Introduction

Patients with esophageal cancer are prone to poor nutrition. Concurrent chemoradiation therapy (CCRT) further influence body compositions including skeletal muscle and adipose tissue which are key indicators of nutritional status.

Aims & Methods

This study aimed to evaluate whether body compositional change during CCRT could be a predictor of prognosis in esophageal cancer patients. From 2006 to 2018, esophageal cancer patients who received CCRT as initial treatment were consecutively enrolled. We assessed body compositions, including subcutaneous fat (SCF), intramuscular fat (IMF), and skeletal muscle (SM) mass by measuring the cross-sectional area (CSA) of the fourth thoracic vertebral body on computed tomography (CT) scan. The body compositional change was assessed by comparing baseline and post-CCRT CSA. The association of body compositions and their changes during CCRT with patient prognosis was analyzed.

Results

A total of 178 patients were enrolled with a mean baseline BMI of 22.0 (SD 3.4). Compared to baseline, a significant decrease in the mean bodyweight (BW), SCF, IMF, and SM after CCRT was noted (p<0.001). Baseline or post-CCRT BMI and body compositions were not significantly associated with patient prognosis. Patients with SCF loss during CCRT had poorer CCRT response (OR 3.7, p<0.001), shorter time to tumor progression (8.5 vs 23.7months, p=0.011), and overall survival (13.7 vs 25.9months, p<0.001) than patients with SCF gain/stable. IMF, SM, and BW change did not correlate with CCRT response or survival. In multivariate Cox regression analysis, SCF loss (HR 1.49, 95%CI: 1.03–2.14, p=0.033) during CCRT was an independent poor prognostic factor after adjusting baseline BMI, cancer stage, treatment modality, and CCRT response.

Conclusion

Body compositional change is more sensitive than weight in predicting CCRT response and survival of esophageal cancer patients. SCF loss during CCRT is associated with worse CCRT response and survival in esophageal cancer patients.

Introduction

Esophageal cancer (EC) exhibits a disproportionate burden in low- and middle-income regions. Magnesium, a critical regulator of metabolic and inflammatory pathways, has been implicated in chronic diseases such as diabetes and cardiovascular disorders. Preclinical studies suggest that magnesium deficiency promotes oxidative stress and systemic inflammation, processes central to cancer progression. However, evidence directly linking magnesium metabolism disorders with esophageal cancer risk remains limited. The Magnesium Depletion Score (MDS), a validated tool integrating diuretic use, proton pump inhibitors, renal dysfunction, and heavy alcohol consumption, offers a novel approach to evaluate magnesium status. The study aims to elucidate the potential mechanisms by which magnesium metabolism may influence the development of esophageal cancer and to provide a scientific basis for future preventive and intervention strategies.

Aims & Methods

This prospective cohort study included 450,700 UK Biobank participants. The Magnesium Depletion Score (MDS) incorporated diuretic use, proton pump inhibitors, renal function (eGFR-based), and heavy alcohol consumption, categorized as low (0–1), moderate (2), or high (3–5). Multivariable Cox proportional hazards models, adjusted for demographics, socioeconomic factors, BMI, smoking, and alcohol use, assessed associations between MDS and esophageal cancer (EC) incidence (ICD-10: C15) and subtypes. Sensitivity analyses excluded participants with <1–3 years of follow-up. Mediation analyses evaluated inflammatory/metabolic biomarkers (e.g., CRP, HbA1c). Subgroup analyses explored effect modification by age, sex, and lifestyle factors, while restricted cubic splines tested nonlinear relationships. Analyses adhered to STROBE guidelines and utilized R v4.2.3.

Results

Among 450,700 participants (54% female, mean age 56.6 years), 1,572 developed esophageal cancer (EC: 645 adenocarcinomas [EAC], 275 squamous cell carcinomas [ESCC], 905 lower EC). EC cases were predominantly male, older (mean +4.8 years vs. non-EC), and exhibited higher Magnesium Depletion Score (MDS), BMI, smoking rates, and socioeconomic deprivation. EAC patients were more likely overweight/obese (BMI >25), while ESCC patients had higher smoking rates and normal BMI.
Higher MDS was significantly associated with increased EC risk (continuous MDS: HR=1.186, 95% CI:1.102–1.277, P<0.001). Compared to low MDS (0–1), moderate (2) and high MDS (3–5) groups showed 29.6% (HR=1.296, P=0.001) and 63.5% (HR=1.635, P<0.001) higher EC risk, respectively. Similar trends were observed for EAC (HR=1.277, P<0.001) and lower EC (HR=1.158, P=0.003). Sensitivity analyses excluding early-diagnosis cases (1–3 years) confirmed robustness. Associations persisted after adjusting for diabetes, hypertension, and H. pylori.
Stratified analyses revealed stronger MDS-EC associations in males, smokers, alcohol consumers, and overweight/obese individuals (BMI>25). MDS did not correlate with all-cause mortality in EC patients (HR=0.963, P=0.370). Mediation analyses identified inflammatory (C-reactive protein: 1.40%, P=0.013; neutrophils: 4.50%, P=0.003) and metabolic biomarkers (HbA1c: 0.91%, P=0.033; glucose: 0.38%, P=0.047) as partial mediators.

Conclusion

In summary, this study demonstrates a significant positive association between MDS and the risk of esophageal cancer, with an especially pronounced impact observed among overweight or obese individuals, males, and alcohol consumers. The findings support the hypothesis that magnesium metabolism may influence esophageal cancer through multiple mechanisms, including inflammation, metabolic abnormalities, and immune dysfunction.

Introduction

Squamous dysplasia is the histopathological precursor of esophageal squamous cell carcinoma (ESCC). The optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. In this study, we aimed to assess the ESCC risk in patients with esophageal squamous dysplasia in a Western country.

Aims & Methods

This nationwide cohort study included all patients with esophageal squamous dysplasia, diagnosed between 1991 and 2020 in the Dutch nationwide histopathology registry (PALGA). Squamous dysplasia was divided in mild-to-moderate dysplasia (consisting of mild, low-grade, and moderate dysplasia) and higher-grade dysplasia (high-grade dysplasia, severe dysplasia, and carcinoma in situ). The primary endpoint was diagnosis of prevalent (within 6 months) and incident (after more than 6 months after squamous dysplasia) ESCC, identified in PALGA and the Netherlands Cancer Registry.

Results

873 patients (55% male, mean age of 68 years SD±13.2) were diagnosed with esophageal squamous dysplasia, comprising mild-to-moderate dysplasia (n=456), higher-grade dysplasia (n=393) and dysplasia not specified (n=24). 57% of the patients with mild-to-moderate dysplasia received endoscopic re-assessment after 12 weeks (IQR 6-29). During first endoscopic-reassessment, ESCC was detected in 5.1%, 1.8% and 12.8% of patients with baseline mild, low-grade, and moderate dysplasia, respectively. In total, ESCC was diagnosed in 77 (17%) patients with mild-to-moderate dysplasia (49 prevalent, 28 incident ESCC) and in 162 (41%) patients with higher-grade dysplasia (128 prevalent, 34 incident ESCC) (Table 1). After excluding prevalent ESCC, the annual risk of ESCC was 4.0% (95% CI: 2.7-5.7%) in patients with mild-to-moderate and 8.5% (95% CI: 5.9-11.7%) per patient-years and higher-grade dysplasia.

Table 1. The proportion of patients with distinct grades of baseline squamous dysplasia diagnosed with prevalent and incident ESCC.

Conclusion

All patients with squamous dysplasia, including those with mild, low-grade, and moderate dysplasia, have a substantial risk of developing ESCC. Consequently, endoscopic surveillance of the esophageal mucosa is recommended for patients with mild-to-moderate dysplasia in Western countries.

Introduction

Endoscopic ultrasound (EUS) and positron emission tomography (PET) have been widely recognized as valuable imaging modalities for tumor-node-metastasis (TNM) staging and treatment decision-making in patients with esophageal cancer. However, the accuracy of EUS and PET in esophageal cancer patients following neoadjuvant concurrent chemoradiotherapy (CCRT) remains inconsistent. Our objective was to conduct a comparative study between EUS and PET to evaluate their accuracy in staging post-CCRT patients who underwent resection surgery and were diagnosed with tumor complete remission.

Aims & Methods

The subjects of this study comprised patients diagnosed with esophageal squamous cell carcinoma and treated with CCRT before surgery at National Taiwan University Hospital (NTUH). Data were collected from May 1, 2007, to May 31, 2022, from a database of 828 esophageal cancer patients who underwent both EUS and PET before and after CCRT, and subsequently underwent resection surgery with pathologically complete response, resulting in a total of 231 patients. After excluding 14 patients who did not receive CCRT, 217 patients were enrolled for further study. The analysis focused on the T and N stages of esophageal cancer as reported by EUS and PET before and after CCRT, correlating clinical stages with pathologic stages. Using pathological diagnosis as the criterion standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS and PET were calculated. Patients who did not receive EUS or PET before CCRT and those who did not receive EUS or PET after CCRT (n=87) were excluded, resulting in a final inclusion of 128 cases for analysis.

Results

Among the 128 recruited patients, the overall accuracy of EUS for T-stage was 6.3%, while PET exhibited an accuracy of 13.3%. For N-stage, the accuracy of EUS was 20.3%, whereas PET demonstrated an accuracy of 33.6%.

Conclusion

In post-CCRT esophageal patients who achieved complete pathological remission, PET exhibited superior accuracy compared to EUS for both T and N staging; however, neither modality attained satisfactory levels of accuracy.

References

• 1. Yen, T. J., et al. (2012). "Comparative study between endoscopic ultrasonography and positron emission tomography-computed tomography in staging patients with esophageal squamous cell carcinoma." Dis Esophagus 25(1): 40-47
• 2. Ajani, J. A., et al. (2019). "Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology." Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 17(7): 855-883.
• 3. Rice, T. W., et al. (2017). "8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice." Ann Cardiothorac Surg 6(2): 119-130.

Introduction

Radiation therapy (Rth) remains an integral part of the multifactorial management of breast cancer (BC). Some reports suggest an increased risk of secondary esophageal cancer (SEC) following Rth for BC, but wide-ranged populational studies on this topic are scarce. We conducted this nationwide registry-based study to analyze the incidence, prognosis, and timing of SEC within BC survivors.

Aims & Methods

We used two high-volume national databases (the National Health Fund Registry and the National Cancer Registry) to identify adult patients with a confirmed diagnosis of primary BC who received oncological treatment either with or without Rth between 2009 and 2019. Those patients were followed-up for the diagnosis of SEC until December 2023. The Fine-Gray competing risk regression models were used to determine and compare the cumulative incidence of SECs in both groups. We applied the Kaplan–Meier method to calculate the 5-year overall survival rates (OS) for SECs in both subsets of BC patients.

Results

We screened 194,598 patients with primary BC, of which 128,625 (66.1%) with available treatment data were included in the final analysis (mean age 61±13yrs.; 99% females). Of these, 89,078 (69%) received Rth within the treatment regime (post-Rth BC) and 39,547 (31%) did not receive Rth (no-Rth BC). The 10-year cumulative incidence of SEC within the post-Rth BC group was 0.06% (95%CI, 0.04%-0.09%), as compared to 0.02% (95%CI, 0.01%-0.04%) within the no-Rth group (Gray test P=.005). In a competing risk model, having received Rth was associated with a >2.5-fold increase in the risk of developing SEC relative to no-Rth BC patients (HR 2.67, 95%CI, 1.27-5.65, P=.010). The median time to SEC occurrence after Rth completion was 3.7 years (interquartile range [IQR], 1.3-6.6). Squamous cell cancers constituted 89% of SECs in the post-Rth BC group, which was higher than within the no-Rth BC group, of which 73% were SCCs. The prognosis of post-Rth SECs was as poor as for no-Rth SECs, with 5-year OS of 23% (95%CI, 14%-37%) and 13% (95%CI, 4.4%-36%), respectively; P=0.3.

Conclusion

Radiotherapy significantly increases the risk of SECs in BC survivors, although the cumulative incidence of this unfavorable event is low. These results raise awareness of SEC after RTH for breast cancer.

Introduction

Quantitative fluorescence molecular endoscopy (qFME) enables real-time in vivo visualization and quantification of fluorescence and can thereby highlight tumor tissue. qFME has proven its potential in detection of lesions and residual disease but is limited to the mucosal side only^1,2. Ultrasound guided needle biopsy (USNB/SFF) single fiber fluorescence spectroscopy may enable assessment of lymph nodes and all tissue layers of the esophageal wall. This pilot study evaluated the clinical impact of USNB/SFF spectroscopy using the fluorescent tracer bevacizumab-800CW for the identification of residual tumor in patients with esophageal cancer.

Aims & Methods

Patients diagnosed with locally advanced esophageal adenocarcinoma scheduled for neoadjuvant chemoradiotherapy followed by surgery were included. Patients were intravenously injected with either 4.5, 10 or 25 mg bevacizumab-800CW 2-3 days prior to the qFME to establish the optimal dose. FME collected real-time white light and fluorescence images of the primary tumor site and normal esophageal tissue. Quantitative fluorescent measurements were acquired superficially using multi-diameter single fiber reflectance / single fiber fluorescence (MDSFR/SFF) and inside the esophageal wall and within lymph nodes using USNB-SFF spectroscopy. Additionally, the reduced scattering coefficient and absorption coefficient were determined from the MDSFR/SFF data.

Results

Fifteen patients were included in the dose-escalation, where 25 mg showed the best differentiation between primary tumor site and normal tissue and was extended with 3 additional patients (TBR: 2.63±0.60, p=0.0002). VEGF immunohistochemistry confirmed the higher uptake of VEGF at the primary tumor site. USNB was evaluated in 6/8 patients from the 25mg cohort. The primary tumor site (p=0.071) and lymph nodes (p=0.090) showed higher fluorescence intensity compared to normal tissue. Fluorescence measurements of normal tissue were comparable between the luminal MDSFR/SFF and USNB/SFF measurements. In 33% of all patients residual tumor was found only below a tumor-free mucosa signifying the need to analyze the deeper tissue layers. Last, the optical properties, the reduced scattering coefficient and absorption coefficient. The combination of the intrinsic fluorescence, absorption and scattering coefficient was converted into the new variable omega and improved the differentiation between tumor and normal tissue even further.

Conclusion

We showed the potential of bevacizumab-800CW combined with qFME and USNB/SFF for response monitoring in esophageal cancer. This combination allows for both in vivo superficial and deeper tissue measurements to ensure that partial responders with a tumor-free mucosa are also adequately selected. A phase II study should establish its value for stratification of patients for active surveillance or surgery.

References

1. Tjalma JJJ, Koller M, Linssen MD, Hartmans E, de Jongh S, Jorritsma-Smit A, et al. Quantitative fluorescence endoscopy: an innovative endoscopy approach to evaluate neoadjuvant treatment response in locally advanced rectal cancer. Gut. 2020;69(3):406-10.
2. Nagengast WB, Hartmans E, Garcia-Allende PB, Peters FTM, Linssen MD, Koch M, et al. Near-infrared fluorescence molecular endoscopy detects dysplastic oesophageal lesions using topical and systemic tracer of vascular endothelial growth factor A. Gut. 2019;68(1):7-10.

Disclosure

Nothing to disclose