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Controversies in the Staging of Patients with Locally Advanced Cervical Cancer.

ABSTRACT: Approximately 10-25% of patients with locally advanced cervical cancer harbor metastases to the para-aortic lymph nodes. Staging of patients with locally advanced cervical cancer can be performed with imaging techniques, such as PET-CT; however, false negative rates can be as high as 20%, especially for patients with pelvic lymph node metastases. Surgical staging can identify patients with microscopic lymph nodes metastases and aid in accurate treatment planning with the administration of extended-field radiation therapy. Data from retrospective studies investigating the impact of para-aortic lymphadenectomy on the oncological outcomes of patients with locally advanced cervical cancer are mixed, while data from randomized controlled trials do not demonstrate a progression-free survival benefit. In the present review, we explore controversies in the staging of patients with locally advanced cervical cancer and summarize the available literature.

SUBMITTER: Nasioudis D

PROVIDER: S-EPMC10217654 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Controversies in the Staging of Patients with Locally Advanced Cervical Cancer.

Nasioudis Dimitrios D George Erin M EM Tanyi Janos L JL

Diagnostics (Basel, Switzerland) 20230516 10

Approximately 10-25% of patients with locally advanced cervical cancer harbor metastases to the para-aortic lymph nodes. Staging of patients with locally advanced cervical cancer can be performed with imaging techniques, such as PET-CT; however, false negative rates can be as high as 20%, especially for patients with pelvic lymph node metastases. Surgical staging can identify patients with microscopic lymph nodes metastases and aid in accurate treatment planning with the administration of extend ...[more]

PMID: 37238231

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Project description:Gastroesophageal cancer (GEC) remains a challenging problem in oncology. Anatomically, GEC is comprised of distal gastric adenocarcinoma (GC), classically associated with Helicobacter Pylori, while proximal esophagogastric adenocarcinoma (EGJ AC) has increased significantly in incidence over the past years. Despite contrasting etiologies, histologies, and molecular phenotypes of distal and proximal GEC, in many cases perioperative (and metastatic) treatment strategies converge to similar approaches. For patients undergoing curative intent surgery, advances in perioperative chemotherapy and/or chemoradiotherapy, either before and/or after surgery, have demonstrated improved survivals compared to surgery alone. This review focuses on how the 'boundary' of the Z-line and/or the anatomical distinction of 'proximal' (EGJ) vs. 'distal' (GC) cancer has led to diverse inclusion/exclusion criteria for clinical trial enrollment, embodying various combinations of chemotherapy and radiation before and/or after surgery. Supporting evidence of each of these approaches consequently has led to a number of varying practices by geographical region and Institution/Physician, based on differing experience, preference, and clinical circumstance. Adequate direct comparison of these approaches is lacking currently, but data from a number of concerted efforts should be available in the next years to further direct best standards of care. Introduction of biologically targeted agents, namely anti-angiogenics and anti-HER family therapeutics are being evaluated to determine whether further therapeutic gains can be realized over classic cytotoxic chemotherapy alone (with/without radiotherapy). To date, novel molecularly targeted agents have yet to demonstrate benefit in this setting. In the following comprehensive review we will address the intricacies of perioperative treatment of locally advanced GEC, with focus on clinical trials supporting the diverse set of perioperative multidisciplinary approaches.

Project description:Purpose: We aimed to investigate the distinct transcriptional landscape in the poor responders to concurrent chemoradiotherapy (CCRT) and to gain mechanistic insights on treatment resistance in cervical cancer. Methods: RNA sequencing was performed using archived pre-treatment tissue biopsies of patients with locally advanced cervical cancer treated with concurrent platinum-based CCRT. Transcriptome data of patients with no durable benefit (NDB; progression-free period < 3 years) and durable clinical benefit (DCB; progression-free period > 5 years) after were compared. NDB score was estimated for each patient using the differentially expressed genes between NDB and DCB patients. Three independent cohorts, including The Cancer Genome Atlas cervical cancer (TCGA-CESC) cohort, were utilized for validation of NDB score. Potential response to PD-1 blockade was estimated with Tumor Immune Dysfunction and Exclusion (TIDE) score and T-cell-inflamed gene expression profile (GEP). Results: Patients with NDB exhibited a distinct transcriptional profile compared to those with DCB such as higher signatures of extracellular matrix organization and epithelial-to-mesenchymal transition. The fraction of cancer-associated fibroblasts (CAFs) within the tumor was significantly higher in NDB than DCB patients. Higher NDB score was significantly associated with poor survival in the TCGA-CESC cohort (n = 274; P = 0.015), but only in patients that received curative aim radiotherapy (P = 0.002) and not in patients who received other treatments (P = 0.57). The transcriptomic characteristics of patients with NDB were recapitulated in patients with high NDB score in TCGA-CESC. Patients with high NDB score displayed significantly higher TIDE prediction score and lower T-cell-inflamed GEP score compared to patients with low NDB scores. Conclusion: Cervical cancer patients with poor treatment outcome following CCRT exhibited a distinct gene signature that was able to predict treatment outcomes. For poor responders, immune checkpoint inhibitors may be less effective and CAF-targeting treatments may be a promising approach.

Dataset Information

Controversies in the Staging of Patients with Locally Advanced Cervical Cancer.

Publications

Controversies in the Staging of Patients with Locally Advanced Cervical Cancer.

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