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.

Optimized treatment parameter by computer simulation for high-intensity focused ultrasound treatment of uterine adenomyosis: Short-term and long-term results.

This study aimed to investigate the efficacy and safety of using optimized parameters obtained by computer simulation for ultrasound-guided high-intensity focused ultrasound (HIFU) treatment of uterine adenomyosis in comparison with conventional parameters. We retrospectively assessed a single-institution, prospective study that was registered at Clinical Research Information Service (CRiS) of Republic of Korea (KCT0003586). Sixty-six female participants (median age: 44 years) with focal uterine adenomyosis were prospectively enrolled. All participants were treated with a HIFU system by using treatment parameters either for treating uterine fibroids (Group A, first 20 participants) or obtained via computer simulation (Group B, later 46 participants). To assess the treatment efficacy of HIFU, qualitative indices, including the clinically effective dysmenorrhea improvement index (DII), were evaluated up to 3 years after treatment, whereas quantitative indices, such as the nonperfused volume ratio and adenomyosis volume shrinkage ratio (AVSR), on MRI were evaluated up to 3 months after treatment. Quantitative/qualitative indices were compared between Groups A and B by using generalized linear mixed effect model. A safety assessment was also performed. Results showed that clinically effective DII was more frequently observed in Group B than in Group A (odds ratio, 3.69; P = 0.025), and AVSR were higher in Group B than in Group A (least-squares means, 21.61; P = 0.001). However, two participants in Group B developed skin burns at the buttock and sciatic nerve pain and required treatment. In conclusion, parameters obtained by computer simulation were more effective than the conventional parameters for treating uterine adenomyosis by using HIFU in terms of clinically effective DII and AVSR. However, care should be taken because of the risk of adverse events.

The new 2023 FIGO staging system for endometrial cancer: what is different from the previous 2009 FIGO staging system?

OBJECTIVE: The International Federation of Gynecology and Obstetrics committee modified the endometrial cancer (EC) staging system based on the histopathological feature and molecular profile. The aim is to evaluate the clinical implications of the new 2023 system compared with the previous 2009 system. METHODS: We retrospectively identified 161 patients with EC who underwent primary surgical treatment between 2014 and 2018 at Seoul National University Hospital. The droplet-digital polymerase chain reaction for POLE mutations and immunohistochemistry for MLH1, PMS2, MS2, MSH6, and p53 were performed using tissues from formalin-fixed, paraffin-embedded blocks. All patients were categorized according to the 2009 and 2023 staging systems. RESULTS: The median follow-up period was 62.9 months (range, 0.3-110.9), and the median age was 57.2 years old (range, 28.0-85.9). The 5-year progression-free survival (PFS) for the 2023 system with molecular classification was 80.3% for stage I, 75.2% for stage II, 61.2% for stage III, and 22.2% for stage IV (p<0.001). Patients with the 2009 stage I and II disease were restaged using the 2023 system. In contrast, patients with stage III and IV disease were fixed in the 2009 and 2023 systems. Molecular classification downstaged 10 patients (71.4%) to IAmPOLEmut and upstaged 6 patients (37.5%) to IICmp53abn. The 2023 system with molecular classification was associated with PFS and overall survival (p<0.001 and p=0.038). CONCLUSION: The 2023 staging system for EC subdivided stages I and II compared to the 2009 system. The 2023 system with molecular classification is a good predictor of survival.

MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia.

BACKGROUND: The mitogen-activated protein kinase (MAPK)/ERK signaling cascade and the phosphoinosytol-3 phosphate/Akt (PI3K/Akt) pathways are involved in proliferation and differentiation of hematopoietic cells. The frequency of PI3K/Akt and MAPK pathway activation in adult acute lymphoblastic leukemia (ALL) still need to be elucidated. AIMS: To assess the activity and prognostic implications of MAPK/ERK and PI3K/Akt pathways in adult (ALL). METHODS: We examined 28 precursor-B-cell ALL and 6 T-cell primary ALL samples. Flow cytometry was employed to analyze the expression levels of phosphorylated ERK and phosphorylated Akt. RESULTS: Ten out of 15 (67%) ALL fresh samples (7 B-cell, 3 T-cell) showed constitutive p-ERK expression. The p-ERK mean fluorescent index ratio (MFI (R)) showed a tendency to be higher in ALL than in normal T lymphocytes (1.26 [0.74-3.10] vs. 1.08 [1.02-1.21], respectively [p = .069]) and was significantly lower than in leukemic cell lines (median MFI (R) 3.83 [3.71-5.97] [p < .001]). Expression of p-Akt was found in 35% (12/34) (10 B-cell, 2 T-cell). The median MFI (R) expression for p-Akt in primary blast cell was 1.13 (0.48-9.90) compared to 1.01 (1.00-1.20) in normal T lymphocytes (p = ns) and lower than in leukemic cell lines (median MFI (R) 2.10 [1.77-3.40] [p = .037]). Moreover, expression of p-ERK was negatively associated with the expression of CD34 (1.22 [0.74-1.33] vs. 1.52 [1.15-3.10] for CD34(+) and CD34(-) group, respectively, p = .009). CONCLUSION: Our findings suggest that both MAPK/ERK and PI3K/Akt are constitutively activated in adult ALL, indicating a targeted therapy potential for ALL by using inhibitors of these pathways.

The novel use and feasibility of hemostatic oxidized regenerated cellulose agent (SurgiGuard®): multicenter retrospective study.

Background: SurgiGuard® is an absorbent hemostatic agent based on oxidized regenerated cellulose. The efficacy, effects and safety of SurgiGuard® are equivalent to existing hemostatic agents in animal experiments. This study was designed to confirm that the use of SurgiGuard® alone is effective, safe and feasible compared to combination with other hemostatic methods. Methods: We retrospectively reviewed clinical data from 12 surgery departments in seven tertiary centers in South Korea nationwide. All surgeries were performed between January and December 2018. Results: A total of 807 patients were enrolled; 447 patients (55.4%) had comorbidities. The rate of major surgery (operative time ≥4 hours) was 44% (n=355 patients). Regarding the type of SurgiGuard® used in surgery, more than 70% of minor surgeries used non-woven types. In major surgery, more than five SurgiGuards® were used in 7.3% (26 patients), and the proportion of co-usage (with four other hemostatic products) was 19.7% (70 patients). The effectiveness score was higher when SurgiGuard® was used alone in both major (5.3±0.5 vs. 5.1±0.6, P=0.048) and minor surgery (5.4±0.6 vs. 5.2±0.4, P<0.001). Seven patients had immediate re-bleeding, and all of them used SurgiGuard® and other products together. Nine patients reported adverse effects, such as abscess, bleeding, or leg swelling, but we found no direct correlation with SurgiGuard®. Conclusions: SurgiGuard® exhibited greater effectiveness when used alone. No direct adverse effects associated with SurgiGuard® use were reported, and SurgiGuard® had stable feasibility. Prospective comparative studies are needed in the future.

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).

Tissue Expression and Prognostic Role of CXCL12 and CXCR4 in High-grade Serous Ovarian Carcinoma.

BACKGROUND/AIM: The complex of C-X-C motif chemokine receptor 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), plays an essential role in cancer cell proliferation, invasion, and metastasis. These are emerging therapeutic targets, and recent studies have reported that inhibition of CXCL12-CXCR4 signaling pathway enhances the effects of immune checkpoint inhibitors. Thus, we aimed to investigate tissue expression of CXCL12 and CXCR4 in high-grade serous ovarian carcinoma (HGSOC) and to determine their potential as prognostic markers. PATIENTS AND METHODS: We used chemotherapy-naïve, formalin-fixed paraffin-embedded primary ovarian cancer tissues obtained from patients with advanced-stage HGSOC at the time of primary cytoreductive surgery. After histological reassessment, we constructed a tissue microarray and performed immunohistochemical staining for CXCL12 and CXCR4. Thereafter, clinicopathological characteristics and survival outcomes were compared between the high- and low-expression groups. RESULTS: A total of 97 patients with FIGO stage IIIC-IV HGSOC were included: 15 (15.5%), 66 (68.0%), and 13 (13.4%) patients showed high expression of CXCL12, CXCR4, and both, respectively. The expression level of each protein was not associated with germline BRCA1/2 mutational status, FIGO stage, or residual tumor after primary cytoreductive surgery. In multivariate analysis adjusted for confounders, high CXCL12 expression was identified as an independent poor prognostic biomarker for progression-free survival (adjusted hazards ratio, 1.990; 95% confidence interval=1.090-3.633; p=0.025). However, CXCR4 expression was not associated with patient survival outcomes. CONCLUSION: The CXCL12 expression level may represent a prognostic biomarker for HGSOC. Proteins related to the CXCL12/CXCR4 complex may serve as therapeutic targets in HGSOC treatment.

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.

Prognostic significance of L1CAM expression in addition to ProMisE in endometrial cancer.

OBJECTIVE: To investigate the prognostic significance of L1 cell-adhesion molecule (L1CAM), ß-catenin, and programmed death-ligand 1 (PD-L1) in endometrial cancer (EC) patients, with a focus on p53 wild-type subgroup, for additional risk stratification. METHODS: This retrospective cohort study included EC patients classified according to Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) who underwent primary surgical treatment at the single center between January 2014 and December 2018. Immunohistochemical staining was performed for four mismatch repair (MMR) proteins, p53, L1CAM, ß-catenin, and PD-L1. DNA polymerase epsilon (POLE) mutation was detected by hot spot sequencing via droplet digital polymerase chain reaction. Survival outcome of each subgroup of L1CAM, ß-catenin, and PD-L1 was measured according to their expression. RESULTS: A total of 162 EC patients were included. Endometrioid histologic type and early-stage disease were 140 (86.4%) and 109 (67.3%), respectively. ProMisE classification assigned 48 (29.6%), 16 (9.9%), 72 (44.4%), and 26 (16.0%) patients to MMR-deficient, POLE-mutated, p53 wild-type, and p53 abnormal subgroups, respectively. L1CAM was identified as an independent poor prognostic factor for progression-free survival (PFS; adjusted hazard ratio [aHR], 3.207; 95% confidence interval (CI), 1.432-7.187; P = 0.005), whereas ß-catenin and PD-L1 positivity were not associated with recurrence (P = 0.462 and P = 0.152, respectively). In p53 wild-type subgroup, L1CAM positivity was associated with worse PFS (aHR, 4.906; 95% CI, 1.685-14.287; P = 0.004). CONCLUSION: L1CAM positivity was associated with poor prognosis in EC and further stratified the risk of recurrence in p53 wild-type subgroup, whereas ß-catenin and PD-L1 were not informative for risk stratification.

Conization before radical hysterectomy in patients with early-stage cervical cancer: A Korean multicenter study (COBRA-R).

OBJECTIVE: To investigate the impact of conization on survival outcomes and to identify a specific population that might benefit from conization before radical hysterectomy (RH) in patients with early-stage cervical cancer. METHODS: From six institutions in Korea, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who underwent primary type C RH between 2006 and 2021. The patients were divided into multiple groups based on tumor size, surgical approach, and histology. We performed a series of independent 1:1 propensity score matching and compared the survival outcomes between the conization and non-conization groups. RESULTS: In total, 1254 patients were included: conization (n = 355) and non-conization (n = 899). Among the matched patients with a tumor size of >2 cm, the conization group showed a significantly better 3-year disease-free survival (DFS) rate compared with the non-conization group when RH was conducted via minimally invasive surgery (MIS), in those with squamous cell carcinoma (96.3% vs. 87.4%, P = 0.007) and non-squamous cell carcinoma (97.0% vs. 74.8%, P = 0.021). However, no difference in DFS was observed between the two groups among the matched patients with a tumor size of ≤2 cm, regardless of surgical approach or histological type. In patients who underwent MIS RH, DFS significantly worsened as the residual tumor size increased (P < 0.001). CONCLUSION: Cervical conization was associated with a lower recurrence rate in patients with early-stage cervical cancer with a tumor size of >2 cm who underwent primary MIS RH. Cervical conization may be performed prior to MIS RH to minimize the uterine residual tumor.

Diagnostic imaging of adnexal masses in pregnancy.

Adnexal masses detected during pregnancy require a prompt and accurate diagnosis to ensure fetal safety and good oncological outcomes. Computed tomography is the most common and useful diagnostic imaging modality for diagnosing adnexal masses; however, it is contraindicated in pregnant women because of the teratogenic effect of radiation on the fetus. Therefore, ultrasonography (US) is commonly used as the main alternative for the differential diagnosis of adnexal masses during pregnancy. Additionally, magnetic resonance imaging (MRI) can assist in the diagnosis when US findings are inconclusive. As each disease has characteristic US and MRI findings, understanding these features is important for the initial diagnosis and subsequent treatment. Thus, we thoroughly reviewed the literature and summarized the key findings of US and MRI to apply these in real-world clinical practice for various adnexal masses detected during pregnancy.

Development and Validation of 18F-FDG PET/CT-Based Models for Predicting Successful Complete Cytoreduction During Primary Cytoreductive Surgery for Advanced Ovarian cancer.

PURPOSE: The aim of this study was to develop an 18F-FDG PET/CT-based model to predict complete cytoreduction during primary cytoreductive surgery (CRS) for ovarian cancer (OC). PATIENTS AND METHODS: We retrospectively identified patients with stage III-IV OC who underwent primary CRS between June 2013 and February 2020 at 2 tertiary centers. Patients from each hospital were assigned to training and test sets. The abdominal cavity was divided into 3 sections, and data for the PET/CT-derived parameters were collected through image analysis. Various prediction models were constructed by combining clinicopathologic characteristics and PET/CT-derived parameters. The performance of the model with the highest area under the receiver operating characteristic curve (AUC) was externally validated. RESULTS: The training and test sets included 159 and 166 patients, respectively. The median age of patients in the test set was 55 years; 72.3% of them had stage III tumors, and 65.4% underwent complete cytoreduction. Metabolic tumor volume, total lesion glycolysis, and the number of metastatic lesions above the upper margin of the renal vein (area A) were selected among the PET/CT parameters. The best predictive multivariable model consisted of CA-125 (<750 or ≥750 IU/mL), number of metastatic lesions (<2 or ≥2), and metabolic tumor volume of area A, predicting complete cytoreduction with an AUC of 0.768. The model was validated using a test set. Its predictive performance yielded an AUC of 0.771. CONCLUSIONS: We successfully developed and validated a preoperative model to predict complete cytoreduction in advanced OC. This model can facilitate patient selection for primary CRS in clinical practice.

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.