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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.
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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.
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Objective@#To investigate the therapeutic efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) as consolidation treatment after completing first-line treatment in patients with advanced ovarian cancer. @*Methods@#A retrospective chart review was conducted on patients treated at the Comprehensive Gynecologic Cancer Center between January 2014 and 2019. Based on the inclusion criteria, 24 eligible patients who received HIPEC (paclitaxel 175 mg/m2, for 90 minutes, at 42°C) (HIPEC group) as consolidation treatment after terminating the adjuvant chemotherapy were identified. Another 24 patients who met the inclusion criteria and did not receive HIPEC were matched, representing the non-HIPEC group. Disease-free survival (DFS) and overall survival (OS) were examined between the two groups. @*Results@#The median DFS was 28.7 and 24.2 months in the HIPEC and non-HIPEC groups, respectively (P=0.688). The 3-year DFS rates in the HIPEC and non-HPEC groups were 39.5% and 32.6%, respectively. However, the median OS was not determined. The 5-year OS rates in the HIPEC and non-HIPEC groups were 86.2% and 81.3%, respectively (P=0.850). One patient developed grade 3 neutropenia. Other patients experienced mild adverse events after HIPEC. @*Conclusion@#This study suggests that consolidation HIPEC could not support the survival benefit after completing the first-line treatment for patients with advanced ovarian cancer, although no severe specific safety issues were found. Therefore, randomized trials evaluating consolidation HIPEC for the management of ovarian cancer are warranted.
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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.
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In 2020 series, we summarized the major clinical research advances in gynecologic oncology with providing representative figures of the most influential study for 1 of each 3 gynecologic cancers: cervix, ovary, and uterine corpus. Review for cervical cancer covered targeted agents and immune checkpoint inhibitors, adjuvant radiation therapy or concurrent/sequential chemoradiation therapy after radical hysterectomy in early cervical cancer, radical surgery in early cervical cancer; and prevention and screening. Ovarian cancer research included studies of various combinations of poly (ADP-ribose) polymerase inhibitors with chemotherapy, immune checkpoint inhibitors, and/or vascular endothelial growth factor inhibitors according to the clinical setting. For uterine corpus cancer, molecular classification upon which the decision of adjuvant treatments might be based, World Health Organization recommendation of 2-tier grading system (low grade vs. high grade), sentinel lymph node assessment and ovarian preservation in clinically early-stage endometrial cancer were reviewed. Molecular targeted agents including immune checkpoint inhibitors which showed promising anti-tumor activities in advanced/recurrent endometrial cancer were also included in this review.
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Objective@#To compare survival outcomes between bevacizumab (BEV) and olaparib (OLA) maintenance therapy in BRCA-mutated, platinum-sensitive relapsed (PSR) high-grade serous ovarian carcinoma (HGSOC). @*Methods@#From 10 institutions, we identified HGSOC patients with germline and/or somatic BRCA1/2 mutations, who experienced platinum-sensitive recurrence between 2013 and 2019, and received second-line platinum-based chemotherapy. Patients were divided into BEV (n=29), OLA (n=83), and non-BEVon-OLA users (n=36). The OLA and non-BEVon-OLA users were grouped as the OLA intent group. We conducted 1:2 nearest neighbor-matching between the BEV and OLA intent groups, setting the proportion of OLA users in the OLA intent group from 65% to 100% at 5% intervals, and compared survival outcomes among the matched groups. @*Results@#Overall, OLA users showed significantly better progression-free survival (PFS) than BEV users (median, 23.8 vs. 17.4 months; p=0.004). Before matching, PFS improved in the OLA intent group but marginal statistical significance (p=0.057). After matching, multivariate analyses adjusting confounders identified intention-to-treat OLA as an independent favorable prognostic factor for PFS in the OLA 65P (adjusted hazard ratio [aHR]=0.505; 95% confidence interval [CI]=0.280−0.911; p=0.023) to OLA 100P (aHR=0.348; 95% CI=0.184−0.658; p=0.001) datasets. The aHR of intention-to-treat OLA for recurrence decreased with increasing proportions of OLA users. No differences in overall survival were observed between the BEV and OLA intent groups, and between the BEV and OLA users. @*Conclusion@#Compared to BEV, intention-to-treat OLA and actual use of OLA maintenance therapy were significantly associated with decreased disease recurrence risk in patients with BRCA-mutated, PSR HGSOC.
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Objective@#To investigate the therapeutic efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) as consolidation treatment after completing first-line treatment in patients with advanced ovarian cancer. @*Methods@#A retrospective chart review was conducted on patients treated at the Comprehensive Gynecologic Cancer Center between January 2014 and 2019. Based on the inclusion criteria, 24 eligible patients who received HIPEC (paclitaxel 175 mg/m2, for 90 minutes, at 42°C) (HIPEC group) as consolidation treatment after terminating the adjuvant chemotherapy were identified. Another 24 patients who met the inclusion criteria and did not receive HIPEC were matched, representing the non-HIPEC group. Disease-free survival (DFS) and overall survival (OS) were examined between the two groups. @*Results@#The median DFS was 28.7 and 24.2 months in the HIPEC and non-HIPEC groups, respectively (P=0.688). The 3-year DFS rates in the HIPEC and non-HPEC groups were 39.5% and 32.6%, respectively. However, the median OS was not determined. The 5-year OS rates in the HIPEC and non-HIPEC groups were 86.2% and 81.3%, respectively (P=0.850). One patient developed grade 3 neutropenia. Other patients experienced mild adverse events after HIPEC. @*Conclusion@#This study suggests that consolidation HIPEC could not support the survival benefit after completing the first-line treatment for patients with advanced ovarian cancer, although no severe specific safety issues were found. Therefore, randomized trials evaluating consolidation HIPEC for the management of ovarian cancer are warranted.
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Purpose@#We evaluated the efficacy and safety of pembrolizumab in patients with recurrent gynecologic cancers in real-world practice. @*Materials and Methods@#We conducted a retrospective, single-institution study of patients with recurrent gynecologic malignancies treated with pembrolizumab. The primary endpoints were the objective response rate (ORR) and safety. @*Results@#Thirty-one patients treated with pembrolizumab were included. The primary disease sites were the uterine cervix (n=18), ovaries (n=8), and uterine corpus (n=5). Fifteen of the 31 patients (48%) had an Eastern Cooperative Oncology Group performance status of ≥2. The median number of prior chemotherapy lines was 2 (range, 1–6), and 14 of 31 patients (45%) had received ≥ 3 prior lines of chemotherapy. The overall ORR was 22.6%: specifically, 22.3% (4 of 18 patients), 12.5% (1 of 8 patients), and 40% (2 of 5 patients) for cervical, ovarian, and endometrial cancers, respectively. During a median follow-up of 4.7 months (range, 0.2–35.3), the median time to response was 1.9 months (range, 1.4–5.7). The median duration of response was not reached (range, 8.8-not reached).The median progression-free survival was 2.5 months (95% confidence interval, 1.7-not reached). Adverse events occurred in 20 patients (64.5%), and only 3 (9.7%) were grade ≥3. There was one case of suspicious treatment-related mortality, apart from which most adverse events were manageable. @*Conclusion@#In real-world practice, pembrolizumab was feasible and effective in heavily treated recurrent gynecologic cancer patients with poor performance status who may not be eligible for enrollment in clinical trials.
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Purpose@#In this study, we investigated the frequencies of mutations in DNA damage repair genesincluding BRCA1, BRCA2, homologous recombination genes and TP53 gene in ovarian highgradeserous carcinoma, alongside those of germline and somatic BRCA mutations, withthe aim of improving the identification of patients suitable for treatment with poly(ADPribose)polymerase inhibitors. @*Materials and Methods@#Tissue samples from 77 Korean patients with ovarian high-grade serous carcinoma weresubjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repairgenes and TP53 gene and their relationships with patient survival were examined. Additionally,we analyzed BRCA germline variants in blood samples from 47 of the patients forcomparison. @*Results@#BRCA1, BRCA2, and TP53 mutations were detected in 28.6%, 5.2%, and 80.5% of the 77patients, respectively. Alterations in RAD50, ATR, MSH6, MSH2, and FANCA were also identified.At least one mutation in a DNA damage repair gene was detected in 40.3% of patients(31/77). Germline and somatic BRCA mutations were found in 20 of 47 patients (42.6%),and four patients had only somatic mutations without germline mutations (8.5%, 4/47).Patients with DNA damage repair gene alterations with or without TP53mutation, exhibitedbetter disease-free survival than those with TP53 mutation alone. @*Conclusion@#DNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma,with somatic BRCAmutations in the absence of germline mutation in 8.5%. Somaticvariant examination, along with germline testing of DNA damage repair genes, has potentialto detect additional candidates for PARP inhibitor treatment.
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No abstract available.
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Genes Supressores de Tumor , Proteína BRCA2 , Proteína BRCA1 , Neoplasias Ovarianas , Neoplasias da MamaRESUMO
The original article contained errors.
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OBJECTIVE: The aim of the present study was to assess the frequency of germline mutations in patients with peritoneal carcinoma (PC) or the fallopian tube carcinoma (FTC), using a multi-gene panel. METHODS: Twenty-six patients diagnosed with either PC or FTC between January 2013 and December 2016 were recruited consecutively. Germline DNA was sequenced using a 6-gene next generation sequencing (NGS) panel following genetic counseling. Surgico-medical information was obtained from hospital records. Genetic variations were detected using the panel and were cross-validated by Sanger direct sequencing. RESULTS: Germline BRCA1/2 mutations were identified in 6 patients (23.1%). Four were detected in patients with PC and 2 were in FTC patients. No mutations were detected in TP53, PTEN, CDH1, or PALB2. We identified 11 variant of uncertain significance (VUS) in 9 patients; 2 in BRCA1, 3 in BRCA2, 2 in TP53, and 4 in CDH1. We also detected a CDH1 c.2164+16->A VUS in 3 patients. CONCLUSION: The prevalence of germline BRCA1/2 mutations in patients with PC or FTC is comparable to that of BRCA1/2 mutations in epithelial ovarian cancer patients.
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Feminino , Humanos , DNA , Neoplasias das Tubas Uterinas , Tubas Uterinas , Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Variação Genética , Mutação em Linhagem Germinativa , Registros Hospitalares , Neoplasias Ovarianas , Neoplasias Peritoneais , Peritônio , PrevalênciaRESUMO
OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of minimal deviation adenocarcinoma (MDA) and to analyze its prognostic factors. METHODS: We retrospectively analyzed the medical records of 17 patients who were diagnosed with MDA at a single institution between January 2005 and December 2015. RESULTS: The median age of the patients was 47.7 years (33–75 years). MDA was diagnosed in 7 patients (41.2%) before performing definitive surgery. Stage IB disease was diagnosed in 12 patients (70.6%) and advanced stage disease (stage II: 3, stage III: 2) in 5. MDA was incidentally diagnosed following hysterectomy for benign conditions in 6 patients. Adjuvant therapy was administered to 13 patients (76.5%). During median follow-up over 33.6 months (7–99 months), 11 patients (64.7%) showed no evidence of disease, 6 (35.3%) showed persistent or recurrent disease and 5 died of the disease. Peutz-Jeghers syndrome was not suspected in any patient, and no mutation was detected in the 3 patients who underwent genetic testing. Univariate analysis showed that advanced stage disease (P=0.016) and lymphovascular space invasion (P=0.002) demonstrated a statistically significant association with poor overall survival (OS) rates. Advanced stage disease continued to show a significant association with poor OS rates (hazard ratio, 2.92; 95% confidence interval, 1.097–7.746; P=0.032) even after multivariate analysis. CONCLUSION: Early diagnosis is important to manage MDA. Clinicians should consider MDA among the differential diagnoses in patients with a suspicious clinical presentation even with negative cervical screening tests.
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Feminino , Humanos , Adenocarcinoma , Colo do Útero , Diagnóstico Diferencial , Diagnóstico Precoce , Seguimentos , Testes Genéticos , Histerectomia , Programas de Rastreamento , Prontuários Médicos , Análise Multivariada , Síndrome de Peutz-Jeghers , Estudos Retrospectivos , Neoplasias do Colo do ÚteroRESUMO
We present a case of an endometrial cancer patient with germline mutation in MutS homolog 6 (MSH6), associated with Lynch syndrome. A 60-year-old Korean woman had a personal history of colon cancer 23 years ago. She also had a family history of endometrial cancer and colon cancer of her sisters and brothers. Immunohistochemistry was negative for MutL homolog 1 (MLH1) and positive for MutS homolog 2 (MSH2). Based on these findings, she underwent genetic counseling and testing that revealed a frameshift germline mutation at MSH6 (c. 3261dupC).
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Feminino , Humanos , Pessoa de Meia-Idade , Colo , Neoplasias do Colo , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias do Endométrio , Aconselhamento Genético , Mutação em Linhagem Germinativa , Imuno-Histoquímica , Coreia (Geográfico) , IrmãosRESUMO
Uterine serosal pregnancy is an extremely rare form of ectopic pregnancy. This is a report of a 35-year-old primigravida woman who was diagnosed with uterine serosal pregnancy via laparoscopic intervention. A 35-year-old woman (gravida 1, para 0) was referred from a local clinic for a ruptured left tubal pregnancy at amenorrhea 5+0 weeks with elevated serum beta human chorionic gonadotropin (16,618 mIU/mL). A pregnancy on the left posterior wall of the uterine serosa was diagnosed during the operation and successfully treated with laparoscopic surgery as a conservative management strategy to enable fertility preservation. With the advantages of ultrasonography and laparoscopy, an early diagnosis of a primary abdominal pregnancy located on the left posterior wall of the uterine serosa was made, prior to the occurrence of severe intra-abdominal massive hemorrhage, which was then treated laparoscopically as a conservative management strategy enabling the preservation of fertility.
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Adulto , Feminino , Humanos , Gravidez , Amenorreia , Gonadotropina Coriônica , Diagnóstico Precoce , Fertilidade , Preservação da Fertilidade , Hemorragia , Laparoscopia , Gravidez Abdominal , Gravidez Ectópica , Gravidez Tubária , Membrana Serosa , UltrassonografiaRESUMO
OBJECTIVE: To compare the oncologic and obstetric outcomes in reproductive-age females with borderline ovarian tumors (BOTs) treated with cyst enucleation (CE) or unilateral salpingo-oophorectomy (USO). METHODS: The medical records of patients with BOTs treated between 1998 and 2014 were retrospectively reviewed. The recurrence rates in the USO and CE groups were compared, and the postoperative obstetric outcomes were assessed via telephone survey. RESULTS: Eighty-nine patients with BOTs underwent USO, and 19 underwent CE. Of these, six patients had recurrent BOTs. The recurrence rate was significantly lower in the USO group (3/89, 3.4%) than in the CE group (3/19, 15.8%) (P=0.032). All patients with recurrent disease were successfully treated with further surgery. Of the 76 patients interviewed by telephone, 71 (93.4%) resumed regular menstruation after surgery. Twenty-six of the 32 patients (81.3%) who attempted to conceive had successful pregnancies. USO (19/24, 79.2%), like CE (7/8, 87.5%), resulted in favorable pregnancy rates for patients with BOTs. CONCLUSION: USO is a suitable fertility-preserving surgery for women with BOTs. CE is also an acceptable option for select patients.
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Feminino , Humanos , Gravidez , Preservação da Fertilidade , Prontuários Médicos , Menstruação , Taxa de Gravidez , Recidiva , Estudos Retrospectivos , TelefoneRESUMO
No abstract available.
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Feminino , Humanos , Neoplasias das Tubas Uterinas/genética , Genes BRCA1 , Genes BRCA2 , Testes Genéticos , Mutação , Neoplasias Ovarianas/genética , Neoplasias Peritoneais/genética , República da Coreia , Sociedades MédicasRESUMO
No abstract available.
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Feminino , Humanos , Neoplasias das Tubas Uterinas/genética , Genes BRCA1 , Genes BRCA2 , Testes Genéticos , Mutação , Neoplasias Ovarianas/genética , Neoplasias Peritoneais/genética , República da Coreia , Sociedades MédicasRESUMO
No abstract available.
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Feminino , Humanos , Neoplasias da Mama , Neoplasias do EndométrioRESUMO
OBJECTIVES: To find differences in Framingham risk scores which predict the probable risk of future cardiovascular disease, among three different occupational categories. METHODS: Subjects were selected from respondents of the 3rd Korean National Health and Nutrition Examination Survey. A total of 2,059 employed people between 20 to 59 years old were selected. The occupational categories were professional and office workers, salespeople and service workers and technicians and elementary occupations. The Framingham risk score was calculated to find the risk of cardiovascular disease within the next 10 years. In addition socio-demographic characteristics, life-styles, the prevalence of chronic disease, and cardiovascular disease were compared among the occupational categories. RESULTS: The average Framingham risk score was 2.77+/-6.44 for professional and office workers (n=771), 5.95+/-6.10 for salespeople and service workers (n=603) and 7.07+/-5.87 for technician and elementary occupations (n=685) Statistically significant multiple regression equations were derived (p<0.001). CONCLUSIONS: Framingham risk scores of technicians and elementary occupations were highest which suggests that this occupational group has the highest risk of cardiovascular disease.