Characteristics Predicting Short-Term and Long-Term Health-Related Quality of Life in Patients with Esophageal Cancer After Neoadjuvant Chemoradiotherapy and Esophagectomy

Background: Esophagectomy is associated with lasting effect on health-related quality of life (HRQOL). Patients desire detailed information on the expected impact of treatment on their postoperative HRQOL. The aim of the present study is to identify clinicopathological characteristics predictive for changes in short-term and long-term HRQOL after neoadjuvant chemoradiotherapy (nCRT) and surgery. Methods: HRQOL was measured using EORTC-QLQ-C30 and QLQ-OES24 questionnaires prior to nCRT, three, six, nine and twelve months postoperatively and at a minimum of six years postoperatively. Based on previous experience and available literature, several subgroups were predefined for different clinicopathological characteristics: baseline global HRQOL, WHO performance status, histology, tumor stage and tumor location. The primary endpoints of the present study were the change compared to baseline in the HRQOL dimensions physical functioning and eating problems. Secondary endpoints were global HRQOL, fatigue and emotional problems. Results:In total, 134 (76%) of 177 patients who received HRQOL questionnaires, responded at baseline. Patients who reported a high baseline global HRQOL had a more severe deterioration in eating problems (+14.5 to + 18.0), global HRQOL (-16.0 to -28.0) and fatigue (+10.5 to +14.9) up to six years postoperatively compared to patients who reported a low baseline global HRQOL. Patients who had stage 2 tumor (UICC 6th edition) had a more severe deterioration in eating problems (+14.6 to +19.0) and global HRQOL (-10.1 to -17.1) than patients who had stage 3 tumor. Conclusions: The results suggest that patients with locally advanced esophageal cancer in favorable condition at baseline decline more in terms of various HRQOL outcomes.</p

Fractures and other chest wall abnormalities after thoracotomy for esophageal cancer:A retrospective cohort study

Background Chest pain following a thoracotomy for esophageal cancer is frequently reported but poorly understood. This study aimed to (1) determine the prevalence of thoracotomy-related thoracic fractures on postoperative imaging and (2) compare complications, long-term pain, and quality of life in patients with versus without these fractures. Methods This retrospective cohort study enrolled patients with esophageal cancer who underwent a thoracotomy between 2010 and 2020 with pre- and postoperative CTs (&lt;1 and/or &gt;6 months). Disease-free patients were invited for questionnaires on pain and quality of life. Results Of a total of 366 patients, thoracotomy-related rib fractures were seen in 144 (39%) and thoracic transverse process fractures in 4 (2%) patients. Patients with thoracic fractures more often developed complications (89% vs. 74%, p = 0.002), especially pneumonia (51% vs. 39%, p = 0.032). Questionnaires were completed by 77 after a median of 41 (P-25-P(75 )28-91) months. Long-term pain was frequently (63%) reported but was not associated with thoracic fractures (p = 0.637), and neither were quality of life scores. Conclusions Thoracic fractures are prevalent in patients following a thoracotomy for esophageal cancer. These thoracic fractures were associated with an increased risk of postoperative complications, especially pneumonia, but an association with long-term pain or reduced quality of life was not confirmed

Development of esophageal squamous cell cancer in patients with FAMMM syndrome: Two clinical reports

Familial atypical multiple mole melanoma (FAMMM) syndrome is a hereditary syndrome characterized by multiple dysplastic nevi and melanoma. Patients with FAMMM may have a heterozygous, inactivating, pathogenic germline variant in the CDKN2A gene, especially the NM_000077.4: c.225_243del19 (p.p75fs) variant, also known as p16-Leiden variant. Patients with this variant are at high risk for developing melanomas and pancreatic cancer due to somatic inactivation of the wild-type CDKN2A allele. The combination of an inactivating germline CDKN2A mutation and somatic inactivation of the wild-type CDKN2A allele in the same cell results in tumor formation. It has been suggested that carriers of a germline CDKN2A mutation are also at increased risk for several other cancer types, including esophageal cancer. Here, we describe two unrelated patients with the p16-Leiden variant who developed esophageal squamous cell cancer. Evidence of loss of the wild-type CDKN2A allele was obtained in the tumor tissue of both patients indicating biallelic inactivation of p16 in the tumor cells. These results suggest that these patients developed esophageal squamous cell cancer in the context of FAMMM syndrome

Active surveillance of oesophageal cancer after response to neoadjuvant chemoradiotherapy:dysphagia is uncommon

BACKGROUND: Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response. METHODS: Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer ('SANO') trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0-100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports. RESULTS: In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3-4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0-0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires. CONCLUSION: Dysphagia and clinically relevant stenosis are uncommon during active surveillance.</p

Active surveillance of oesophageal cancer after response to neoadjuvant chemoradiotherapy:dysphagia is uncommon

BACKGROUND: Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response. METHODS: Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer ('SANO') trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0-100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports. RESULTS: In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3-4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0-0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires. CONCLUSION: Dysphagia and clinically relevant stenosis are uncommon during active surveillance.</p

Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer:The Randomized Controlled CROSS Trial

PURPOSE: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS: The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION: The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): A prospective multicenter diagnostic cohort study

Background: After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. Methods: Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. Discussion: If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial). Trial registration: The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019)

Collaborative multidisciplinary management and expertise of cT2-3 locally advanced operable esophageal squamous cell carcinoma:two case reports

Background: The accurate clinical staging of esophageal squamous cell carcinoma (ESCC) is pivotal for guiding treatment strategies. However, the current precision in staging for clinical T (cT)2 and cT3 stages remains unsatisfactory. This article discusses the role of multidisciplinary teams (MDTs) in the clinical staging and formulation of neoadjuvant treatment strategies for locally advanced operable ESCC. These challenges underscore the importance of precise staging in the decision-making process for appropriate therapeutic interventions.Case Description: Through the lens of two patient case studies with locally advanced resectable ESCC, the article showcases the intricate process of treatment planning undertaken by MDTs. It captures a range of expert perspectives from Japan, China, Hong Kong (China), Korea, the USA, and Europe, focusing on the challenges of differentiating between cT2 and cT3 stages of the disease, which is a critical determinant in the management and therapeutic approach for patients.Conclusions: The article concludes that the accurate staging of ESCC is a cornerstone in determining the most suitable treatment strategies. It underscores the vital role that MDTs play in both clinical staging and the decision-making process for treatment. Highlighting the limitations in current diagnostic methods, the article emphasizes the urgent need for advanced research and the refinement of diagnostic tools to improve the precision of staging, particularly between the cT2 and cT3 stages. It suggests that future research should consider whether a reclassification of these stages could be warranted to enhance treatment planning and outcomes for patients with ESCC.<br/