Somatic genomic landscape of East Asian epithelial ovarian carcinoma and its clinical implications from prospective clinical sequencing: A Korean Gynecologic Oncology Group study (KGOG 3047).

Through the wide adaptation of next-generation sequencing (NGS) technology within clinical practice, molecular profiling of the tumor has been the principal component of personalized treatment. In our study, we have generated a large collection of cancer genomes on East Asian epithelial ovarian carcinoma (EOC) patients and demonstrate the feasibility and utility of NGS platforms to explore the dynamic interrelations of major cancer driver alterations and their impacts on clinical prognosis and management. A total of 652 EOC patients have undergone clinical NGS panels to determine the prevalence of germline and somatic mutations. Notably, TP53 was the most frequently altered event (73%), followed by both BRCA1 and BRCA2 (22% each) and MYC (19%) through pan-EOC analysis. When analyzed based on individual histopathological levels, TP53 mutation was highly dominant in high-grade serous and mucinous histology, whereas mutations in PIK3CA and ARID1A were mostly observed in clear cell carcinoma, and KRAS, BRAF, and CDKN2A mutations were enriched in endometrioid, low-grade serous, and mucinous tumors, respectively. The network-based probabilistic model showed significant co-occurrences of TP53 with BRCA1 and ALK with BRCA2, NOTCH1, and ROS1, whereas mutual exclusivity of TP53 with KRAS and PIK3CA was evident. Furthermore, we utilized machine-learning algorithms to identify molecular correlates that conferred increased sensitivity to platinum and olaparib treatments including somatic mutations in BRCA1, ATM, and MYC. Conversely, patients with ALK mutation were considerably resistant to both treatment modalities. Collectively, our results demonstrate the clinical feasibility of prospective genetic sequencing to facilitate personalized treatment opportunities for patients with EOC.

Comparative performance of various human papillomavirus assays available in Korea for detecting cervical intraepithelial neoplasia.

AIM: The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. METHODS: Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. RESULTS: A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9-44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p < 0.05) compared to Cobas 4800, in aspect of high-risk HPV positive, Anyplex II HPV28 showed increased sensitivity (96.9%, p < 0.05). CONCLUSION: The performance of the HPV genotype test that were commonly used in Korea was concordant with Cobas HPV test. Further studies are needed to evaluate the safety, efficiency, and cost-effectiveness of the various commercially available domestic HPV assays.

Discrepancy between Cytology and Histology in Cervical Cancer Screening: a Multicenter Retrospective Study (KGOG 1040).

BACKGROUND: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells. Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. METHODS: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. RESULTS: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7 (19-88) years and mean BMI was 22.5 (16.9-34.1) kg/m². The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475-3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367-0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385-2.469). CONCLUSION: Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Antitumor Effects of Selenium.

Functions of selenium are diverse as antioxidant, anti-inflammation, increased immunity, reduced cancer incidence, blocking tumor invasion and metastasis, and further clinical application as treatment with radiation and chemotherapy. These functions of selenium are mostly related to oxidation and reduction mechanisms of selenium metabolites. Hydrogen selenide from selenite, and methylselenol (MSeH) from Se-methylselenocyteine (MSeC) and methylseleninicacid (MSeA) are the most reactive metabolites produced reactive oxygen species (ROS); furthermore, these metabolites may involve in oxidizing sulfhydryl groups, including glutathione. Selenite also reacted with glutathione and produces hydrogen selenide via selenodiglutathione (SeDG), which induces cytotoxicity as cell apoptosis, ROS production, DNA damage, and adenosine-methionine methylation in the cellular nucleus. However, a more pronounced effect was shown in the subsequent treatment of sodium selenite with chemotherapy and radiation therapy. High doses of sodium selenite were effective to increase radiation therapy and chemotherapy, and further to reduce radiation side effects and drug resistance. In our study, advanced cancer patients can tolerate until 5000 µg of sodium selenite in combination with radiation and chemotherapy since the half-life of sodium selenite may be relatively short, and, further, selenium may accumulates more in cancer cells than that of normal cells, which may be toxic to the cancer cells. Further clinical studies of high amount sodium selenite are required to treat advanced cancer patients.

Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708).

BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer. METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes. RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively). CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.

Real-world effectiveness of bevacizumab based on AURELIA in platinum-resistant recurrent ovarian cancer (REBECA): A Korean Gynecologic Oncology Group study (KGOG 3041).

PURPOSE: To evaluate the effectiveness of bevacizumab with single-agent chemotherapy for platinum-resistant ovarian cancer in a real-world setting. PATIENTS AND METHODS: We enrolled recurrent platinum-resistant ovarian cancer patients from 27 institutions. All had received bevacizumab with single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin (PLD), topotecan) between 2015 and 2017 for second- or third-line chemotherapy in routine clinical practice. The primary endpoint was progression-free survival (PFS) and safety. Secondary endpoints included the objective response rate (ORR), PFS2, overall survival, duration of chemotherapy, and reasons for discontinuing chemotherapy. RESULTS: Of 391 patients, 259 (66.2%) received bevacizumab with PLD, 94 (24.0%) with topotecan, and 38 (9.7%) with weekly paclitaxel. The median PFS was 6.1 months with all forms of bevacizumab-containing therapy. Although the cohort with weekly paclitaxel had a better PFS than the PLD cohort (P = 0.028), this finding was not found in patients with a previous platinum-free interval of less than three months. The median duration of therapy was five cycles (range, one to 20 cycles), and 29 patients (7.4%) discontinued treatment because of adverse events from bevacizumab-containing regimens. The PLD cohort had fewer grade ≥ 3 adverse events than the other regimens (PLD, 35.8%; weekly paclitaxel, 52.6%; topotecan, 51.1%; P = 0.012), especially events of hematologic toxicities. CONCLUSION: In Korean ovarian cancer patients, the safety and effectiveness of chemotherapy with bevacizumab in a real-world setting was consistent with the results from a randomized controlled study. The effectiveness and toxicity profiles varied among the chemotherapy regimens, and this finding should be considered in practice. CLINICAL TRIALS REGISTRATION: NCT03367182.

Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer.

OBJECTIVE: The aim of the present study was to investigate unclassified variants (UVs) in BRCA1 and 2 of Korean patients with ovarian cancer. METHODS: We retrospectively analyzed 138 patients diagnosed with ovarian/fallopian tubal/peritoneal cancer between January 2013 and January 2016, whose BRCA genetic test results and clinical characteristics were available for review. Patient peripheral blood lymphocyte specimens were assessed for BRCA mutations and variations by direct sequencing. Identified UVs were classified according to several algorithms. RESULTS: The results of genetic testing revealed 31 (22.5%, 31/138) pathogenic BRCA mutations (24 BRCA1, 7 BRCA2 mutations). The BRCA1 c.390C>A mutation was observed in 4 patients (12.9%, 4/31). Thirty-four (24.6%, 34/138) BRCA UVs were identified in 33 patients. Of these, the BRCA1 c.4883T>C and BRCA2 c.8187G>T variants were each detected in 4 patients (4/34, 11.8%). According to the used algorithms and cosegregation test, the BRCA1 c.5339T>C and BRCA2 c.8437_8439delGGA variants were both predicted to be likely pathogenic. CONCLUSIONS: The 2 identified likely pathogenic UVs require further verification with clinical evidence. Clarifying the clinical significance of UVs is an increasingly important step for cancer treatment in the current era of precision medicine.

Practice Patterns of Hereditary Ovarian Cancer Management in Korea.

OBJECTIVE: This study aims to evaluate practice patterns for managing hereditary ovarian cancer among Korean gynecologic oncologic physicians. METHODS: Members of the Korean Society of Gynecologic Oncology participated in the inaugural Hereditary Gynecologic Cancer Symposium or were invited to this survey by e-mail from January to February 2016. The survey was conducted using a self-administered questionnaire. RESULTS: Most physicians (66.7%, 36/54) responded to draw a pedigree of patients with a family history. The rate of genetic test recommendations for patients at risk for ovarian cancer was high (96.3%, 52/54). Physicians tended to select appropriate candidates for the genetic test. Of the respondents, genetic counseling was commonly performed before the genetic test (76.6%, 36/47) and provided by the specialist consultant(s) (78.7%, 37/47) or the physician alone (12.8%, 6/47). Participants showed mature response to risk management for the BRCA carriers: at least annual gynecologic surveillance (89.4%, 42/47), recommendation for chemoprevention (76.6%, 36/47), and advice for risk-reducing salpingo-oophorectomy (85.1%, 40/47). Risk-reducing salpingectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy was considered to recommend in most of respondents (91.5%, 43/47). CONCLUSIONS: Gynecologic oncologic physicians in Korea had high awareness to genetic risk assessment, candidate selection to genetic test, and risk-reducing strategies for the management of hereditary ovarian cancer.

Comparison of the efficacy of Poly(I:C) immunization with live vaccine and formalin-killed vaccine against viral hemorrhagic septicemia virus (VHSV) in olive flounder (Paralichthys olivaceus).

Viral hemorrhagic septicemia (VHS) in olive flounder, Paralichthys olivaceus, causes significant economic loss for the flounder aquaculture industry in Korea. In this study, the immunogenicity of Poly(I:C) immunization with a live vaccine against the VHS virus (VHSV) was compared with that of a formalin-treated vaccine in the olive flounder. In vaccine trial I, fish pre-injected with Poly(I:C) were highly protected from VHSV infection 2 d later (survival rate: 96%) and the surviving fish (Poly(I:C)-VHSV group) showed a 100% survival rate against VHSV re-challenge. Mortality in fish pre-injected with diethylpyrocarbonate-treated water followed by injection with formalin-treated VHSV was only 2% (1 of 50 fish), whereas survivors (DEPC-FT VHSV group) showed an 80% survival rate. In vaccine trial II, 100% survival was observed in all Poly(I:C) vaccination groups-Poly(I:C)-VHSV 6, Poly(I:C)-VHSV 5, and Poly(I:C)-VHSV 4. In contrast, the survival rates of the groups administered the formalin-treated VHSV at a dose of 10(6), 10(5), and 10(4) TCID50 100 µL(-1) fish(-1) (DEPC-FT VHSV 6, DEPC-FT VHSV 5, and DEPC-FT VHSV 4) were only 8%, 12%, and 12%, respectively. The differences in the survival rates of the formalin-treated vaccine groups in trial I and trial II were attributed to the difference in the formalin-treatment period: the formalin-treated VHSV administered in trial I was not completely inactivated and worked as a live vaccine, which explains the 80% survival rate against VHSV challenge. Specific antibodies against VHSV were detected in sera from all vaccinated survivors, except the DEPC-VHSV 4 group. Furthermore, the specific antibody titers of fish vaccinated with the live and dead VHSV vaccines were similar, but the protective effects of the live and dead vaccines varied considerably. Our findings show that Poly(I:C) immunization with the live vaccine offers better protection than the formalin-treated vaccine against VHS in olive flounder and revealed that antibody levels are not a reliable indicator of the protective effect of the vaccine against the pathogen. In the future, elements of T cell immunity may be used as a means of evaluating the protective efficacy of a vaccine against VHSV instead of ELISA.

Placental Site Trophoblastic Tumors: Analysis of the Clinicopathologic Characteristics of 20 Cases in Korea.

OBJECTIVES: The aim of this study was to evaluate the clinicopathologic features of placental site trophoblastic tumors (PSTTs) in Korea. METHODS/MATERIALS: Twenty patients given a diagnosis of PSTT in Korea (1990-2013) were evaluated retrospectively, including 14 patients identified through a literature review and 6 patients identified through a medical chart review of a single institution. The analysis included patient age, antecedent pregnancies, time since antecedent pregnancy, presenting symptoms, serum ß-human chorionic gonadotropin level, International Federation of Gynecology and Obstetrics stage, treatment, outcome, and follow-up. RESULTS: The mean age of the 20 patients was 32 years (range, 25-53 years). The antecedent pregnancies included 8 term pregnancies, 8 abortions, and 2 molar pregnancies. The time since the antecedent pregnancy was less than 1 year in 16 patients (80%). Nineteen patients (95%) presented with abnormal vaginal spotting or amenorrhea. Serum ß-human chorionic gonadotropin levels ranged from normal to 13,480 mIU/mL, although most patients (80%) had a level less than 1000 mIU/mL. Seventeen patients (85%) presented with stage I disease. Ten patients (50%) underwent hysterectomy, and 14 patients (70%) were treated with chemotherapy with or without hysterectomy. In 11 evaluated patients, the median mitotic count index was 3.4 (0.4-10) per 10 high-power fields. The median follow-up time was 17 months (range, 1-68 months). There was no recurrence or death from disease. CONCLUSIONS: Korean patients with PSTT often have early-stage disease, which has a favorable prognosis even with fertility-preserving therapy. However, international studies are necessary to determine the optimal treatment and prognostic factors.

Microscopic Omental Metastasis in Clinical Stage I Endometrial Cancer: A Meta-analysis.

BACKGROUND: A patient with early-stage endometrial cancer may possibly have microscopic metastasis in the omentum, which is associated with a poor prognosis. The purpose of this study was to identify risk factors for microscopic omental metastasis in patients with clinical stage I endometrial cancer to establish the indications for selective omentectomy. METHODS: We searched the PubMed, EMBASE, and Cochrane Library databases for published studies from inception to August 2014, using terms such as 'endometrial cancer' or 'uterine cancer' for disease, 'omentectomy' or 'omental biopsy' for intervention, and 'metastasis' for outcome. Two reviewers independently identified the studies that matched the selection criteria. We calculated the pooled risk ratios (RRs) with 95 % confidence intervals (CI) of each surgicopathologic finding for microscopic omental metastases in clinical stage I endometrial cancer. We also calculated the prevalence of microscopic omental metastases. RESULTS: Among 1163 patients from ten studies, 22 cases (1.9 %) of microscopic omental metastases were found, which accounted for 26.5 % of all omental metastases. Positive lymph nodes (RR 8.71, 95 % CI 1.38-54.95), adnexal metastases (RR 16.76, 95 % CI 2.60-107.97), and appendiceal implants (RR 161.67, 95 % CI 5.16-5061.03) were highly associated with microscopic omental metastases. CONCLUSIONS: Microscopic omental metastases were not negligible in patients with clinical stage I endometrial cancer. Those with a risk factor of microscopic omental metastases were recommended for selective omentectomy.

Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations.

OBJECTIVES: To investigate and analyze the BRCA mutations in Korean ovarian cancer patients with or without family history and to find founder mutations in this group. METHODS/MATERIALS: One hundred two patients who underwent a staging operation for pathologically proven epithelial cancer between January 2013 and December 2014 were enrolled. Thirty-two patients declined to analyze BRCA1/2 gene alterations after genetic counseling and pedigree analysis. Lymphocyte specimens from peripheral blood were assessed for BRCA1/2 by direct sequencing. RESULTS: BRCA genetic test results of 70 patients were available. Eighteen BRCA1/2 mutations and 17 unclassified variations (UVs) were found. Five of the BRCA1/2 mutations and 4 of the UVs were not reported in the Breast Cancer Information Core database. One BRCA2 UV (8665_8667delGGA) was strongly suspicious to be a deleterious mutation. BRCA1/2 mutations were identified in 11 (61.1%) of 18 patients with a family history and in 7 (13.5%) of 52 patients without a family history.Candidates for founder mutations in Korean ovarian cancer patients were assessed among 39 BRCA1/2 mutations from the present study and from literature reviews. The analysis showed that 1041_1043delAGCinsT (n = 4; 10.2%) and 3746insA (n = 4; 10.2%) were possible BRCA1 founder mutations. Only one of the BRCA2 mutations (5804_5807delTTAA) was repeated twice (n = 2; 5.1%). CONCLUSIONS: The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.

Photodynamic therapy for premalignant lesions of the vulva and vagina: A long-term follow-up study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate responses to photodynamic therapy (PDT) and its long-term efficacy in preserving normal anatomy and function in women with premalignant lesions of the lower genital tract. STUDY DESIGN/MATERIALS AND METHODS: Fifteen patients received PDT for vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), or vulvar Paget's disease between January 2003 and December 2013. Patients underwent colposcopy and/or vulvoscopy for assessment of lesions. Surface photoillumination with a 630-nm red laser light was applied to the lesions 48 hours after intravenous injection of 2 mg/kg photosensitizer (PSZ; Photogem®). The light dose to the lesions was 150 J/cm2 . RESULTS: The median age of the 15 patients (VIN II: 3, VIN III: 4, VAIN II: 2, VAIN III: 3, Paget's disease: 3) was 42.3 years. The complete response (CR) rate was 80% (12/15) at the 3-month follow-up and 71.4% (10/14) at the 1-year follow-up. There were two cases of persistent disease at the 3-month follow-up. One patient with persistent disease underwent partial vulvectomy three times for repetitive recurrence, and the other received secondary PDT with topical 5-aminolevulinic acid (5-ALA) and subsequently showed no evidence of disease (NED). Another patient achieved 90% remission through a combination of additional alternative treatments after showing partial response (PR). In two cases of CR, recurrence was observed at the 1-year follow-up. Regarding adverse events, photosensitivity reactions such as facial edema and urticaria occurred in 13.3% (2/15) and perineal pain occurred in one patient. CONCLUSIONS: PDT may be an effective alternative treatment for premalignant lesions of the female lower genital tract to preserve normal anatomy and sexual function without therapeutic impairment. Lasers Surg. Med. 47:566-570, 2015. © 2015 Wiley Periodicals, Inc.

Dysregulated microRNA expression in adenocarcinoma of the uterine cervix: clinical impact of miR-363-3p.

OBJECTIVE: Adenocarcinoma (ACA) of the uterine cervix is increasing in incidence and currently accounts for approximately 20% of all cervical malignancies. MicroRNAs (miRNAs) have been investigated as potential biomarkers of cervical cancer; however, their role in ACA remains unknown. Here, we characterized miRNA expression profiles and investigated miRNAs as diagnostic and prognostic factors in ACA. METHODS: Evaluation of genome-wide miRNA expression profiles in ACA by microarray led to the identification of ten candidate miRNAs, whose expression patterns were validated by qRT-PCR in 45 ACA, 10 normal control, and 15 squamous cell carcinoma samples. The association between miRNA expression and prognosis was analyzed in patients with ACA. RESULTS: Microarray analysis identified 86 miRNAs that were dysregulated more than 2.0-fold (p<0.05) in ACA relative to normal tissues of the uterine cervix. Five most over- and underexpressed miRNAs were selected respectively and their expression patterns were confirmed in the validation set. MiR-135b, miR-192, and miR194 were overexpressed in ACA, and miR-363-3p, miR-195 and miR-199b were significantly associated with conventional prognostic factors. Overexpression of miR-363-3p by more than 2.5-fold relative to the normal control was a strong predictor of favorable prognosis (hazard ratio, 0.1; 95% confidence interval, 0.009-0.779) after adjusting for confounders. CONCLUSIONS: MiR-135b, miR-192, and miR-194 are altered in uterine cervical ACA, and miR-363-3p is an independent favorable prognostic factor in ACA. These miRNAs could be of value as biomarkers for the diagnosis and prognosis of ACA.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology consensus statement.

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.

Fertility preservation via photodynamic therapy in young patients with early-stage uterine endometrial cancer: a long-term follow-up study.

OBJECTIVE: We evaluated the effectiveness of photodynamic therapy (PDT) as a conservative fertility-sparing treatment in young women with early-stage endometrial cancer. METHODS: We reviewed the medical records of patients with endometrial cancer who had been treated with PDT. Of the patients with endometrioid adenocarcinoma, we included those younger than 35 years and in whom the lesion was confined to the endometrium. Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine endometrial cavity and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. Complete response was pathologically defined as the complete disappearance of adenocarcinoma or hyperplastic tissue. RESULTS: Sixteen patients were included in the study. Their mean age was 30.7 years, and the mean body mass index was 24.6 kg/m(2). The mean follow-up period was 78 months. Photodynamic therapy was used in 11 patients as primary treatment and in 5 patients as secondary treatment for recurrence after primary hormonal therapy. Complete remission was observed in 12 (75%) of the 16 patients. Of these 12 patients, 4 experienced recurrence (33%). Two of the 4 patients who experienced recurrence showed complete remission after the next course of PDT, and 1 of the 4 nonresponders also showed complete remission after the second course of PDT. The final response rate was therefore 68%. Of the 7 women who attempted to get pregnant, 4 had 7 successful pregnancies (57%, 4/7), resulting in 6 live births. No tumor-related deaths or PDT-related severe adverse effects were noted. CONCLUSIONS: Photodynamic therapy can be an effective conservative treatment method for fertility sparing in young patients with early-stage endometrial adenocarcinoma.

Photodynamic therapy for management of cervical intraepithelial neoplasia II and III in young patients and obstetric outcomes.

OBJECTIVE: To evaluate the response and efficacy of photodynamic therapy (PDT) with or without loop electrosurgical excision procedure (LEEP)/conization (Cone) to preserve fertility in young patients with cervical intraepithelial neoplasia (CIN) II and III. METHODS: We reviewed the medical records of patients with CIN who had been treated by PDT. Among a total of 73 patients who received PDT for CIN II/III between September 2000 and August 2011, 59 patients aged 40 or younger and who wished to preserve fertility were included. Patients were divided into four groups: group (I) only PDT without LEEP (n = 13), group (II) PDT combined with LEEP/Cone (n = 15), group (III) PDT due to positive LEEP/Cone margin (n = 25), group (IV) PDT for recurrent CIN after LEEP/Cone (n = 6). Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine cervix and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. RESULTS: The median age of the 59 patients (CIN 2: 4, CIN 3: 22, carcinoma in situ: 31, adenocarcinoma in situ: 2) was 30.4 years. Twenty-two patients were unmarried and 38 were nulliparous. The complete remission (CR) rate was 98.1% (52/53) at 1 year follow-up except six patients followed up loss. The remaining one had recurred at 1 year after PDT, and one residual case at 3 months follow-up was regarded as CR showing NED after secondary PDT. Human papilloma virus (HPV) typing was performed. Before treatment HPV infection rate was 96.3% (52/54). HPV DNA could be no longer detected in 89.8% (44/49) and 87.0% (40/46) at 3 and 12 months after PDT. Among 29 patients who tried to be pregnant, 18 patients achieved 25 pregnancies (6 abortions, 1 ectopic, 1 preterm, 15 term, and 2 ongoing pregnancies.) There has been no fetal loss due to incompetent internal os of cervix. For adverse events, photosensitivity occurred in 13.6% (8/59) and cervical stenosis occurred in one patient. CONCLUSIONS: PDT combined with or without LEEP/Cone may be a potential alternative for effective conservative treatment of CIN in young patients who wish to preserve fertility.

Peritoneal and Nodal Gliomatosis Mimicking Metastasis on FDG PET/CT in a Patient With Ovarian Immature Teratoma.

ABSTRACT: Peritoneal and nodal gliomatosis is a rare disease condition characterized by implants of mature glial tissue on the peritoneum and lymph nodes. It is typically associated with teratoma and has no adverse effect on prognosis. We present a case of 22-year-old woman who underwent FDG PET/CT for the staging of ovarian immature teratoma. PET/CT revealed mildly increased FDG uptake in the peritoneal cavity and increased FDG uptake in the internal mammary and cardiophrenic angle lymph nodes, which were histopathologically diagnosed as peritoneal and nodal gliomatosis. This case suggests that PET/CT findings of peritoneal and nodal gliomatosis could mimic metastasis.

Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies.

PURPOSE: We investigated the treatment outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with recurrent gynecologic cancers. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 20 patients who underwent rechallenge with PD-1 inhibitors for recurrent gynecologic cancers at two tertiary centers between January 2018 and September 2022. RESULTS: The median age of the patients was 56 years (range, 35-79). Seven (35%), 1 (5%), 11 (55%), and 1 (5%) patients presented with cervical, vulvar, ovarian, and endometrial cancers, respectively. Sixteen (80%) patients received pembrolizumab and 4 (20%) received nivolumab at first treatment. Eight (40%) and 12 (60%) patients received pembrolizumab and nivolumab, respectively, at second treatment. At initial ICI treatment, 1 (5%) and 4 (20%) cases of a complete response (CR) and a partial response (PR) were observed, respectively, with a median progression-free survival (PFS) of 2.8 months (range, 1.4-49.6). Reasons for first ICI discontinuation were disease progression (n=16), severe adverse events (AEs) (n=2), and treatment withdrawal (n=2). During second ICI treatment, 1 (5%) patient achieved CR, 2 (10%) showed PR, and 5 (25%) experienced stable disease. The median PFS to second ICI was 1.8 months (range, 0.4-10.4). The median overall survival was 21.3 months (range, 10.1-52.7). Neither patient who discontinued ICI treatment due to AEs experienced AE relapse during second ICI treatment. CONCLUSION: These results suggest that responses to ICI rechallenge are not as intolerable as responses to previous ICI. Clinicians should carefully consider rechallenge with PD-1 inhibitors outside of clinical trials until there are sufficient data to routinely support this practice.

Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy.

Importance: Hyperthermic intraperitoneal chemotherapy (HIPEC) followed by interval cytoreductive surgery (ICS) has shown survival benefits for patients with advanced-stage ovarian cancer. However, there is still a lack of consensus regarding the integration of HIPEC into clinical practice. Objective: To evaluate the safety and effectiveness of ICS with HIPEC compared with ICS alone in clinical practice for patients with advanced-stage ovarian cancer. Design, Setting, and Participants: This prospective, multicenter, comparative effectiveness cohort study enrolled 205 patients with stage III or IV ovarian cancer who had received at least 3 cycles of neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC at 7 Korean Gynecologic Oncology Group institutions between September 1, 2017, and April 22, 2022. Nine patients were excluded because they did not meet the inclusion criteria. Exposures: Neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC. Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Overall survival (OS) and the safety profile were the key secondary end points. Results: This study included 196 patients (median age, 58.0 years [range, 38-82 years]), of whom 109 underwent ICS with HIPEC and 87 underwent ICS without HIPEC. The median duration of follow-up was 28.2 months (range, 3.5-58.6 months). Disease recurrence occurred in 128 patients (65.3%), and 30 patients (15.3%) died. Interval cytoreductive surgery with HIPEC was associated with a significant improvement in median PFS compared with ICS without HIPEC (22.9 months [95% CI, 3.5-58.6 months] vs 14.2 months [95% CI, 4.0-56.2 months]; P = .005) and median OS (not reached [95% CI, 3.5 months to not reached] vs 53.0 [95% CI, 4.6-56.2 months]; P = .002). The frequency of grade 3 or 4 postoperative complications was similar in both groups (ICS with HIPEC, 3 of 109 [2.8%] vs ICS without HIPEC, 3 of 87 [3.4%]; P > .99). Among patients with recurrence, the frequency of peritoneal recurrence was lower in the ICS with HIPEC group than in the ICS without HIPEC group (21 of 64 [32.8%] vs 41 of 64 [64.1%]; P = .001). Conclusions and Relevance: This study suggests that ICS in conjunction with HIPEC was associated with longer PFS and OS than ICS without HIPEC for patients with advanced-stage ovarian cancer and was not associated with higher rates of postoperative complications. The lower rate of peritoneal recurrence after HIPEC may be associated with improved OS.