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Exploring New Approaches for Locally Advanced Gastroesophageal Adenocarcinomas: TNT, Irinotecan, and ctDNA.

ABSTRACT: The authors of a recent pilot study incorporated novel concepts including total neoadjuvant therapy with induction triplet FOLFIRINOX then chemoradiotherapy before surgery, along with ctDNA minimal residual disease analyses demonstrating both feasibility of this approach as well as confirming prognostic value of ctDNA analysis before and after surgery.See related article by Wo et al., p. 6343.

SUBMITTER: Catenacci DVT

PROVIDER: S-EPMC8639623 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Exploring New Approaches for Locally Advanced Gastroesophageal Adenocarcinomas: TNT, Irinotecan, and ctDNA.

Catenacci Daniel V T DVT

Clinical cancer research : an official journal of the American Association for Cancer Research 20210929 23

The authors of a recent pilot study incorporated novel concepts including total neoadjuvant therapy with induction triplet FOLFIRINOX then chemoradiotherapy before surgery, along with ctDNA minimal residual disease analyses demonstrating both feasibility of this approach as well as confirming prognostic value of ctDNA analysis before and after surgery.<i>See related article by Wo et al., p. 6343</i>. ...[more]

PMID: 34588214

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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:BackgroundTotal neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta-analysis to assess such concerns.Materials and methodsHead-to-head phase II/III RCTs were searched in Embase, PubMed, Web of Science, and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), local recurrence-free survival, distant metastasis-free survival, and the R0 resection rate.ResultsEight phase II/III RCTs involving 2,196 patients with LARC were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (odds ratio, 1.77; 95% confidence interval [CI], 1.28-2.45; p = .0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard chemoradiotherapy (hazard ratio [HR], 0.83; 95% CI, 0.72-0.96; p = .03 and HR, 0.88; 95% CI, 0.74-1.05; p = .15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR, 0.81; 95% CI, 0.68-0.95; p = .012).ConclusionThe overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS and reduce the risk of distant metastasis.Implications for practiceLocally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis because of its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta-analysis found that TNT in LARC is associated with a significant improvement in overall pathologic complete response rate, disease-free survival, overall survival, and distant metastasis-free survival compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.

Dataset Information

Exploring New Approaches for Locally Advanced Gastroesophageal Adenocarcinomas: TNT, Irinotecan, and ctDNA.

Publications

Exploring New Approaches for Locally Advanced Gastroesophageal Adenocarcinomas: TNT, Irinotecan, and ctDNA.

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