A Comprehensive Analysis of Alterations in DNA Damage Repair Pathways Reveals a Potential Way to Enhance the Radio-Sensitivity of Esophageal Squamous Cell Cancer

Abstract Background Endoscopic resection is the treatment of choice for early esophageal cancers. However, resections comprising more than 70–80 % of the circumference are associated with a high risk of stricture formation. Currently, repetitive local injections and/or systemic steroids are given for prevention. Case report We present here the case of a 78-year-old male patient who had a near circumferential endoscopic submucosal dissection for a pT1a mm, L0, V0, R0, G2 esophageal squamous cell cancer. At the end of endoscopic resection, 80 mg of triamcinolone was injected locally. The patient was then treated with oro-dispersible budesonide tablets (2 × 1 mg/day) and nystatin (4 × 100 000 I.E.) for 8 weeks. This treatment resulted in complete healing without any stricture formation and did not result in any complications. Discussion Treatment with orodispersible budesonide tablets could help prevent strictures after large endoscopic resections in the esophagus.

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Low cardiac dose and neutrophil-to-lymphocyte ratio predict overall survival in inoperable esophageal squamous cell cancer patients after chemoradiotherapy

Scientific Reports ◽

10.1038/s41598-021-86019-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yu-Chieh Ho ◽

Yuan-Chun Lai ◽

Hsuan-Yu Lin ◽

Ming-Hui Ko ◽

Sheng-Hung Wang ◽

...

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Squamous Cell ◽

Squamous Cell Cancer ◽

Performance Status ◽

Cell Cancer ◽

Esophageal Squamous Cell Cancer ◽

Lymphocyte Ratio ◽

Cardiac Dose

AbstractWe aimed to determine the prognostic significance of cardiac dose and hematological immunity parameters in esophageal cancer patients after concurrent chemoradiotherapy (CCRT). During 2010–2015, we identified 101 newly diagnosed esophageal squamous cell cancer patients who had completed definitive CCRT. Patients' clinical, dosimetric, and hematological data, including absolute neutrophil count, absolute lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR), at baseline, during, and post-CCRT were analyzed. Cox proportional hazards were calculated to identify potential risk factors for overall survival (OS). Median OS was 13 months (95% confidence interval [CI]: 10.38–15.63). Univariate analysis revealed that male sex, poor performance status, advanced nodal stage, higher percentage of heart receiving 10 Gy (heart V10), and higher NLR (baseline and follow-up) were significantly associated with worse OS. In multivariate analysis, performance status (ECOG 0 & 1 vs. 2; hazard ratio [HR] 3.12, 95% CI 1.30–7.48), heart V10 (> 84% vs. ≤ 84%; HR 2.24, 95% CI 1.26–3.95), baseline NLR (> 3.56 vs. ≤ 3.56; HR 2.36, 95% CI 1.39–4.00), and follow-up NLR (> 7.4 vs. ≤ 7.4; HR 1.95, 95% CI 1.12–3.41) correlated with worse OS. Volume of low cardiac dose and NLR (baseline and follow-up) were associated with worse patient survival.

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Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment

Cancers ◽

10.3390/cancers11091289 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1289 ◽

Cited By ~ 4

Author(s):

Xing Bian ◽

Wenchu Lin

Keyword(s):

Lung Cancer ◽

Dna Damage ◽

Dna Replication ◽

Dna Damage Repair ◽

Predictive Biomarkers ◽

Replication Stress ◽

Genotoxic Stress ◽

Repair System ◽

Damage Repair ◽

Repair Pathways

Small cell lung cancer (SCLC), accounting for about 15% of all cases of lung cancer worldwide, is the most lethal form of lung cancer. Despite an initially high response rate of SCLC to standard treatment, almost all patients are invariably relapsed within one year. Effective therapeutic strategies are urgently needed to improve clinical outcomes. Replication stress is a hallmark of SCLC due to several intrinsic factors. As a consequence, constitutive activation of the replication stress response (RSR) pathway and DNA damage repair system is involved in counteracting this genotoxic stress. Therefore, therapeutic targeting of such RSR and DNA damage repair pathways will be likely to kill SCLC cells preferentially and may be exploited in improving chemotherapeutic efficiency through interfering with DNA replication to exert their functions. Here, we summarize potentially valuable targets involved in the RSR and DNA damage repair pathways, rationales for targeting them in SCLC treatment and ongoing clinical trials, as well as possible predictive biomarkers for patient selection in the management of SCLC.

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