Esophageal Squamous Cell Cancer Research Articles

State-of-the-art therapy and innovative treatment strategies in esophageal squamous cell cancer

SummaryRecent advances in the development of new therapeutic agents and the execution of numerous randomized controlled trials have changed the landscape of systemic therapy approaches in patients with esophageal squamous cell cancer (ESCC). Particularly the inclusion of immunotherapy permits clinicians to improve patient management in multiple settings. This review gives an overview of standard-of-care treatment and sheds light on new therapeutic options, recently approved treatments, and ongoing trials.

Retracted] miR‑92a‑3p promotes the proliferation, migration and invasion of esophageal squamous cell cancer by regulating PTEN.

Following the publication of this paper, a concerned reader drew to the Editor's attention that it appeared as if the authors had calculated the apoptotic rates erroneously. The authors were asked to provide an explanation to account for the concerns raised by the interested reader; however, they did not respond to this request submitted by the Editorial Office. Therefore, owing to the lack of responsiveness on the part of the authors, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the journal. The Editor would like to apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 973‑981, 2019; DOI: 10.3892/ijmm.2019.4258].

The carcinogenesis of esophageal squamous cell cancer is positively regulated by USP13 through WISP1 deubiquitination.

The objective was to determine whether USP13 stabilizes WISP1 protein and contributes to tumorigenicity and metastasis in ESCC through the Wnt/CTNNB1 signaling pathway. ESCC cell lines (KYSE150 and TE10) were treated with the proteasome inhibitor MG-132, followed by siRNA screening of deubiquitinases (DUBs) to identify regulators of WISP1. Mass spectrometry, immunoprecipitation, and in vitro functional assays were conducted to explore the interaction between USP13 and WISP1 and to assess the effects of USP13 downregulation on cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis. Additionally, in vivo experiments using mouse models were performed to evaluate the impact of USP13 knockdown on tumor growth and metastasis. USP13 was identified as a key regulator of WISP1, stabilizing its protein levels through deubiquitination. Downregulation of USP13 resulted in reduced WISP1 protein stability, decreased cell proliferation, migration, and EMT, and increased apoptosis in vitro. In vivo, USP13 knockdown significantly inhibited tumor growth and lung metastasis. WISP1 overexpression in USP13-knockdown cells partially rescued these phenotypes, confirming the functional role of the USP13/WISP1 axis. Furthermore, knockdown of USP13 or WISP1 impaired the activation of the Wnt/CTNNB1 signaling pathway and reduced immune checkpoint marker expression, indicating a mechanism by which USP13 promotes immune evasion in ESCC. USP13 stabilizes WISP1 through deubiquitination, enhancing ESCC progression by activating the Wnt/CTNNB1 pathway and promoting immune evasion, making USP13 a potential therapeutic target in ESCC.

Comparison of neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma: a retrospective study with 3-year survival analysis

BackgroundNeoadjuvant chemoimmunotherapy (nCIT) for locally advanced esophageal squamous cell cancer (ESCC) has shown short-term benefits, but long-term survival outcomes are unclear. This study compares nCIT and neoadjuvant chemotherapy (nCT) in resectable ESCC.Patients and methodsA retrospective analysis was conducted on ESCC patients who underwent nCT or nCIT followed by esophagectomy. Propensity score matching (PSM) with a caliper of 0.02 was employed to minimize bias. The primary endpoints included disease-free survival (DFS) and overall survival (OS).ResultsA total of 131 comparable pairs of ESCC patients receiving nCT and nCIT were selected for the final analysis. The nCIT had higher rates of pathological complete response (pCR) and major pathological response (mPR) compared to nCT. Additionally, nCIT led to significant tumor down-staging, higher rates of R0 resection, and increased lymph node clearance during surgery. Patients who received nCIT exhibited improved disease-free survival (DFS) and overall survival (OS) at the 3-year follow-up. The incidence of distant and mixed relapses was lower in the nCIT group compared to the nCT group. However, the risk of locoregional relapse was comparable between the two groups. Subgroup analyses showed that the benefits of nCIT were generally observed across most patient subgroups. Interestingly, in patients without pCR or mPR, nCIT still demonstrated better survival benefits than nCT.ConclusionnCIT demonstrated superior pathological response rates and improved 3-year DFS and OS compared to nCT alone in locally advanced ESCC, but long-term survival validation is needed.

Survival comparison between open and thoracoscopic esophagectomy for node-negative esophageal squamous cell cancer: an ambispective cohort study.

It is controversial whether there is a survival difference between open esophagectomy (OE) and thoracoscopic esophagectomy (TE) for esophageal cancer (EC). Therefore, this study aimed to compare the differences in survival and safety between two surgical approaches in patients with node-negative esophageal squamous cell carcinoma (ESCC). This ambispective cohort study included 1104 patients with node-negative ESCC who received OE or TE treatment at a Grate-A tertiary hospital in Henan Province between January 2015 and December 2016. The primary endpoint was 5-year overall survival (OS) and disease-free survival (DFS), and the secondary endpoint was surgical safety. Multivariable Cox regression analysis was used to analyze the effect of surgical approaches on OS and DFS, and propensity score matching (PSM) was performed to match confounding factors between two groups. Patients were followed up ranged from 1.03 to 91.60months, with a median follow-up time of 67.37months. Kaplan-Meier survival analysis showed statistically significant differences between OE and TE in OS (70.05% vs 83.73%, P < 0.001) and DFS (67.15% vs 77.76%, P < 0.001). Furthermore, multivariate Cox regression analysis also demonstrated significant differences in long-term survival between the two groups (OS, HR (95%CI): 0.54 (0.41,0.70); DFS, HR (95% CI): 0.68 (0.54, 0.86)). TE was associated with a reduction in intraoperative bleeding (median: 100ml vs. 200ml, P < 0.001), and an increase in the number of lymph nodes dissection (median: 23 vs. 28, P < 0.001). Similar results were found after PSM. In a selected cohort of patients with node-negative ESCC, TE surgical treatment was safer and had better long-term survival outcomes compared to OE. This provided corresponding clinical guidance to enhance survival benefits for patients. In the future, we hope to further explore the reasons for TE achieving higher survival rates.

Spatial dynamics of CD39+CD8+ exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer

Despite the success of immune checkpoint blockade (ICB) therapy for esophageal squamous cell cancer, the key immune cell populations that affect ICB efficacy remain unclear. Here, imaging mass cytometry of tumor tissues from ICB-treated patients identifies a distinct cell population of CD39+PD-1+CD8+ T cells, specifically the TCF1+ subset, precursor exhausted T (CD39+ Tpex) cells, which positively correlate with ICB benefit. CD39+ Tpex cells are predominantly in the stroma, while differentiated CD39+ exhausted T cells are abundantly and proximally within the parenchyma. Notably, CD39+ Tpex cells are concentrated within and around tertiary lymphoid structure (TLS). Accordingly, tumors harboring TLSs have more of these cells in tumor areas than tumors lacking TLSs, suggesting Tpex cell recruitment from TLSs to tumors. In addition, circulating CD39+ Tpex cells are also increased in responders following ICB therapy. Our findings show that this unique subpopulation of CD39+PD-1+CD8+ T cells is crucial for ICB benefit, and suggest a key role in TLS-mediated immune responses against tumors.

Using high-repeatable radiomic features improves the cross-institutional generalization of prognostic model in esophageal squamous cell cancer receiving definitive chemoradiotherapy

ObjectivesRepeatability is crucial for ensuring the generalizability and clinical utility of radiomics-based prognostic models. This study aims to investigate the repeatability of radiomic feature (RF) and its impact on the cross-institutional generalizability of the prognostic model for predicting local recurrence-free survival (LRFS) and overall survival (OS) in esophageal squamous cell cancer (ESCC) receiving definitive (chemo) radiotherapy (dCRT).MethodsNine hundred and twelve patients from two hospitals were included as training and external validation sets, respectively. Image perturbations were applied to contrast-enhanced computed tomography to generate perturbed images. Six thousand five hundred ten RFs from different feature types, bin widths, and filters were extracted from the original and perturbed images separately to evaluate RF repeatability by intraclass correlation coefficient (ICC). The high-repeatable and low-repeatable RF groups grouped by the median ICC were further analyzed separately by feature selection and multivariate Cox proportional hazards regression model for predicting LRFS and OS.ResultsFirst-order statistical features were more repeatable than texture features (median ICC: 0.70 vs 0.42–0.62). RFs from LoG had better repeatability than that of wavelet (median ICC: 0.70–0.84 vs 0.14–0.64). Features with smaller bin widths had higher repeatability (median ICC of 8–128: 0.65–0.47). For both LRFS and OS, the performance of the models based on high- and low-repeatable RFs remained stable in the training set with similar C-index (LRFS: 0.65 vs 0.67, p = 0.958; OS: 0.64 vs 0.65, p = 0.651), while the performance of the model based on the low-repeatable group was significantly lower than that based on the high-repeatable group in the external validation set (LRFS: 0.61 vs 0.67, p = 0.013; OS: 0.56 vs 0.63, p = 0.013).ConclusionsApplying high-repeatable RFs in modeling could safeguard the cross-institutional generalizability of the prognostic model in ESCC.Critical relevance statementThe exploration of repeatable RFs in different diseases and different types of imaging is conducive to promoting the proper use of radiomics in clinical research.Key PointsThe repeatability of RFs impacts the generalizability of the radiomic model.The high-repeatable RFs safeguard the cross-institutional generalizability of the model.Smaller bin width helps improve the repeatability of RFs.Graphical

Computed tomography-based radiomics nomogram for prediction of lympho-vascular and perineural invasion in esophageal squamous cell cancer patients: a retrospective cohort study

PurposeLympho-vascular invasion (LVI) and perineural invasion (PNI) have been established as prognostic factors in various types of cancers. The preoperative prediction of LVI and PNI has the potential to guide personalized medicine strategies for patients with esophageal squamous cell cancer (ESCC). This study investigates whether radiomics features derived from preoperative contrast-enhanced CT could predict LVI and PNI in ESCC patients.Methods and materialsA retrospective cohort of 544 ESCC patients who underwent esophagectomy were included in this study. Preoperative contrast-enhanced CT images, pathological results of PNI and LVI, and clinical characteristics were collected. For each patient, the gross tumor volume (GTV-T) and lymph nodes volume (GTV-N) were delineated and four categories of radiomics features (first-order, shape, textural and wavelet) were extracted from GTV-T and GTV-N. The Mann–Whitney U test was used to select significant features associated with LVI and PNI in turn. Subsequently, radiomics signatures for LVI and PNI were constructed using LASSO regression with ten-fold cross-validation. Significant clinical characteristics were combined with radiomics signature to develop two nomogram models for predicting LVI and PNI, respectively. The area under the curve (AUC) and calibration curve were used to evaluate the predictive performance of the models.ResultsThe radiomics signature for LVI prediction consisted of 28 features, while the PNI radiomics signature comprised 14 features. The AUCs of the LVI radiomics signature were 0.77 and 0.74 in the training and validation groups, respectively, while the AUCs of the PNI radiomics signature were 0.69 and 0.68 in the training and validation groups. The nomograms incorporating radiomics signatures and significant clinical characteristics such as age, gender, thrombin time and D-Dimer showed improved predictive performance for both LVI (AUC: 0.82 and 0.80 in the training and validation group) and PNI (AUC: 0.75 and 0.72 in the training and validation groups) compared to the radiomics signature alone.ConclusionThe radiomics features extracted from preoperative contrast-enhanced CT of gross tumor and lymph nodes have demonstrated their potential in predicting LVI and PNI in ESCC patients. Furthermore, the incorporation of clinical characteristics has shown additional value, resulting in improved predictive performance.

The role of SEC14L4 in esophageal squamous cell cancer: insights into clinical relevance and molecular pathways.

Esophageal squamous cell cancer (ESCC) is the most common type of esophageal cancer. This study aimed to elucidate the role of Saccharomyces cerevisiae-like 4 (SEC14L4) in ESCC. To elucidate the role of SEC14L4 in ESCC, this study analyzed the clinical data, gene sequencing data, and other relevant data retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) of the National Center for Biotechnology Information. The methodology involved several analytical approaches, including nomogram model analysis, co-expression analysis, gene set enrichment and variation analysis, weighted correlation network analysis, drug susceptibility analysis, and single-cell analysis. These methods were employed to evaluate the significance of SEC14L4 in ESCC. The expression of SEC14L4 was evaluated via quantitative real-time polymerase chain reaction (qRT-PCR). SEC14L4 expression (P<0.001) was significantly elevated in those with ESCC, especially in patients with locally advanced disease (P=0.005), and indicated a poor prognosis (P=0.045). Findings from the nomogram model analysis identified the contribution of clinical indicators to survival prediction with good efficacy. Subsequently, the single-nucleotide polymorphisms and co-expressed genes of SEC14L4 were identified. Furthermore, pathways associated with SEC14L4, including DNA metabolic process, transcription factor binding, apoptosis, and others, were examined. Notably, SEC14L4 expression was predominantly observed in monocytes. Drug sensitivity analysis indicated the association of SEC14L4 expression with sensitivity of ESCC to the common chemotherapy drugs AICAR, BMS.708163, GNF.2, Nutlin.3a, PD.0325901, and RDEA119. Verification of the high expression of SEC14L4 in KYSE520 and KYSE150 was conducted, thereby confirming the study's findings. High expression of SEC14L4 is associated with poorer clinical outcomes, highlighting its potential as a therapeutic target and suggesting its involvement in the molecular mechanisms underlying ESCC.

Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts

BackgroundThis study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China.MethodsFrom February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1–6 and the second for cases 7–9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test.ResultsThe second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76–0.81; mean Hmean = 2.11–3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63–0.64; mean Hmean = 5.66–7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature.ConclusionsWe have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.

Immune checkpoint inhibitors for first-line treatment of advanced esophageal squamous cell carcinoma

Immunotherapy has revolutionized the treatment landscape of esophageal squamous cell carcinoma. He etal. present the final results of the randomized phase 3 ESCORT-1st trial, confirming positive survival outcomes when adding the anti-PD1 inhibitor camrelizumab to first-line chemotherapy treatment in Chinese patients with esophageal squamous cell cancer.1.

313. CLINICAL EVALUATION OF PEMBROLIZUMAB PLUS CISPLATIN AND FLUOROURACIL AS INDUCTION FOR PATIENTS WITH CT4B ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Definitive chemoradiotherapy (dCRT) is a standard treatment for patients with cT4b esophageal squamous cell cancer (ESCC). In these 3 decades, radiation technique has been improved, and chemotherapy with cisplatin, fluorouracil, and/or taxans was combined before and after dCRT. However, its CR rate remains around 25% and its 3-year survival rate also remains below 30%. Although conversion surgery has been applied to improve the survival of these patients, no study has shown significant superiority to CR after dCRT in survival to date. Chemotherapy of pembrolizumab plus cisplatin and fluorouracil was applied to patients with unresectable or recurred esophageal cancer and demonstrated significant survival benefit and good objective response. We provided this therapy as induction to improve the therapeutic result of patients with cT4b ESCC. Method From April 2022 to August 2023, 11 untreated patients with cT4b ESCC had this chemotherapy as induction, with pembrolizumab 200 mg plus chemotherapy (5-fluorouracil 800 mg/m2 on days 1-5 plus cisplatin 80 mg/m2 on day 1) once every 3 weeks. Patients with cervical lymph node metastasis were included. After 2 or 3 cycles, the therapeutic effect was evaluated according to RECIST. Adverse events were evaluated according to CTCAE. Result Average age was 70, and 3 patients had cervical lymph node metastasis. Objective response rate was 82% (CR 1, PR 8). In these 9 patients, the volume of tumors shrank by more than 60% within 11 weeks. Over Grade 3 neutropenia developed in 2 (18%), but no G-CSF was administered. Gastric ulcer perforation developed in 1 (9%). In 2 patients, the dose of cisplatin should be modified due to renal damage. One patient had prolonged renal damage and had conversion surgery after 1 cycle. Eight patients had dCRT. One of 8 terminated dCRT due to another disease. Two of 8 just finished dCRT, and one is under dCRT. Of 3 were evaluated as CR, and followed without any treatment. Local and lymphatic recurrence developed in one PR patient. To date, no specific adverse events relating to pembrolizumab developed during and after dCRT. Of the 2 had conversion surgery without any severe post-operative complications. Discussion and Conclusion In our preliminary study, chemotherapy of pembrolizumab plus cisplatin and fluorouracil showed good objective response (82%) and early tumor shrinkage (more than 60% within 11 weeks). Over grade 3 hematological adverse events developed in only 18% of patients. These results suggest this regimen could be administered to patients with cT4b ESCC as induction especially followed by dCRT. This regimen can reduce tumor volume and control lymphatic spread, and these factors seem to improve prognosis and prevent fatal complications such as fistula or stricture of patients with cT4b ESCC who have dCRT. We plan a clinical trial of this chemotherapy followed by dCRT for patients with cT4b ESCC.

A Review on Heavy Metals in Ecosystems, Their Sources, Roles, and Impact on Plant Life

The presence of heavy metals (HMs) on Earth is essential to all forms of life. These metals are essential for plant and animal development but can have numerous negative effects on the living environment. In this review, we looked at where HMs come from, why they are harmful, and how they affect plants. Articles indexed in Google Scholar, PubMed, Research Gate, Science Direct, and a few books on heavy metals were consulted for this study. Heavy metals are essential for plant development and growth. According to this analysis, the hazardous effects of HMs are on the rise all throughout the globe, and this trend may be attributed mostly to human activity. Because of its impact on agricultural productivity and environmental changes, soil pollution caused by HMs is among the most crucial elements. Plants have evolved very sophisticated defense systems to deal with these environmental challenges. The threat that HM stress poses to plants has attracted a lot of attention worldwide because it could stunt agriculture’s long-term expansion. In spite of their importance for plants, this study found that HMs pose a significant threat to plant life. The novelty of this review lies in its detailed examination of both the beneficial and detrimental roles of HMs, providing a balanced perspective often overlooked in current literature. The significance of this work is underscored by its potential to inform sustainable agricultural practices and environmental management strategies, as it highlights the delicate balance required to harness the benefits of HMs while mitigating their risks. Despite their necessity for plant development, this review underscores the significant risks HMs pose to plant health and ecosystems.Less than 10 cases have been reported in the literature of the association of germline BRCA1 and Squamous cell Carcinoma – the esophagus. The article focuses on the probable pathogenesis of BRCA1 mutation with non-classic malignancies and the response of Poly adenosine diphosphate ribose polymerase inhibitors (PARP) inhibitors in such a scenario. We report an unusual manifestation of the BRCA1 gene with second primary oesophageal squamous cell cancer occurring five years later to triple-negative breast cancer.

The addition of pembrolizumab to neoadjuvant chemoradiotherapy did not increase the risk of developing postoperative anastomotic leakage for ESCC: an analysis from a prospective cohort

BackgroundTo compare the difference of postoperative anastomotic leakage (AL) rate between neoadjuvant chemoradiotherapy (NCRT) with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced esophageal squamous cell cancer (ESCC).Materials and methodsThe GF was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established.ResultsA total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p < 0.05). Multivariate logistic regression analysis indicated that tumor length (p = 0.012), volume of GF (p = 0.003) and mean dose of GF (p = 0.007) were independently predictors for postoperative AL. Using receiver operating characteristics analysis, the mean dose limit on the GF was defined as 14 Gy.ConclusionBased on our prospective database, no significant difference of developing AL were observed between NCRT with pembrolizumab and NCRT group. We established an individualized nomograms based on mean GF dose combined with clinical indicators to predict AL in the early postoperative period.

Comparison of immunochemotherapy followed by surgery or chemoradiotherapy in locally advanced esophageal squamous cell cancer

BackgroundSeveral studies have shown that the survival outcomes of chemoradiotherapy (CRT) are not inferior to surgery alone in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to compare survival outcomes of ESCC treated with immunochemotherapy (ICT) followed by surgery or definitive CRT and to explore subgroups of patients who could benefit from one treatment strategy. MethodsPooled data were obtained from two prospectively registered clinical trials of patients with ESCC at the Affiliated Cancer Hospital of Nanjing Medical University. One trial involved treatment with neoadjuvant ICT followed by surgery, while the other involved induction ICT followed by definitive CRT. To balance potential biases, we conducted an overlap weighting (OW) analysis to compare the rates of 2-year progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant relapse-free survival (DRFS), and overall survival (OS). Additionally, propensity score matching (PSM) was performed to analyze failure pattern. ResultsThe median follow-up time of the survivors was 39.3 months. After overlap weighting, the rates of 2-year PFS, LRRFS, DRFS, and OS for patients undergoing surgery and CRT were 61.5 % and 59.7 %, 67.2 % and 69.9 %, 81.3 % and 90.7 %, 84.6 % and 79.1 %, respectively (P>.05 for all). A trend for improved 2-year OS was observed in the surgery group in patients who did not respond to ICT (P=.07). ConclusionThe differences in the rates of 2-year PFS, LRRFS, DRFS, and OS between the surgery group and the chemoradiotherapy group did not reach statistical significance.

Circulating tumor DNA analysis in patients with esophageal cancer treated with neoadjuvant chemoradiotherapy followed by surgery.

69 Background: The aim of this prospectively study is to investigate circulating tumor DNA (ctDNA) as a prognostic marker for survival in locally advanced esophageal squamous cell cancer (ESCC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and surgery. Methods: Serial plasma samples were collected from 68 ESCC patients treated with neoadjuvant chemoradiotherapy before surgery. ctDNA was detected before treatment, after neoadjuvant chemoradiotherapy and after surgery by personalized, next-generation sequencing assay. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for recurrence-free survival (RFS) and overall survival (OS). Results: ctDNA was detectable in 89.7%, 17.2%, and 6.9% of pretreatment, post-neoadjuvant chemoradiotherapy and post-surgery plasma samples, respectively. The conversion of ctDNA status from positive at baseline to negative at 4-6 weeks after neoadjuvant chemoradiotherapy was significantly associated with pathological complete response (pCR) ( P = 0.02). Significant worse RFS was related to detectable ctDNA after neoadjuvant chemoradiotherapy ( P = 0.008) or after surgery ( P = 0.001). Detectable ctDNA at baseline ( P = 0.01) and after surgery ( P = 0.008) were associated with worse OS. In multivariate analysis, detectable postoperative ctDNA was significantly associated with RFS ( P = 0.012) and OS ( P = 0.025) after adjusting for other clinicopathological risk factors. Conclusions: ctDNA status is a strong prognostic factor of recurrence in locally advanced ESCC patients. Consequently, ctDNA could potentially improve pre- and post-treatment risk assessment and facilitate individual therapy for ESCC patients.

Comparison of the treatment outcomes of different neoadjuvant chemoradiotherapy regimens for resectable locally advanced esophageal cancer

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used, and their comparative efficacy and safety remain unclear. MethodsPatients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in this study. Of note, 3 different nCRT regimens were retrospectively compared: conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial (CROSS). The overall survival (OS), pathologic complete response (pCR), toxicity, and treatment compliance rates were analyzed. ResultsAmong the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. The OS rates at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (P = .653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and nonhematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, and 5.5% and 0.8% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P = .002 and P = .030). Weight loss of > 5% was observed in 44.0%, 51.4%, and 32.5% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). In the multivariate analysis, clinical T stage (P = .004), N stage (P = .012), FP chemotherapy regimen (P = .013), surgical resection (P < .001), hematologic toxicity (P = .001), and weight loss (P = .004) were significantly associated with poor OS. ConclusionThe choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting that it may be the optimal treatment option among the groups.

Functional status and quality of life in older patients with advanced esophageal squamous cell cancer receiving second-line nivolumab ± ipilimumab therapy: A post hoc analysis of the phase 2, multicenter RAMONA study

IntroductionThe phase 2 RAMONA study demonstrated that second-line nivolumab ± ipilimumab immunotherapy was feasible and effective in older patients with advanced esophageal squamous cell cancer (ESCC). Here, we presented results from functional status (FS) and quality-of-life (QoL) analyses. Materials and MethodsPatients aged ≥65 years with advanced ESCC and disease progression following first-line therapy were enrolled for study treatment with nivolumab ± ipilimumab. Geriatric assessments (GA) consisting of G8 and GoGo/SlowGo evaluation, and quality of life (QoL) assessments with EORTC QLQ-C30 questionnaires were conducted at baseline and during the treatment. A post hoc analysis was performed to compare therapy efficacy, toxicity, and QoL between age groups (≥70 years vs. <70 years) and functionality groups (G8 > 14 vs. ≤14 and GoGo vs. SlowGo). ResultsIn 66 treated patients with a median age of 70.5 years, older patients had non-inferior overall survival and tumor response compared to younger patients, with no increased treatment-related adverse events. Fitter patients (G8 > 14, GoGo) had a clinically, yet not statistically significant, survival advantage than less fit patients (G8 ≤ 14, SlowGo) patients. Moreover, FS by G8 and GoGo/SlowGo significantly correlated with QoL. Overall, QoL was impaired at baseline but remained stable in all scales over the course of immunotherapy. DiscussionThe administration of nivolumab ± ipilimumab second-line immunotherapy in older patients with ESCC did not show age-dependent effects and maintained QoL. GA could identify functional deficits and limitations of QoL and should be implemented in the context of immunotherapy.ClinicalTrials.gov: NCT03416244.

Prognostic value of sarcopenia and myosteatosis alterations on survival outcomes for esophageal squamous cell carcinoma before and after radiotherapy

ObjectiveWe assessed the impact and prognostic significance of alterations in muscle quality and quantity (myosteatosis and sarcopenia, respectively) in patients with esophageal cancer treated with radiotherapy (RT). MethodsWe retrospectively pooled 258 patients with esophageal squamous cell cancer who underwent RT. Myosteatosis and sarcopenia were determined based on the skeletal muscle index derived from the muscle area and attenuation at the L3 level from computed tomography images. Subgroups were formed as 2 subgroups of non-sarcopenia/myosteatosis and sarcopenia/myosteatosis (with or without other muscle status) at either timepoint of RT, 3 subgroups of only-sarcopenia, only myosteatosis (without other muscle status), and the co-presence of sarcopenia and myosteatosis at either timepoint of RT, as well as 4 subgroups of continuous sarcopenia/myosteatosis, developed sarcopenia/myosteatosis, reduced sarcopenia/myosteatosis and non-sarcopenia/myosteatosis according to alterations of muscle status at both timepoints of RT. Overall survival (OS) was compared. Univariate and multivariate analyses based on Cox regression identified independent risk factors for prognosis. ResultsEither pre- or post-RT, patients with sarcopenia and myosteatosis (with or without other muscle status) had poor OS. Patients with only myosteatosis (without other muscle status) showed the best OS (1352 days pre-RT vs. 1648 days post-RT), while patients with concurrent myosteatosis and sarcopenia had the worst OS (907 days pre-RT vs. 706 days post-RT). The ascending order of OS for sarcopenia alterations was as follows: continuous sarcopenia (1093 days), non-sarcopenia (1740 days), developed sarcopenia (2187 days), and reduced sarcopenia (2208 days) (P = 0.002). The ascending order of OS for myosteatosis alterations was ranked as follows: continuous myosteatosis (1165 days), reduced myosteatosis (1275 days), developed myosteatosis (1783 days), and non-myosteatosis (1942 days) (P = 0.061). Univariate and multivariate Cox regression analyses revealed that increased age, longer tumor length, developed myosteatosis, and continuous myosteatosis were independent prognostic factors for OS. ConclusionsMuscle mass status at presentation and alterations in patients with esophageal cancer before and after RT should be considered prognostic indicators.

Germline BRCA1 Mutation inSquamous Cell Carcinoma of Oesophagus: Driver versus Passenger Mutation

We report a rare case of 62-year-old South Asian women who visited the Molecular Pathology and Genomics Department for hereditary germline cancer genetic testing after being diagnosed with oesophageal cancer, reported as invasive keratinizing squamous cell carcinoma metastasized to the lymph nodes. Her personal history revealed that she was diagnosed with triple-negative breast cancer five years before oesophageal cancer. Germline cancer testing showed pathogenic variants in BRCA1 gene c.68_69delAG, which proved it a hereditary breast and ovarian cancer syndrome. She was started on PARP inhibitors but developed some secondary respiratory failure and succumbed to death. Less than 10 cases have been reported in the literature of the association of germline BRCA1 and Squamous cell Carcinoma – the esophagus. The article focuses on the probable pathogenesis of BRCA1 mutation with non-classic malignancies and the response of Poly adenosine diphosphate ribose polymerase inhibitors (PARP) inhibitors in such a scenario. We report an unusual manifestation of the BRCA1 gene with second primary oesophageal squamous cell cancer occurring five years later to triple-negative breast cancer.