Association between glycemic status and the risk of gastric cancer in pre/peri-and postmenopausal women: A nationwide cohort study.

PURPOSE: This study aimed to assess the correlation between glycemic status (prediabetes and type 2 diabetes mellitus) and the risk of gastric cancer according to menopausal status. METHODS: A total of 982,559 pre/peri-menopausal and 1445,419 postmenopausal women aged ≥ 40, who underwent the Korean national health screening in 2009, were included and followed up until 2018. Hazard ratio (HR) and 95% confidence interval (CI) were calculated for development of gastric cancers according to hyperglycemic status in both groups using Cox proportional hazards models. RESULTS: Over a mean follow-up period of 8.3 years, 3259 (0.33%) pre/peri-menopausal women and 13,245 (0.92%) postmenopausal women were diagnosed with gastric cancer. In postmenopausal women, only diabetes mellitus conferred a higher risk of gastric cancer compared to normal glycemic status (HR, 1.15; 95% CI, 1.09-1.20), with an increasing trend of gastric cancers from prediabetes to diabetes (P for trend < 0.001) observed regardless of menopausal status. Obesity, smoking, and heavy alcohol consumption was associated with increased gastric cancer risk mainly in the postmenopausal period. CONCLUSIONS: The risk of gastric cancer escalates with deteriorating glycemic status in a dose-response manner. Diabetes mellitus is linked with an elevated risk of gastric cancer in postmenopausal women.

Impact of Bevacizumab on Clinical Outcomes in Patients With Platinum-resistant Relapsed Ovarian Cancer.

BACKGROUND/AIM: Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinum-resistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. PATIENTS AND METHODS: We retrospectively divided patients with PR-ROC into two groups: bevacizumab plus chemotherapy (BEV-CT group) and chemotherapy alone (CT group). Progression-free survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. RESULTS: A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. CONCLUSION: In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity.

Association between menopausal hormone therapy and the risk of gastric cancer: A Korean nationwide population-based cohort study.

OBJECTIVE: Gastric cancer (GC) is more common in men than women, but also more common among postmenopausal than premenopausal women. The protective effect of reproductive hormones against GC remains unclear. Therefore, we evaluated the association between menopausal hormone therapy (MHT) and the risk of GC in women. METHODS: We investigated the national cohort data of women aged over 40 years who underwent health checkups by the Korean National Health Insurance Service in 2009. After excluding individuals with missing data and those previously diagnosed with cancer, 1,354,621 postmenopausal women were included and divided into groups according to their MHT history. We followed the study population until 2018 and analyzed the hazard ratios (HR) with 95 % confidence intervals (CIs) for the incidence rate of GC in a multivariate adjusted model. RESULTS: The number of women with and without a history of MHT was 214,723 (15.9 %) and 1,139,898 (84.1 %), respectively. During the mean 8.32 ± 0.8 years of follow-up, a total of 12,496 GC cases developed in the study population (10,962 MHT non-users; 1534 MHT users). In the adjusted model, MHT was associated with a 12 % decrease in the development of GC relative to non-use of MHT (HR 0.88; 95 % CI 0.83-0.93). Exposure to MHT for >2 years was linked to a reduction in GC risk, particularly when initiated before the age of 50, giving a 45 % risk reduction. CONCLUSIONS: According to our large-scale prospective national cohort study, exogenous MHT is associated with a decreased risk of GC in postmenopausal women.

Clinical implications of histologic subtypes on survival outcomes in primary mucinous ovarian carcinoma.

OBJECTIVE: In 2014, the World Health Organization introduced a new histologic classification by dividing primary mucinous ovarian carcinoma (PMOC) into two: expansile (ES) or infiltrative subtypes (IS). This study investigated the clinical implications of these histological subtypes on survival outcomes. METHODS: Data from 131 patients with PMOC who underwent primary surgery between 2003 and 2021 were analyzed. The patients baseline characteristics, surgical and pathological information were collected. Survival outcomes were calculated, while factors affecting them were also investigated. RESULTS: During 55.9 months of median follow-up, 27 (20.6%) patients experienced recurrence and 20 (15.3%) died. Among 131 patients, 113 patients were classified into 87 (77%) ES and 26 (23%) IS after a slide review. Advanced stage, lymph node involvement, and residual tumors after surgery were more common in the IS, showing poorer prognosis. In multivariate analyses, advanced stage and residual tumors after surgery were associated with worse survival, while the IS showed no statistical significance. In subgroup analysis for stage I disease, survival did not vary between subtypes. Nevertheless, patients in the IS group who underwent fertility-sparing surgeries demonstrated a 5-year progression-free survival (PFS) rate of 83.3%, significantly lower than patients without fertility preservation, irrespective of histologic subtypes (5-year PFS rate: 97.9%; P = 0.002 for the ES, 5-year PFS rate: 100%; P = 0.001 for the IS). CONCLUSIONS: The IS of PMOC had poorer survival outcomes and a higher proportion of advanced-stage tumors. Although its independent prognostic significance remains uncertain, adjuvant chemotherapy should be considered for patients with fertility preservation in the IS group.

Impact of supradiaphragmatic lymphadenectomy on the survival of patients in stage IVB ovarian cancer with thoracic lymph node metastasis.

Introduction: To evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM). Methods: We retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into <5 vs ≥5 mm in the abdominal and supradiaphragmatic areas. Based on the site of recurrence, they were divided into abdominal, supradiaphragmatic and other areas. Results: A total of 120 patients underwent primary debulking surgery (PDS, n=68) and interval debulking surgery after neoadjuvant chemotherapy (IDS/NAC, n=53). Residual tumors in the supradiaphragmatic area ≥5 mm adversely affected progression-free survival (PFS) and overall survival (OS) with marginal significance after PDS despite the lack of effect on survival after IDS/NAC (adjusted hazard ratios [HRs], 6.478 and 6.370; 95% confidence intervals [CIs], 2.224-18.864 and 0.953-42.598). Further, the size of residual tumors in the abdominal area measuring ≥5 mm diminished OS after IDS/NAC (adjusted HR, 9.330; 95% CIs, 1.386-62.800). Conclusion: Supradiaphragmatic lymphadenectomy during PDS may improve survival in patients diagnosed with stage IVB ovarian cancer manifesting thoracic LNM. Further, suboptimal debulking surgery in the abdominal area may be associated with poor OS after IDS/NAC. Trial registration: ClinicalTrials.gov (NCT05005650; https://clinicaltrials.gov/ct2/show/NCT05005650; first registration, 13/08/2021).Research Registry (Research Registry UIN, researchregistry7366; https://www.researchregistry.com/browse-the-registry#home/?view_2_search=researchregistry7366&view_2_page=1).

Survival outcomes of laparoscopic versus open radical hysterectomy in early cervical cancer with incidentally identified high-risk factors.

OBJECTIVE: Previously, we suggested that patients with cervical cancer (CC) with tumors ≤2 cm on preoperative magnetic resonance imaging (MRI) are safe candidates for laparoscopic radical hysterectomy (LRH). Here, we aim to investigate whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors; lymph node metastasis (LNM) or parametrial invasion (PMI). METHODS: We identified patients with 2009 FIGO stage IB1 CC who underwent Type C LRH or open radical hysterectomy (ORH) at three tertiary hospitals between 2000 and 2019. Those with a tumor ≤2 cm on preoperative MRI who were not suspicious of LNM or PMI preoperatively were included, while those who were indicated to receive adjuvant treatment but did not actually receive it were excluded. Survival outcomes were compared between the LRH and ORH groups in the overall population, then narrowed down to those with LNM, and then to those with PMI. RESULTS: In total, 498 patients were included: 299 in the LRH group and 199 in the ORH group. The LRH and ORH groups showed similar 3-year progression-free survival (PFS) (94.0% vs. 93.6%; P = 0.615) and 5-year overall survival (OS) rates (97.2% vs. 96.8%; P = 0.439). On pathologic examination, 49 (9.8%) and 16 (3.2%) patients had LNM and PMI, respectively, and 10 (2.0%) had both. In the LNM subgroup, 5-year PFS rate was not significantly different between the LRH and ORH groups (73.2% vs. 91.7%; P = 0.169). In the PMI subgroup, no difference in PFS was observed between the two groups (P = 0.893). CONCLUSIONS: LRH might not deteriorate recurrence and mortality rates in CC patients with tumors ≤2 cm when adjuvant treatment is appropriately administered, even if pathologic LNM and PMI are incidentally identified.

Proteomic Discovery of Plasma Protein Biomarkers and Development of Models Predicting Prognosis of High-Grade Serous Ovarian Carcinoma.

Ovarian cancer is one of the most lethal female cancers. For accurate prognosis prediction, this study aimed to investigate novel, blood-based prognostic biomarkers for high-grade serous ovarian carcinoma (HGSOC) using mass spectrometry-based proteomics methods. We conducted label-free liquid chromatography-tandem mass spectrometry using frozen plasma samples obtained from patients with newly diagnosed HGSOC (n = 20). Based on progression-free survival (PFS), the samples were divided into two groups: good (PFS ≥18 months) and poor prognosis groups (PFS <18 months). Proteomic profiles were compared between the two groups. Referring to proteomics data that we previously obtained using frozen cancer tissues from chemotherapy-naïve patients with HGSOC, overlapping protein biomarkers were selected as candidate biomarkers. Biomarkers were validated using an independent set of HGSOC plasma samples (n = 202) via enzyme-linked immunosorbent assay (ELISA). To construct models predicting the 18-month PFS rate, we performed stepwise selection based on the area under the receiver operating characteristic curve (AUC) with 5-fold cross-validation. Analysis of differentially expressed proteins in plasma samples revealed that 35 and 61 proteins were upregulated in the good and poor prognosis groups, respectively. Through hierarchical clustering and bioinformatic analyses, GSN, VCAN, SND1, SIGLEC14, CD163, and PRMT1 were selected as candidate biomarkers and were subjected to ELISA. In multivariate analysis, plasma GSN was identified as an independent poor prognostic biomarker for PFS (adjusted hazard ratio, 1.556; 95% confidence interval, 1.073-2.256; p = 0.020). By combining clinical factors and ELISA results, we constructed several models to predict the 18-month PFS rate. A model consisting of four predictors (FIGO stage, residual tumor after surgery, and plasma levels of GSN and VCAN) showed the best predictive performance (mean validated AUC, 0.779). The newly developed model was converted to a nomogram for clinical use. Our study results provided insights into protein biomarkers, which might offer clues for developing therapeutic targets.

Image-Guided Versus Conventional Brachytherapy for Locally Advanced Cervical Cancer: Experience of Single Institution with the Same Practitioner and Time Period.

PURPOSE: This study aimed to compare treatment outcomes and toxicity profile between imaged-guided brachytherapy (IGBT) versus conventional brachytherapy (CBT) performed by the same practitioner during the same time period. MATERIALS AND METHODS: Medical records of 104 eligible patients who underwent brachytherapy for locally advanced cervical cancer were retrospectively reviewed. Fifty patients (48.1%) underwent IGBT, and 54 (51.9%) patients underwent CBT. All patients underwent concurrent chemoradiation with cisplatin. High-dose-rate intracavitary brachytherapy with dose prescription of 25-30 Gy in 4-6 fractions was performed for all patients. Late lower gastrointestinal (GI) and urinary toxicities occurred more than 3 months after the end of brachytherapy were included for comparative and dosimetric analyses. RESULTS: The median follow-up period was 18.33 months (range, 3.25 to 38.43 months). There were no differences in oncologic outcomes between the two groups. The IGBT group had lower rate of actuarial grade ≥ 3 toxicity than the CBT group (2-year, 4.5% vs. 25.7%; p=0.030). Cumulative equieffective D2cc of sigmoid colon was significantly correlated with grade ≥ 2 lower GI toxicity (p=0.033), while equieffective D2cc of rectum (p=0.055) and bladder (p=0.069) showed marginal significance with corresponding grade ≥ 2 toxicities in the IGBT group. Half of grade ≥ 3 lower GI toxicities impacted GI tract above the rectum. Optimal thresholds of cumulative D2cc of sigmoid colon and rectum were 69.7 Gy and 70.8 Gy, respectively, for grade ≥ 2 lower GI toxicity. CONCLUSION: IGBT showed superior toxicity profile to CBT. Evaluating the dose to the GI tract above rectum by IGBT might prevent some toxicities.

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.

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.

Impact of hemodynamic instability during cytoreductive surgery on survival in high-grade serous ovarian carcinoma.

BACKGROUND: To evaluate the impact of intraoperative hypotension and hemodynamic instability on survival outcomes in patients with high-grade serous ovarian carcinoma (HGSOC). METHODS: We retrospectively identified patients with HGSOC, who underwent primary or interval debulking surgery between August 2013 and December 2019. We collected anesthesia-related variables, including the arterial blood pressure measurements (at 1-min intervals) during the surgery of patients. The cumulative duration of mean arterial blood pressure (MAP) readings under 65 mmHg and two performance measurements (median performance error [MDPE] and wobble) were calculated. We investigated associations between the factors indicating hemodynamic instability and prognosis. RESULTS: In total, 338 patients were included. Based on the cumulative duration of MAP under 65 mmHg, we divided patients into two groups: ≥30 min and <30 min. The progression-free survival (PFS) was worse in the ≥30 min group (n = 107) than the <30 min group (n = 231) (median, 18.2 vs. 23.7 months; P = 0.014). In multivariate analysis adjusting for confounders, a duration of ≥30 min of MAP under 65 mmHg was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.376; 95% CI, 1.035-1.830; P = 0.028). Shorter PFS was observed in the group with a MDPE <-4.0% (adjusted HR, 1.351; 95% CI, 1.024-1.783; P = 0.033) and a wobble ≥7.5% (adjusted HR, 1.445; 95% CI, 1.100-1.899; P = 0.008). However, no differences were observed in overall survival. CONCLUSION: This study suggests that the three intraoperative variables for hemodynamic instability, cumulative duration of MAP <65 mmHg, MDPE, and wobble, might be novel prognostic biomarkers for disease recurrence in patients with HGSOC.

Is increased chronological age a contraindication to debulking surgery for elderly patients with advanced ovarian cancer?

We collected data of elderly patients aged 65 years and older who underwent debulking surgery for advanced ovarian cancer in order to explore the impact of old age on surgical outcomes and complications. A total of 120 patients were classified as follows: group 1, 65-69 years (n = 58); group 2, 70-74 years (n = 38); group 3, 75-79 years (n = 17); group 4, ≥80 years (n = 7). There were no differences in most of the characteristics, surgical extent and outcomes, and postoperative complications between the four groups, whereas polypharmacy was more common (6 vs. 5-16; p=.02) and operation time was shorter (median, 194 vs. 285-330 min; p=.02) in group 4. Factors related to frailty rather than age, polypharmacy, preoperative albumin level, estimated blood loss and transfusion increased the risk of postoperative complications. Thus, the impact of old age on surgical extent, outcomes and postoperative complications may be minimal in elderly patients with advanced ovarian cancer. Impact StatementWhat is already known on this subject? Optimal debulking surgery is a significant factor in improving the prognosis of ovarian cancer but it is not easy to perform such radical surgery on elderly patients in fear of increasing surgical morbidity and mortality. Some studies suggest that underlying comorbidities may be a stronger contributing factor to increasing such risk rather than old age although there is not enough evidence yet.What do the results of this study add? Through this study, we could see that increased age is not the determining cause of increased morbidity and mortality in elderly patients who undergo optimal debulking surgery in ovarian cancer. There are other aspects describing a patient's health status that can predict prognosis better rather than age.What are the implications of these findings for clinical practice and/or further research? Old age need not be a contraindication when performing optimal debulking surgery in elderly patients with advanced ovarian cancer.

Open versus minimally invasive radical hysterectomy for early cervical cancer: A two-center retrospective cohort study with pathologic review of usual-type adenocarcinoma and adenosquamous carcinoma.

OBJECTIVE: To compare survival outcomes of minimally invasive surgery (MIS) and open surgery for radical hysterectomy (RH) in early cervical cancer patients with histologic subtypes of usual-type adenocarcinoma and adenosquamous carcinoma. METHODS: From two centers' cervical cancer cohorts, patients with 2009 FIGO stage IB1-IB2 who underwent RH between 2007 and 2020 were retrospectively identified. Patients with usual-type adenocarcinoma and adenosquamous carcinoma were included in the analysis after pathologic review according to the updated World Health Organization Classification of Tumors. Clinicopathologic characteristics and survival outcomes were compared in terms of open surgery or MIS. RESULTS: This study included 161 patients. No significant differences were noted in overall survival (OS; P = 0.241) and disease-free survival (DFS; P = 0.156) between patients with usual-type adenocarcinoma (n = 136) and those with adenosquamous carcinoma (n = 25). MIS RH group (n = 99) had a significantly smaller tumor size (P < 0.001), lesser pathologic parametrial invasion (P = 0.001), and lesser lymph node metastasis (P < 0.001) than open RH group (n = 62). MIS and open RH groups showed similar OS (P = 0.201) and 3-year DFS rate (87.9% vs. 75.1%; P = 0.184). In multivariate analysis, worse DFS was not associated with MIS (P = 0.589) but was associated with pathologic parametrial invasion (adjusted HR, 3.41; 95% CI, 1.25-9.29; P = 0.016). Consistent results were observed among patients with usual-type adenocarcinoma; MIS was not associated with worse DFS. CONCLUSIONS: Comparable survival outcomes were found for MIS and open RH in early-stage cervical usual-type adenocarcinoma and adenosquamous carcinoma. Although MIS RH was not a poor prognostic factor, pathologic parametrial invasion was significantly associated with worse DFS in cervical usual-type adenocarcinoma and adenosquamous carcinoma.

Impact of no residual disease on postoperative computed tomography on survival in patients with optimally debulked advanced high-grade serous ovarian cancer during upfront surgery.

OBJECTIVE: We sought to investigate the impact of size of residual tumors as determined by postoperative computed tomography (CT) on survival of patients with advanced, high-grade serous ovarian carcinoma (HGSC) who achieved residual disease less than 1 cm after primary debulking surgery (PDS). METHODS: We collected data of patients with stage III HGSC who had residual tumor less than 1 cm after PDS between 2013 and 2018. Surgeon-assessed residual disease during surgery was defined as sR0 (no gross residual) or sR1 (gross residual <1 cm), and radiologist-assessed residual disease on postoperative CT was defined as rR0 (no evidence of disease) or rRany (existing residual disease). All patients were classified into the following groups: sR0/rR0, sR1/rR0, sR0/rRany, and sR1/rRany. RESULTS: A total of 436 patients was placed into the sR0/rR0 (n = 187, 42.9%), sR1/rR0 (n = 59, 13.5%), sR0/rRany (n = 79, 18.1%), or sR1/rRany group (n = 111, 25.5%). Discrepancies between surgical and radiological assessments were recorded for 176 patients (40.4%) including 38 cases of sR1/rRany group with discordant residual tumor location indicated between two methods. During multivariate analysis, patients with ascites on preoperative CT, sR0/rRany group inclusion, and sR1/rRany group inclusion showed unfavorable progression-free and overall survival. CONCLUSIONS: The incorporation of surgical and radiological evaluations for determining the size of residual tumors was more accurate than surgical evaluation only for predicting survival among patients with advanced ovarian cancer who underwent PDS to residual disease less than 1 cm.

Cervical conization before primary radical hysterectomy has a protective effect on disease recurrence in early cervical cancer: A two-center matched cohort study according to surgical approach.

OBJECTIVE: To ascertain whether cervical conization before radical hysterectomy (RH) has a protective effect on survival outcomes in early cervical cancer, taking into account the surgical approach. METHODS: From cervical cancer cohorts of two institutions, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH between July 2006 and June 2020. Patients were divided into conization group (n = 144) and control group (n = 434). We conducted three independent 1:1 propensity score matching processes for histology, lymphovascular space invasion, cervical tumor size, and surgical approach (all patients, those who underwent open surgery, and those who underwent minimally invasive surgery [MIS]). Survival outcomes were compared. RESULTS: Overall, the conization group had less cervical tumor size and received MIS more frequently (P = 0.010) and adjuvant treatment less often (P = 0.002) versus the controls. After matching, the conization group showed significantly better disease-free survival (DFS) versus control (3-year DFS rate, 94.2% vs. 86.3%; P = 0.012), but similar overall survival. Among the open RH matched patients (n = 96), no difference in DFS was observed between the conization and control groups (P = 0.984). In contrast, among the MIS RH matched patients (n = 192), the conization group showed significantly better DFS versus control (3-year DFS rate, 95.7% vs. 82.9%; P = 0.005). In multivariate analysis adjusting for cervical tumor size and adjuvant treatment, conization was identified as an independent favorable prognostic factor for DFS (adjusted HR, 0.318; 95% CI, 0.134-0.754; P = 0.009). CONCLUSIONS: Preoperative cervical conization might reduce the disease recurrence rate in early cervical cancer patients who undergo primary MIS RH.

Identification of Patients with Recurrent Epithelial Ovarian Cancer Who Will Benefit from More Than Three Lines of Chemotherapy.

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.

Survival impact of additional chemotherapy after adjuvant concurrent chemoradiation in patients with early cervical cancer who underwent radical hysterectomy.

BACKGROUND: To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). METHODS: We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB-IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). RESULTS: A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552-2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621-5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139). CONCLUSIONS: Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.

Machine Learning Models to Predict Survival Outcomes According to the Surgical Approach of Primary Radical Hysterectomy in Patients with Early Cervical Cancer.

We purposed to develop machine learning models predicting survival outcomes according to the surgical approach for radical hysterectomy (RH) in early cervical cancer. In total, 1056 patients with 2009 FIGO stage IB cervical cancer who underwent primary type C RH by either open or laparoscopic surgery were included in this multicenter retrospective study. The whole dataset consisting of patients' clinicopathologic data was split into training and test sets with a 4:1 ratio. Using the training set, we developed models predicting the probability of 5-year progression-free survival (PFS) and overall survival (OS) with tenfold cross validation. The developed models were validated in the test set. In terms of predictive performance, we measured the area under the receiver operating characteristic curve (AUC) values. The logistic regression models comprised of preoperative variables yielded AUCs of 0.679 and 0.715 for predicting 5-year PFS and OS rates, respectively. Combining both logistic regression and multiple machine learning models, we constructed hybrid ensemble models, and these models showed much improved predictive performance, with 0.741 and 0.759 AUCs for predicting 5-year PFS and OS rates, respectively. We successfully developed models predicting disease recurrence and mortality after primary RH in patients with early cervical cancer. As the predicted value is calculated based on the preoperative factors, such as the surgical approach, these ensemble models would be useful for making decisions when choosing between open or laparoscopic RH.

Laterally Extended Endopelvic Resection Versus Chemo or Targeted Therapy Alone for Pelvic Sidewall Recurrence of Cervical Cancer.

BACKGROUND: Laterally extended endopelvic resection (LEER) has been introduced for treatment of pelvic sidewall recurrence of cervical cancer (PSRCC), which occurs in only 8% of patients with relapsed cervical cancer. LEER can only be performed by a proficient surgeon due to the high risk of surgical morbidity and mortality, but there is no evidence as to whether LEER is may be more effective than chemo or targeted therapy alone for PSRCC. Thus, we aimed to compare the efficacy and safety between LEER and chemo or targeted therapy alone for treatment of PSRCC. METHODS: We prospectively recruited patients with PSRCC who underwent LEER between December 2016 and December 2019. Moreover, we retrospectively collected data on patients with PSRCC who received chemo or targeted therapy alone between January 2000 and December 2019. We compared treatment-free interval (TFI), progression-free survival (PFS), treatment-free survival (TFS), overall survival (OS), tumor response, neurologic disturbance of the low extremities, and pelvic pain severity in the different patient groups. RESULTS: Among 1295 patients with cervical cancer, we included 28 (2.2%) and 31 (2.4%) in the prospective and retrospective cohorts, respectively. When we subdivided all patients into two groups based on the median value of prior TFI (PTFI, 9.2 months), LEER improved TFI, PFS, TRS and OS compared to chemo or targeted therapy alone (median, 2.8 vs. 0.9; 7.4 vs. 4.1; 30.1 vs. 16.9 months; P ≤ 0.05) in patients with PTFI < 9.2 months despite no difference in survival in those with PTFI ≥ 9.2 months, suggesting that LEER may lead to better TFI, PFS, TRS and OS in patients with PTFI < 9.2 months (adjusted hazard ratios, 0.28, 0.27, 0.44 and 0.37; 95% confidence intervals, 0.12-0.68, 0.11-0.66, 0.18-0.83 and 0.15-0.88). Furthermore, LEER markedly reduced the number of morphine milligram equivalents necessary to reduce pelvic pain when compared with chemo or targeted therapy alone. CONCLUSION: Compared to chemo or targeted therapy alone, LEER improved survival in patients with PSRCC and PTFI < 9.2 months, and it was effective at controlling the pelvic pain associated with PSRCC. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02986568.

Lymph Node Ratio Is a Strong Prognostic Factor in Patients with Early-Stage Cervical Cancer Undergoing Minimally Invasive Radical Hysterectomy.

PURPOSE: To determine whether the prognostic impact of lymph node ratio (LNR), defined as the ratio between the number of positive lymph nodes and removed lymph nodes, differs between open and minimally invasive surgical approaches for radical hysterectomy (RH) in node-positive, early-stage cervical cancer. MATERIALS AND METHODS: We retrospectively identified 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 patients who underwent primary type C RH between 2010 and 2018. Among them, only those with pathologically proven lymph node metastases who received adjuvant radiation therapy were included. The prognostic significance of LNR was investigated according to open surgery and minimally invasive surgery (MIS). RESULTS: In total, 55 patients were included. The median LNR (%) was 9.524 (range, 2.083-62.500). Based on receiver operating characteristic curve analysis, the cut-off value for LNR (%) was determined as 8.831. Overall, patients with high LNR (≥8.831%; n=29) showed worse disease-free survival (DFS) than those with low LNR (<8.831%, n=26) (p=0.027), whereas no difference in overall survival was observed. Multivariate analyses adjusting for clinicopathologic factors revealed that DFS was adversely affected by both MIS [adjusted hazard ratio (HR), 8.132; p=0.038] and high LNR (adjusted HR, 10.837; p=0.045). In a subgroup of open surgery cases, LNR was not associated with disease recurrence. However, in a subgroup of MIS cases, high LNR was identified as an independent poor prognostic factor for DFS (adjusted HR, 14.578; p=0.034). CONCLUSION: In patients with node-positive, early-stage cervical cancer, high LNR was associated with a significantly higher disease recurrence rate. This relationship was further consolidated among patients who received MIS RH.