bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCND1 and PTEN gene copy number variations as markers of vulvar cancer progression.
Authors: Petrusenko Natalia A. , Kutilin Denis S. , Busarova Angelina V. , Porkhanova Natalya V. , Kit Oleg I. 
Published: June 2022

e17531 Background: More than 90% of malignant vulvar tumors and almost 5% of all gynecological cancers are squamous cell carcinoma. 1/3 of patients with vulvar cancer relapse after initial treatment, and the 2-year overall survival is less than 15%. Development of more effective treatments requires understanding of the molecular pathogenesis of vulvar cancer. The aim of this study was the screening of potential prognostic tumor markers in vulvar cancer based on relative copy number analysis (CNV) of MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, AEPX1, NFKBIA, MTAP, BIRC2, SYNE1, KMT2C genes. Methods: The study was performed on 300 patients aged 29-80 years diagnosed with vulvar squamous cell carcinoma with lymph nodes metastases (n = 150) and without metastases (n = 150). The material for the study was DNA from FFPE-blocks of tumor and non-tumor vulvar tissues. The RT-qPCR method was used to evaluate the relative copy number of MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, AEPX1, NFKBIA, MTAP, BIRC2, SYNE1, KMT2C, GAPDH and B2M genes (the last two were reference genes). Differences were assessed using the Mann-Whitney test (Bonferroni correction was used). Results: All genes showed a change in the dose in vulva tumor cells relative to normal ones: amplifications for the MYC, MCL1, AEPX1, NFKBIA, CCND1, PIK3CA, TP53, MDM2, BIRC2, SYNE1, KMT2C genes, respectively, in 46%, 36%, 28%, 40%, 56%, 43%, 62%, 39%, 57%, 35%, 44% of cases, and a decrease in copy number for PTEN, MTAP, CDKN2A genes, respectively, in 34%, 28%, 35% of cases. At the same time, a statistically significant increase in the CNV of the CCND1 gene (p < 0.05) by 1.7 times and a decrease in the PTEN gene (p < 0.05) by 1.9 times were observed in the group of vulvar squamous cell carcinoma patients with lymph nodes metastases. No statistically significant change in the CNV of other genes was found. Conclusions: Thus, the identified aberrant copy numbers of CCND1 and PTEN genes can serve as prognostic markers for vulvar cancer patients.
Expression of markers of epithelial-mesenchymal transition in various forms of vulvar cancer.
Authors: Ulianova Elena P. , Busarova Angelina V. , Porkhanova Natalya V. , Sagakyants Aleksandr B. , Petrusenko Natalia A. , Shulgina Oksana G. , Chernikova Elena N. , Bakulina Svetlana M. , Pushkareva Tatiana F. , Verenikina Ekaterina V. 
Published: June 2022

e17532 Background: Vulvar cancer is a rare gynecologic tumor accounting for 2–5% of all gynecologic cancers. The epithelial-mesenchymal transition (EMT) is considered one of the factors contributing to the aggressive behavior of vulvar squamous cell carcinoma. E- and N-cadherins are key regulators of this transition. The purpose of our study was to identify the features of the expression of EMT markers in vulvar cancer as prognostic factors. Methods: The study included 30 patients aged 39-70 years, mean age 52 years, with vulvar cancer: control group (n = 15) with vulvar cancer T1-2N0-M0 (G2); main group (n = 15) with vulvar cancer T1-2N1-M0 (G2) with metastases to inguinal lymph nodes. Immunohistochemical study was performed on sections from paraffin blocks of tumors using monoclonal mouse antibodies to E-cadherin (12#, Cloud-Clone Corp.) and N-cadherin (389, Invitrogen) and the UltraVision Quanto Detection System HRP DAB. Expression of E- and N-cadherin was semiquantitatively analyzed according to the cell percentage and stain intensity: 0 (0-10%); 1+ (11-30%); 2+ (31-70%); 3+ (> 70%). Expression was considered positive if the score was ≥2. Pearson's χ² test and Spearman's correlation coefficient were used for statistical analysis. Results: The maximum staining for E-cadherin was observed in the control group (in 73%), for N-cadherin - in the main group (in 59%). Median expressions of E- and N-cadherin differed: in the control group, 70 [40-78] and 26 [0-40]; in the main group, 47 [45-60] and 59 [27-65]. Pearson's chi-squared test showed that patients with E-cadherin+ tumors (p = 0.006) statistically significantly prevailed in the control group, and patients with N-cadherin+ tumors (p = 0.027) prevailed in the main group. However, when considering the correlation between E-cadherin and N-cadherin in the groups, no statistically significant differences were found (rs = -0.042 in the control group and rs = 0.250 in the main group at p > 0.05), apparently due to the limited sample. Conclusions: The immunohistochemical study revealed a tendency towards loss of E-cadherin and increased expression of N-cadherin, which is often associated with poor prognosis.
Phase I clinical safety and efficacy observation of αPD-1-mesoCAR-T cells in the treatment of advanced gynecologic cancer.
Authors: Xia Yong , Liu Zhuqing , Zhu Zhongzheng , Lin Zhicai , Xue Hui , Song Zongchang , Yu Yanyan , Guan Xinhong , Sun Yuying , Miao Zhifeng , Yang Yaping , Wang Sitong , Li Zhong , Lv Linjie , Xu Qing , Sun Yan , Lou Jin-xing , Qian Qijun 
Published: June 2022

e17535 Background: Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death among women. Most of patients often have refractory or relapse. We have developed a CAR T cell secreting PD-1 nanoantibodies and targeting mesothelin (αPD-1-mesoCAR-T) and conducted a phase I clinical trial for evaluation of safety and efficacy of the αPD-1-mesoCAR-T cells in gynecologic tumors. Methods: This study is a single-arm, open, dose-increasing clinical study and two infusions (interval 14-35 days). Patients with advanced gynecological cancer were enrolled when immunohistochemical analysis for positive mesothelin over 70% and failed second-line treatment in Mengchao Cancer Hospital affiliated to Shanghai University and Shanghai Tenth People's Hospital affiliated to Tongji University. All patients underwent lymphodepletion before infusion at a dose of 1 to 15x106/kg. CAR copies, nanobody levels, cytokines, T lymphocyte subtypes were determined before and after infusion. Results: a total of 7 patients were enrolled so far and completed the first evaluation. After treatment, most symptoms of the patients were alleviated, two patients (#2, #3) had their lesions decreased. By RECIST 1.1, all 7 patients’ diseases became stable, and the disease control rate was 100%. The PFS of #3 patient with stable disease (SD) was 5.3 months, the patient #2 was 4.1 months. The frequent adverse events were fever, fatigue, nausea and pruritus. No sever adverse events above grade 3 occurred. The number of CAR-T cells in the peripheral blood increased significantly during day 4-14 after the infusion, and the PD-1 nanoantibody levels and the contents of INF-γ、IL-6、IL-2 and MCP-1 also increased at day 1-4. Conclusions: The preliminary clinical study showed that the aPD-1-mesoCAR-T cells are safe for the treatment of gynecologic cancer and stabilized the diseases. More data of the treatment is warrantied to continually follow up these patients.
Stochasticity in threshold of homologous recombination deficiency (HRD) score.
Authors: Xu Bai , Xu Bai , Kai Zhentian , Nguyen Thi Phuong Anh , Xia Chaoran , Shi Weiwei 
Published: June 2022

e17561 Background: HRD test from Myriad Inc. was approved by FDA as a biomarker for niraparib in ovarian cancer. Its threshold (as 42) was initially established by capturing 95% of tumors with BRCA1/2 mutation and BRCA1 promoter methylation in the training cohort. Here, we explored the stochasticity of such threshold, when the test noises themselves were concerned. Methods: We simulated HRD scores from figure 1 of Telli et al., 2016 by assigning the median from each histogram bin to the associated samples. The threshold was calculated, as described in the original paper, and the standard error (SE) and confidence interval (CI) for such threshold were estimated from bootstrapping the cohort. Furthermore, the entire cohort was down-sampled to determine the effect of sample size on the threshold. Results: The threshold of 42.5 was calculated from our simulated dataset, close to the original one, with SE of 1.62 and 95% CI of 40.75 - 47.5 for the bootstrap. As expected, SE steadily increased to 2.21, 2.84, 2.97 when the sample sizes decreased to 250, 230, and 210 respectively. When the dataset was further down-sampled to include only 200 BRCA deficient samples, SE increased to 3.76, and drastically, CI ranged between 36.5 and 51.2. Conclusions: We have showed there exists manifest stochasticity in the original threshold of 42 for the Myriad HRD test, which is likely close to platform noise in magnitude. The minimum size of BRCA deficient patients to obtain a stable threshold is 200, as shown in our study.
Exploring the value of intraoperative frozen section in the diagnosis and treatment of patients with early-stage ovarian cancer: A retrospective analysis of 421 patients.
Authors: Chen Jinghong , Gong Zhaolin , Zhang Mengpei , Yin Rutie 
Published: June 2022

e17568 Background: Rapid and accurate judgment of the source and nature of tumors is conducive for surgeons to select the appropriate scope and method of surgery, and avoid unnecessary over-treatment or under-treatment. This study aimed to explore the diagnostic and treatment value of intraoperative frozen section pathology in patients with early-stage ovarian cancer (EOC) in the real world. Methods: We retrospectively collected the clinical and pathological data of EOC at West China Second University Hospital between January,2013 and December,2017, which diagnosed as stage ⅠA- IIA EOC according to the International Federation of Gynecology and Obstetrics (FIGO) 2014 standard of Ovarian cancer, fallopian tube cancer and peritoneal cancer. Results: There were totally 421 cases of EOC in the Second West China Hospital of Sichuan University from 2013 to 2017. The average age was 42.9 ± 13.5 years old. There were 395 patients who had finished the comprehensive staging surgeries. Group A consisted of 239 patients (60.5%) who had completed staging operation through only one surgery, while Group B consisted of 156 cases (39.5%) who had completed that through a second-time surgery. The frozen section submission rate of staging operation in the two groups were 99.2% (237/239) and 35.3% (55/156), respectively. Meanwhile, the coincidence rates of frozen and paraffin sections in the two groups were 98.3% (233/237) and 70.9% (39/55). The submission rate and coincidence rate of intraoperative frozen sections in Group A were higher than those in Group B (the submission rate: X2= 199.983, P< 0.05; the coincidence rate: X2= 52.541, P < 0.05). Conclusions: Our results confirm that increasing the submission rate of intraoperative frozen section and improving the accuracy of frozen section attach great importance to the diagnosis and treatment of EOC. Once identified, timely and comprehensive staging surgery can help improve patient outcomes for those who do not take fertility preservation into consideration.[Table: see text]
Interim analysis from a phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer: APGOT-ov4/ OPEB-01.
Authors: LEE Jung-Yun , Kim Jae-Weon , Kim Byoung-Gie , Kim Sang Wun , Kim Hee Seung , Kim Se Ik , Lim Myong Cheol , Choi Chel Hun , Ngoi Natalie , Tan David Shao Peng , Kim Yoo Na 
Published: June 2022

e17579 Background: The optimal treatment of BRCA wild-type patients with platinum-sensitive recurrent (PSR) ovarian cancer remains controversial. This single arm phase 2 study (OPEB-01) evaluated a triple combination regimen with olaparib, bevacizumab, and pembrolizumab as 2nd-line maintenance treatment in BRCA non-mutated, PSR ovarian cancer. Methods: Women with PSR ovarian cancer who had a partial or complete response to their most recent platinum-based regimen were eligible. Patients received olaparib 300mg PO bid daily, bevacizumab 15mg/kg IV q3w, and pembrolizumab 200mg IV q3w until progressive disease or unacceptable toxicity. The primary endpoint of the study was 6-month PFS rate. A simon 2-stage design was utilized. Target accrual was 22 patients in the first stage; 13 or more patients with non-progressive disease at 6 months was required to proceed to second stage. Results: 22 patients were enrolled at the first stage. Median age was 60 years old and most of the patients (90.9%) had high-grade serous carcinoma. Secondary cytoreductive surgery was performed in 6 (27.3%) patients. The objective response rate (ORR) was 68.2% and the disease control rate (DCR) was 90.9%. At the time of data analysis (data cutoff Jan 19 2022), 20 (90.9%) had non-progressive disease at 6 months. No grade 4 adverse events were reported and no treatment related adverse events leading to treatment discontinuation was observed. Additional correlative data regarding homologous recombination deficiency and PD-L1 will be presented at the meeting. Conclusions: OPEB-01 is the first trial to suggest the potential benefit of triple combination maintenance in BRCA wild-type patients. These combinations showed a manageable safety profile. Accrual is ongoing in the second stage. Clinical trial information: NCT4361370.
POSTCare-O: A survivorship care transition for women with ovarian cancer.
Authors: Kvale Elizabeth Ann , Phillips Farya 
Published: June 2022

e17583 Background: The POSTCare survivorship care transition is efficacious as a quality-of-life intervention for patients diagnosed with breast cancer but has not been studied in women with ovarian cancer. Ovarian cancer patients who complete treatment face unprecedented uncertainty regarding survivorship including life expectancy, and the balance of healthcare demands with living well. The routine provision of automated survivorship care plans (SCPs) by advanced practice providers (APPs) is a standardized approach which does not consider the unique needs of ovarian cancer survivors. Aim: To adapt the POSTCare intervention for ovary cancer patients by incorporating a component of concurrent palliative care and tailoring the skills of an existing workforce. Methods: We provided web-based training to APPs from Gyn Oncology programs. Qualitative methods explored the POSTCare protocol, ideas for adapting the intervention, and training preferences. We conducted semi-structured interviews with nurses who completed the POSTCare-O web-based training and utilized components of the POSTCare model in clinical care. The goal was to discover the elements of the model that worked well in their setting, which elements they can utilize routinely to meet the needs of patients, and which elements they find most satisfying. Results: Nine advanced practice providers completed online training and follow up assessment. All participants passed the final competency assessment (role play skills check). Exit interview data revealed four areas where participants reported changes in their own perceptions and skills related to survivorship care that they attributed to the POSTCare-O training program. APPs reported the training increased their competency in palliative care skills and left them better able to support survivors in the face of uncertainty. Specifically, the training; (1) enhanced their communication skills; (2) developed their understanding of survivorship care as more than just surveillance; and (3) demonstrated how to implement patient driven goal setting. Conclusions: POSTCare intervention can serve as a platform for delivery of components of early concurrent palliative care that is acceptable to ovarian cancer patients who remain focused on life-prolonging treatments. POSTCare-O web based training improved APPs appreciation of the scope of survivorship care beyond just surveillance and management of physical effects. This training provided the tools necessary for clinicians to provide whole person care while implementing patient driven survivorship care planning.
Evaluating the utility of ctDNA in detecting residual cancer and predicting recurrence in patients with serous ovarian cancer.
Authors: Akbari Mohammad R. , Zhu Jie Wei , Wong Fabian , Szymiczek Agata , Ene Gabrielle , Zhang Shiyu , May Taymaa , Narod Steven A , Kotsopoulos Joanne 
Published: June 2022

e17588 Background: Ovarian cancer remains the most fatal gynecological malignancy. Patients who have no visible residual disease after surgical resection have a relatively good prognosis. Among these patients, those who later succumb to their cancer are believed to harbour non-detectable cancer cells in the peritoneal cavity after treatment which later lead to recurrence. Analyzing circulating tumour DNA (ctDNA) in the blood may offer a sensitive method to detect occult (non-visible) residual disease after surgery and to predict disease recurrence. We proposed to determine the proportion of ovarian cancer patients with and without visible residual disease documented after surgery who had detectable ctDNA from their primary tumour in their blood and to evaluate if the presence of ctDNA is associated with survival. Methods: We included biological samples and clinical information from 48 women diagnosed with high-grade serous ovarian cancer. Plasma, formalin-fixed paraffin-embedded (FFPE) tumour tissue, and white blood cells were used to extract circulating free DNA (cfDNA), tumour DNA and germline DNA, respectively. The plasma sample was collected after surgery and before initiating chemotherapy. We sequenced DNA samples for a panel of 59 breast and ovarian cancer driver genes. DNA variants in matched germline and tumour DNAs were compared to determine tumour specific variants (TSVs) and cfDNA was searched for TSVs to identify the presence of ctDNA in the plasma. The Kaplan-Meier method was used to estimate overall and recurrence-free survival according to the presence or absence of ctDNA. Results: We found TSVs in 47 patients that were used for detecting ctDNA in their post-surgery plasma. Fifteen (31.9%) of the 47 patients had visible residual disease; of these, all 15 had detectable ctDNA. Among the 31 (68.1%) pateints with no visible residual disease, 24 (77.4%) patients had detectable ctDNA. Of those with no visible residual disease, those patients with detectable ctDNA in post-surgery samples had a higher mortality risk compared to those without detectable ctDNA (HR 2.32; 95% CI: 0.67-8.05), although this difference was not statistically significant (p = 0.18). Conclusions: These findings suggest potential clinical utility in ctDNA to improve upon surgical classification of the residual disease status and a potential predictor of recurrence among women with ovarian cancer. Larger studies are necessary to validate these findings.
Patterns and prevalence of pathogenic germline mutations using multi-gene panel testing in patients with ovarian cancer: The Jordanian Exploratory Cancer Genetics (Jo-ECAG) Ovarian Study.
Authors: Al-Azzam Khansa , Abu-Fares Hala , Abu Sheikha Areej , Abujamous Lama , Alkyam Mais , Bani Hani Hira , Bater Rayan , Heald Brandie , Esplin Edward D. , Abdel-Razeq Hikmat 
Published: June 2022

e17593 Background: Ovarian cancer is one of the most common gynecological malignancies. Because of the absence of effective screening methods, ovarian cancer is usually diagnosed at late stages contributing to high mortality rates. Patients with BRCA1 and BRCA2 pathogenic germline variants (PGVs) harbor elevated risk of developing both ovarian and breast cancer. Identifying PGVs may help optimize management options and improve outcomes. The worldwide prevalence of gene mutations is variable. Multiple series have demonstrated differences in PGVs according to ethnicity and geographic area. Data about prevalence of the aforementioned PGVs among Arab patients with ovarian cancer is not well understood. Methods: Patients with epithelial ovarian, fallopian tube or primary peritoneal carcinomatosis were referred for 20 or 84-multi-gene panel testing (MGPT). All patients had their diagnosis, treatment and follow up at a single cancer center. Following detailed counselling, MGPT was performed at no-cost to all patients at two reference laboratories. Descriptive statistics were performed, groups outcome was determined by two-tailed Fisher’s exact test and unpaired t-test. The study was approved by the Institutional Review Board (IRB) at King Hussein Cancer Center and all patients signed informed consent. Results: During the study period, 152 patients, median age (range): 50 (18-79) years were tested. Two patients had fallopian tube cancer, while all others had epithelial ovarian cancer. The majority (n = 100, 65.8%) had high-grade serous carcinoma, and 106 patients (69.7%) had metastatic disease on presentation. In total, 38 (25.0%) had PGVs while 47 (30.9%) others had variants of uncertain significance (VUS). PGVs were mostly in BRCA1 (n = 21, 13.8%) and in BRCA2 (n = 12, 7.9%), while only 5 (3.3%) had PGVs in non- BRCA1/2 genes ( CHECK2, MUTYH, PMS2, RAD51D, and RB1) . Age (< 50 versus ≥50) at diagnosis, histological tumor subtype, and disease stage had no impact on pathogenic variant rates. However, PGVt rates were significantly higher (60.0%, p = 0.022) among patients with positive family history of ovarian cancer and 40.4% (p = 0.017) among patients with positive family history of breast cancer. The two patients with fallopian tube cancer were both positive for BRCA1 PGVs. Only one patient underwent prophylactic bilateral mastectomies. Conclusions: PGVs in patients with ovarian cancer are common among Arabs and mostly in BRCA1/2 and rates are significantly higher among patients with family history of ovarian or breast cancers.