Current Oncology

Research

14 pages, 1452 KiB

Open AccessArticle

Prognostic Relevance of Weight and Weight Loss during Multimodal Therapy for Oesophagogastric Tumours

by Alessandro Lorusso, Dmitry Bichev, Anica Högner, Prisca Bartels, Alexej Ballhausen, Christoph Treese, Matthias Biebl and Peter Thuss-Patience

Curr. Oncol. 2022, 29(4), 2706-2719; https://doi.org/10.3390/curroncol29040221 - 12 Apr 2022

Cited by 2 | Viewed by 2090

Abstract

The prognostic meaning of weight loss (WL) during standard treatment for operable oesophagogastric cancer is still unclear. The aim of this study is to analyse the prognostic effect of WL during perioperative chemotherapy (PC) for gastric cancer (GC) and oesophageal adenocarcinomas (OAC). We [...] Read more.

The prognostic meaning of weight loss (WL) during standard treatment for operable oesophagogastric cancer is still unclear. The aim of this study is to analyse the prognostic effect of WL during perioperative chemotherapy (PC) for gastric cancer (GC) and oesophageal adenocarcinomas (OAC). We retrospectively analysed data from 128 patients (pts) with GC and OAC who underwent surgery in the context of multimodal treatment with PC. We collected data on WL during different steps of therapy together with other histopathologic and demographic information. We analysed the effects on overall survival (OS) and disease-free survival (DFS). Results: Pts with WL ≥ 5% during neoadjuvant chemotherapy exhibited significantly worse OS compared with pts with WL < 5% (median OS: 23.6 months [95% CI: 4.4–42.9] vs. 63.5 months [95% CI: 50.7–76.2], p = 0.007) and DFS (median DFS: 12.5 months [95% CI: 2.9–22.1] vs. 63.5 months [95% CI: 31.6–95.4], p = 0.016). Pts with WL ≥ 14% during the whole treatment exhibited significantly worse OS compared with pts with WL < 14% (median OS: 43.7 months [95% CI: 13.2–74.2] vs. not reached, p = 0.028) and DFS (median DFS: 34.3 months [95% CI: 14.0–54.5] vs. not reached, p = 0.038). Conclusion: WL patterns during neoadjuvant chemotherapy and during the whole treatment correlate with a significantly worse prognosis in operated pts with curative GC or OAC in the context of a multimodal treatment with PC. A validation of this prognostic effect in prospective studies is warranted. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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14 pages, 1852 KiB

Open AccessArticle

Impact of Postoperative Chemotherapy in Patients with Gastric/Gastroesophageal Adenocarcinoma Treated with Perioperative Chemotherapy

by Alexej Ballhausen, Prisca Bartels, Ines Iacovella, Anica Hoegner, Alessandro Lorusso, Dmitry Bichev, Severin Daum and Peter Thuss-Patience

Curr. Oncol. 2022, 29(3), 1983-1996; https://doi.org/10.3390/curroncol29030161 - 14 Mar 2022

Cited by 2 | Viewed by 2568

Abstract

Perioperative chemotherapy is the standard of care for patients undergoing curative resection for gastroesophageal adenocarcinoma. However, less than 50% of patients complete postoperative chemotherapy, and the added benefit to preoperative chemotherapy remains unclear. The aim of this study was to compare disease-free and [...] Read more.

Perioperative chemotherapy is the standard of care for patients undergoing curative resection for gastroesophageal adenocarcinoma. However, less than 50% of patients complete postoperative chemotherapy, and the added benefit to preoperative chemotherapy remains unclear. The aim of this study was to compare disease-free and overall survival (DFS and OS) in patients with perioperative chemotherapy to those who received preoperative chemotherapy only. In addition, a current literature overview is included. This multicenter, retrospective case series included 124 patients with gastroesophageal adenocarcinoma undergoing potentially curative resection and receiving pre- or perioperative chemotherapy between 2006 and 2010. Histopathological, demographic, clinical, and survival data were used to identify the impact of perioperative vs. preoperative chemotherapy on DFS and OS. Patients with perioperative chemotherapy had significantly improved DFS and OS (median DFS 28.0 months; 95%CI 0–62.4 vs. 19.0 months; 95%CI 10.5–27.5; p = 0.008 and median OS 35.7 months; 95%CI 0–73.6 vs. 19.2 months; 95%CI 7.8–30.4; p = 0.002). However, in contrast to patients with tumor-free lymph nodes at the time of resection, patients with positive lymph node status did not significantly benefit from additional postoperative chemotherapy in subgroup analysis. Further studies are encouraged to investigate optimal adjuvant treatment strategies for primary chemotherapy-resistant patients. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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12 pages, 2339 KiB

Open AccessArticle

HMGA1 Has Predictive Value in Response to Chemotherapy in Gastric Cancer

by Diana Pádua, Débora Filipa Pinto, Paula Figueira, Carlos Filipe Pereira, Raquel Almeida and Patrícia Mesquita

Curr. Oncol. 2022, 29(1), 56-67; https://doi.org/10.3390/curroncol29010005 - 23 Dec 2021

Cited by 8 | Viewed by 3979

Abstract

Gastric cancer is a serious health problem worldwide. Although its incidence is decreasing, the five-year survival rate remains low. Thus, it is essential to identify new biomarkers that could promote better diagnosis and treatment of patients with gastric cancer. High-mobility group AT-hook 1 [...] Read more.

Gastric cancer is a serious health problem worldwide. Although its incidence is decreasing, the five-year survival rate remains low. Thus, it is essential to identify new biomarkers that could promote better diagnosis and treatment of patients with gastric cancer. High-mobility group AT-hook 1 (HMGA1) is a non-histone, chromatin-binding protein that has been found overexpressed in several tumor types. It has been correlated with invasion, metastasis, and drug resistance, leading to worse patient survival. The aim of this work was to evaluate the clinical value of HMGA1 in gastric cancer. HMGA1 expression was analyzed by immunohistochemistry in a single hospital series (n = 323) of gastric adenocarcinoma cases (stages I to IV) with clinicopathological and treatment data. In this series, HMGA1 expression showed no significant relevance as a prognostic biomarker. Nevertheless, a significantly better overall survival was observed in cases with high levels of HMGA1 when they were treated with chemotherapy, compared to the nontreated ones, implying that they can benefit more from treatment than patients with low expression of HMGA1. We thereby show for the first time that HMGA1 expression has a substantial value as a biomarker of response to chemotherapy in gastric cancer. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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Review

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11 pages, 380 KiB

Open AccessReview

Immunotherapy in Squamous Cell Cancer of the Esophagus

by Peter Thuss-Patience and Alexander Stein

Curr. Oncol. 2022, 29(4), 2461-2471; https://doi.org/10.3390/curroncol29040200 - 30 Mar 2022

Cited by 24 | Viewed by 6110

Abstract

Treatment of esophageal carcinoma has changed dramatically following several landmark trials, which have proven the benefit of immunotherapy. The selective PD-1 (programmed cell death ligand-1)-inhibitor nivolumab has been shown to improve DFS in the adjuvant therapy setting (CheckMate-577). In the first-line treatment, PD-L1 [...] Read more.

Treatment of esophageal carcinoma has changed dramatically following several landmark trials, which have proven the benefit of immunotherapy. The selective PD-1 (programmed cell death ligand-1)-inhibitor nivolumab has been shown to improve DFS in the adjuvant therapy setting (CheckMate-577). In the first-line treatment, PD-L1 positive (CPS ≥ 10) squamous cell carcinoma patients (pts) have been shown to have an increased OS following treatment with the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). Nivolumab also improved overall survival in the first line setting either combined with ipilimumab or with chemotherapy (CheckMate 648) compared to chemotherapy alone. In Asian first-line patients, phase III trials investigating camrelizumab (ESCORT 1), toripalimab (JUPITER 06), or sintilimab (ORIENT 15) in addition to chemotherapy also showed significant survival benefits. In the second-line setting, monotherapy with nivolumab (ATTRACTION-03), pembrolizumab (KEYNOTE-181), camrelizumab (ESCORT), and tislelizumab (RATIONALE 302) demonstrated a benefit in OS in comparison to chemotherapy. Here we will review these trials and integrate them into the current treatment algorithm. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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24 pages, 3114 KiB

Open AccessReview

A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/β-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response

by Uttam Sharma, Masang Murmu, Tushar Singh Barwal, Hardeep Singh Tuli, Manju Jain, Hridayesh Prakash, Tea Kaceli, Aklank Jain and Anupam Bishayee

Curr. Oncol. 2022, 29(4), 2326-2349; https://doi.org/10.3390/curroncol29040189 - 26 Mar 2022

Cited by 12 | Viewed by 4499

Abstract

Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of [...] Read more.

Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of the cancer phenotype are under the control of complex cancer-related signaling pathways. In this review, we provide comprehensive knowledge about long non-coding RNAs (lncRNAs) related to Wnt/β-catenin and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ESCC and its implications in hindering the efficacy of chemotherapeutic drugs. We observed that a pool of lncRNAs, such as HERES, TUG1, and UCA1, associated with ESCC, directly or indirectly targets various molecules of the Wnt/β-catenin pathway and facilitates the manifestation of multiple cancer phenotypes, including proliferation, metastasis, relapse, and resistance to anticancer treatment. Additionally, several lncRNAs, such as HCP5 and PTCSC1, modulate PI3K/Akt/mTOR pathways during the ESCC pathogenesis. Furthermore, a few lncRNAs, such as AFAP1-AS1 and LINC01014, block the efficiency of chemotherapeutic drugs, including cisplatin, 5-fluorouracil, paclitaxel, and gefitinib, used for ESCC treatment. Therefore, this review may help in designing a better therapeutic strategy for ESCC patients. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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16 pages, 553 KiB

Open AccessEditor’s ChoiceReview

Immunotherapy in Gastric Cancer

by Anica Högner and Markus Moehler

Curr. Oncol. 2022, 29(3), 1559-1574; https://doi.org/10.3390/curroncol29030131 - 2 Mar 2022

Cited by 87 | Viewed by 12882

Abstract

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal [...] Read more.

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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12 pages, 506 KiB

Open AccessReview

Circulating Tumor DNA in Gastric and Gastroesophageal Junction Cancer

by Lisa Paschold and Mascha Binder

Curr. Oncol. 2022, 29(3), 1430-1441; https://doi.org/10.3390/curroncol29030120 - 25 Feb 2022

Cited by 8 | Viewed by 3913

Abstract

Tumor cells shed DNA into the plasma. “Liquid biopsy” analysis of mutations or other genomic alterations in circulating cell-free DNA (cfDNA) may provide us with a tool to detect minimal residual cancer, comprehensively profile the genomic tumor landscape in search of druggable targets, [...] Read more.

Tumor cells shed DNA into the plasma. “Liquid biopsy” analysis of mutations or other genomic alterations in circulating cell-free DNA (cfDNA) may provide us with a tool to detect minimal residual cancer, comprehensively profile the genomic tumor landscape in search of druggable targets, and monitor cancers non-invasively over time for treatment failure or emerging treatment-resistant tumor subclones. While liquid biopsies have not yet entered routine clinical management in patients with gastric and gastroesophageal junction cancers, this group of diseases may benefit from such advanced diagnostic tools due to their pronounced genetic spatiotemporal heterogeneity and limitations in imaging sensitivity. Moreover, as the armamentarium of targeted treatment approaches and immunotherapies expands, cfDNA analyses may reveal their utility not only as a biomarker of response but also for precision monitoring. In this review, we discuss the different applications of cfDNA analyses in patients with gastric and gastroesophageal junction cancer and the technical challenges that such liquid biopsies have yet to overcome. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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Other

Jump to: Research, Review

7 pages, 607 KiB

Open AccessCommentary

Hereditary Diffuse Gastric Cancer—Update Based on the Current Consort Recommendations

by Christoph Treese, Britta Siegmund and Severin Daum

Curr. Oncol. 2022, 29(4), 2454-2460; https://doi.org/10.3390/curroncol29040199 - 30 Mar 2022

Cited by 4 | Viewed by 3491

Abstract

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant inherited cancer syndrome that has been associated with a mutation of the CDH1, and rarely the CTNNA1 gene, respectively. HDGC is characterized histologically by multifocal growth and signet ring cells in the gastric [...] Read more.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant inherited cancer syndrome that has been associated with a mutation of the CDH1, and rarely the CTNNA1 gene, respectively. HDGC is characterized histologically by multifocal growth and signet ring cells in the gastric mucosa and lobular type breast cancer. In cases of a proven pathogenic CDH1 mutation, a prophylactic gastrectomy, or alternatively, an annual surveillance gastroscopy in expert centers is recommended. Additionally, MR imaging of the breast should be performed annually starting from the age of 30, to detect lobular breast cancer. In 2020, the International Gastric Cancer Linkage Consortium (IGCLC) additionally defined new clinical groups with specific recommendations: (1) the group of patients with a proven mutation in the CDH1 gene, but exclusive manifestation as lobular breast cancer, was defined as hereditary lobular breast cancer (HLBC); (2) the group, which clinically fulfills familial HDGC criteria, in the absence of a relevant mutation, was designated as HDGC-like. This update summarizes relevant aspects of hereditary gastric cancer and the current recommendation criteria of the IGCLC published in 2020. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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