Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer.

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

The effectiveness of CA125 and HE4 as clinical prognostic markers in epithelial ovarian cancer patients with BRCA mutation.

OBJECTIVE: To investigate the efficacy of cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting survival outcomes based on breast cancer gene (BRCA) mutational status in epithelial ovarian cancer. METHODS: Medical records of 448 patients diagnosed with epithelial ovarian cancer at a single tertiary institution in Korea were retrospectively analyzed. Area under the curve, sensitivity, specificity, and accuracy were assessed using the CA125 and HE4 values after surgery and 3 cycles of chemotherapy to predict 1-year survival based on the BRCA mutational status. Kaplan-Meier analysis was used to obtain progression-free and overall survival to evaluate CA125 and HE4 effectiveness in predicting survival outcomes. RESULTS: A total of 423 patients were analyzed, including 180 (42.6%) who underwent interval debulking surgery (IDS) and 243 (57.4%) who underwent primary debulking surgery (PDS). BRCA mutations were observed in 37 (15.2%) and 44 (22.4%) patients in the PDS and IDS groups, respectively. CA125 and HE4 normalization demonstrated the highest specificity in patients with or without BRCA mutations, with specificities of 97.1% and 99.1% in the PDS group and 78.6% and 86.2% in the IDS group, respectively. Normalizing HE4 alone may be an effective prognostic marker, with an area under the curve of 0.774 and specificity of 75.0%, in patients with BRCA mutations. CONCLUSION: Normalizing both biomarkers emerged as the most effective predictive marker for the 1-year recurrence rate, regardless of BRCA mutational status. A negative HE4 value can be a useful predictor for 1-year recurrence-free survival in patients with BRCA mutations.

Psychosocial barriers and facilitators for cascade genetic testing in hereditary breast and ovarian cancer: a scoping review.

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.

Clinical practice guidelines for cervical cancer: the Korean Society of Gynecologic Oncology guidelines.

This fifth revised version of the Korean Society of Gynecologic Oncology practice guidelines for the management of cervical cancer incorporates recent research findings and changes in treatment strategies based on version 4.0 released in 2020. Each key question was developed by focusing on recent notable insights and crucial contemporary issues in the field of cervical cancer. These questions were evaluated for their significance and impact on the current treatment and were finalized through voting by the development committee. The selected key questions were as follows: the efficacy and safety of immune checkpoint inhibitors as first- or second-line treatment for recurrent or metastatic cervical cancer; the oncologic safety of minimally invasive radical hysterectomy in early stage cervical cancer; the efficacy and safety of adjuvant systemic treatment after concurrent chemoradiotherapy in locally advanced cervical cancer; and the oncologic safety of sentinel lymph node mapping compared to pelvic lymph node dissection. The recommendations, directions, and strengths of this guideline were based on systematic reviews and meta-analyses, and were finally confirmed through public hearings and external reviews. In this study, we describe the revised practice guidelines for the management of cervical cancer.

Application of Small Cell Lung Cancer Molecular Subtyping Markers to Small Cell Neuroendocrine Carcinoma of the Cervix: NEUROD1 as a Poor Prognostic Factor.

Cervical small cell neuroendocrine carcinoma (CSCNEC) is a rare, aggressive type of cervical cancer. The treatment for CSCNEC follows the chemotherapeutic regimens used for small cell lung cancer (SCLC), with which it shares similar clinical and histologic features. For the first time, we applied neuroendocrine (NE) and SCLC molecular subtyping immunohistochemical markers [achaete-scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3), and yes-associated protein 1] in 45 patients with CSCNEC. For the combined NE score, 51.1% of NE-high and 48.9% of NE-low subtypes were identified. The NE-high subtype tended to show worse progression-free survival and overall survival (OS) than the NE-low subtype ( P =0.059 and P =0.07, respectively). Applying the SCLC molecular subtyping, 53.3% of cases were identified as NEUROD1-dominant, 17.8% as ASCL1-dominant, 13.3% as YAP-dominant, and 4.4% as POU2F3-dominant, while 11.1% of cases showed negative expression for all markers; the distribution was different from that of SCLC. The NEUROD1-dominant subtype exhibited the worst OS, while the POU2F3 subtype exhibited the best OS ( P =0.003), similar to SCLC. In addition, the ASCL1-dominant and NEUROD1-dominant subtypes showed high NE scores, while yes-associated protein 1-dominant and POU2F3-dominant subtypes showed low NE scores ( P =0.008). In multivariate analysis, the NEUROD1 expression was further identified as the independent prognostic factor for worse OS, together with the high FIGO stage. CSCNEC was revealed to be a heterogeneous disease with different biological phenotypes and to share some similarities and differences with SCLC. Regarding the ongoing development of tailored treatments based on biomarkers in SCLC, the application of biomarker-driven individualized therapy would improve clinical outcomes in patients with CSCNEC.

Comparison of Single-Port Laparoscopy with Other Surgical Approaches in Endometrial Cancer Surgical Staging: Propensity-Score-Matched Analysis.

This single-institution, retrospective study aimed to compare the surgical outcomes of single-port, multi-port, and robot-assisted laparoscopy, as well as laparotomy, in patients with endometrial cancer who underwent surgical staging between January 2006 and December 2017. This study evaluated various parameters, including disease-free survival (DFS), overall survival (OS), recurrence rate (RR), recurrence site, and intra- and postoperative complications. Propensity score matching was performed to account for baseline characteristics, and a total of 881 patients were included in the analysis. The 3-year DFS of single-port laparoscopy was similar to that of the other groups, but laparotomy exhibited a lower 3-year DFS compared to multi-port (p = 0.001) and robot-assisted (p = 0.031) laparoscopy. Single-port laparoscopy resulted in a significantly higher 3-year OS than laparotomy (p = 0.013). After propensity score matching, the four groups demonstrated similar survival outcomes (3-year DFS: p = 0.533; 3-year OS: p = 0.328) and recurrence rates (10.3%, 12.1%, 10.3%, and 15.9% in the single-port, multi-port, and robot-assisted laparoscopy and laparotomy groups, respectively, p = 0.552). Recurrence most commonly occurred in distant organs. The single-port laparoscopy group had the longest operative time (205.1 ± 76.9 min) but the least blood loss (69.5 ± 90.8 mL) and the shortest postoperative hospital stay (5.2 ± 2.3 days). In contrast, the laparotomy group had the shortest operative time (163.4 ± 51.0 min) but the highest blood loss (368.3 ± 326.4 mL) and the longest postoperative hospital stay (10.3 ± 4.6 days). The transfusion rate was 0% in the single-port laparoscopy group and 3.7% in the laparotomy group. Notably, the laparotomy group had the highest wound complication rate (p = 0.001), whereas no wound hernias were observed in the three minimally invasive approaches. In conclusion, the survival outcomes were comparable between the methods, with the benefit of lower blood loss and shorter hospital stay observed in the single-port laparoscopy group. This study suggests that single-port laparoscopy is a feasible approach for endometrial cancer surgical staging.

Initial experience with the da Vinci SP robot-assisted surgical staging of endometrial cancer: a retrospective comparison with conventional laparotomy.

To compare the perioperative outcomes of surgical staging performed using conventional laparotomy (LT) or the da Vinci SP robotic system (SP) in patients with endometrial cancer. We retrospectively analyzed 180 patients with stage I-III endometrial cancer who underwent surgical staging using LT (n = 126) or SP (n = 54) at the Yonsei Cancer Center between November 2018 and December 2022. Propensity score matching (PSM) was performed to mitigate potential confounding biases. Fifty-one pairs of patients were matched by PSM. SP required longer total operation time than LT (221 vs. 142 min in SP vs. LT, respectively, p < 0.001). However, estimated blood loss and postoperative hemoglobin change were lower in SP than in LT (30 vs. 100 mL, p < 0.001; 0.6 vs. 1.6 g/dL, p < 0.001 for SP vs. LT respectively). Furthermore, postoperative minor complications (13.7% in SP vs. 33.3% in LT, p = 0.02), perioperative transfusion rate (0% in SP vs. 11.8% in LT, p = 0.03), and postoperative hospital stay (2 days for SP vs. 8 days for LT, p < 0.001) were lower in SP than in LT. Although the patient-controlled analgesia administration rate was lower in SP (13.8% in SP vs. 100% in LT, p < 0.001), the median postoperative pain score at 6, 12, and 24 h after surgery was lower in SP than in LT (2 vs. 3, p = 0.002; 2 vs. 3, p = 0.005; 2 vs. 3, p = 0.001 for SP vs. LT, respectively). Although SP required longer total operation time, it demonstrated several advantages over LT in endometrial cancer staging.

Clinical Relevance of Red Blood Cell Distribution Width (RDW) in Endometrial Cancer: A Retrospective Single-Center Experience from Korea.

BACKGROUND: Red blood cell distribution width (RDW) is a standard parameter of complete blood count and indicates the variability in red blood cell size. This study aimed to determine whether preoperative RDW can be used to predict the recurrence and prognosis of endometrial carcinoma. METHODS: The medical records of 431 patients diagnosed with endometrial carcinoma were retrospectively reviewed between May 2006 and June 2018. In addition to RDW, the clinicopathological factors, survival curves, and prognoses of the patients with endometrial carcinoma were compared between the high (n = 213) and low (n = 218) groups according to the median RDW value (12.8%). RESULTS: The patients with high RDW had significantly advanced-stage (p = 0.00) pelvic lymph node metastasis (p = 0.01) and recurrence (p = 0.01) compared to those in the low-RDW group. In univariate analysis with DFS as the endpoint, surgical stage, type II histology, grade, RDW, and lymph node metastasis were independently associated with survival. Patients with high RDW values had significantly shorter disease-free survival and overall survival than those with low RDW values (log-rank p = 0.03, log-rank p = 0.04, respectively). CONCLUSION: Our results demonstrate that RDW is a simple and convenient indicator of endometrial carcinoma recurrence. Prospective studies are needed to validate the findings of the current study.

Comparing surgical outcomes of da Vinci SP and da Vinci Xi for endometrial cancer surgical staging in a propensity score-matched study.

The number of studies comparing robotic systems in endometrial cancer staging is limited. This retrospective study analyzed the medical records of 42 consecutive endometrial cancer patients, who underwent robotic staging using the da Vinci SP (SP) system, and 126 propensity score-matched patients who underwent staging using the da Vinci Xi (Xi) system. Median console and total operation times were longer in the SP group than those in the Xi group (125 vs. 77 min, p < 0.001; 225 vs. 154.5 min, p < 0.001, respectively). Notably, the median console time of the first 10 cases using SP was 184 min; it subsequently decreased to 99.5 min in the fourth 10 cases. SP had lesser postoperative hemoglobin (Hb) change (0.6 ± 0.7 g/dL vs. 1.8 ± 0.9 g/dL in Xi, p < 0.001) and lower median pain score at 6 h after surgery (2 vs. 3 in Xi, p = 0.046). Moreover, median postoperative hospital stay was shorter in the SP group (2 days) than that in the Xi group (6 days) (p < 0.001). Although SP was correlated with lower postoperative Hb change, shorter postoperative hospital stay, and lower pain score than those in Xi, it required longer operation times. Further prospective randomized studies are needed to validate the benefits of SP compared to other robotic platforms.

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer.

AIM: Sentinel lymph node (SLN) mapping allows node-negative patients to be spared from the surgical comorbidities associated with total lymphadenectomy. This study aimed to evaluate the oncological outcomes of SLN biopsy versus complete lymph node dissection in patients with early-stage endometrial carcinoma. METHODS: Retrospective analyses were performed in patients with pathologically confirmed endometrioid endometrial carcinoma, who underwent minimally invasive surgical staging with SLN biopsy or complete lymph node dissection at Yonsei Cancer Center between 2015 and 2019. RESULTS: A total of 301 patients were included in this study. Eighty-two patients underwent SLN biopsy, while 219 underwent complete lymph node dissection. There were no significant differences in patient characteristics between the two groups. In terms of operative characteristics, the SLN biopsy-only group had a significantly shorter surgical duration (p < 0.001) than the lymphadenectomy group. The mean follow-up period was 41.4 months. There were no differences in progression-free survival (PFS) and overall survival (OS) between the two groups (SLN biopsy vs. complete lymph node dissection; p = 0.798 and 0.301, respectively). Multivariate analysis revealed that SLN biopsy was not an independent prognostic factor for PFS or OS. CONCLUSION: Our results showed that SLN biopsy provided oncological outcomes similar to those of lymphadenectomy.

Vaginal Cuff Dehiscence and a Guideline to Determine Treatment Strategy.

In this retrospective study, our aim was to investigate a novel treatment strategy guideline for vaginal cuff dehiscence after hysterectomy based on the mode of operation and time of occurrence in patients who underwent hysterectomy at Severance Hospital between July 2013 and February 2019. We analyzed the characteristics of 53 cases of vaginal cuff dehiscence according to the mode of hysterectomy and time of occurrence. Out of a total of 6530 hysterectomy cases, 53 were identified as vaginal cuff dehiscence (0.81%; 95% confidence interval: 0.4-1.6%). The incidence of dehiscence after minimally invasive hysterectomy was significantly higher in patients with benign diseases, while malignant disease was associated with a higher risk of dehiscence after transabdominal hysterectomy (p = 0.011). The time of occurrence varied significantly based on menopausal status, with dehiscence occurring relatively earlier in pre-menopausal women compared to post-menopausal women (93.1% vs. 33.3%, respectively; p = 0.031). Surgical repair was more frequently required in cases of late-onset vaginal cuff dehiscence (≥8 weeks) compared to those with early-onset dehiscence (95.8% vs. 51.7%, respectively; p < 0.001). Patient-specific factors, such as age, menopausal status, and cause of operation, may influence the timing and severity of vaginal cuff dehiscence and evisceration. Therefore, a guideline may be indicated for the treatment of potentially emergent complications after hysterectomy.

LncRNA SNHG4 Modulates EMT Signal and Antitumor Effects in Endometrial Cancer through Transcription Factor SP-1.

Long non-coding RNAs (lncRNAs) are implicated in the initiation and progression of a variety of tumors, including endometrial cancer. However, the mechanisms of lncRNA in endometrial cancer formation and progression remain largely unknown. In this study, we confirmed that the lncRNA SNHG4 is upregulated in endometrial cancer and correlates with lower survival rates in endometrial cancer patients. Knock-down of SNHG4 significantly reduced cell proliferation, colonization, migration, and invasion in vitro, as well as modulating the cell cycle and reduced tumor growth of endometrial cancer in vivo. In addition, the effect of SNHG4 by the transcription factor SP-1 was confirmed in vitro. We found in this study that SNHG4/SP-1 plays an important role in endometrial cancer progression and may be used as a potential therapeutic and prognostic biomarker for endometrial cancer.

Comprehensive genomic and immunohistochemical profiles and outcomes of immunotherapy in patients with recurrent or advanced cervical cancer.

Purpose: This study aimed to investigate genomic and immunohistochemical (IHC) profiles and immunotherapy outcomes in patients with cervical cancer. Methods: Patients with recurrent cervical cancer who underwent tumor next-generation sequencing (NGS) with the TruSight Oncology 500 panel at Yonsei Cancer Center between June 2019 and February 2022, were identified. Patients who received treatment with checkpoint inhibitors during the same period were also identified. Clinical information, including histology, stage, human papillomavirus (HPV) genotype, IHCs profile, and therapy outcome, was reviewed. Results: We identified 115 patients treated for recurrent cervical cancer, including 74 patients who underwent tumor NGS. Most of these 74 patients were initially diagnosed with advanced stage (63.6%) and had squamous cell histology (52.7%), and high-risk HPV (76.9%). Based on IHC analysis, the programmed death-ligand 1 combined positive score (PD-L1 CPS) was higher in patients with squamous cell carcinoma (SCC) than in those with adeno or mucinous types (P=0.020). HER2 receptor expression of 2+ and 3+ were identified in 5 and 1 patients, respectively, and significantly varied based on histology (p=0.002). Among the 74 patients, single nucleotide variants (SNVs) and copy number variations (CNVs) were identified in 60 (81.1%) and 13 patients (17.6%), respectively. The most common SNVs were PIK3CA, TP53, STK11, FAT1, and FBXW7 mutations. Mutations in PIK3CA, with two hotspot mutations, were frequently observed in patients with SCC histology, whereas mutations in TP53 were frequently observed in patients with non-SCC histology. Additionally, variations in FAT1 were exclusively identified in patients with SCC histology. Mutations in homologous recombination repair-associated genes were identified in 18 patients (24.3%). The most frequent CNV alteration was CCNE1 amplification. Moreover, among the 36 patients who underwent NGS and received immunotherapy, the tumor mutational burden and microsatellite instability were significantly correlated with immunotherapy duration. During this timeframe, 73 patients received pembrolizumab monotherapy, among whom a small portion showed a durable response. Conclusion: Comprehensive genomic and IHC profiling may help identify potential candidates for targeted immunotherapy in patients with cervical cancer.

Clinical Relevance of Vaginal Cuff Dehiscence after Minimally Invasive versus Open Hysterectomy.

This study aimed to evaluate the clinical relevance of vaginal cuff dehiscence following a hysterectomy. Data were prospectively collected from all patients who underwent hysterectomies at a tertiary academic medical center between 2014 and 2018. The incidence and clinical factors of vaginal cuff dehiscence after minimally invasive versus open hysterectomy were compared. Vaginal cuff dehiscence occurred in 1.0% (95% confidence interval [95% CI], 0.7-1.3%) of women who underwent either form of hysterectomy. Among those who underwent open (n = 1458), laparoscopic (n = 3191), and robot-assisted (n = 423) hysterectomies, vaginal cuff dehiscence occurred in 15 (1.0%), 33 (1.0%), and 3 (0.7%) cases, respectively. No significant differences in cuff dehiscence occurrence were identified in patients who underwent various modes of hysterectomies. A multivariate logistic regression model was created using the variables indication for surgery and body mass index. Both variables were identified as independent risk factors for vaginal cuff dehiscence (odds ratio [OR]: 2.74; 95% CI, 1.51-4.98 and OR: 2.20; 95% CI, 1.09-4.41, respectively). The incidence of vaginal cuff dehiscence was exceedingly low in patients who underwent various modes of hysterectomies. The risk of cuff dehiscence was predominantly influenced by surgical indications and obesity. Thus, the different modes of hysterectomy do not influence the risk of vaginal cuff dehiscence.

Clinical Relevance of Uterine Manipulation on Oncologic Outcome in Robot-Assisted versus Open Surgery in the Management of Endometrial Cancer.

In this study, we investigated the impact of uterine manipulation on endometrial cancer survival outcomes. We analyzed patients with endometrial cancer who underwent robot-assisted staging and open staging surgery between 2010 and 2020. Either uterine manipulators or vaginal tubes were utilized in robot-assisted staging. Propensity score matching was performed to correct baseline characteristics. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curve analysis. In total, 574 patients, including those undergoing robot-assisted staging with a uterine manipulator (n = 213) or vaginal tube (n = 147) and staging laparotomy (n = 214), were analyzed. Propensity score matching was performed for age, histology, and stage as covariates. Before matching, Kaplan-Meier curve analysis showed that PFS and OS were significantly different among the three groups (p < 0.001 and p = 0.009, respectively). In the propensity-matched cohorts of 147 women, the previously suggested differences in PFS and OS were not observed in patients undergoing robot-assisted staging with a uterine manipulator or vaginal tube or open surgery. In conclusion, robotic surgery using a uterine manipulator or vaginal tube did not compromise survival outcomes in endometrial cancer management.

Ovarian Real-World International Consortium (ORWIC): A multicentre, real-world analysis of epithelial ovarian cancer treatment and outcomes.

Introduction: Much drug development and published analysis for epithelial ovarian cancer (EOC) focuses on early-line treatment. Full sequences of treatment from diagnosis to death and the impact of later lines of therapy are rarely studied. We describe the establishment of an international network of cancer centers configured to compare real-world treatment pathways in UK, Portugal, Germany, South Korea, France and Romania (the Ovarian Real-World International Consortium; ORWIC). Methods: 3344 patients diagnosed with EOC (2012-2018) were analysed using a common data model and hub and spoke programming approach applied to existing electronic medical records. Consistent definition of line of therapy between sites and an efficient approach to analysis within the limitations of local information governance was achieved. Results: Median age of participants was 53-67 years old and 5-29% were ECOG >1. Between 62% and 84% of patients were diagnosed with late-stage disease (FIGO III-IV). Sites treating younger and fitter patients had higher rates of debulking surgery for those diagnosed at late stage than sites with older, more frail patients. At least 21% of patients treated with systemic anti-cancer therapy (SACT) had recurrent disease following second-line therapy (2L); up to 11 lines of SACT treatment were recorded for some patients. Platinum-based SACT was consistently used across sites at 1L, but choices at 2L varied, with hormone therapies commonly used in the UK and Portugal. The use (and type) of maintenance therapy following 1L also varied. Beyond 2L, there was little consensus between sites on treatment choice: trial compounds and unspecified combinations of other agents were common. Discussion: Specific treatment sequences are reported up to 4L and the establishment of this network facilitates future analysis of comparative outcomes per line of treatment with the aim of optimizing available options for patients with recurrent EOC. In particular, this real-world network can be used to assess the growing use of PARP inhibitors. The real-world optimization of advanced line treatment will be especially important for patients not usually eligible for involvement with clinical trials. The resources to enable this analysis to be implemented elsewhere are supplied and the network will seek to grow in coverage of further sites.

HOXA­AS3 induces tumor progression through the epithelial­mesenchymal transition pathway in epithelial ovarian cancer.

HOXA cluster antisense RNA 3 (HOXA­AS3) is considered to be involved in several malignancies, however, its biological function in the progression of epithelial ovarian cancer (EOC) remains unclear. The present study compared the expression of HOXA­AS3 in ovarian cancer and normal ovarian tissues and analyzed the association between the expression of HOXA­AS3 and the survival outcomes of patients with ovarian cancer. RNA interference was used to suppress HOXA­AS3 expression in ovarian cancer cell lines in order to demonstrate the function of HOXA­AS3 in ovarian cancer progression. The associations between HOXA­AS3 and epithelial­mesenchymal transition (EMT) markers were explored to verify the mechanism of action of HOXA­AS3 in ovarian cancer. The results of the present study revealed that ovarian cancer tissues exhibited higher HOXA­AS3 expression than normal ovarian tissues. Clinical data indicated that HOXA­AS3 was a significant predictor of progression­free survival and overall survival. Patients with high HOXA­AS3 expression had a poorer prognosis than patients with low HOXA­AS3 expression. In vitro experiments using HOXA­AS3­knockdown ovarian cancer cell lines demonstrated that HOXA­AS3 knockdown inhibited cell proliferation and migration. HOXA­AS3 was a potent inducer and modulator of the expression of EMT pathway­related markers and interacted with both the mRNA and protein forms of HOXA3. Collectively, the findings of the present study demonstrated that HOXA­AS3 expression is associated with ovarian cancer progression and thus, may be employed as a prognostic marker and therapeutic target in EOC.

Preclinical investigation of patient-derived cervical cancer organoids for precision medicine.

OBJECTIVE: Advanced cervical cancer is still difficult to treat and in the case of recurrent cancer, it is desirable to utilize personalized treatment rather than uniform treatment because the type of recurrence is different for each individual. Therefore, this study aimed to establish a patient-derived organoid (PDO) platform to determine the effects of chemotherapy, radiation therapy, and targeted therapy in cervical cancer. METHODS: We established organoids from 4 patients with various types of cervical cancer. The histopathological and gene profiles of these organoid models were compared to determine their characteristics and the maintenance of the patient phenotype. Each type of organoid was also subjected to anticancer drug screening and radiation therapy to evaluate its sensitivity. RESULTS: We established PDOs to recapitulate the main elements of the original patient tumors, including the DNA copy number and mutational profile. We selected 7 drugs that showed growth inhibition in cervical cancer organoids out of 171 using an Food and Drug Administration -approved drug library. Moreover, adenocarcinoma and large-cell neuroendocrine carcinoma showed resistance to radiation therapy. whereas squamous cell carcinoma and villoglandular carcinoma showed a significant response to radiotherapy. CONCLUSION: Our results showed that patient-derived cervical cancer organoids can be used as a platform for drug and radiation sensitivity testing. These findings suggest that patient-derived cervical cancer organoids could be used as a personalized medicine platform and may provide the best treatment options for patients with various subtypes of cervical cancer.

Role of diagnostic laparoscopy in deciding primary treatment in advanced-stage ovarian cancer.

OBJECTIVE: We evaluated the usefulness of preoperative diagnostic laparoscopy for treatment planning in patients with advanced-stage ovarian cancer. METHODS: We retrospectively analyzed 614 patients diagnosed with advanced-stage ovarian cancer between January 2010 and May 2018. Primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery were selected based on preoperative laparoscopic (Group 1, n=192) and computed tomography findings (Group 2, n=422). The primary outcomes in the PDS and NAC groups were suboptimal cytoreduction (residual disease >1 cm) rate and non-high-grade serous carcinoma (non-HGSC) rate, respectively. RESULTS: The patients who underwent PDS in group 1 and group 2 were 49 (25.5%) and 279 (66.1%), respectively. The suboptimal cytoreduction rate after PDS was lower in Group 1 than in Group 2 (2.0% vs 11.1%, p=0.023). Moreover, Group 1 showed a tendency toward a lower proportion of non-HGSC patients who underwent NAC than that in Group 2 (9.1% vs. 15.4%, p=0.069). Further, Group 1 showed lower rates of postoperative morbidity than Group 2 (5.2% vs. 10.4%, p=0.033). However, Kaplan-Meier analysis showed no significant differences in survival outcomes between the 2 groups. CONCLUSION: Diagnostic laparoscopy reduced the suboptimal cytoreduction rate in the PDS group and the implementation rate of NAC in non-HGSC patients. Moreover, it reduced postoperative morbidity without affecting survival in both groups. Thus, diagnostic laparoscopy is a valuable diagnostic tool for determining the primary treatment.

Secondary cytoreductive surgery with and without hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer.

Background: Secondary cytoreductive surgery (CRS) can afford promising results in patients with recurrent ovarian cancer; however, the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear. We compared the outcomes of secondary CRS combined with and without HIPEC in patients with recurrent ovarian cancer. Methods: We retrospectively evaluated patients with recurrent ovarian cancer who underwent secondary CRS, with or without HIPEC (n=46), at the Yonsei Cancer Center between January 2006 and February 2021. Of the 46 included patients, 20 underwent secondary CRS-plus-HIPEC, while 26 underwent secondary CRS without HIPEC (henceforth referred to as secondary CRS-only). Results: Of the 46 patients, 84.8% and 89.1% had undergone optimal surgery and platinum-based chemotherapy, respectively, as the initial treatment before the first relapse. Overall, 32.6% of patients received maintenance therapy, such as bevacizumab or polyadenosine diphosphate ribose polymerase inhibitors. The median follow-up period was 15.9 months. The median progression-free survival (PFS) was 32.7 and 25.1 months in the secondary CRS-plus-HIPEC and secondary CRS-only groups, respectively; however, both groups failed to reach the median overall survival (OS). Based on the Kaplan-Meier analysis, there was no difference in PFS (P=0.587) or OS (P=0.239) between the two groups. We identified patients with epithelial ovarian cancer and found that the median PFS was 25.1 months in the secondary CRS-only group; this was not achieved in the secondary CRS-plus-HIPEC group (P=0.244). Conclusions: In patients with recurrent ovarian cancer, secondary CRS with HIPEC did not improve survival when compared with CRS without HIPEC. However, on subgrouping patients with epithelial ovarian cancer, the addition of HIPEC to secondary CRS tended to improve PFS.