Synchronous Esophageal Squamous Cell Carcinoma Research Articles

279. CLONAL RELATIONSHIP AND ALCOHOL CONSUMPTION-ASSOCIATED MUTATIONAL SIGNATURE IN SYNCHRONOUS HYPOPHARYNGEAL TUMORS AND ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract The patients with dual esophageal squamous cell carcinoma (ESCC) and head and neck cancers have poor prognosis, but the underlying genetic pathogenesis is unclear. We hypothesize that independent origin rather than multifocality, which means local or lateral spreading involves the development of synchronous ESCC and hypopharyngeal cancer (HPC). We also hypothesize that multi-regional assessment provides better understanding of the evolution of tumor subclones and assessment of intra-tumor heterogeneity to guide personalized treatment with prognostic implications. Multiple region whole-exome sequencing (M-WES) and clonality analysis were used to assess clonal relationship and spatial inter- or intra-tumor heterogeneity (ITH) in 62 tumor regions, six normal tissues, and 15 blood samples from eight dual ESCC/HPC and ten ESCC patients. All synchronous ESCC/HPC patients had COSMIC 16 mutation signature compared to only 40% ESCC in the current study (p = 0.013) and public ESCC dataset (n = 165, p = 0.003). The mutational landscape and copy number variation (CNV) profiles were completely distinct between the ESCC/HPC; clonality analysis further suggested the two primary tumors shared no or only one clone accompanying independent subclone evolution. The M-WES strategy demonstrated higher sensitivity and accuracy for detection of mutational prevalence and the late branch mutations among different regions in the ESCC tumors compared to traditional single biopsy strategy. Patients with high ITH was significantly associated with both relapse and survival. Our hypothesis-generating M-WES ITH assessment data have implications for prognostication. We are the first to show a distinctive CNV and genetic mutation profile, the predominant alcohol-related COSMIC 16 mutational signature in synchronous ESCC/HPC, providing genetic evidence for a multi-centric independent origin for clonal evolution and the theory of field cancerization implicating an etiologic role of alcohol metabolism in dual ESCC/HPC carcinogenesis.

Simultaneous endoscopic submucosal dissection for synchronous multiple early esophageal squamous cell carcinoma: a propensity score-matched analysis.

The clinical effect of endoscopic submucosal dissection (ESD) in the treatment of early esophageal squamous cell carcinoma (EESCC) is widely recognized. However, the long-term treatment outcome of simultaneous ESD for multiple EESCC currently remained unknown. Hence, this study was aimed at further evaluating the long-term outcome of simultaneous ESD for synchronous multiple EESCC by comparing with ESD for single EESCC. Consecutive patients who underwent ESD for EESCC from June 2008 to June 2018 were included. Propensity score-matched analysis was used to compensate for the differences in age, sex, tumor location, tumor size, and tumor invasion depth between simultaneous and single ESD groups. Treatment outcomes including en bloc resection rate, curative resection rate, complication rate, and long-term outcomes including overall survival (OS), recurrence-free survival (RFS), metachronous recurrence were compared between the 2 groups after matching. The propensity score-matched analysis included 332 lesions (166 patients) and 332 lesions (332 patients) in simultaneous and single ESD groups, respectively. Among all the outcomes, en bloc resection, curative resection, 5-year OS, and 5-year RFS rates were comparable. Complications were more common in the simultaneous ESD group (15.06% vs. 9.64%, P = 0.073). The 5-year metachronous recurrence rates were significantly high in the simultaneous ESD groups (24.28% vs. 6.99%). Simultaneous ESD is an effective and safe methodology for synchronous multiple EESCC; it also reduces hospital stay and medical expenses. The risk of metachronous recurrence is higher for patients with synchronous multiple EESCC; thus, more intensive strategies are required.

Prevalence of Synchronous ESCN in Head and Neck Cancer: A Single-Institution Perspective.

The primary objective was to determine the prevalence of synchronous esophageal squamous cell carcinoma in head and neck squamous cell carcinoma (HNSCC) patients. The secondary objective was to determine risk factors for the development of synchronous esophageal squamous cell carcinoma (ESCN). Cross sectional observation study. A prospective cross sectional, observational study on consecutive 300 newly diagnosed oral cavity, oropharynx, hypopharynx, and laryngeal squamous cell carcinoma patients who underwent trans-nasal esophageal endoscopy with white light imaging and narrow band imaging. Among 300 patients, index HNSCCs were located in the oral cavity (n = 154, 51.3%), oropharynx (n = 63, 21%), larynx (n = 53, 17.7%), and hypopharynx (n = 30, 10%). The prevalence of synchronous ESCN was 2.7% (n = 8), including four low-grade, two high-grade dysplasia, and two squamous cell carcinomas. On logistic regression analysis, moderate to heavy alcohol consumption (OR 8.7, P = .01) and primary HNSCC involving supraglottis [(OR 12.5, P = .02) were risk factors for synchronous ESCN. The association of pyriform sinus carcinoma and synchronous ESCN was of borderline significance (P = .054, OR 10.92). The prevalence of synchronous ESCN in HNSCC was 2.7%. Routine trans-nasal esophagoscopy should be performed in all newly diagnosed patients with carcinoma of the supraglottis and pyriform sinus, and those with consumption of moderate to heavy alcohol for the screening of synchronous ESCN. 2b Laryngoscope, 131:E807-E814, 2021.

Clonal relationship of synchronous head and neck cancer and esophageal cancer assessed by single nucleotide polymorphism-based loss of heterozygosity analysis

BackgroundThe prognoses of head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC) are poor, especially when both tumors occur at the same time. We examined the clonal relatedness of HNSCCs with synchronous ESCCs to confirm whether the second tumors were metastasis or separate second primary malignancies (SPMs) using loss of heterozygosity (LOH) analysis.MethodsTwenty-one pairs of formalin-fixed paraffin-embedded tissue from HNSCC patients with synchronous esophageal cancer were analyzed by single nucleotide polymorphism (SNP) array using the Illumina HumanCytoSNP FFPE-12 BeadChip (San Diego, CA), which contains approximately 300,000 probes. LOH was identified using Nexus Copy Number software (El Segundo, CA).ResultsComparing the LOH pattern between HNSCC and paired ESCC, we found that 20 out of 21 paired tissues had a high number of discordant LOHs (LOH identified solely in the primary HNSCC but not in synchronous ESCC at the same genomic location) and a low number of concordant LOHs (LOH at the same genomic location in both HNSCC and ESCC). Only one case fell into the undetermined category. Therefore, these 20 ESCCs were classified as SPMs or second field tumors (SFTs). Moreover, the HNSCC patients with molecularly confirmed esophageal SPM had significantly poorer survival than the other patients.ConclusionsWe propose the use of a genome-wide SNP array as a tool to differentiate metastatic tumors from SPM/SFT. The SNP array offers genome-wide LOH information that earlier microsatellite analysis studies lack. The ability to accurately identify SPM should contribute to a better treatment plan and follow-up care of these patients.

Treatment Outcomes of Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy

The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3–4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3–4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival.

Natural history of superficial head and neck squamous cell carcinoma under scheduled follow-up endoscopic observation with narrow band imaging: retrospective cohort study.

BackgroundThe incidence rate has been increasing for superficial head and neck squamous cell carcinoma (HNSCC) discovered through surveillance endoscopic study using narrow band imaging (NBI), a procedure mainly used for high-risk patients with esophageal squamous cell carcinoma (ESCC). However, there are few reports on the natural history of superficial HNSCC. The aim of this retrospective study was to investigate the natural history of superficial HNSCC.MethodsFrom January 2007 to December 2012, 535 consecutive histologically confirmed superficial HNSCCs at the oropharynx, hypopharynx, or larynx in 319 patients were detected by endoscopic surveillance examination by using NBI. Of those, 20 untreated and observed lesions fulfilled the eligibility criteria and were analyzed in this study.ResultsTwenty lesions from 17 patients were analyzed. All patients were men ranging from 52 to 86 years of age, with a median age of 69 years. The median endoscopic follow-up period was 20 months (range, 6–71); 17 lesions progressed in size. In this study, four patients died; the causes of death were synchronous ESCC, synchronous HNSCC, acute myocardial infarction, and unknown causes. No patient died from progression of superficial HNSCC.ConclusionsMost superficial HNSCC has the potential to change progressively. Therefore, superficial HNSCC should be detected at an early stage and be treated less invasively, such as with endoscopic resection or partial resection.

Human papillomavirus infection on initiating synchronous esophageal neoplasia in patients with head and neck cancer.

Human papillomavirus (HPV) is a risk factor for head and neck squamous cell carcinoma (HNSCC) as well as esophageal squamous cell carcinoma (ESCC). We aimed to investigate whether HPV infection underlies the field cancerization phenomenon over upper aerodigestive tract to develop synchronous multiple cancers. A case control study. The presence and subtype of HPV-DNA sequence in cancers were examined by polymerase chain reaction and sequencing in a prospective cohort with 100 HNSCCs, 50 of which had synchronous ESCCs. The clinicopathologic characteristics were further analyzed according to the presence of HPV. Twelve patients were HPV-positive, of which 11 were positive for HPV-16. The prevalence of HPV infection were not different between the synchronous and HNSCC alone groups (P = 0.357). Testing for HPV in paired HNSCC and ESCC tissues from the same patient revealed that none were concomitantly HPV-positive. Multivariate logistic regression showed drinking alcohol (odds ratio [OR], 18.75; P = 0.030), alcohol flushing (OR, 2.53; P = 0.041), and body mass index (OR, 0.77; P = 0.001) but not HPV infection were independent risk factors for synchronous phenotype. The patients with synchronous ESCCs had significantly poorer survival than those with HNSCC alone (5-year overall survival: 30% vs. 70%; log-rank P < 0.001). However, patients with HPV-positive HNSCC tend to have favorable outcome than those with HPV-negative HNSCC. HPV infection plays little role in field cancerization phenomenon to initiate synchronous SCC. The synchronous HNSCC and ESCC from the same patients had no clonal relationship. Routine endoscopic examination of the esophagus should be recommended for patients with risk factors identified. NA. Laryngoscope, 126:1097-1102, 2016.

Clinico-molecular study of synchronous head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC).

e17080 Background: The prognoses of HNSCC and ESCC are poor, especially when two primary tumors occur at the same time. In an earlier study, we found 12.4% of all HNSCC patients had a synchronous ESCC at the time of diagnosis. To confirm whether these second tumors were of metastatic origin or a separate second primary tumor (SPT), we employed genome-wide SNP array analysis to analyze the differential LOH pattern of each synchronous tumor pair. The clinical information of the patients with synchronous tumors was also summarized. Methods: Twenty-one synchronous HNSCC formalin-fixed paraffin-embedded (FFPE) tissue samples and their ESCC counterparts were subjected to DNA extraction, quality assessment, and subsequent SNP array experiments using Illumina HumanCytoSNP12 FFPE BeadChip, which contains 300,000 probes. Signal intensity and B-allele frequency data of each pair were analyzed to identify Copy Number Variation (CNV) and LOH using Nexus Copy Number software suite. Results: Comparing the LOH pattern of each primary HNSCC to its esophageal tumor counterpart, we found 20 out of 21 pairs had a low number of concordant LOHs (LOH at the same genomic location seen in both HNSCC and ESCC) and a high number of discordant LOHs (LOH identified solely in primary HNSCC, but not in second ESCC at the same genomic location). Only one of the cases fell into the undetermined category. We conclude that the second esophageal tumors in our patients were indeed individual SPTs. Synchronous HNSCC and ESCC are considered to be of worse prognostic value compared with non synchronous tumors. Conclusions: We propose here the use of a genome-wide SNP array as a tool to differentiate metastatic tumors from SPT. The SNP array offers genome-wide LOH information that earlier microsatellite analysis studies lack. The ability to accurately identify SPT should contribute to a better treatment plan and follow-up care of this group of patients. Clinical correlation using a larger study group may help clarify the clinical characteristics of SPT.

Endoscopic resection for synchronous esophageal squamous cell carcinoma and gastric adenocarcinoma in early stage is a possible alternative to surgery.

Background/AimsWe investigated the clinical outcomes according to the method of treatment in synchronous esophageal and gastric cancer.MethodsSynchronous esophageal squamous cell carcinoma and gastric adenocarcinoma were diagnosed in 79 patients between 1996 and 2010. We divided the patients into four groups according to treatment; Group 1 received surgical resection for both cancers or surgery for gastric cancer with chemoradiotherapy for esophageal cancer (n=27); Group 2 was treated by endoscopic resection with or without additional treatment (n=14); Group 3 received chemoradiotherapy only (n=18); and Group 4 received supportive care only (n=20).ResultsThe median survival times in groups 1 and 2 were 86 and 60 months, respectively. The recurrence rate and mortality were 23% and 48%, respectively, in group 1 and 21% and 4%, respectively, in group 2. The median survival time was 12 months in group 3 and 9 months in group 4. Multivariate analysis showed that age (p<0.001) and treatment group (p=0.019) were significantly associated with death. Compared with group 1, treatment in the intensive care unit (p=0.003), loss of body weight (p=0.042), and decrease in hemoglobin (p=0.033) were worse in group 1.ConclusionsEndoscopic resection for synchronous esophageal and gastric cancer could be considered as a possible alternative to surgery for early-stage cancer.

Su1957 Clinical Outcomes of Synchronous Esophageal Squamous Cell Carcinoma and Gastric Adenocarcinoma According to Method of Treatment

Su1957 Clinical Outcomes of Synchronous Esophageal Squamous Cell Carcinoma and Gastric Adenocarcinoma According to Method of Treatment

The treatment outcomes of synchronous and metachronous esophageal squamous cell carcinoma and head and neck squamous cell carcinoma

The treatment outcomes of patients with esophageal squamous cell carcinoma (ESCC) and head and neck squamous cell carcinoma (HNSCC) have been poorly documented. We investigated 50 patients with synchronous and metachronous ESCC and HNSCC. We focused on the treatment results of 20 patients with synchronous ESCC and HNSCC who received simultaneous chemoradiotherapy (CRT). There were 34 patients (68.0 %) with stage 0–I ESCC and 40 patients (80.0 %) with stage II–IV HNSCC. A total of 13 (26.0 %) patients underwent endoscopic mucosal resection and 28 (56.0 %) underwent CRT for ESCC, and 35 (70.0 %) of the patients with HNSCC were treated with CRT. The 5-year overall survival rates of the 50 patients with synchronous and metachronous ESCC and HNSCC was 57.8 %. For the 20 patients with synchronous ESCC and HNSCC who received simultaneous CRT, the CRT was completed in 19 (95.0 %) patients. Although grade 3–4 adverse events were observed in five (25.0 %) patients, there were no therapy-related deaths. Complete responses (CRs) of both ESCC and HNSCC were observed in ten (50.0 %) patients. The 5-year overall survival rate of the 20 patients was 60.0 %. CRs of both ESCC and HNSCC were obtained in seven (58.3 %) patients by using a cisplatin/5-FU regimen (n = 12), and in the other three (37.5 %) patients by a platinum-based monotherapy regimen (n = 8). The surveillance of double cancer and the use of radical treatment contributed to the favorable outcome of the patients with ESCC and HNSCC. The optimal chemotherapy regimen for simultaneous CRT remains to be determined.

Screening of high-risk patients with head and neck cancer for early detection of synchronous esophageal squamous cell carcinoma by chromoendoscopy using lugols solution

Screening of high-risk patients with head and neck cancer for early detection of synchronous esophageal squamous cell carcinoma by chromoendoscopy using lugols solution