Cancer Research and Treatment

Original Articles

Efficacy of Chemotherapy Following Prior PARP-Inhibitor Treatment in Patients with Ovarian Cancer: Jung Chul Kim, Junsik Park, Yong Jae Lee, Eun Ji Nam, Sang Wun Kim, Sung-Hoon Kim, Young Tae Kim, Se Ik Kim, Jae-Weon Kim, Byoung-Gie Kim, Jung-Yun Lee; Received December 23, 2024 Accepted March 16, 2025 Published online March 19, 2025; DOI: https://doi.org/10.4143/crt.2024.1202 [Accepted]

Abstract PDF: Purpose
Considering the current lack of consensus on post-poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) treatment strategies, this study aimed to evaluate the efficacy of subsequent therapy and compare the outcomes of regimes in patients with recurrent ovarian cancer after PARPi treatment.
Materials and Methods
This multi-center retrospective cohort study analyzed data on patients diagnosed with ovarian cancer between January 2012 and June 2023 who had previously used PARPi after first- to fourth-line platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS), which was the interval between recurrence after using PARPi and subsequent recurrence in the case of recurrence.
Results
Of 318 patients, 147/318 (46.2%) recurred after the PARPi maintenance. Patients were categorized into groups based on subsequent therapy except non-treated (11/147, 7.5%): platinum-based chemotherapy (89/147, 60.5%), non-platinum-based chemotherapy (21/147, 14.3%), other treatments (26/147, 17.7%), and the median PFS (mPFS) for each group were 7.3, 4.8 and 11.4 months, respectively. Among the platinum-based chemotherapy group, the gemcitabine + carboplatin regimen demonstrated a longer mPFS (10.1 months) than the other regimens (6.6 months, p=0.0194). In non-platinum-based chemotherapy, no statistically significant differences were observed among the regimens. And, in the other therapy group, where the proportion of patients with oligometastasis was as high as 88.5%, no significant differences were observed among the therapies, including other modalities.
Conclusion
In the subsequent chemotherapy of recurrent ovarian cancer after platinum-based chemotherapy and PARPi, the gemcitabine + carboplatin regimen demonstrated a potential to delay recurrence more effectively compared to other therapies.

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Time-Trend Analysis and Risk Factors for Niraparib-Induced Nausea and Vomiting in Ovarian Cancer: A Prospective Study: Young Wook Jeong, Dongkyu Eugene Kim, Ji Hyun Kim, Se Ik Kim, Hyeong In Ha, Sang-Yoon Park, Myong Cheol Lim; Received September 14, 2024 Accepted November 2, 2024 Published online November 4, 2024; DOI: https://doi.org/10.4143/crt.2024.899 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Nausea and vomiting are major non-hematological adverse events associated with niraparib maintenance therapy. This study aimed to investigate the time-trend patterns of niraparib-induced nausea and vomiting (NINV) and the associated risk factors in patients with ovarian cancer.
Materials and Methods
In this prospective study, we enrolled patients with stage III-IV epithelial ovarian cancer who received niraparib as frontline maintenance therapy. The clinicopathological characteristics and time-trend patterns of patients with NINV were collected through in-person surveys and electronic medical records from the National Cancer Center.
Results
Of 53 patients, 50 (94.3%) were diagnosed with high-grade serous ovarian carcinoma. BRCA mutations and homologous recombination deficiency (HRD) were identifi ed in 23 (43.4%) and 32 (60.4%) patients, respectively. Thirty-one patients (58.5%) had NINV. Time-trend analyses revealed that the fi rst peak intensity of NINV was reached at 3 h post-dose, and the second peak intensity was reached at 11 hour post-dose. NINV signifi cantly decreased from week 1 to weeks 8 and 12. In multivariate analyses of risk factors for NINV, HRD-positive tumors (p < 0.001) and prior experience of chemotherapy-induced nausea and vomiting (p=0.004) were associated with the occurrence of NINV.
Conclusion
Pre-emptive treatment with antiemetics is required to manage early-phase NINV during niraparib maintenance therapy in patients with risk factors. Additional larger studies are needed to confi rm these fi ndings and to develop optimal preventive strategies for NINV.

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Gynecologic cancer

Effect of BRCA1/2 Mutational Status on Survival Outcomes According to Secondary Cytoreductive Surgery and Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer: A Real-World Evidence Study: Se Ik Kim, Hyunji Lim, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song, Maria Lee; Cancer Res Treat. 2023;55(1):245-257. Published online July 19, 2022; DOI: https://doi.org/10.4143/crt.2022.232

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to investigate the impact of BRCA1/2 mutational status on survival outcomes in patients with platinum-sensitive relapsed (PSR) epithelial ovarian cancer (EOC).
Materials and Methods
We retrospectively identified patients who received secondary treatment for PSR EOC at our institution between January 2007 and June 2021 and who underwent BRCA1/2 gene testing by either germline or somatic methods. The association between BRCA1/2 mutational status and survival outcomes was evaluated. Both secondary cytoreductive surgery (CRS) and maintenance therapy were stratified considering real-world clinical practice.
Results
Of 262 patients, 91 (34.7%) and 171 (65.3%) were assigned to BRCA1/2 mutation and wild-type groups, respectively. The two groups had similar proportions of patients undergoing secondary CRS (26.4% vs. 32.7%, p=0.286) and maintenance therapy (54.9% vs. 46.2%, p=0.178). Overall, no differences in progression-free survival (PFS; median, 19.7 vs. 15.1 months, p=0.120) and overall survival (OS; p=0.400) were observed between the two groups. In multivariate analyses, BRCA1/2 mutational status was not associated with PFS (adjusted hazard ratio, 0.816; 95% confidence interval, 0.596 to 1.119; p=0.207). BRCA1/2 mutational status did not affect PFS among patients who underwent secondary CRS (n=80) and among those who did not (n=182) (p=0.074 and p=0.222, respectively). PFS did not differ in the BRCA1/2 mutational status among the patients who received bevacizumab maintenance (n=90, p=0.992).
Conclusion
In this real-world evidence study, BRCA1/2 mutational status itself was not associated with PFS and OS in PSR EOC, which was consistent with whether secondary CRS or not and with bevacizumab maintenance.

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Identification of Patients with Recurrent Epithelial Ovarian Cancer Who Will Benefit from More Than Three Lines of Chemotherapy: Aeran Seol, Ga Won Yim, Joo Yeon Chung, Se Ik Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong Sang Song; Cancer Res Treat. 2022;54(4):1219-1229. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.1010

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to identify patients who would benefit from third and subsequent lines of chemotherapy in recurrent epithelial ovarian cancer (EOC).
Materials and Methods
Recurrent EOC patients who received third, fourth, or fifth-line palliative chemotherapy were retrospectively analyzed. Patients’ survival outcomes were assessed according to chemotherapy lines. Based on the best objective response, patients were divided into good-response (stable disease or better) and poor response (progressive disease or those who died before response assessment) groups. Survival outcomes were compared between the two groups, and factors associated with chemotherapy responses were investigated.
Results
A total of 189 patients were evaluated. Ninety-four and 95 patients were identified as good and poor response group respectively, during the study period of 2008 to 2021. The poor response group showed significantly worse progression-free survival (median, 2.1 months vs. 9.7 months; p < 0.001) and overall survival (median, 5.0 months vs. 22.9 months; p < 0.001) compared with the good response group. In multivariate analysis adjusting for clinicopathologic factors, short treatment-free interval (TFI) (hazard ratio [HR], 5.557; 95% confidence interval [CI], 2.403 to 12.850), platinum-resistant EOC (HR, 2.367; 95% CI, 1.017 to 5.510), and non-serous/endometrioid histologic type (HR, 5.045; 95% CI, 1.152 to 22.088) were identified as independent risk factors for poor response. There was no difference in serious adverse events between good and poor response groups (p=0.167).
Conclusion
Third and subsequent lines of chemotherapy could be carefully considered for palliative purposes in recurrent EOC patients with serous or endometrioid histology, initial platinum sensitivity, and long TFIs from the previous chemotherapy regimen.

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CircSETDB1 contributes to paclitaxel resistance of ovarian cancer cells by sponging miR-508-3p and regulating ABCC1 expression
Chunyan Huang, Li Qin, Sailan Chen, Qin Huang
Anti-Cancer Drugs.2022;[Epub] CrossRef

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Germline and Somatic BRCA1/2 Gene Mutational Status and Clinical Outcomes in Epithelial Peritoneal, Ovarian, and Fallopian Tube Cancer: Over a Decade of Experience in a Single Institution in Korea: Se Ik Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song; Cancer Res Treat. 2020;52(4):1229-1241. Published online July 27, 2020; DOI: https://doi.org/10.4143/crt.2020.557

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to present a single institutional experience with BRCA1/2 gene tests and the effects of pathogenic mutations in epithelial peritoneal, ovarian, and fallopian tube cancer (POFTC) on survival outcomes.
Materials and Methods
We identified patients with epithelial POFTCs who underwent BRCA1/2 gene testing by either germline or somatic methods between March 2007 and March 2020. Based on the BRCA1/2 test results, patients were divided into BRCA mutation and wild-type groups, followed by comparisons of clinicopathologic characteristics and survival outcomes after primary treatment.
Results
The annual number of POFTC patients who received BRCA1/2 gene tests increased gradually. In total, 511 patients were included and BRCA1/2 mutations were observed in 143 (28.0%). Among 57 patients who received both germline and somatic tests, three (5.3%) showed discordant results from the two tests. Overall, no differences in progression-free survival (PFS; p=0.467) and overall survival (p=0.641) were observed between the BRCA mutation and wild-type groups; however, multivariate analyses identified BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted hazard ratio [aHR], 0.765; 95% confidence interval [CI], 0.593 to 0.987; p=0.040). In 389 patients with International Federation of Gynecology and Obstetrics stage III-IV, different results were shown depending on primary treatment strategy: while BRCA1/2 mutation significantly improved PFS in the subgroup of neoadjuvant chemotherapy (aHR, 0.619; 95% CI, 0.385 to 0.995; p=0.048), it did not affect patient PFS in the subgroup of primary debulking surgery (aHR, 0.759; 95% CI, 0.530 to 1.089; p=0.135).
Conclusion
BRCA1/2 mutations are frequently observed in patients with epithelial POFTCs, and such patients showed better PFS than did those harboring wild-type BRCA1/2.

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Overview of Molecular Diagnostics in Irish Clinical Oncology
Tyler Medina, Seán O. Hynes, Maeve Lowery, Paddy Gillespie, Walter Kolch, Cathal Seoighe
HRB Open Research.2024; 7: 16. CrossRef
Trends in the Incidence and Survival Rates of Primary Ovarian Clear Cell Carcinoma Compared to Ovarian Serous Carcinoma in Korea
Se Ik Kim, Hyeong In Ha, Kyung Jin Eoh, Jiwon Lim, Young-Joo Won, Myong Cheol Lim
Frontiers in Oncology.2022;[Epub] CrossRef
Characteristics of homologous recombination repair pathway genes mutation in ovarian cancers
Zongbi Yi, Min Chen, Shaoxing Sun, Chunxu Yang, Zijie Mei, Hui Yang, Qingming Xiang, Hui Qiu
Cancer Innovation.2022; 1(3): 220. CrossRef

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214 Download
12 Web of Science
3 Crossref

Development of Web-Based Nomograms to Predict Treatment Response and Prognosis of Epithelial Ovarian Cancer: Se Ik Kim, Minsun Song, Suhyun Hwangbo, Sungyoung Lee, Untack Cho, Ju-Hyun Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Dae-Shik Suh, Taesung Park, Yong-Sang Song; Cancer Res Treat. 2019;51(3):1144-1155. Published online November 20, 2018; DOI: https://doi.org/10.4143/crt.2018.508

Abstract PDF Supplementary Material PubReader ePub

Purpose
Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC.
Materials and Methods
We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients’ clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied.
Results
The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively.
Conclusion
We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.

Citations

Citations to this article as recorded by

Comprehensive analyses of mitophagy-related genes and mitophagy-related lncRNAs for patients with ovarian cancer
Jianfeng Zheng, Shan Jiang, Xuefen Lin, Huihui Wang, Li Liu, Xintong Cai, Yang Sun
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Peripheral and tumor‐infiltrating immune cells are correlated with patient outcomes in ovarian cancer
Weiwei Zhang, Yawen Ling, Zhidong Li, Xingchen Peng, Yazhou Ren
Cancer Medicine.2023; 12(8): 10045. CrossRef
Nonalcoholic fatty liver disease and early prediction of gestational diabetes mellitus using machine learning methods
Seung Mi Lee, Suhyun Hwangbo, Errol R. Norwitz, Ja Nam Koo, Ig Hwan Oh, Eun Saem Choi, Young Mi Jung, Sun Min Kim, Byoung Jae Kim, Sang Youn Kim, Gyoung Min Kim, Won Kim, Sae Kyung Joo, Sue Shin, Chan-Wook Park, Taesung Park, Joong Shin Park
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Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer Part 2: Medical Perspectives
Stanislas Quesada, Michel Fabbro, Jérôme Solassol
Cancers.2022; 14(4): 1098. CrossRef
Construction and validation of a transcription factors-based prognostic signature for ovarian cancer
Qingyuan Cheng, Liman Li, Mingxia Yu
Journal of Ovarian Research.2022;[Epub] CrossRef
Predicting preterm birth through vaginal microbiota, cervical length, and WBC using a machine learning model
Sunwha Park, Jeongsup Moon, Nayeon Kang, Young-Han Kim, Young-Ah You, Eunjin Kwon, AbuZar Ansari, Young Min Hur, Taesung Park, Young Ju Kim
Frontiers in Microbiology.2022;[Epub] CrossRef
Prognostic nomogram that predicts progression-free survival and overall survival of patients with ovarian clear cell carcinoma
Jiayi Li, Dongyan Cao
Frontiers in Oncology.2022;[Epub] CrossRef
Recent Advances and Future Directions of Diagnostic and Prognostic Prediction Models in Ovarian Cancer
Judan Zeng, Wenjiao Cao, Lihua Wang
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Sphingolipids as multifaceted mediators in ovarian cancer
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Jiani Yang, Jun Ma, Yue Jin, Shanshan Cheng, Shan Huang, Nan Zhang, Yu Wang
Scientific Reports.2021;[Epub] CrossRef
Prediction Models for the Clinical Severity of Patients With COVID-19 in Korea: Retrospective Multicenter Cohort Study
Bumjo Oh, Suhyun Hwangbo, Taeyeong Jung, Kyungha Min, Chanhee Lee, Catherine Apio, Hyejin Lee, Seungyeoun Lee, Min Kyong Moon, Shin-Woo Kim, Taesung Park
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Development of Machine Learning Models to Predict Platinum Sensitivity of High-Grade Serous Ovarian Carcinoma
Suhyun Hwangbo, Se Ik Kim, Ju-Hyun Kim, Kyung Jin Eoh, Chanhee Lee, Young Tae Kim, Dae-Shik Suh, Taesung Park, Yong Sang Song
Cancers.2021; 13(8): 1875. CrossRef
M2 Macrophage-Based Prognostic Nomogram for Gastric Cancer After Surgical Resection
Jianwen Hu, Yongchen Ma, Ju Ma, Yanpeng Yang, Yingze Ning, Jing Zhu, Pengyuan Wang, Guowei Chen, Yucun Liu
Frontiers in Oncology.2021;[Epub] CrossRef
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Ji-Bin Liu, Kai-Jian Chu, Chang-Chun Ling, Ting-Miao Wu, Hui-Min Wang, Yi Shi, Zhi-Zhen Li, Jing-Han Wang, Zhi-Jun Wu, Xiao-Qing Jiang, Gao-Ren Wang, Yu-Shui Ma, Da Fu
Current Problems in Cancer.2020; 44(6): 100612. CrossRef
Can we predict who lives long with ovarian cancer?
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Comparison of Quality of Life and Sexuality between Cervical Cancer Survivors and Healthy Women: Yumi Lee, Myong Cheol Lim, Se Ik Kim, Jungnam Joo, Dong Ock Lee, Sang-Yoon Park; Cancer Res Treat. 2016;48(4):1321-1329. Published online February 12, 2016; DOI: https://doi.org/10.4143/crt.2015.425

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to compare quality of life (QoL) and sexual functioning between sexually active cervical cancer survivors and healthy women.
Materials and Methods
In this cross-sectional study, propensity-score-matched cervical cancer survivors (n=104) and healthy women (n=104) were compared. All women had engaged in sexual activity within the previous 3 months, and cervical cancer survivors showed no evidence of disease after primary treatment. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Cervical Cancer Module (EORTC QLQ-CX24), and the Female Sexual Function Index (FSFI).
Results
Significantly higher scores for lymphedema were observed in the cervical cancer survivors group compared with the healthy women group (mean, 20.2 vs. 12.2; p < 0.05). Sexuality, both in terms of sexual activity, sexual enjoyment, and sexual worry (EORTC QLQ-CX24), and in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain (FSFI) were similar between the groups. When the scale of sexual/vaginal functioning in EORTC QLQ-CX24 was divided into individual questions, cervical cancer survivors reported shorter vaginal length than the control group, but without statistical significance (mean, 80.6 vs. 85.4; p=0.077).
Conclusion
Compared with healthy women, sexuality was not impaired in cervical cancer survivors who showed no evidence of disease after primary treatment and engaging in sexual activity. Further prospective cohort studies are warranted to confirm this finding.

Citations

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