International Journal of Gynecological Cancer最新文献

Objective: Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma has a worse prognosis compared to its HPV-associated counterpart. We sought to characterize the mutational landscape and the tumor microenvironment of HPV-independent vulvar cancer.

Methods: Primary, untreated vulvar cancers with known HPV-independent vulvar cancer or without definitive HPV association between 2006 and 2016 were identified. Pathology re-review, p16 immunohistochemistry, and HPV 16 and 18 polymerase chain reaction were performed to determine HPV status. HPV-independent vulvar cancers underwent targeted tumor-normal panel sequencing and NanoString gene expression analysis. Multiplex immunofluorescence analysis for CD8, programmed cell death protein-1, and PD-L1 was performed for HPV-independent and HPV-associated vulvar squamous cell carcinomas.

Results: Of the 93 vulvar squamous cell carcinomas identified, 19 were HPV-independent. Targeted sequencing revealed recurrent somatic mutations affecting TP53 (13/19, 68%), FAT1 (6/19, 32%), NOTCH1 (5/19, 26%), and CDKN2A (5/19, 26%). Five (26%) of the 19 cases had a dominant apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-related mutational signature, whereas the remaining had dominant clock/aging-related mutational signatures. Expression of genes related to immune response including the chemokine CXCL8 and HLA-DRB5 were found to be significantly higher in primary HPV-independent vulvar squamous cell carcinomas that did not recur compared to those with subsequent recurrence (p = .02). Multiplex immunofluorescence analysis revealed that HPV-independent vulvar squamous cell carcinomas were characterized by tumor infiltration with CD8+programmed cell death protein-1+ T cells and their interaction with CD68+PD-L1+ macrophages.

Conclusions: HPV-independent vulvar squamous cell carcinoma is a heterogeneous disease with mutations affecting cell cycle-related genes, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide and clock-like mutational signatures, and evidence of an immune-active tumor microenvironment in primary tumors. Our data provide the basis for exploration of immune biomarkers and therapeutics in this disease.

Objective: To describe the oncological and obstetrical outcomes of women diagnosed with borderline ovarian tumors or epithelial ovarian cancer during pregnancy.

Methods: This is an international retrospective cohort study. Patients were eligible for inclusion if they were diagnosed with borderline tumor or invasive ovarian cancer during pregnancy, with histologic confirmation either before or after delivery, and were registered in the International Network on Cancer, Infertility and Pregnancy database between 1982 and 2019.

Results: A total of 129 patients were included, of whom 69 (53%) with borderline and 60 (47%) with invasive cancer. Diagnosis was established in the first, second, and third trimesters in 59 (46%), 48 (37%), and 22 (17%) patients, respectively. In total, 47 (36%) patients did not receive any treatment during pregnancy. The majority of patients (64%) underwent surgery with or without chemotherapy during pregnancy. Birthweight was significantly lower in women who received chemotherapy during pregnancy as compared to those who did not (median birthweight 2528 g vs 3031 g, p = .01) Among patients with borderline tumors, 20 (29%) experienced a relapse of whom 2 subsequently died from the disease. The 5-year survival probability was 98.5% (95% CI 95.6 to 100). Recurrence was associated with incomplete surgical staging (p = .02). Among patients with epithelial ovarian cancer, the relapse rate was 25% and the 5-year survival probability was 83.6% (95% CI 74.3 to 94.1). The oncological outcome was worse for patients with advanced-stage disease (p = .03). In addition, 66% of patients who relapsed after pregnancy did not undergo adequate surgical staging.

Conclusions: Treatment of patients with ovarian cancer during pregnancy can result in favorable oncological and obstetrical outcomes. Better oncological outcomes are achieved when treatment adheres to the standard of care in non-pregnant patients, as those who did not undergo surgical staging experienced a higher relapse rate.

Objective: Clinical trials require the inclusion of all relevant demographic groups, including under-represented populations, to ensure accurate and representative findings. The aim of the study was to assess the status quo of inclusion, diversity, equity, and access in clinical trials across various countries.

Methods: An 18-item online survey was developed and administered to 5 people. The questionnaire was distributed to delegates from gynecologic research groups in the Gynecologic Cancer Intergroup Network worldwide. All the analyses are purely descriptive.

Results: A total of 73 participants (86.3% physicians and 47.9% female) from 33 countries participated in the survey; 91.8% deemed the inclusion of under-represented groups in clinical trials important, and 91.2% supported increasing representation in phase III trials. Most participants believed that language barriers (68.7%) and restricted eligibility criteria (56.7%) were the main reasons for under-representation. Language barriers are seen as more significant in Africa and Europe than in Asia (83.3% and 75.0% vs 58.6%, respectively). Limited patient knowledge about clinical trials (73.1%) was also cited as a key issue. Only 20.5% reported having a minimal data set to document demographic groups. The most helpful measure was the provision of trial information in various languages (69.7%). Overall, women were more supportive of all the suggested improvement measures than were men.

Conclusions: There is a need for better strategies to improve diversity in clinical trials, focusing on overcoming language barriers and eligibility constraints.

Objective: This study aimed to explore the frequency of BRCA mutations and testing, age at diagnosis, and incidence of ovarian cancer and to describe oncologic outcomes in patients carrying BRCA mutation compared with those not carrying mutation, in 1 cancer center that covers two-thirds of the Norwegian population.

Methods: Patients with ovarian cancer treated at Oslo University Hospital-Radiumhospital 2008-2019 who accepted BRCA testing were prospectively registered in the study. Patients carrying mutation and their families received genetic counseling and risk-reducing surgery. For patients treated from 2014 to 2019 (N = 1032), detailed clinicopathologic data (International Federation of Gynecology and Obstetrics stage, histopathology, type of surgery, residual disease, chemotherapy, first recurrence, and survival) were obtained. Overall and progression-free survival were analyzed using Kaplan-Meier curves and Cox regressions. Linear trends were assessed using linear regressions. Using data delivered by the Cancer Registry of Norway, we assessed ovarian cancer incidence in the uptake area of Oslo University Hospital-Radiumhospital throughout the study period.

Results: A total of 1579 patients were registered. Throughout the study period, BRCA mutation frequency was decreasing, from 14.5% to 6.8%, and mean age at diagnosis increasing, from 59.4 to 63.8 years, in 2008 and 2019, respectively. Patients carrying BRCA1 mutation were younger at diagnosis than were patients carrying BRCA2 mutation and those not carrying mutation. Patients carrying BRCA mutation had almost exclusively high-grade serous histology, and had more often advanced disease and higher cancer antigen 125 levels at the time of diagnosis and were more often treated with interval debulking surgery than were those not carrying mutation. Patients carrying BRCA2 mutation had better overall survival than did those not carrying mutation. The incidence rate of ovarian cancer was decreasing throughout the study, from 22 to 18 per 100,000 person-years in 2008 and 2019, respectively.

Conclusion: BRCA mutation testing in patients with ovarian cancer has become more widely incorporated into clinical practice over time, owing to its importance for prognosis and for risk-reducing measures in the families of patients carrying mutation, and possibly contributes to a decrease in ovarian cancer incidence.

Objective: Oral contraceptives reduce ovarian cancer risk, but the mechanism of risk reduction is not understood. We examined whether oral contraceptive pill (OCP) use influences p53 signatures, which are putative early fallopian tube precursors for high-grade serous ovarian carcinomas.

Methods: For this retrospective cohort (n = 250) of subjects aged over 50 years who had fallopian tubes removed at the time of a benign gynecologic procedure, we used health records to identify 72 patients who used OCPs for at least 5 years and 178 subjects with no history of OCP use. Immunohistochemistry for p53 was performed on all fallopian tube sections, with 8 individuals removed for lack of identifiable tissue. p53 Signatures were identified and stratified based on size. Logistic regressions were run to estimate the association between OCP use and p53 lesion and lesion size.

Results: There was no difference in the occurrence of p53 lesions with 20 of 70 of OCP users (28.6%) and 57 of 172 of those with no history of OCP use (33.1%). Subjects who used OCPs were more likely to have a small lesion (OR 1.98, 95% CI 1.03 to 3.83) and had decreased risk of having a medium/large lesion (OR 0.38, 95% CI 0.18 to 0.79). A total of 2 serous tubal intraepithelial lesions and 2 serous tubal intraepithelial carcinomas were identified in OCP-naive patients, whereas none were found in those with a history of OCP use.

Conclusions: OCP exposure was associated with a shift toward smaller p53 lesion size but was not found to be associated with a difference in the number of p53 lesions between OCP-exposed and unexposed patients. Future research should examine whether OCP use reduces proliferation and clonal expansion of p53 signature lesions toward higher risk precursors and, eventually, cancer. There were no serous tubal intraepithelial lesions and serous tubal intraepithelial carcinomas in patients with OCP exposure.

Objective: Multimodal prehabilitation is a multi-disciplinary program that includes exercise, nutrition, and psychological intervention before surgery to improve pre-operative functional capacity. This study aims to assess the impact of a prehabilitation program on the pre-operative functional status of gynecologic oncology patients.

Methods: This single-center, prospective observational study included all consecutive patients diagnosed with gynecologic cancer who were scheduled for surgery and enrolled in a structured prehabilitation program from January 2018 to May 2024. Only patients with both baseline and pre-operative evaluations were included. Functional status data were compared before (baseline) and after (pre-operative) the prehabilitation intervention. The primary outcome measured was functional capacity, as determined by the 6-minute walk test (6MWT). Secondary outcomes included hand grip strength, the Malnutrition Universal Screening Tool (MUST) score, and the Hospital Anxiety and Depression Scale score. The type of training and adherence were also evaluated.

Results: A total of 77 patients underwent both baseline and pre-operative evaluation at the prehabilitation unit. The median duration of the program was 25.2 days (range; 9-63). Significant pre-operative improvements were observed in 6MWT (baseline: 435.7 m, standard deviation [SD] = 115.9 vs pre-operative: 455.7 m, SD = 118.9, p < .001), hand grip strength (baseline: 19.0 kg, SD = 5.5 vs pre-operative: 20.4 kg, SD = 5.9, p = .012), MUST score (baseline MUST ≥2 in 14.3% patients vs pre-operative 3.9%, p = .03), and Hospital Anxiety and Depression Scale score (baseline anxiety score: 7.4, SD = 4.3 vs pre-operative: 6.3, SD = 3.6, p < .001; and baseline depression score: 5.5, SD = 4.2 vs pre-operative: 4.3, SD = 3.6, p < .001). Among the different training programs, patients participating in supervised CrossFit training showed greater improvement in the 6MWT (33.4 m), compared to the hospital-supervised group (27.1 m), and the non-supervised home training group (14.0 m).

Conclusions: A structured multimodal prehabilitation program improves pre-operative functional capacity in gynecologic oncology patients, with the greatest improvements seen in those who participated in supervised high-intensity training, such as CrossFit.