Sanghoon Lee

Concordance of Genomic Alterations in Ovarian Cancer Tissues and Circulating-Tumor DNA: A Pilot Study

High-grade serous ovarian carcinoma (HGSOC) is characterized by profound genomic instability and spatial heterogeneity. Liquid biopsy, utilizing circulating tumor DNA (ctDNA), offers a non-invasive approach to capture the comprehensive mutational landscape of the disease. This pilot study evaluated the concordance of genomic alterations between cell-free DNA (cfDNA) and matched tumor tissue in patients with HGSOC. Twelve patients with HGSOC undergoing primary cytoreductive surgery were enrolled. Using the Macrogen® Axen™ Cancer Panel 2 with unique molecular identifier (UMI) technology for error suppression, we achieved a theoretical limit of detection of ~0.36% VAF. The mean cfDNA concentration was 107.3 ng/mL, showing a significant positive correlation with FIGO stage (p = 0.016). While the sensitivity of cfDNA to detect tissue-confirmed mutations was 57.6%, the overall gene-level concordance was 95.3%, largely driven by negative agreement in wild-type genes. Liquid biopsy revealed a significantly broader mutational spectrum (mean 9.67 alterations/patient) compared to tissue (5.50/patient). Crucially, concordant mutations exhibited high variant allele frequencies (VAFs) (mean 41.4%), whereas plasma-unique discordant mutations showed significantly lower VAFs (mean 7.31%, p < 0.001). These preliminary findings suggest that while tissue biopsy likely reflects the dominant clonal population, liquid biopsy may serve as a potential molecular mirror, capturing subclonal variants from spatially distinct metastatic sites and hypoxic niches.

Fertility-sparing treatments for patients with endometrial cancer: A comprehensive review

Endometrial cancer (EC) in young women is relatively likely to be early-stage, low-grade, and without risk factors. Fertility-sparing treatment with progestin is a potential primary approach for certain patients. However, several factors should be considered according to available guidelines. The potential indication for fertility-sparing treatment in patients with EC, as recommended by various societies of gynecologic oncology, includes young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Other imaging modalities may also be used to exclude extrauterine disease. Various fertility-sparing therapies exist, the most common of which is high-dose oral progestin. After initiating fertility-sparing treatment, pathological re-evaluation of the endometrium at 3 to 6 months is recommended. The optimal duration of fertility-sparing treatment is up to 15 months, but guidelines recommend continuing progestin therapy until attempting conception. Ovarian stimulation drugs used for pregnancy are considered safe after a complete response is achieved. Hysterectomy is recommended after childbearing, while oophorectomy is not mandatory for young women. Close surveillance should continue for women who do not wish to undergo surgery after childbirth. Based on existing evidence, fertility-preserving treatments have demonstrated effectiveness and do not appear to negatively impact prognosis. If a qualified patient expresses a strong desire for fertility preservation despite the potential for recurrence, the physician should consider fertility-sparing treatment while maintaining vigilant monitoring.

Surgical and Blood-Based Minimal Residual Disease in Patients with Ovarian Cancer after First-line Therapy: Clinical Outcomes and Translational Opportunities

Abstract Purpose: Minimal residual disease (MRD) after first-line treatment of advanced-stage ovarian cancer remains a long-standing barrier to cure. We investigated the prognostic and translational value of MRD detection by second-look laparoscopy (SLL) and ctDNA at the completion of first-line therapy. Experimental Design: Patients with high-grade epithelial ovarian cancer who had a complete clinical response to first-line therapy and underwent SLL and plasma collection for ctDNA were included. Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients. Results: Forty of 95 (42.1%) patients had surgically detected MRD, which was associated with worse PFS (median PFS 7.4 vs. 23.8 months; P < 0.001) and OS (median OS 33.9 vs. not reached; P < 0.001). SLL positivity was an independent negative prognostic factor for OS (HR, 4.40; 95% confidence interval, 1.37–14.21; P = 0.013) in multivariable analysis. Among 44 patients who underwent SLL and had ctDNA testing, 34% (15/44) were ctDNA-positive, which was associated with worse PFS (6.4 vs. 28.1 months; P < 0.001) and OS (32.4 months vs. not reached; P = 0.008). We demonstrated the feasibility of spatial multiomics in studying MRD and their ability to provide hypothesis-generating observations, implicating the upregulation of the hypoxia signaling pathway, expression of multiple druggable targets (CDK6, GLS, MSLN, ERBB2), and immune exclusion in MRD lesions. Conclusions: Approximately half of patients in clinical remission after first-line therapy have assessable MRD, which can inform prognosis, therapeutic target discovery, and clinical trials.

The Value of the Naples Prognostic Score at Diagnosis as a Predictor of Cervical Cancer Progression

Background and Objectives: The Naples prognostic score (NPS), which incorporates inflammatory and nutritional indicators, is increasingly used as a prognostic score for various malignancies. Nonetheless, few studies have specifically evaluated the NPS as a prognostic factor for cervical cancer. This study aimed to assess the value of NPS at diagnosis as a predictor of cancer progression. Materials and Methods: This study included patients diagnosed with cervical cancer at Korea University Anam Hospital from January 2019 to December 2023. Patients with incomplete data or those who were lost to follow-up were excluded. The NPS was calculated based on laboratory results at the time of diagnosis, categorizing patients into the low-NPS group (NPS 0–1) and high-NPS group (NPS ≥ 2). Survival analysis was performed using the Kaplan–Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Results: Out of 178 patients, 98 and 80 were categorized into the low-NPS and high-NPS groups, respectively. Kaplan–Meier survival analysis showed that the high-NPS group had significantly lower disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.02) rates than the low-NPS group. Multivariate Cox regression analysis identified the NPS as an independent prognostic factor for DFS (adjusted hazard ratio, 1.98; p = 0.017), but not for OS. Conclusions: This study demonstrated that the NPS measured at diagnosis may serve as a useful independent prognostic factor for cancer progression in patients with cervical cancer.

Comparing efficacy of high-dose rate brachytherapy versus helical tomotherapy in the treatment of cervical cancer

Boost radiation using brachytherapy (BT) is a standard treatment for local disease control in concomitant chemoradiation therapy (CCRT) for advanced cervical cancer. However, it is associated with gastrointestinal and genitourinary complications. Hence, this study investigates the feasibility of helical tomotherapy (HT) as an alternative to BT. Medical records of patients who underwent CCRT between 2000 and 2017 at a single institution were retrospectively reviewed. Patients with stage IIB-IVA cancers were selected based on the 2009 criteria of The International Federation of Gynaecology and Obstetrics. External beam radiation combined with chemotherapy was followed by either BT or HT. The propensity score matching of both groups was calculated using logistic regression analysis. Disease outcomes and treatment-related adverse events were compared between the 2 groups. The matched population included 70 BT patients and 35 HT patients. The 5-year progression-free survival rates for BT and HT were 72.6% and 72.5%, respectively (p=0.721). There was no difference in the overall survival rate between the two groups (p=0.203). The presence of acute and chronic gastrointestinal complications was also similar between the groups (p=0.460 and p=0.563, respectively). The chronic genitourinary toxicities were also comparable (p=0.105). HT boost treatment showed comparable disease outcomes with those observed with conventional BT in patients with advanced cervical cancer. HT could be a complementary boost protocol as a single modality or hybrid with BT in selected patients. Further studies with longer follow-up periods are warranted to confirm long-term outcomes.

Combination Therapy with Copanlisib and Niraparib in Patients with Recurrent Endometrial and Ovarian Cancer (COPANIRA): Efficacy, Toxicity, and Translational Insights

Abstract Purpose: Patients with recurrent endometrial or ovarian cancer have poor survival outcomes. We evaluated the clinical efficacy and toxicity of copanlisib [a phosphatidylinositol 3-kinase (PI3K) inhibitor] and niraparib [a poly (ADP-ribose) polymerase inhibitor (PARPi)] in this patient population with translational insights. Patients and Methods: This was a phase Ib trial. Copanlisib was administered intravenously on days 1, 8, and 15 of a 28-day cycle, and niraparib was given orally once daily. Four dose levels were explored over a dose-limiting toxicity (DLT) window of 28 days. The primary objective was to determine the recommended phase II dose (RP2D) of this combination. Secondary objectives included safety, objective response rate (ORR), and pharmacokinetics. Tumor biopsies were analyzed using reverse phase protein array (RPPA) to identify molecular correlates of response. Results: Thirty patients were enrolled. An RP2D was not established due to DLTs, most commonly a grade 3 maculopapular rash attributed to copanlisib. The ORR was 12.5% (95% confidence interval, 2.8%–33.6%). RPPA was performed on tumors from eight patients. PI3K pathway activity did not correlate with PI3K mutational status. Nineteen proteins were differentially expressed between patients with stable disease and those with progressive disease; many were substrates of Akt (protein kinase B), implicating downstream PI3K signaling in response. Conclusions: The combination of copanlisib and niraparib demonstrated limited tolerability, and the ORR was modest. However, functional proteomic analyses identified candidate biomarkers—particularly Akt pathway substrates—which may inform future strategies to optimize PI3K and PARPi combinations.