Unsupervised Clustering of Immunohistochemical Markers to Define High-Risk Endometrial Cancer

Abstract Aim We investigate the role of preoperative PET parameters to determine risk classes and prognosis of endometrial cancer (EC). Methods We enrolled 81 patients with EC who underwent preoperative F-18 FDG PET/CT. PET parameters (SUVmax, SUVmean, MTV, TLG), grade, histology and size of the primary tumor, stage of the disease, the degree of myometrial invasion (MI), and the presence of lymphovascular invasion (LVI), cervical invasion (CI), distant metastasis (DM) and lymph node metastasis (LNM) were recorded. The relationship between PET parameters, clinicopathological risk factors and overall survival (OS) was evaluated. Results The present study included 81 patients with EC (mean age 60). Of the total sample, 21 patients were considered low risk (endometrioid histology, stage 1A, grade 1 or 2, tumor diameter < 4 cm, and LVI negative) and 60 were deemed high risk. All of the PET parameters were higher in the presence of a high-risk state, greater tumor size, deep MI, LVI and stage 1B-4B. MTV and TLG values were higher in the patients with non-endometrioid histology, CI, grade 3 and LNM. The optimum cut-off levels for differentiating between the high and low risk patients were: 11.1 for SUVmax (AUC = 0.757), 6 for SUVmean (AUC = 0.750), 6.6 for MTV(AUC = 0.838) and 56.2 for TLG(AUC = 0.835). MTV and TLG values were found as independent prognostic factors for OS, whereas SUVmax and SUVmean values were not predictive. Conclusions The PET parameters are useful in noninvasively differentiating between risk groups of EC. Furthermore, volumetric PET parameters can be predictive for OS of EC.

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Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer

Journal of Translational Medicine ◽

10.1186/s12967-021-02722-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Weiwei Feng ◽

Nan Jia ◽

Haining Jiao ◽

Jun Chen ◽

Yan Chen ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Tumor Recurrence ◽

Disease Free Survival ◽

Circulating Tumor Dna ◽

Plasma Samples ◽

Free Survival ◽

Tumor Relapse ◽

Disease Free ◽

Tumor Dna

Abstract Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

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Salvage Radiation for Pelvic Relapse after Surgically Treated Endometrial Cancer

Cancers ◽

10.3390/cancers13061367 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1367

Author(s):

Kristina Lindemann ◽

Elisabeth Smogeli ◽

Milada Cvancarova Småstuen ◽

Kjersti Bruheim ◽

Jone Trovik ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Risk Group ◽

Cox Model ◽

Figo Stage ◽

Target Volume ◽

Lymph Node Involvement ◽

High Risk Group ◽

Curative Intent ◽

Pelvic Relapse

(1) Background: This study evaluated the clinical outcome after salvage radiotherapy for first pelvic relapse after endometrial cancer (EC). (2) Methods: This multicenter retrospective study included EC patients with first central pelvic relapse without lymph node involvement treated with curative intent. Progression-free (PFS) and overall survival (OS) were calculated with the Kaplan–Meier method and possible predictive factors for risk of relapse and mortality were identified using the Cox model. (3) Results: We included 139 patients with median EQD2 (Equivalent Dose in 2 Gy fractions) to the clinical target volume of 70.0 Gy. During follow up of median 6.66 years, 39.6% patients developed a second relapse. Risk group classification at primary diagnosis based on histology, grading and FIGO stage and how the pelvic tumor boost was administered were independently associated with PFS and OS. Five-year OS was 68% (95% CI (59–75)) for the whole cohort. Five-year OS was 88% (95% CI (75–94)), 72% (95% CI (55–84)) and 38% (95% CI (15–60)) for the stage I low-, intermediate- and high-risk group, respectively. (4) Conclusions: The majority of central pelvic recurrences in RT-naive EC women can be successfully salvaged with radiotherapy. However, survival in patients with high-risk disease remains poor and warrants a more individualized approach to optimize outcome.

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