ABSTRACT
BACKGROUND: The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery-based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery-based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC. METHODS: Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups. RESULTS: The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3-year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681-2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3-year OS: surgery 68.1%, dCRT 51.8%, p = 0.117). CONCLUSIONS: There was no clear difference in survival outcome between surgery-based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients.
Subject(s)
Chemoradiotherapy , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophagectomy , Humans , Esophagectomy/methods , Male , Female , Aged , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/pathology , Retrospective Studies , Chemoradiotherapy/methods , Esophageal Neoplasms/therapy , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Survival Rate , Aged, 80 and over , Treatment Outcome , PrognosisABSTRACT
BACKGROUND: Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC. METHODS: In this randomised, open-label, phase 3 trial, patients aged 20-75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1-5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1-5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1-4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete. FINDINGS: A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8-70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4-77·8] vs 62·6% [55·5-68·9]; hazard ratio [HR] 0·68, 95% CI 0·50-0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3-74·3]; HR 0·84, 0·63-1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group. INTERPRETATION: Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy. FUNDING: Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Docetaxel , Esophageal Neoplasms , Fluorouracil , Neoadjuvant Therapy , Humans , Middle Aged , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Male , Female , Neoadjuvant Therapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Aged , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Adult , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/mortality , Chemoradiotherapy/methods , EsophagectomyABSTRACT
PURPOSE: This study aimed to determine the clinicopathologic and prognostic significance of squamous cell carcinoma antigen (SCC-Ag) in patients with esophageal SCC who underwent radical surgery without neoadjuvant therapy. METHODS: This study included 566 patients with primary esophageal SCC who underwent radical resection without neoadjuvant therapy at 15 Japanese hospitals between 2008 and 2016. The cutoff value of SCC-Ag was 1.5 ng/mL based on the receiver operating characteristic curves. Preoperative SCC-Ag and postoperative SCC-Ag were analyzed to evaluate clinicopathological and prognostic significance. Survival curves were compared between the SCC-Ag-positive group and the SCC-Ag-negative group. The prognostic impact of SCC-Ag was evaluated using univariate and multivariate analyses. RESULTS: The preoperative SCC-Ag-positive rate was 23.5% (133/566). SCC-Ag-positive status was significantly associated with old age (p = 0.042), tumor depth (p <0.001), and tumor stages (p <0.001). The preoperative SCC-Ag-positive group had significantly poorer overall survival than the SCC-Ag-negative group (p = 0.030), but it was not an independent predictor of poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for poor overall survival (p = 0.034). CONCLUSION: Both pre- and postoperative SCC-Ag-positive statuses were significantly associated with poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for predicting overall survival.
Subject(s)
Antigens, Neoplasm , Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Serpins , Humans , Esophageal Squamous Cell Carcinoma/surgery , Prognosis , Japan , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Neoplasm Staging , Treatment Outcome , Biomarkers, Tumor , Retrospective StudiesABSTRACT
BACKGROUND/AIM: Brain metastasis, a leading cause of cancer death, is a clinical challenge. Recently, genetic characterization of brain metastatic lesions based on next generation sequencing-based advanced technologies, such as single-cell RNA sequencing, has been performed to develop novel efficient therapies. The present study aimed to investigate brain-metastasis-specific biomarkers as well as relevant prognostic factors. PATIENTS AND METHODS: The genetic profiles and expression levels of immune response-associated genes and 820 cancer-associated genes were compared between primary cancer lesions and metastatic cancer lesions obtained from nine cancer patients at the Shizuoka Cancer Center. Cytokine and chemokine marker genes were analyzed via quantitative PCR. T-cell receptor (TCR) repertoire profiling was performed for the same patients. For survival analysis, survival data of 52 cancer patients with brain metastases were utilized. RESULTS: Comparison of driver mutation profiling between primary and metastatic lesions revealed shared core mutations in both lesions and a few new mutations in metastatic lesions. A high tumor mutation burden (TMB) was detected in metastatic lesions. Volcano plot analysis revealed specific features of the metastatic tumor microenvironment, such as cancer signaling promotion and immune suppression due to decreased immune cell infiltration. Survival analysis revealed that three genes, the TREML2 gene, the BTLA gene on activated microglia and the CERS2 gene on metastatic tumor, were potent prognostic factors. CONCLUSION: High TMB in metastatic lesions indicates potential benefit from immune checkpoint inhibitor usage for brain metastasis and TREML2 and BTLA are factors associated with poor prognosis. Activated microglia may be novel targets for the treatment of brain metastasis.
Subject(s)
Biomarkers, Tumor , Brain Neoplasms , Humans , Brain Neoplasms/secondary , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Female , Male , Biomarkers, Tumor/genetics , Middle Aged , Prognosis , Aged , Mutation , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Gene Expression Regulation, NeoplasticABSTRACT
In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Humans , Esophageal Neoplasms/surgery , Esophageal Neoplasms/drug therapy , Endoscopy , Chemoradiotherapy , Carcinoma, Squamous Cell/pathologyABSTRACT
Chemoradiotherapy has been considered as one of the standard treatment options for clinical T1bN0M0 esophageal squamous cell carcinoma with organ preservation. However, 20% of patients develop locoregional recurrence after chemoradiotherapy, which requires salvage treatment including salvage surgery and endoscopic resection. Salvage surgery can cause complications and treatment-related death. Interestingly, chemoradiotherapy with elective nodal irradiation has been reported to reduce the locoregional recurrence of advanced esophageal squamous cell carcinoma. Hence, we are conducting a clinical trial to confirm whether modified chemoradiotherapy with elective nodal irradiation was superiority to that without elective nodal irradiation for the patients with cT1bN0M0 esophageal squamous cell carcinoma. The primary endpoint is major progression-free survival, defined as the time from randomization to the date of death or disease progression, excluding successful curative resection through salvage endoscopic resection. We plan to enroll 280 patients from 54 institutions over 4 years. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031200067).
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Neoplasm Recurrence, Local/pathology , Chemoradiotherapy , Japan , Treatment Outcome , Salvage Therapy , Retrospective StudiesABSTRACT
BACKGROUND/AIM: Recently, inactivating somatic mutations of SWI/SNF chromatin-remodeling genes in cancers have been reported. However, few studies have been performed regarding the immunological analysis of the tumor microenvironment (TME) in chromatin remodeling complex gene-mutated tumors. In the present study, we identified cancer patients harboring various mammalian SWI/SNF complex mutations and investigated the immunological features in those mutated cancers. PATIENTS AND METHODS: Cancer patients harboring any type of chromatin remodeling complex gene mutation were selected and clinicopathological features were compared between chromatin remodeling complex gene expression-low and expression-high groups. Specifically, expression levels of immune response-associated genes and cancer-associated genes were compared between the SMARCA4 expression-low and expression-high groups using volcano plot analysis. RESULTS: Among cancers harboring PBRM1, SAMRACA4 and ARID2 gene mutations, T-cell marker and mature B-cell marker genes were up-regulated in the tumor. Specifically, T-cell effector genes (CD8B, CD40LG), central memory marker genes (CD27, CCR7) and mature B-cell marker genes (CD20, CD38, CD79 and IRF4) were up-regulated, and cancer-associated genes including MYB, MYC and AURKB genes were down-regulated in the SMARCA4 expression-low group. Remarkably, heatmap of gene expression and immunohistochemistry (IHC) data demonstrated that the tertiary lymphoid structure (TLS) gene signature of mature B cells was up-regulated in SMACA4 gene-mutated stomach cancers. CONCLUSION: These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.
Subject(s)
Neoplasms , Tumor Microenvironment , Animals , Humans , Tumor Microenvironment/genetics , Mutation , Neoplasms/genetics , Mammals , DNA Helicases/genetics , Nuclear Proteins/genetics , Transcription Factors/geneticsABSTRACT
INTRODUCTION: The albumin-bilirubin (ALBI) score evaluates liver dysfunction severity. However, this score had prognostic effects in patients with hepatocellular, pancreatic, and gastric carcinomas. We aimed to assess the predictive value of the ALBI score in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Data from 154 patients with ESCC who consecutively underwent neoadjuvant chemotherapy (NAC) and subtotal esophagectomy were retrospectively investigated. The ALBI score was calculated as pre-NAC ALBI and categorized into grades 1, 2a, 2b, and 3; low-ALBI group (n = 134) was assigned with ALBI grade 1 and the other grades were assigned to the high-ALBI group (n = 20). RESULTS: The pre-NAC ALBI was significantly associated with relapse-free survival (RFS) and overall survival (P = 0.003 and P = 0.014, respectively). Based on multivariate analysis, pre-NAC ALBI, pathological T factor, and N factor were identified as independent prognostic factors for poor RFS. Multivariate and univariate analyses limited to factors were obtained before treatment, indicating high pre-NAC ALBI as an independent prognostic factor of poor overall survival (P = 0.039) and RFS (P = 0.008). With respect to pathological response to NAC, patients in the high pre-NAC ALBI group had a significantly lower response than patients in the low pre-NAC ALBI group (P = 0.010). CONCLUSIONS: Our results suggested that the pre-NAC ALBI marker predicts the long-term outcome and pathological response to NAC in patients with ESCC consecutively undergoing NAC and a subtotal esophagectomy.
Subject(s)
Carcinoma, Hepatocellular , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Liver Neoplasms , Humans , Esophageal Squamous Cell Carcinoma/therapy , Bilirubin/therapeutic use , Esophageal Neoplasms/pathology , Retrospective Studies , Serum Albumin/analysis , Clinical Relevance , Neoplasm Recurrence, Local , Prognosis , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgeryABSTRACT
BACKGROUND: There is no clear evidence on the prevention of postoperative delirium with pharmacotherapy in elderly patients with esophageal cancer. This retrospective study aimed to evaluate the efficacy of ramelteon and suvorexant in preventing postoperative delirium in this patient group. METHODS: Data on 251 patients who received radical esophagectomy for thoracic esophageal cancer were collected from January 2010 to September 2021. In total, 74 patients did not receive preventive intervention, and 177 received ramelteon and suvorexant. After propensity score matching, the rate of postoperative delirium was compared between the two groups. RESULTS: Seventy-two well-balanced patients in each group demonstrated similar clinical and pathological characteristics. The mean ages of the intervention and control groups were 70.8 and 70.3 years, respectively. All the patients underwent McKeown esophagectomy, and in the volume of intraoperative blood loss or operative time did not significantly differ between the two groups. The incidence rates of postoperative hyperactive delirium were 7% (5/72) in the intervention group and 32% (23/72) in the control group (p < 0.001). No severe adverse event potentially attributable to the intervention drug was observed. The multivariate analysis showed that the use of ramelteon and suvorexant was the only independent protective factor against postoperative delirium (hazard ratio 0.157, 95% CI 0.055-0.448, p < 0.001). CONCLUSIONS: Ramelteon and suvorexant may play an important role in reducing postoperative delirium in elderly patients with esophageal cancer.
Subject(s)
Delirium , Emergence Delirium , Esophageal Neoplasms , Humans , Aged , Retrospective Studies , Delirium/epidemiology , Delirium/etiology , Delirium/prevention & control , Esophageal Neoplasms/complications , Esophageal Neoplasms/surgeryABSTRACT
Gastrointestinal stromal tumors (GIST) with KIT exon 11 deletions involving in codons 557-558 (KIT Δ557-558) exhibit higher proliferation rates and shorter disease-free survival times compared with GISTs with other KIT exon 11 mutations. We analyzed 30 GIST cases and observed genomic instability and global DNA hypomethylation only in high-risk malignant GISTs with KIT Δ557-558. Whole-genome sequencing revealed that the high-risk malignant GISTs with KIT Δ557-558 (12 cases) had more structural variations (SV), single-nucleotide variants, and insertions and deletions compared with the low-risk, less malignant GISTs with KIT Δ557-558 (six cases) and the high-risk (six cases) or low-risk (6 cases) GISTs with other KIT exon 11 mutations. The malignant GISTs with KIT Δ557-558 showed higher frequency and significance in copy number (CN) reduction on chromosome arms 9p and 22q, and 50% of them had LOH or CN-dependent expression reduction in CDKN2A. In addition, SVs with driver potential were detected in 75% of them, in which AKT3 and MGMT were recurrently identified. Genome-wide DNA methylation and gene expression analyses showed global intergenic DNA hypomethylation, SNAI2 upregulation, and higher expression signatures, including p53 inactivation and chromosomal instability, as characteristics of malignant GISTs with KIT Δ557-558 that distinguished them from other GISTs. These genomic and epigenomic profiling results revealed that KIT Δ557-558 mutations are associated with increased genomic instability in malignant GISTs. Significance: We present genomic and epigenomic insights into the malignant progression of GISTs with KIT exon 11 deletions involving in 557-558, demonstrating their unique chromosomal instability and global intergenic DNA hypomethylation.
Subject(s)
Gastrointestinal Stromal Tumors , Humans , DNA, Intergenic , Epigenomics , Exons/genetics , Gastrointestinal Stromal Tumors/genetics , Genomic Instability , Sequence Deletion/geneticsABSTRACT
BACKGROUND: The clinical effectiveness of tumor markers for estimating prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. We assessed the clinical impact of changes in perioperative serum p53 antibodies (s-p53-Abs) titers in ESCC. METHODS: From January 2011 to March 2021, 249 patients were enrolled in this study. Titers of s-p53-Abs were measured before the initial treatment and 3 months after esophagectomy. Patients were divided into a s-p53-Abs decreased or unchanged group (Group D, n = 217) and an increased group (Group I, n = 32). Short- and long-term outcomes were compared between the groups. RESULTS: There was no correlation between the changes in squamous cell carcinoma antigen and carcinoembryonic antigen titers and recurrence site, number of recurrent lesions, and prognosis. However, the recurrence rate was significantly higher in Group I than in Group D (53.1% vs. 28.6%, p = 0.008), especially for distant organ recurrence (37.5% vs. 18.4%, p = 0.019). Furthermore, the rate of polyrecurrence was higher in Group I than in Group D (34.4% vs. 14.3%, p = 0.009). Recurrence-free survival (RFS) was significantly worse in Group I than in Group D (median survival time, 21.2 months vs. 36.7 months, p = 0.015). Multivariate analysis revealed that lymphatic vessel infiltration (hazard ratio [HR], 1.721; 95% CI 1.069-2.772; p = 0.026), blood vessel infiltration (HR, 2.348; 95% CI 1.385-3.982; p = 0.002), advanced pathological stage (≥ III) (HR, 3.937; 95% CI 2.295-6.754; p < 0.001), and increased s-p53-Abs titers (HR, 2.635; 95% CI 1.488-4.667; p = 0.001) were independent predictors of poor RFS. CONCLUSIONS: Elevation of s-p53-Abs titers after esophagectomy can predict polyrecurrence in distant organs and poor prognosis.
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/surgery , Prognosis , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Tumor Suppressor Protein p53ABSTRACT
BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting. METHODS: We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0-1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups. RESULTS: The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22-2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10-11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10-3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57-1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02-3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58-2.22; P = 0.717). CONCLUSIONS: NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Retrospective Studies , Esophageal Neoplasms/pathology , Chemoradiotherapy , Prognosis , Neoadjuvant Therapy , EsophagectomyABSTRACT
BACKGROUND: We herein investigated the association between early tumor shrinkage (ETS) and depth of response (DpR) and clinical outcomes in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil (bDCF) using data from the JCOG0807, a phase I/II trial of bDCF as first-line chemotherapy for metastatic esophageal cancer. METHODS: ETS was defined as a percent decrease in the sum of the target lesions' longest diameter after 8 weeks, whereas DpR was defined as a percentage of the maximal tumor shrinkage during the treatment course. Multivariable analyses were conducted to identify significant prognostic variables in progression-free survival (PFS) and overall survival (OS): one for ETS and covariates, and another for DpR and covariates. RESULTS: Among 53 patients, 35 patients with ETS ≥ 20% (66.0%) had longer PFS (7.5 vs. 3.4 months, hazard ratio [HR]: 0.26, 95% confidence interval [95% CI] 0.14-0.49), OS (13.8 vs. 6.1 months, HR 0.20, 95% CI 0.11-0.39), and PPS (6.4 vs. 2.8 months, HR 0.38, 95% CI 0.20-0.72) than those with ETS < 20%. In addition, 37 patients with DpR ≥ 30% (69.8%) had longer PFS (7.5 vs. 2.9 months, HR 0.17, 95% CI 0.08-0.34), OS (13.8 vs. 6.0 months, HR 0.14, 95% CI 0.07-0.27), and PPS (6.8 vs. 2.8 months, HR 0.30, 95% CI 0.15-0.58) than those with DpR < 30%. Multivariable analyses revealed that each ETS and DpR was an independent factor of longer PFS and OS. CONCLUSIONS: ETS and DpR might be associated with clinical outcomes in patients with metastatic esophageal cancer treated with bDCF.
Subject(s)
Esophageal Neoplasms , Stomach Neoplasms , Humans , Cisplatin/therapeutic use , Docetaxel/therapeutic use , Esophageal Neoplasms/drug therapy , Fluorouracil/therapeutic use , Kaplan-Meier Estimate , Stomach Neoplasms/pathology , Treatment OutcomeABSTRACT
BACKGROUND: Previous studies have evaluated the clinicopathological significance of carcinoembryonic antigen (CEA) of esophageal cancer in relatively small numbers of patients. Therefore, this study aimed to clarify the prognostic significance of CEA in 1822 patients with esophageal squamous cell carcinoma (SCC). METHODS: Based on the Japanese Esophageal Society nationwide multi-institutional retrospective study, a total of 1,748 surgically treated ESCC from 15 hospitals were enrolled to evaluate prognostic impact of preoperative CEA values. Among them, 605 patients were categorized to up-front surgery group, and 1,217 patients were categorized to neoadjuvant therapy group. The CEA threshold for positivity was 3.7 ng/ml. The clinicopathological and prognostic impact of CEA was evaluated by univariate and multivariate analysis in each treatment modality groups. RESULTS: In total, the CEA positive rate was 25.8% (470/1822). CEA-positive status was significantly associated with distant metastasis (P = 0.004) but not associated with other factors. CEA-positive status was associated with poor overall survival (P < 0.001) in univariate analysis as well as multivariate analysis (P = 0.003). CONCLUSIONS: CEA was an independent prognostic determinant of overall survival in esophageal SCC. Based on the subgroup analysis, regardless of the treatment modality, patients with high pretreatment CEA showed poor overall survival.
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Serpins , Humans , Esophageal Squamous Cell Carcinoma/surgery , Carcinoembryonic Antigen , Prognosis , Esophageal Neoplasms/pathology , Retrospective Studies , Japan/epidemiology , Carcinoma, Squamous Cell/pathology , Antigens, Neoplasm , Biomarkers, TumorABSTRACT
BACKGROUND: Extensive lymph node dissection increases the risk of postoperative complications, especially in salvage surgery, after definitive chemoradiotherapy (≥ 50 Gy) in patients with esophageal squamous cell carcinoma. The purpose of this retrospective study is to compare the outcomes of salvage esophagectomy with selective lymphadenectomy of only clinically positive lymph nodes. METHODS: Clinically positive lymph nodes, diagnosed as metastases using computed and positron emission tomography performed before chemoradiotherapy or salvage surgery, were targeted for dissection in selective lymphadenectomy. We compared postoperative complications between 52 patients who underwent salvage esophagectomy with selective lymphadenectomy and 207 controls who underwent nonsalvage esophagectomy with 3-field lymphadenectomy. We also analyzed postoperative recurrence pattern and survival in salvage group. RESULTS: The mean number of dissected lymph nodes was 12.9 in the salvage esophagectomy group compared with 48.1 in the 3-field lymphadenectomy group (p < 0.001). Differences in the number of postoperative complications, comparing Clavien-Dindo all-grade and ≥ grade 3, were not significant between the groups. Both 30- and 90-day mortality were 0% (0/52) in the salvage group. Five cases had recurrence only in the locoregional area without distant metastasis. Of these five cases, only one had recurrence in the subcarinal lymph node without prophylactic mediastinal lymphadenectomy. A 3-year recurrence-free survival and 3-year overall survival from salvage esophagectomy were 43.3% and 46.3%, respectively. CONCLUSIONS: It may contribute to obtaining good short- and long-term outcomes by dissecting only clinically positive lymph nodes in salvage esophagectomy.
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/surgery , Esophagectomy , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphatic Metastasis/pathology , Postoperative Complications/etiology , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: The clinical significance of circumferential resection margin (CRM) in esophageal squamous cell carcinoma (ESCC) remains unclear. Optimal CRM for predicting the recurrence of pathological T3 ESCC was investigated. METHODS: Seventy-three patients were retrospectively investigated in the development cohort. Patients were divided into CRM-negative and CRM-positive groups, and clinicopathological factors and survival outcomes were compared between the groups. The cutoff value was validated in another validation cohort (n = 99). RESULTS: Receiver operating characteristic analysis in the development cohort showed the cutoff value of CRM was 600 µm. In the validation cohort, patients in the CRM-positive group showed a significantly higher rate of locoregional recurrence (p = 0.006) and worse recurrence-free survival (RFS) (p < 0.001) than those in the CRM-negative group. Multivariate analysis identified positive CRM as an independent predictive factor for poor RFS (hazard ratio, 2.695; 95% confidence interval, 1.492-4.867; p = 0.001). The predictive value of our criteria of positive CRM for RFS was higher than that of the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP) criteria. Stratified analysis in the neoadjuvant chemotherapy groups also revealed that the rate of locoregional recurrence was higher in the CRM-positive group than in the CRM-negative group both in the pathological N0 and N1-3 subgroups. CONCLUSIONS: CRM of 600 µm can be the optimal cutoff value rather than the RCP and CAP criteria for predicting locoregional recurrence after esophagectomy. These results may support the impact of perioperative locoregional control of locally advanced ESCC.
ABSTRACT
INTRODUCTION AND IMPORTANCE: There is no clear consensus on a specific treatment for esophageal perforation. The surgical approach is deemed necessary for local severe infection and pleural contamination requiring debridement. PRESENTATIONS OF CASE: We have reported herein the case of a patient with esophageal perforation with severe mediastinal and thoracic abscess after endoscopic balloon dilation for stenosis due to endoscopic submucosal dissection and chemoradiotherapy. A surgical approach with primary closure was performed, but not found effective; while conservative treatment with mediastinal drainage via posterior neck and recovery of nutritional status was found to be effective. For the recovery of nutritional status, enteral nutrition was assessed using a polymeric formula through a percutaneous endoscopic gastrojejunostomy tube. DISCUSSION: Esophageal perforation is a life-threatening condition. Iatrogenic injuries are the frequent cause of esophageal perforation. For esophageal perforation, not only surgical interventions but also conservative treatments including various endoscopic approaches have been performed. If the inflammation is not localized, surgical intervention is often needed; however, if the patient's general condition is stable, conservative treatment with drainage, antibiotics, and nutritional management may be considered, even in cases of esophageal perforation. CONCLUSIONS: Esophageal perforation with a large perforation site with widespread inflammation can be improved with proper thoracic and mediastinal drainage and adequate nutrition support if the patient's condition is mild.
ABSTRACT
OBJECTIVE: Data are sparse regarding the multidisciplinary perioperative enhanced recovery after surgery protocol (E-P) for thoracic esophageal cancer surgery that was newly used at another institution. Therefore, this study aimed to retrospectively evaluate the effectiveness and safety of the protocol. METHODS: We enrolled 101 patients who underwent transthoracic esophagectomy for E-P at the Shizuoka Cancer Center Hospital (SCC). The outcomes obtained at the SCC were compared with the outcomes of 140 patients treated with E-P at the Saitama Medical University International Medical Center (SMU). At the SMU, we compared the results before and after the introduction of E-P. RESULTS: The rates of morbidity, pulmonary complications, and postoperative pneumonia were 44%, 31%, and 6.9% at the SCC and 44%, 27%, and 6.5% at the SMU (P = 0.91, 0.55, and 0.88, respectively). The mean time to walk was 1.1 and 1.5 days at the SCC and SMU, respectively (P < 0.001). The median length of hospital stay was longer at the SMU than at the SCC (24.0 versus 20.8 days; P = 0.004). In the comparative study before and after the introduction of E-P, the rate of postoperative pneumonia was 16% in the conventional management group and 6.5% in the E-P group (P = 0.02). CONCLUSION: Postoperative pneumonia was reduced before and after introduction of E-P. As similar short-term postoperative outcomes were promising (except for the time to walk and postoperative hospital stay), the same E-P that was safely performed at the SMU can be implemented as a standard practice.