International Journal of Gynecological Cancer最新文献

Background: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed.

Primary objective: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment.

Study hypothesis: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment.

Trial design: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery.

Major inclusion/exclusion criteria: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFI_PARPi) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible).

Primary endpoint: Progression-free survival.

Sample size: 124 patients.

Estimated dates for completing accrual and presenting results: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029.

Trial registration: NCT05704621.

Objective: The tumor immune microenvironment in ovarian clear cell carcinoma has not been clearly defined. We analyzed the immunological changes from treatment-naive to recurrence to correlate them with clinical outcomes.

Method: We compared the changes in immune infiltration of advanced-stage ovarian clear cell carcinoma samples before treatment and at the time of recurrence via immunohistochemistry (Programmed Cell Death-ligand 1 (PD-L1), cluster of differentiation 8 (CD8+), forkhead box P3 (Foxp3+)), tumor-infiltrating lymphocytes (TIL), and next-generation sequencing (54 patients). We analyzed the association between platinum sensitivity status and tumor immune microenvironment.

Results: Immunohistochemistry revealed significantly increased PD-L1 (p=0.048) and CD8+T cells (p=0.022) expression levels after recurrence. No significant differences were observed in TIL density or Foxp3+T cells. There was no significant correlation between TIL, PD-L1, CD8+T cell, and Foxp3+T cell levels in treatment-naive tumors and survival outcomes. The most common genomic alterations were PIK3CA (41.7%) and ARID1A (41.7%) mutations. There were no differences in the immunological changes or survival outcomes according to PIK3CA and ARID1A mutations. Patients with recurrent platinum-sensitive disease showed higher TIL expression levels. There were no significant differences in PD-L1, CD8+T cells, or Foxp3+T cells between platinum-sensitive and platinum-resistant diseases.

Conclusion: We characterized the tumor immune microenvironment in patients with advanced-stage ovarian clear cell carcinoma. PD-L1 and CD8+T cell expression significantly increased after recurrence. Whether this could be used to select patients for immunotherapy in the recurrence setting should be investigated.

Objectives: As cervical cancer screening programs are implemented and expanded, an increasing number of women require loop electrosurgical excision procedure (LEEP) for treatment of pre-invasive cervical disease. Our objective was to describe the pathological results of LEEP specimens performed as part of the MULHER study and identify factors associated with positive LEEP margins.

Methods: The MULHER study enrolled 9014 women who underwent HPV testing followed by visual assessment for treatment (VAT) using visual inspection with acetic acid (VIA) and thermal ablation for those with positive results. Participants with lesions ineligible for ablation underwent LEEP. Pathology reports were reviewed for specimen size/volume, number of fragments, pathological diagnosis and margin status. Multivariable regression analysis was performed to identify variables associated with positive LEEP margins.

Results: 169 participants underwent LEEP. The median age was 38 years (range 30-49). 65.1% were women living with HIV. Pathological diagnosis was available for 154 patients and included cancer (n=6, 3.9%); cervical intraepithelial neoplasia (CIN) 2/3 (n=75, 48.7%); CIN 1 (n=67, 43.5%); and normal/benign findings (n=6,3.9%). 31.8% of LEEP specimens were removed in more than one fragment. The mean specimen volume was 2.9 cm³ (range 0.2-15.0). LEEP margin status was available for 130 patients. Positive margins (ectocervical/endocervical only, or both) were noted in 76 (58.5%) patients and associated with HIV+status (p=0.0499) and a diagnosis of CIN 2 or worse (p=0.0197). There were no associations between margin status and age, number of fragments or specimen volume.

Conclusion: Our results showed a high number of LEEP specimens with positive margins. Additional evaluation is needed to better understand the characteristics of precancerous cervical lesions in this high-risk population. As cervical cancer screening programs are scaled in Mozambique and other lower-resource countries, there is a need to train providers to perform high-quality LEEP and for accurate and timely pathological interpretation.

Objective: Sentinel lymph node (SLN) mapping may reduce the morbidity of lymphadenectomy while maintaining diagnostic accuracy. Nevertheless, SLN mapping in epithelial ovarian cancer is still under investigation. This systematic review and meta-analysis aimed to assess the detection rate and diagnostic accuracy of SLN mapping for each field (pelvic and para-aortic), and to evaluate the tracers and doses used.

Methods: A systematic search was conducted in PubMed, Cochrane Library, Scopus, and Web of Science. Patients with clinical stages I-II ovarian cancer undergoing SLN biopsy (index test) and a systematic pelvic and para-aortic lymphadenectomy (reference standard) were included. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A meta-analysis was performed to assess SLN mapping detection rates and diagnostic accuracy for each field (pelvic and para-aortic) and by subgroups (type of tracer and dosage).

Results: 239 patients from four studies were included. The SLN detection rate was 59.5% (95% CI 50.2 to 68.1%) and 64.4% (95% CI 58.2 to 70.2%) for the pelvic and para-aortic fields, respectively. The use of technetium-99 (^99mTc), alone or in combination, compared with the use of indocyanine green alone, was associated with a higher detection rate in both the pelvic (66.6%; 95% CI 53.3 to 78.3%; p=0.1211) and para-aortic (87.1%; 95% CI 76.9 to 93.9%, p=0.0000013) fields. The use of 0.2-0.5 mL of indocyanine green was associated with higher pelvic (68%; 95% CI 53.3 to 80.4%, p=0.1057) and para-aortic (88.3%, 95% CI 77.4 to 95.2%, p=0.0000018) detection rates compared with a 2 mL indocyanine green injection. Diagnostic accuracy, sensitivity, specificity, and negative predictive value of SLN for lymph node metastasis were: 100% each for the pelvic field and 98.1%, 85.7%, 100%, and 97.8%, respectively, for the para-aortic field.

Conclusion: The use of ^99mTc in combination with a low volume injection (0.2-0.5 mL) of indocyanine green increased SLN detection rates. In apparent early stage epithelial ovarian cancer, SLN is a feasible technique with a high diagnostic accuracy.

Trial registration: PROSPERO CRD42024544812.

Objective: To investigate whether performing a lymph node dissection during hysterectomy improves overall survival in patients with clinical stage III endometrial cancer who received neoadjuvant chemotherapy.

Methods: The National Cancer Database was queried to identify all patients with clinical stage III endometrial cancer who had undergone pre-operative chemotherapy as first course of treatment followed by hysterectomy with or without lymph node dissection between the years 2004 and 2020. Univariable and multivariable models were performed to investigate prognostic factors on overall survival.

Results: This study analyzed 2882 patients with clinical stage III endometrial cancer who received upfront chemotherapy. Among those who underwent lymph node dissection, 38% had positive lymph nodes. Factors found to be independently associated with improved survival included lymph node dissection (p<0.001), adjuvant radiation (p<0.001), histology (p<0.001), tumor grade (p<0.001), pathologic node status (p<0.001), age (p<0.001), type of insurance (p=0.027), and race (p<0.001). Patients who underwent lymph node dissection at time of hysterectomy had a significantly better overall survival (107 vs 85 months; p<0.001). Multivariate and propensity score analyses robustly demonstrated that lymph node dissection significantly improved overall survival (HR 0.69, 95% CI 0.57 to 0.84, p<0.001), even among patients with pathologically negative lymph nodes.

Conclusion: Our study suggests that performing lymph node dissection at the time of hysterectomy is associated with improved overall survival in all patients with stage III endometrial cancer who receive upfront chemotherapy, regardless of age, race, insurance status, histologic subtype, tumor grade, pathologic node status, adjuvant radiation or chemotherapy. Notably, patients with high-risk disease may particularly benefit from this approach.

Objective: To describe sociodemographic and racial disparities in receipt of poly ADP-ribose polymerase inhibitors (PARPi) and bevacizumab among insured patients with ovarian cancer.

Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify patients with advanced stage, high grade serous ovarian cancer diagnosed between 2010 and 2019. The primary outcome of interest was receipt of PARPi or bevacizumab at any time after diagnosis. χ² tests were used to compare categorical variables. Factors independently associated with the receipt of PARPi and/or bevacizumab were identified using a multivariable logistic regression.

Results: The cohort included 6242 patients; 276 (4.4%) received PARPi, 2142 (34.3%) received bevacizumab, and 389 (6.2%) received both. Receipt of either targeted treatment increased over the study period. On univariate analysis, patients who received either targeted therapy were younger (63% vs 48% aged <75 years; p<0.001), had a lower comorbidity index (86% vs 80% Charlson Comorbidity Index 0-1; p<0.001), and higher socioeconomic status (74% vs 71% high socioeconomic status; p=0.047) compared with those who did not receive targeted therapy. In the multivariable model, non-Hispanic black patients were less likely than non-Hispanic white patients to receive either targeted therapy (odds ratio 0.77; 95% confidence interval 0.61 to 0.98; p=0.032). Older patients (aged >74 years) were also less likely to receive PARPi or bevacizumab compared with those aged 65-69 years (all p<0.001).

Conclusion: Sociodemographic and racial disparities exist in receipt of PARPi and bevacizumab among patients with advanced ovarian cancer insured by Medicare. As targeted therapies become more commonly used, a widening disparity gap is likely.

After the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer. Recent studies assessed the role of a non-radical approach in low risk cervical cancer and showed no survival difference compared with radical hysterectomy. However, there is a gap in knowledge regarding the oncologic outcomes of minimally invasive simple hysterectomy in low risk cervical cancer. This review offers an overview of the current evidence on the role of the minimally invasive approach in low risk cervical cancer and raises the need for a new clinical trial in this setting.