Journal of Gynecologic Oncology最新文献

Objective: Systemic chemotherapy in recurrent cervical cancer is a palliative treatment approach with limited oncologic outcome. As emerging evidence supports favorable prognosis following radical local treatment strategies for oligometastatic recurrence in gynecologic malignancies, there is an unmet clinical need to define prognostic implications of surgical metastasectomy in recurrent cervical cancer.

Methods: Data of 139 consecutive cervical cancer patients, who underwent primary external-beam radiotherapy with concomitant chemotherapy, followed by magnetic resonance image-guided adaptive brachytherapy between 2015 and 2019, was analyzed. Oncologic outcomes of recurrence patterns, defined according to the European Society for Radiotherapy and Oncology (ESTRO) and the American Society for Radiation Oncology (ASTRO) consensus, was assessed according to the type of recurrence therapy.

Results: Of 54 patients (38.8%) with metachronous disease recurrence, 21 (38.8%) classified as metastatic and 22 (40.7%) as oligometastatic. Oligometastatic recurrence was associated with improved progression-free survival after recurrence (PFS2; hazard ratio [HR]=2.95; 95% confidence interval [CI]=1.23-7.08; p=0.015) and disease-specific survival after recurrence (HR=3.28; 95% CI=1.40-7.70; p=0.006) irrespective of the type of recurrence therapy. An exploratory subgroup analysis of oligometastatic patients undergoing surgical resection ± adjuvant therapy (n=12) suggested reduced risk of second disease recurrence (odds ratio=0.15; 95% CI=0.02-0.92; p=0.020) and improved PFS2 (HR=0.24; 95% CI=0.06-0.99; p=0.048) as compared to palliative systemic treatment (n=7).

Conclusion: A relevant number of recurrences qualifies as oligometastatic according to the ESTRO-ASTRO consensus, which associate with improved prognosis irrespective of the type of recurrence therapy. Patients experiencing oligometastatic recurrence should be carefully evaluated for potentially curative treatment approaches.

Objective: Triage testing is an integral part of high-risk human papillomavirus (HPV)-based cervical screening programs. This study assesses, from a healthcare payer perspective in Singapore, the cost-effectiveness of p16/Ki-67 dual-stained cytology (DS) compared to current standard of care (SOC).

Methods: A decision-analytic Markov microsimulation model with a lifetime horizon was built to simulate the outcomes from HPV screening in Singaporean women aged 30-65 years. The intervention (primary testing with HPV genotyping followed by DS reflex test) was compared to current SOC (HPV genotyping followed by cytology) according to Singaporean clinical management guidelines. The progression through health states and associated costs and health outcomes were based on local clinical care data in Singapore. Screening impact was assessed by cost saving, number of colposcopy and quality-adjusted life years (QALYs).

Results: Compared to SOC, implementation of HPV genotyping + DS was estimated to decrease the number of screening test (-2.02 times per patient) and colposcopy (-0.16 times per patient), and reduce the overall costs to the Singaporean healthcare system by S$225.59 per patient (95% confidence interval [CI]=S$199.05 to S$249.99). The total QALYs estimates for the 2 approaches were similar (-0.0003; 95% CI=-0.0031 to 0.0022). Sensitivity analyses confirmed the robustness of expected cost-savings and that the full value of avoided colposcopies may be larger than projected in the current analysis.

Conclusion: This economic modelling analysis projected that using DS instead of conventional cytology as the reflex test for positive test with non-HPV-16/18 subtypes significantly reduced the financial costs of cervical cancer screening in Singapore.

Objective: We aimed to compare tumor response and treatment outcomes between human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) endocervical adenocarcinomas (ADCs) treated with definitive concurrent chemoradiotherapy (CCRT) and to identify prognostic factors.

Methods: We conducted a retrospective review of 40 patients with endocervical ADCs treated with definitive CCRT (stages I-IVA) between 2011 and 2022. Based on pathological review the cases were categorized as HPVA or HPVI ADCs. Statistical analyses were performed to compare the characteristics, complete response (CR) rates, and survival outcomes.

Results: Of 40 patients, 22 (55.0%) had HPVA and 18 (45.0%) had HPVI ADCs. HPVI patients had significantly higher rates of parametrial invasion (94.4% vs. 45.5%, p=0.001). CR was achieved in 57.5% of patients and was significantly more common in the HPVA group (81.8% vs. 27.8%, p=0.001). Patients with HPVI had higher recurrence rates (88.9% vs. 50.0%, p=0.016) and lower 3-year progression-free survival (PFS, 16.7% vs. 49.8%, p=0.001), distant metastasis-free survival (DMFS, 38.1% vs. 80.8%, p=0.001), and overall survival (OS, 42.3% vs. 90.7%, p=0.002) rates. HPVA remained a significant factor for PFS (hazard ratio [HR]=3.44; 95% confidence interval [CI]=1.09-10.81; p=0.035) and OS rates (HR=6.83; 95% CI=1.17-39.80; p=0.033) in multivariate analysis.

Conclusion: HPVI ADC was associated with a lower response to definitive CCRT and worse prognosis than HPVA ADC. These findings suggest the need for tailored treatment strategies based on the HPV status.

Objective: Up-frameshift protein 1 (UPF1) can contribute to the progression of a variety of cancers. Currently, there is limited research on UPF1 in cervical cancer, and further investigation is necessary to understand its regulatory mechanisms in cervical cancer.

Methods: mRNA expression was detected by quantitative real-time polymerase chain reaction, while protein expression was quantified by western blotting assay. Cell function was assessed by cell counting kit-8 assay, Transwell assay and wound-healing assay. A xenograft mouse model assay was performed to analyze the effect of UPF1 silencing on tumor formation. Differentially expressed genes in cell samples were screened using the R Bioconductor package DESeq2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis was performed to determine the functional categories of the differentially expressed genes.

Results: UPF1 expression was downregulated in cervical cancer tissues and cells. Additionally, UPF1 silencing promoted invasion and migration of cervical cancer cells and tumor formation. There were a total of 188 upregulated genes in the SiHa cells after UPF1 silencing. Biological analysis showed that these upregulated genes were enriched in pathways related to regulation of cell proliferation, positive regulation of gene expression, cell adhesion, and Hippo signaling pathway. Additionally, UPF1 depletion promoted SiHa cell proliferation, invasion and migration, whereas the effects were attenuated after silencing of bone morphogenetic protein 6 (BMP6) or long non-coding RNA (lncRNA) WAKMAR2.

Conclusion: UPF1 inhibited cervical cancer cell migration and invasion through the regulation of nonsense-mediated decay of BMP6 and lncRNA WAKMAR2.

Objective: Pembrolizumab administration can improve concurrent chemoradiotherapy (CCRT) efficacy in newly diagnosed, high-risk, locally advanced cervical cancer (LACC). Given the importance of balancing the costs of innovative therapeutics against their efficacy, this study was developed to assess the cost-effectiveness from the perspective of payers in Americas, Europe, and Asia.

Methods: The main survival and other relevant parameters of 1,060 LACC patients from the KEYNOTE-A18 trial were collected to establish a lifetime 3-state Markov model to evaluate the cost and effectiveness of pembrolizumab-CCRT and placebo-CCRT. Primary outcome measures included total cost, life-years (LYs), quality-adjusted LYs (QALYs), incremental cost-effectiveness ratio (ICER), incremental net monetary benefit, and incremental net health benefits (INHBs) at countries' traditional willingness-to-pay (WTP) thresholds. Model stability was also examined through sensitivity analyses.

Results: The USA, Italy, and China are selected as representative countries for each of the 3 continents, assuming that their WTP thresholds were $150,000, $43,749, and $37,766 per QALY. The increased efficacy and costs of pembrolizumab-CCRT versus placebo-CCRT were 2.52 QALYs (3.11 LYs) and $346,479, 2.30 QALYs (2.81 LYs) and $236,776, 1.79 QALYs (2.12 LYs) and $29,027, calculating the ICER for the 3 countries as $137,500/QALY ($111,499/LY), $102,758/QALY ($84,192/LY), and $16,217/QALY ($13,726/LY), respectively. The respective INHBs were 0.21 QALY, -3.11 QALY, and 1.02 QALY, and pembrolizumab-CCRT was exhibited cost-effectiveness opportunities of 62.68%, 12.53%, and 75.23% at the selected WTP threshold, respectively.

Conclusion: At current prices, pembrolizumab-CCRT represents a cost-effective alternative for patients with LACC in the USA and China, but not in Italy.

Objective: In advanced ovarian cancer, achieving R0 resection is a critical strategy for improving prognosis. However, even with R0 resection, the prognosis of patients with a high tumor burden remains poor. This study aimed to assess whether the introduction of poly(ADP-ribose) polymerase inhibitors (PARPi) has enhanced outcomes in such cases.

Methods: We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV ovarian cancer treated between January 2015 and December 2021. Patients were classified into Group A (pre-PARPi introduction) and Group B (post-PARPi introduction). Complete macroscopic resection was defined as R0. Progression-free survival (PFS), stratified by the Aletti Surgical Complexity Score (Aletti_SCS), was the primary endpoint and was evaluated using Cox regression models.

Results: A total of 434 patients were included. In Group A, among those who achieved R0, the median PFS was 23.5 months for patients with high Aletti_SCS (95% confidence interval [CI]=14-30) and not reached for those with low Aletti_SCS (95% CI=30-not reached; adjusted hazard ratio [HR]=0.36, 95% CI=0.20-0.62). In Group B, the median PFS was not reached in both patients with high Aletti_SCS (95% CI=not reached-not reached) and low Aletti_SCS (95% CI=22-not reached; adjusted HR=4.98, 95% CI=1.14-21.78).

Conclusion: Following the introduction of PARPi, there was a trend toward improved PFS in patients with a higher Aletti_SCS who underwent R0 resection. These findings suggest that R0 resection may improve prognosis even in cases with a high tumor burden in the PARPi era.

Objective: Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated favorable therapeutic responses in patients with chemorefractory gestational trophoblastic neoplasia. The need for combined surgery to remove resistant foci in patients treated with anti-PD-1 therapy after complete remission (CR), however, has not been investigated. We therefore compared the prognosis of patients with high-risk chemorefractory or relapsed choriocarcinoma who underwent anti-PD-1 therapy with or without surgery.

Methods: Patients with high-risk chemorefractory or relapsed choriocarcinoma who experienced CR following immunotherapy in conjunction with either surgical or non-surgical interventions were selected at Peking Union Medical College Hospital (PUMCH) between August 2018 and December 2023. Study endpoints included progression-free survival (PFS) and overall survival (OS). The results were analyzed using Mann-Whitney U tests and Kaplan-Meier analysis.

Results: Forty-three patients who received andi-PD-1 therapy were enrolled in this study, including 18 patients with surgery and 25 without. Most of the foci in the surgery group were solitary (77.8%). The median maximum diameters of resistant foci before immunotherapy were 2.9 (0.7-7.3) cm and 1.4 (0.8-11.2) cm in the surgery and non-surgery groups, respectively (p=0.184). The 2-year PFS rate was both 91.5% in the non-surgery group and 90.9% in the surgery group. The 2-year and 3-year OS rates were 100.0% in both groups. There was no significant difference in PFS (p=0.849) or OS (p=0.371) between the 2 groups.

Conclusion: These results suggest that surgical resection of drug-resistant lesions may not be necessary in patients with high-risk chemorefractory or relapsed choriocarcinoma who achieve CR after anti-PD-1 therapy.

Objective: In the present study, molecular subtypes were determined, programmed death-ligand 1 (PD-L1) and tumor-associated immune cells (TAICs) were quantitatively detected, and their effect on prognosis in uterine carcinosarcoma (UCS) was analyzed.

Methods: The study included 65 UCS cases. Direct sequencing of POLE exonuclease domain and immunohistochemistry of mismatch repair (MMR) deficiency proteins and p53 were used to stratify molecular subtypes. QuPath was used for quantitative immunohistochemical detection of PD-L1 and TAICs. The chi square test was used to determine the association between molecular subtypes and expression of PD-L1 and TAICs. The Kaplan-Meier method and Cox proportional hazards regression were used for plotting and survival analysis.

Results: In 65 UCS cases, 1 case (1.5%) was POLE ultramutated (POLEmut) subtype, 11 cases (16.9%) were deficient MMR (dMMR) subtype, 32 cases (49.3%) were p53 mutant (p53mut) subtype, and 21 cases (32.3%) were nonspecific molecular profile (NSMP) subtype. The positive density of PD-L1 in tumor (p=0.022), CD8 in stroma (p=0.036), and CD163 in stroma (p=0.025) were significantly associated with molecular subtypes. The patients with POLEmut and dMMR subtypes had a relatively better prognosis trend than patients with NSMP and p53mut subtypes. The patients with high positive density of PD-L1 in tumor had significantly better prognosis; however, high positive density of CD163 in stroma showed significantly worse prognosis.

Conclusion: UCS could be classified into four molecular subtypes associated with prognosis. PD-L1 and M2 macrophages could effectively predict the prognosis of patients with UCS.

Objective: To address the relation among pelvic inflammatory disease (PID), genetic vulnerability and ovarian cancer (OC) risk, we assessed the association between PID and OC risk, alongside the interplay with germline homologous recombination repair (gHR) mutation, utilizing the UK Biobank.

Methods: We conducted a prospective cohort study in the UK Biobank by tracking OC incidences between individuals with and without a PID history. Identification of gHR mutations (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1) carriers were accomplished through paired whole-exome sequencing data. We used Cox's regression models to evaluate the hazard ratios (HRs) for OC risks under PID.

Results: In the large prospective cohort study, the adjusted HR for OC in patients with PID was 1.45 (95% confidence interval [CI]=0.90, 2.32) compared with those with non-PID. Intriguingly, age-stratified analysis unveiled a positive association between PID history and OC risk in those aged under 55 years (HR=1.92; 95% CI=1.02, 3.63). Moreover, individuals aged younger than 55 years harboring both a history of PID and gHR mutations exhibited the highest risk of OC (HR=7.40; 95% CI=1.03, 53.10).

Conclusion: An association between PID and OC risk emerged, notably in the subgroup aged younger than 55 years old. Individuals with both a PID history and gHR mutations exhibited the highest risk of OC. These findings imply PID as a potential precursor for OC, underscoring the importance of early intervention, particularly in the younger population with gHR mutations.

Objective: To evaluate and compare the perioperative and oncologic outcomes of laparoscopic and robotic-assisted surgeries in patients with low-risk endometrial cancer who underwent minimally invasive surgery (MIS) for complete surgical staging, including sentinel lymph node mapping.

Methods: A retrospective study included 190 patients diagnosed with low-risk endometrial cancer who underwent MIS combined with sentinel lymph node navigation surgery (SNNS) between December 2016 and December 2021. Among these patients, 66 underwent laparoscopic surgery, while 124 underwent robotic-assisted surgery. The analysis focused on patient characteristics, perioperative outcomes, and prognostic factors, including recurrence-free survival (RFS) and overall survival (OS). Statistical analysis was performed using Kaplan-Meier survival curves and appropriate comparative tests for outcome evaluation.

Results: The median operative time and estimated blood loss were significantly longer and greater in the robotic surgery group than in the laparoscopic group (209.5 vs. 157.5 min, 20 vs. 5 mL, respectively). The identification rates of sentinel nodes were 97% and 95.2% in the laparoscopic and robotic groups, respectively, with no significant difference between the 2. Recurrence was observed in two and three cases in the laparoscopic robotic surgery groups, respectively. The 3-year RFS rates were 97.6% (95% confidence interval [CI]=0.8482-0.9769) and 93.9% (95% CI=0.9277-0.9922) for the robotic and laparoscopic groups, respectively, while the 3-year OS rates were 99.2% (95% CI=0.8561-0.9902) and 96.1% (95% CI=0.9450-0.9989), respectively, with no statistically significant differences.

Conclusion: MIS combined with SNNS is a highly effective approach for managing low-risk endometrial cancer, providing comparable oncologic outcomes to laparoscopy while enhancing the quality of life of patients.