Search

PurposeThis study aimed to investigate genomic and immunohistochemical (IHC) profiles and immunotherapy outcomes in patients with cervical cancer.MethodsPatients with recurrent cervical cancer who underwent tumor next-generation sequencing (NGS) with the TruSight Oncology 500 panel at Yonsei Cancer Center between June 2019 and February 2022, were identified. Patients who received treatment with checkpoint inhibitors during the same period were also identified. Clinical information, including histology, stage, human papillomavirus (HPV) genotype, IHCs profile, and therapy outcome, was reviewed.ResultsWe identified 115 patients treated for recurrent cervical cancer, including 74 patients who underwent tumor NGS. Most of these 74 patients were initially diagnosed with advanced stage (63.6%) and had squamous cell histology (52.7%), and high-risk HPV (76.9%). Based on IHC analysis, the programmed death-ligand 1 combined positive score (PD-L1 CPS) was higher in patients with squamous cell carcinoma (SCC) than in those with adeno or mucinous types (P=0.020). HER2 receptor expression of 2+ and 3+ were identified in 5 and 1 patients, respectively, and significantly varied based on histology (p=0.002). Among the 74 patients, single nucleotide variants (SNVs) and copy number variations (CNVs) were identified in 60 (81.1%) and 13 patients (17.6%), respectively. The most common SNVs were PIK3CA, TP53, STK11, FAT1, and FBXW7 mutations. Mutations in PIK3CA, with two hotspot mutations, were frequently observed in patients with SCC histology, whereas mutations in TP53 were frequently observed in patients with non-SCC histology. Additionally, variations in FAT1 were exclusively identified in patients with SCC histology. Mutations in homologous recombination repair-associated genes were identified in 18 patients (24.3%). The most frequent CNV alteration was CCNE1 amplification. Moreover, among the 36 patients who underwent NGS and received immunotherapy, the tumor mutational burden and microsatellite instability were significantly correlated with immunotherapy duration. During this timeframe, 73 patients received pembrolizumab monotherapy, among whom a small portion showed a durable response.ConclusionComprehensive genomic and IHC profiling may help identify potential candidates for targeted immunotherapy in patients with cervical cancer.

PurposeCervical smear samples are easily obtainable and may effectively reflect the tumor microenvironment in gynecological cancers. Therefore, we investigated the feasibility of genomic profiling based on tumor DNA analysis from cervical smear samples from endometrial cancer patients.Materials and methodsPreoperative cervical smear samples were obtained via vaginal sampling in 50 patients, including 39 with endometrial cancer and 11 with benign uterine disease. Matched blood samples were obtained simultaneously. Genomic DNA (gDNA) from cervical smear and/or cell-free DNA from whole blood were extracted and sequenced using the Pan100 panel covering 100 endometrial cancer-related genes.ResultsCervical swab-based gDNA analysis detected cancer with 67% sensitivity and 100% specificity, showing a superior performance compared to that of the matched blood or Pap smear tests. Cervical swab-based gDNA effectively identified patients with loss of MSH2 or MSH6 and aberrant p53 expression based on immunohistochemistry. Genomic landscape analysis of cervical swab-based gDNA identified PTEN, PIK3CA, TP53, and ARID1A as the most frequently altered genes. Furthermore, 26 endometrial cancer patients could be classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer.ConclusionCervical swab-based gDNA test showed an improved detection potential and allowed the classification of patients, which has both predictive and prognostic implications.

To evaluate the additive effects of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval debulking surgery (IDS) in patients with advanced-stage ovarian cancer. From January 2015 to February 2019, 123 patients with stages IIIC-IV ovarian cancer were treated with neoadjuvant chemotherapy (NAC) followed by IDS with optimal cytoreduction. Forty-three patients received IDS with HIPEC and 80 patients had IDS without HIPEC. The median follow-up period was 34.4 months. No differences in baseline characteristics in patients were found between the two groups. The IDS with HIPEC group had fewer median cycles of chemotherapy (P = 0.002) than the IDS group. The IDS with HIPEC group had a higher rate of high surgical complexity score (P = 0.032) and higher rate of complete resection (P = 0.041) compared to the IDS group. The times to start adjuvant chemotherapy were longer in the IDS with HIPEC group compared to the IDS group (P < 0.001). Postoperative grade 3 or 4 complications were similar in the two groups (P = 0.237). Kaplan-Meier analysis showed that HIPEC with the IDS group had better progression-free survival (PFS) (P = 0.010), while there was no difference in overall survival between the two groups (P = 0.142). In the multivariate analysis, HIPEC was significantly associated with better PFS (HR, 0.60; 95% CI, 0.39 - 0.93). The addition of HIPEC to IDS resulted in longer PFS than IDS without HIPEC not affecting the safety profile. Further research is needed to evaluate the true place of HIPEC in the era of targeted treatments.