic characteristics and prognoses of patients in these two groups were compared [Supplementary Table 2, https://links.lww.com/CM9/B827]. A significantly higher percentage of LVSI was observed in patients with VTE (P = 0.033); however, no significant differences were detected in other parameters. There were no fatalities caused directly by VTE-related complications in our study. Not counting one patient who was lost to follow-up during the first month, the median follow-up time was 49.9 months and ranged from 6.8 months to 146.5 months. The median PFS for the entire cohort was 42.3 months (95% CI, 44.9–58.7). Patients with perioperative VTE had a shorter median PFS than those without (13.3 months vs. 47.3 months, P = 0.001) [Figure 1A]. The median OS in the overall population was 49.2 months (95% CI, 50.6–63.6), and consistent with PFS, the median OS of patients with VTE was significantly shorter than that in patients without (19.8 months vs. 57.0 months, P = 0.008) [Figure 1B]. When stratified according to disease stage, significant differences in survival were only observed in the early stages. The median PFS of patients with stage I/II disease was 63.2 months (95% CI, 59.9–76.9) in the non-VTE population vs. 17.1 months (95% CI, 13.0–48.0) in those with perioperative VTE (P = 0.047) [Figure 1C]. Furthermore, the median OS was 65.3 months (95% CI, 62.3–78.7) vs. 23.1 months (95% CI, 17.9–50.5), respectively, in this subgroup (P = 0.001) [Figure 1D]. As shown in Figure 1, a more marked difference in OS was observed when the analysis was limited to patients with stage I/II ECCC (Figure 1Bvs.Figure 1D).Figure 1: Kaplan–Meier survival curves comparing patients with ECCC who experienced perioperative VTE to those who did not. (A) PFS in patients with all disease stages, (B) OS in patients with all disease stages, (C) PFS among patients with stage I/II ECCC, (D) OS among patients with stage I/II ECCC, ECCC: Endometrial clear cell carcinoma; OS: Overall survival; PFS: Progression-free survival; VTE: Venous thromboembolism.On univariate analysis, patients with perioperative VTE had a 3.3-fold increase in the risk of tumor progression (HR, 3.3; 95% CI, 1.6–7.0; P = 0.002) and a 3.3-fold increase in the risk of death (HR, 3.3; 95% CI, 1.3–8.5; P = 0.012) overall. After controlling for known survival-related factors, we used multivariate Cox regression analysis and found that VTE status, age at diagnosis, comorbidities, tumor stage, and gross residual disease were independently associated with tumor progression and death, whereas adjuvant therapy, LVSI, DMI, or tumor histology did not significantly influence survival. Compared with the non-VTE group (all stages), increases of 7.1-fold (95% CI, 2.1–23.7; P = 0.001) and 4.0-fold (95% CI, 1.7–9.3; P = 0.002) were found in the risk of death and disease progression in the perioperative VTE group, respectively. Additionally, a more marked increase in the risk of death was observed when the analysis was limited to patients with early-stage disease (HR, 24.9; 95% CI, 1.6–382.0) (Supplementary Table 3, https://links.lww.com/CM9/B827 for all stages and Supplementary Table 4, https://links.lww.com/CM9/B827 for stage I/II). In the present study, 16.1% of the patients received perioperative VTE during primary treatment. LVSI and other well-known survival risk factors were included in our regression analyses, and perioperative VTE, age ≥60 years, advanced-stage disease, and suboptimal cytoreductive surgery were independently associated with worse survival outcomes in the overall cohort. Perioperative VTE during primary treatment was linked to shorter PFS and OS without being a direct cause of death. When stratified according to tumor stage, VTE diagnosis at primary surgery remained an independent risk factor for survival in patients with stage I/II disease. A remarkably lower incidence rate of VTE was reported in a retrospective study of 422 patients with EC of all types (6.16% overall and 0.7% within 60 days post-surgery),[1] suggesting that the ECCC tumor biology may specifically play a role in thrombogenesis. In the present study. Perioperative VTE and other factors without LVSI were independently associated with worse survival outcomes in the cohort overall. Patients without VTE experienced longer PFS and OS than those with the condition, whether overall or in the early-stage population alone. A similar phenomenon was observed in patients with OCCC, wherein Diaz et al[2] observed a difference in survival rates among patients with early-stages disease. A potential explanation could be that the increased tumor burden and compromised health status of individuals with advanced-stage CCC may supersede the negative impact of VTE on survival. The relationship between VTE and survival outcomes in patients with EC was first described by Matsuo et al[3], who concluded that VTE could be regarded as a surrogate for EC aggressiveness; however, only 25 of 516 patients with clear cell histology (4.9%) were included in their analyses. Several cancer-specific mechanisms that may contribute to thrombogenesis have been proposed, including leucocytosis, thrombocytosis, increased levels of tissue factor (TF)-positive microvesicles and hypofibrinolysis.[4] The expression of TF (a transmembrane receptor with potent pro-coagulant function) by activating the extrinsic coagulation cascade pathway has been detected in certain cancerous tissues.[5] There is only limited evidence regarding the potential mechanism of cancer-related thrombosis in the field of endometrial carcinoma; hence, further studies are required to understand the etiology of thrombogenesis in this population. It was previously proposed that VTE itself might contribute to tumor invasion and metastasis, as elevated levels of preoperative serum TF have been positively correlated with death from ovarian cancer. Nevertheless, the tumor-type specific mechanism underlying the association between VTE and poor survival in ECCC remains to be elucidated. We found no significant association between adjuvant therapy and survival in our study, which was in contrast to data from Cetinkaya et al's study.[6] Adjuvant therapies for ECCC were highly individualized in our research, which could potentially lead to compromised anti-tumor efficiency. Studies involving larger cohorts ought to elucidate the value of adjuvant therapies in patients with ECCC. Given the limited information on ECCC, a rare disease, ours is one of the few studies to investigate the influence of perioperative VTE status on survival using a relatively large cohort from a single institution. Patients with no VTE were found to have significantly longer PFS and OS, and VTE at the time of primary surgery was found to be an independent predictor of disease progression and death. These results further emphasize the importance of preoperative screening and postoperative surveillance for DVT in patients with cancer, as well as better awareness of its potentially negative impact on survival, especially in patients with CCC. Given that our study was limited by its retrospective nature and by the fact that the analysis was correlative, we were unable to extract certain details regarding molecular subtypes or anticoagulant management, which would have strengthened the data derived from our multivariate models. Prospective studies and in vitro assays may further validate our findings and improve our understanding of the relevant mechanisms. In summary, we found that 16.1% of patients with ECCC developed VTE perioperatively regardless of tumor stage. Perioperative VTE at primary surgery was independently associated with a significantly higher risk of cancer recurrence and death, although the greater risk of death was not directly caused by the VTE itself. Funding This study was supported by the National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-B-083), the Capital's Funds for Health Improvement and Research (No. 2022-1-4011), and the National Natural Science Foundation of China (NSFC) (No. 82271886). Conflicts of interest None.

Background:This research aimed to create a predictive model and an innovative risk classification system for patients with gallbladder cancer who undergo radical surgery. Methods:A cohort of 1387 patients diagnosed with gallbladder cancer was selected from the SEER database. The researchers devised a prognostic tool known as a nomogram, which was subjected to assessment and fine-tuning using various statistical measures such as the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve, decision curve analysis (DCA), and risk stratification were included in the catalog of comparisons. An external validation set comprising 93 patients from Nanchong Central Hospital was gathered for evaluation purposes. Results:The nomogram effectively incorporated seven variables and demonstrated satisfactory discriminatory ability, as evidenced by the C-index (training cohort: 0.737, validation cohort: 0.730) and time-dependent AUC (>0.7). Additionally, calibration plots confirmed the excellent alignment between the nomogram and actual observations. Our investigation unveiled NRI scores of 0.79, 0.81, and 0.81 in the training group, while the validation group exhibited NRI values of 0.82, 0.77, and 0.78. Additionally, when evaluating CSS at three-, six-, and nine-year intervals using DCA curves, our established nomograms demonstrated significantly improved performance compared to the old model (P < 0.05), showcasing enhanced discriminatory ability. The results of the external validation set proved the above results. Conclusions:The current investigation has devised a practical prognostic nomogram and risk stratification framework to aid healthcare practitioners in evaluating the postoperative outlook of individuals who have received extensive surgical treatment for gallbladder carcinoma.

OBJECTIVE:To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). METHODS:Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS:Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3-28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6-95.3) and the DCR was 95.8% (95% CI=78.9-99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4-34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. CONCLUSION:Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative first-line treatment option for patients with R/M CC. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04973904.

OBJECTIVE:To explore the effectiveness of HPV 16/18 E7 oncoprotein in detecting high-grade cervical intraepithelial neoplasia (CIN) and predicting disease outcomes in HPV 16/18-positive patients. METHODS:The present study was a cross-sectional study with a 2-year follow up. We collected 915 cervical exfoliated cell samples from patients who tested positive for HPV 16/18 in gynecologic clinics of three tertiary hospitals in Beijing from March 2021 to October 2022 for HPV 16/18 E7 oncoprotein testing. Subsequently, 2-year follow up of 408 patients with baseline histologic CIN1 or below were used to investigate the predictive role of HPV 16/18 E7 oncoprotein in determining HPV persistent infection and disease progression. RESULTS:The positivity rate of the HPV 16/18 E7 oncoprotein assay was 42.06% (249/592) in the inflammation/CIN 1 group and 85.45% (277/324) in the CIN2+ group. For CIN2+ detection, using the HPV 16/18 E7 oncoprotein assay combined with HPV 16/18 testing, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.45%, 57.94%, 52.57%, and 87.95%, respectively. During the 2-year follow up, the sensitivity, specificity, PPV, and NPV for predicting persistent HPV infection were 48.44%, 58.21%, 34.64%, and 71.18% in the baseline inflammation and CIN1 group. CONCLUSIONS:As a triage method for high-grade CIN screening in HPV 16/18-positive patients, HPV 16/18 E7 oncoprotein demonstrated a relatively high NPV, making it suitable for clinical use in triaging HPV 16/18-positive cases and potentially reducing the colposcopic referral rate. HPV 16/18 E7 oncoprotein exhibited a preferably predictive value in determining HPV infection outcomes and disease progression.

Abstract Objective To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients. Methods Patients with BOTs younger than 20 years who underwent FSS were included in this study. Results A total of 34 patients were included, with a median patient age of 17 (range, 3–19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8–40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10–148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%. Conclusions Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.

Backgrounds Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease.Results Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of "fear and worry about choriocarcinoma recurrence". We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases.Conclusions IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients.Clinical trial registration N/A.

OBJECTIVE:To elucidate the clinicopathological characteristics and oncological outcomes of a special group of patients with gestational trophoblastic neoplasia (GTN) initially presenting with isolated lung lesions, elevated human chorionic gonadotropin (hCG) levels, and unobserved pelvic lesions. METHODS:Overall, 2358 patients with GTN treated at our hospital between 2000 and 2023 were retrospectively reviewed, and 40 patients were evaluated. The demographic characteristics, clinicopathological features, treatment data, and follow-up information of each patient were collected. The primary outcome was progression free survival. Kaplan-Meier analysis and univariate and multivariate Cox proportional hazard analyses were used to identify the risk factors. RESULTS:Among the 40 patients, 95.0 % had solitary lung lesions, with a median size of 1.9 cm. Moreover, 72.5 % of patients were pathologically confirmed as epithelioid trophoblastic tumors (ETT). During a median follow-up period of 53.5 months (range, 2-143), 11 patients experienced recurrence, including all patients who received chemotherapy alone as the initial treatment, and no death was observed. Relapse treatment involved lung segmentectomy and lobectomy combined with chemotherapy and immunotherapy. Univariate and multivariate Cox analyses identified comparing with surgery±chemotherapy, chemotherapy alone as the initial treatment (hazard ratio [HR] =7.738, 95 % confidence interval [CI] 1.698-35.269, P = 0.008) as independent risk factor for recurrence. CONCLUSIONS:In patients with a history of pregnancy exhibiting isolated pulmonary lesions, elevated hCG levels (mostly <1000 mIU/mL), and unobserved pelvic lesions, ETT should be considered first. Surgical resection of lung lesion is crucial for optimal management. When chemotherapy is considered, multidrug regimen is recommended.

BackgroundThis study aimed to develop a prognostic model for patients with advanced ductal adenocarcinoma aged ≥50 years.MethodsPatient information was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to screen the model variables. Cases from Nanchang Central Hospital were collected for external validation. The new nomogram and the American Joint Committee on Cancer (AJCC) criteria were evaluated using integrated discrimination improvement (IDI) and net reclassification index (NRI) indicators. Survival curves presented the prognosis of the new classification system and AJCC criteria.ResultsIn total, 17,621 eligible patients were included. Lasso Cox regression selected 4 variables including age, chemotherapy, radiotherapy and AJCC stage. The C-index of the training cohort was 0.721. The C-index value of the validation cohort was 0.729. The AUCs for the training cohorts at 1, 2, and 3 years were 0.749, 0.729, and 0.715, respectively. The calibration curves showed that the predicted and actual probabilities at 1, 2, and 3 years matched. External validation confirmed the model’s outstanding predictive power. Decision curve analysis indicated that the clinical benefit of the nomogram was higher than that of the AJCC staging system. The model evaluation indices preceded the AJCC staging with NRI (1-year: 0.88, 2-year: 0.94, 3-year: 0.72) and IDI (1-year: 0.24, 2-year: 0.23, 3-year: 0.22). The Kaplan–Meier curves implied that the new classification system was more capable of distinguishing between patients at different risks.ConclusionsThis study established a prognostic nomogram and risk classification system for advanced pancreatic cancer in patients aged ≥50 years to provide a practical tool for the clinical management of patients with pancreatic ductal adenocarcinoma.

Objectives: To evaluate the expression of emerging immune targets in the tumor-infiltrating immunocytes (TIIs) of human gestational trophoblastic neoplasia (GTN) specimens, and to analyze the correlation between the expression patterns and prognosis of GTN patients.Methods: Between January 2008 and December 2017, patients who were diagnosed histologically with GTN were included in this study. The expression densities of LAG-3, TIM-3, GAL-9, PD-1, CD68, CD8, and FOXP3 in the TIIs were assessed independently by two pathologists blinded to clinical outcomes. The expression patterns and correlation with patient outcomes were analyzed to identify prognostic factors.Results: We identified 108 patients with GTN, including 67 with choriocarcinoma, 32 with placental site trophoblastic tumor (PSTT), and 9 with epithelioid trophoblastic tumor (ETT). Almost all GTN patients showed expression of GAL-9, TIM-3, and PD-1 in TIIs (100%, 92.6%, and 90.7%, respectively); LAG-3 was expressed in 77.8% of the samples. The expression densities of CD68 and GAL-9 were significantly higher in choriocarcinoma than that in PSTT and ETT. The TIM-3 expression density in choriocarcinoma was higher than that in PSTT. In addition, the expression density of LAG-3 in the TIIs of choriocarcinoma and PSTT was higher than that in ETT. There was no statistical difference in the expression pattern of PD-1 among different pathological subtypes. The positive expression of LAG-3 in tumor TIIs was a prognostic factor for disease recurrence, and patients with positive expression of LAG-3 in the TIIs had poorer disease-free survival (p = 0.026).Conclusion: Our study evaluated the expression of immune targets PD-1, TIM-3, LAG-3, and GAL-9 in the TIIs of GTN patients and found that they were widely expressed but not associated with patients’ prognoses, excepting the positive expression of LAG-3 was a prognostic factor for disease recurrence.

Objective. To analyze the methods, feasibility, efficiency, and fertility outcomes of fertility-sparing treatment for patients with placental site trophoblastic tumor (PSTT). Methods. Clinical data of patients diagnosed with PSTT between April 1998 and April 2020 from Peking Union Medical College Hospital (PUMCH) were retrospectively collected. The clinical features, treatment, and outcomes of patients received fertility-sparing treatment were analyzed and compared with patients suffered hysterectomy. Results. In total, 126 patients were included in the study and 29 of them received fertility-sparing treatment. Besides significantly younger age and lower proportion of antecedent term delivery were seen in fertility-sparing group than hysterectomy group, no significant differences were observed in stage, serum beta-hCG level, or interval from antecedent pregnancy between the two groups. Conservative surgery was selected individualized and none of them suffered salvage hysterectomy. Patients with clinical or pathological high-risk factors received adjuvant chemotherapy, yet the fertility-sparing treatment did not significantly lengthen chemotherapy duration. All pa-tients in fertility-sparing group achieved complete remission without relapse after 36 to 176 months of follow-up and had sixteen healthy term delivery more than one year after the treatment. Conclusions. Fertility-sparing treatment for PSTT can be considered for young patients with localized uterine lesions who strongly desire to preserve their fertility potential. With individualized conservative surgery and se-lected adjuvant chemotherapy, fertility-sparing treatment will not influence the risk of relapse or overall survival and patients will achieve favorable pregnancy and live birth outcomes. (c) 2023 Published by Elsevier Inc.

OBJECTIVE:To evaluate the prognosis and recurrence in patients with residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia after initial treatment, and to explore the clinical significance of pulmonary resection. METHODS:A retrospective analysis was performed on 606 patients with residual lesions from pulmonary metastasis after receiving standardized chemotherapy as initial treatment in Peking Union Medical College Hospital from January 2002 to December 2018. Patients were divided into surgery (51 patients) and non-surgery (555 patients) groups. The prognosis of these patients was compared. Risk factors affecting recurrence were analyzed to explore the effect of pulmonary resection. RESULTS:Among low risk patients, complete remission rate was 100% and recurrence rate was <1% in both groups. Among high risk patients, complete remission and recurrence rates were 93.5% and 10.3% in the surgery group and 94.7% and 14.3% in the non-surgery group, respectively. There was no significant difference in prognostic features between the two groups (all p>0.05). No significant difference was found in recurrence rates based on recurrence risk factors (≥3.2 cm residual lung lesions, prognosis score ≥9.0, and drug resistance) between the two groups (all p>0.05). CONCLUSION:After standardized chemotherapy, pulmonary resection was not necessary for initially treated stage III gestational trophoblastic neoplasia patients whose blood β human chorionic gonadotropin levels normalized and residual lung lesions remained stable. These patients should be closely monitored during follow-up, regardless of the size of the residual lung lesions or high/low risk score, especially within a year after complete remission.

Abstract Background Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. Methods We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0–4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. Discussion Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. Trial registration ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020–9-24, version 1.0).

ObjectiveThis study aimed to explore the single-agent chemotherapy actinomycin D on ovarian reserve by measuring the anti-Mullerian hormone (AMH) levels before, during, and after chemotherapy. MethodsThis study recruited premenopausal women aged 15 to 45 with a newly diagnosed low-risk gestational trophoblastic neoplasia needing actinomycin D. AMH was measured at baseline, during chemotherapy, and 1, 3, and 6 months after the last chemotherapy. The reproductive outcomes were also documented. ResultsOf the 42 women recruited, we analyzed 37 (median: 29 years; range 19-45) with a complete dataset. The follow-up was 36 months (range 34-39). Actinomycin D significantly decreased AMH concentrations during treatment, from 2.38 +/- 0.92 ng/mL to 1.02 +/- 0.96 ng/mL (p<0.05). Partial recovery was seen at 1 month and 3 months after treatment. Full recovery was reached 6 months after treatment among patients younger than 35 years. The only factor correlated with the extent of AMH reduction at 3 months was age (r=0.447, p<0.05). Notably, the number of courses of actinomycin D was not associated with the extent of AMH reduction. A total of 18 (90%) of 20 patients who had a desire to conceive had live births with no adverse pregnancy outcomes. ConclusionActinomycin D has a transient and minor effect on ovarian function. Age is the only factor that impacts the patient's rate of recovery. Patients will achieve favorable reproductive outcomes after actinomycin D treatment.

Objective:To compare the oncological outcomes of radical surgery and radical radiotherapy in elderly (over 65 years) patients with early-stage cervical cancer (IB-IIA).Methods:Elderly patients with stage IB-IIA cervical cancer treated at Peking Union Medical College Hospital from January 2000 to December 2020 were retrospectively reviewed. All patients were divided into the radiotherapy group (RT group) and the operation group (OP group) according to their primary intervention. Propensity score matching (PSM) analysis was performed to balance the biases. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and adverse effects.Results:A total of 116 patients were eligible for the study (47 in the RT group, and 69 in the OP group), and after PSM, 82 patients were suitable for further analysis (37 in the RT group, and 45 in the OP group). In the real-world setting, it was found that compared with radiotherapy, operation was more frequently selected for elderly cervical cancer patients with adenocarcinoma (P < 0.001) and IB1 stage cancer (P < 0.001). The 5-year PFS rates between the RT and OP groups were not significant (82.3% vs. 73.6%, P = 0.659), and the 5-year OS rate of the OP group was significantly better than that in the RT group (100% vs. 76.3%, P = 0.039), especially in patients with squamous cell carcinoma (P = 0.029) and tumor size of 2~4 cm with G2 differentiation (P = 0.046). There was no significant difference in PFS between the two groups (P = 0.659). In the multivariate analysis, compared with operation, radical radiotherapy was an independent risk factor of OS (hazard ratio = 4.970, 95% CI, 1.023~24.140, P = 0.047). No difference was observed in adverse effects between the RT and OP groups (P = 0.154) and in ≥grade 3 adverse effects (P = 0.852).Conclusion:The study found that surgery was more frequently selected for elderly cervical cancer patients with adenocarcinoma and IB1 stage cancer in the real-world setting. After PSM to balance the biases, it showed that compared with radiotherapy, surgery could improve the OS of elderly early-stage cervical cancer patients and was an independent protective factor of OS in elderly early-stage cervical cancer patients.

Our study aimed to analyze the prognosis and reproductive outcomes of patients with advanced-stage serous borderline ovarian tumors (SBOTs) who underwent fertility-sparing surgery (FSS). This study included patients aged ≤ 45 years diagnosed with advanced-stage (International Federation of Gynecology and Obstetrics II and III) SBOTs who were treated with FSS. Conservative surgeries were performed in 65 patients with advanced-stage SBOT with a median age of 28 years (range, 16–44 years). Nine patients had invasive implants. The median follow-up was 81.7 months. Forty-six patients (70.8%) had a relapse (median time to first recurrence, 22.8 months). Thirteen patients subsequently developed recurrence as an invasive disease, and two died due to disease progression. After multivariate analysis, age < 30 years and incomplete cytoreduction were independent risk factors for recurrence. Invasive implants and postoperative residual tumors were significantly associated with shorter disease-free survival. Of 35 patients attempting to conceive, 12 underwent assisted reproductive technology. Additionally, 19 pregnancies, including 15 full-term births, were documented. FSS provides a good chance of reproductive success in women with advanced-stage SBOT who desire fertility preservation, but it has a high recurrence rate and risk of malignancy transformation. Patients with invasive implants should be strictly selected for FSS.

Background Synergistic antitumor effects of immunotherapy and chemotherapy have been demonstrated in several solid tumors. However, this combination strategy has not been addressed in gestational trophoblastic neoplasia (GTN) cases. We therefore compared the safety and therapeutic effect of anti-programmed cell death 1 (PD-1) therapy combined with chemotherapy versus anti-PD-1 monotherapy among high-risk chemorefractory or relapsed GTN patients.Methods This retrospective cohort study was conducted at three teaching hospitals in China. Chemorefractory or relapsed GTN cases receiving anti-PD-1 therapy combined with chemotherapy or anti-PD-1 monotherapy were selected from each center between August 2018 and March 2022. Study endpoints included objective response rate (ORR), treatment duration, overall survival (OS) and progression-free survival (PFS). The nature, prevalence and severity of treatment-related adverse events (TRAEs) were evaluated. Findings This work enrolled 66 cases. Thirty-five and 31 patients received anti-PD-1 therapy alone and combined with chemotherapy, respectively. The combined treatment dramatically increased the objective response rate from 62.9% (22/35) to 96.8% (30/31) (p < 0.001). The median durations until complete response were 2.2 (interquartile range [IQR], 1.4-4.2) and 2.8 (IQR, 1.8-2.8) months in the anti-PD-1 monotherapy and combined treatment cohorts, respectively (P = 0.299). The complete response rate (CRR) for anti-PD-1-refractory patients to salvage chemotherapy was 84.6% (11/13). No significant difference in OS [HR 0.50 (95% CI 0.07-3.24), p = 0.499] was detected between anti-PD-1 cohort and anti-PD-1 plus chemotherapy cohort. The PFS in combined group was significantly longer than in anti-PD-1 group [HR 0.06 (95% CI 0.02-0.16), p < 0.001]. TRAEs were observed in 27 (77.1%) and 25 (80.6%) patients receiving anti-PD-1 therapy monotherapy and combined therapy, respectively (p = 0.729).Interpretation Anti-PD-1 therapy combined with chemotherapy exhibits sustainably improved antitumor effect and tolerable toxic effects among high-risk chemorefractory or relapsed GTN cases. Patients not responding to PD-1 inhibitors can be effectively rescued with salvage chemotherapy.Funding The study was supported by National Natural Science Foundation of China (81971475 and 81972451), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-083 and 2022-PUMCH-B-084). 2023;59: Published 2023 https://doi.org/10. 1016/j.eclinm.2023. 101974

Objective: To investigate the triaging efficacy of the human papillomavirus (HPV) 16/18 E7 oncoprotein assay for high-grade cervical intraepithelial neoplasia (CIN2+) screening in HPV 16/18-positive patients in a tertiary hospital in China. Methods: We collected 476 cervical cell samples from women who tested positive for HPV 16/18 in the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2022 and analyzed them by the HPV 16/18 E7 oncoprotein assay before colposcopy and biopsy. The study assessed the triaging efficacy of the HPV 16/18 E7 oncoprotein assay in HPV 16/18-positive patients by analyzing its performance against the gold standard of histologically confirmed CIN2+. Results: The positive rate of the HPV 16/18 E7 oncoprotein assay was 41.0% (114/278) in the negative for intraepithelial lesions and malignancy/CIN1 group and 80.3% (159/198) in the CIN2+ group. For triage of women with a positive HPV 16/18 test for CIN2+ detection, the HPV 16/18 E7 oncoprotein assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 80.3%, 59.4%, 58.5%, and 80.9%, respectively. Furthermore, longitudinal follow-up of five patients showed a good correlation between the expression of the HPV 16/18 E7 oncoprotein and cervical lesion grades. Conclusions: As a triage method for HPV 16/18-positive patients, the HPV 16/18 E7 oncoprotein assay improves the specificity, reduces the colposcopy referral rate, and has the potential for long-term monitoring of high-grade CIN.

Abstract Objective To describe myeloid sarcoma (MS) that mimic gynecological tumors and provide guidelines for improving the diagnosis and treatment of patients. Methods This case series study retrospectively analyzed the clinicopathological characteristics and oncological outcomes of female patients who were histologically diagnosed with MS after initially presenting with reproductive-system tumors at the Peking Union Medical College Hospital between January 2000 and March 2022. Results There were eight cases in which MS mimicked cervical cancer, ovarian cancer, or hysteromyoma. Six patients had isolated MS, and the other two had acute myeloid leukemia (AML)-M2. The average age was 39.00 ± 14.26. They each sought advice from a gynecological oncologist at the initial visit, complaining of irregular bleeding (3/8), low abdominal pain (3/8), dysmenorrhea (1/8), or an accidentally found mass (1/8). CT/MRI exams revealed that the average tumor size reached 5.65 ± 2.35 cm, with 50% of the tumors being larger than 8 cm. The final diagnoses were confirmed by biopsy (2/8) or postoperative pathology (6/8); the most frequent positive immunohistochemical markers were Ki-67 (60–90%), MPO (100%), LCA (62.5%), CD43 (62.5%), CD117 (62.5%), CD99 (50%), vimentin (37.5%), and lysozyme (25%). MLL/AF9 gene fusions and CEBPA, JAK2, NRAS, and FLT3-TKD mutations were found in the patients. Six (75%) of the patients showed a complete response after upfront treatment using chemotherapy + surgery and experienced no recurrence during follow-up. The overall survival (OS) rate was 72.9%, and the 5-year OS rate was 72.9% (95%CI: 0.4056–1.000). The median OS was 26 months (range: 3–82). Conclusion For patients with isolated MS, treatment by chemotherapy and surgery are radical procedure, and initial treatment using chemotherapy alone should be considered for MS with synchronous intramedullary AML. Poor response to chemotherapy, short interval to leukemia occurrence, and heavy tumor burden (> 10 cm) could indicate a poor prognosis for patients with MS.

Introduction To evaluate the prognosis and recurrence in initially treated patients with pulmonary metastasis from gestational trophoblastic neoplasia (GTN), and to explore the clinical significance of pulmonary resection. Methods Retrospective analysis was performed on 606 GTN patients with pulmonary metastasis who received standardized chemotherapy as initial treatment in Peking Union Medical College Hospital (PUMCH) from January 2002 to December 2018. The patients were divided into the surgery (51 patients) and non-surgery groups (555 patients). The prognosis of these patients was compared. Risk factors affecting recurrence were analyzed to explore the effect of pulmonary resection. Results Among low-risk patients, CR rate is 100% and recurrence rate is below 1% in both groups .Among high-risk patients, CR rate and recurrence rate are 93.5% and 10.3% in the surgery group and 94.7% and 14.3% in the non-surgery group, respectively.There was no significant difference in all prognosis features between the two groups.(all with P>0.05). No significant difference was found in recurrence rates considering the recurrence risk factors(≥3.2 cm residual lung lesions; FIGO score≥9.0;drug resistance) between the two groups (all with P>0.05). Conclusion/Implications After standardized chemotherapy, pulmonary resection is not necessary for initially treated stage III GTN patients whose blood β-hCG drop to normal levels and residual lung lesions remain stable . These patients should be closely monitored during the follow-up regardless of the size of residual lung lesions or high/low risk score, especially within 1 year after CR.