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Contains fulltext : 293634.pdf (Publisher’s version ) (Open Access) Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet-ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well-formed glands), which is a possible confounder. We studied the pre- and post-treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well-formed glands, extracellular mucin, SRCs, and PCCs were scored in pre-treatment biopsies and post-treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3-4 (i.e. >10% residual tumour), overall survival, and disease-free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre-treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre-treatment histopathological factors were unrelated to tumour regression grade. Pre-treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19-2.53). Patients with post-treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10-2.99). In conclusion, pre-treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre-treatment and any SRCs post-treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts. 01 juli 2023

Objective: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer.Summary of Background Data: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer.Methods: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods.Results: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% (P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P Conclusion: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

Malignancies of the peritoneal cavity are associated with a dismal prognosis. Systemic chemotherapy is the gold standard for patients with unresectable peritoneal disease, but its intraperitoneal effect is hampered by the peritoneal-plasma barrier. Intraperitoneal chemotherapy, which is administered repeatedly into the peritoneal cavity through a peritoneal implanted port, could provide a novel treatment modality for this patient population. This review provides a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. Several anticancer drugs have been studied for intraperitoneal application, with the taxanes paclitaxel and docetaxel as the most commonly used drug. Repeated intraperitoneal chemotherapy, mostly in combination with systemic chemotherapy, has shown promising results in Phase I and Phase II studies for several tumor types, such as gastric cancer, ovarian cancer, colorectal cancer, and pancreatic cancer. Two Phase III studies for intraperitoneal chemotherapy in gastric cancer have been performed so far, but the results regarding the superiority over standard systemic chemotherapy alone, are contradictory. Pressurized intraperitoneal administration, known as PIPAC, is an alternative way of administering intraperitoneal chemotherapy, and the first prospective studies have shown a tolerable safety profile. Although intraperitoneal chemotherapy might be a standard treatment option for patients with unresectable peritoneal disease, more Phase II and Phase III studies focusing on tolerability profiles, survival rates, and quality of life are warranted in order to establish optimal treatment schedules and to establish a potential role for intraperitoneal chemotherapy in the approach to unresectable peritoneal disease.

Introduction: This population-based cohort study analysed treatment, overall survival (OS), and independent prognostic factors for OS in gastric cancer patients with liver metastases. Methods: Between 2015 and 2017, patients with synchronous metastatic gastric or gastroesophageal junction adenocarcinoma limited to the liver were included from the prospectively maintained population-based Netherlands Cancer Registry. Liver oligometastatic disease (OMD) was defined as ≤3 liver metastases. The primary outcome was OS. Independent prognostic factors for OS were analysed using multivariable Cox regression analysis. Results: A total 295 patients with metastases limited to the liver were included. The primary tumour was resected in four patients (1.4%). Treatment for liver metastases consisted of chemotherapy alone (28.1%), trastuzumab plus chemotherapy (4.7%), surgery (1.0%), or best supportive care (67.5%). Median OS across all included patients was 4.0 months (95% confidence interval [CI]: 3.1–4.5). Liver OMD was detected in 77 patients (26%). Treatment for liver OMD consisted of chemotherapy alone (24.6%), trastuzumab plus chemotherapy (5.2%), surgery (3.9%), or best supportive care (67.5%). Median OS among patients with liver OMD was 5.7 months (95% CI: 4.8–7.5). Across all patients, better OS was independently associated with liver OMD (hazard ratio [HR] 0.66, 95% CI: 0.50–0.87), trastuzumab (HR 0.41, 95% CI: 0.23–0.72) but not with triplet compared with doublet chemotherapy (HR 0.94, 95% CI: 0.57–2.87). Worse OS was independently associated with unknown nodal stage versus cN0 (HR 1.74, 95% CI: 1.17–2.60), diffuse-type versus intestinal-type adenocarcinoma (HR 2.06, 95% CI: 1.32–3.20), and monotherapy or best supportive care versus doublet chemotherapy (HR 1.72, 95% CI: 1.03–2.87, and HR 3.61, 95% CI: 2.55–5.10, respectively). Conclusion: In this population-based cohort study, liver OMD was detected in 26% of patients. Liver OMD and trastuzumab treatment were independently associated with better OS while triplet as compared with doublet chemotherapy was not. OS among patients with liver OMD nevertheless remained poor. The concept of OMD and the benefit of resection of liver OMD may still have been relatively unknown in this disease type during the study inclusion years.

Objective: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery.Background: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission.Methods: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival.Results: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤ 65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6–4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4–23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65–0.84).Conclusions: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

Introduction: Few studies have been conducted into how physicians use steering behaviour that may persuade patients to choose for a particular treatment, let alone to participate in a randomised trial. The aim of this study is to assess if and how surgeons use steering behaviour in their information provision to patients in their choice to participate in a stepped-wedge cluster randomised trial investigating an organ sparing treatment in (curable) oesophageal cancer (SANO trial). Materials and methods: A qualitative study was performed. Thematic content analysis was applied to audiotaped and transcribed consultations of twenty patients with eight different oncological surgeons in three Dutch hospitals. Patients could choose to participate in a clinical trial in which an experimental treatment of ‘active surveillance’ (AS) was offered. Patients who did not want to participate underwent standard treatment: neoadjuvant chemoradiotherapy followed by oesophagectomy. Results: Surgeons used various techniques to steer patients towards one of the two options, mostly towards AS. The presentation of pros and cons of treatment options was imbalanced: positive framing of AS was used to steer patients towards the choice for AS, and negative framing of AS to make the choice for surgery more attractive. Further, steering language, i.e. suggestive language, was used, and surgeons seemed to use the timing of the introduction of the different treatment options, to put more focus on one of the treatment options. Conclusion: Awareness of steering behaviour can help to guide physicians in more objectively informing patients on participation in future clinical trials.

Objective. We aimed to gain consensus on HCPs’ perspectives on self-management support information needs of patients with esophageal cancer during the preoperative phase. Methods. Based on the literature, observations of clinical consultations, and hospital patient information leaflets, a survey was created. HCPs were surveyed twice about their opinion on importance of information, from “not essential” to “absolutely essential,” using Delphi methods. Topics were included in the second round if predetermined criteria were met. To be included in the final list, topics had to meet criteria for consensus and stability. Results. 64 information items and 6 sources of support were identified. Survey response rates were 59% (68 out of 116, first round) and 75% thereafter. The final list included 33 topics, including logistical information, expectations for future health condition, complications, follow-up care, nutrition during treatment, and nutrition during recovery as topics with 100% agreement. Consensus on the source of support was reached for face-to-face contact, written information, information video, and a case manager. Conclusion. This study provides a list of important topics, from the perspectives of HCPs, to guide the systematic provision of education to support EC patients’ self-management during the preoperative phase. Additionally, the most preferred sources of support were face-to-face contact and a case manager.

Background Patients with different ethnic and genetic backgrounds may respond differently to anticancer therapies. This study aimed to assess whether patients with oesophageal squamous cell carcinoma (OSCC) treated with neoadjuvant chemoradiotherapy (nCRT) in East Asia had an inferior pathological response compared with patients treated in Northwest Europe. Methods Patients with OSCC who underwent nCRT according to the CROSS regimen (carboplatin and paclitaxel with concurrent 41.4 Gy radiotherapy) followed by oesophagectomy between June 2012 and April 2020 were identified from East Asian and Dutch databases. The primary outcome was pCR, defined as ypT0 N0. Groups were compared using propensity score matching, adjusting for sex, Charlson Co-morbidity Index score, tumour location, cT and cN categories, interval between nCRT and surgery, and number of resected lymph nodes. Results Of 725 patients identified, 133 remained in each group after matching. A pCR was achieved in 37 patients (27.8 per cent) in the Asian database and 58 (43.6 per cent) in the Dutch database (P = 0.010). The rate of ypT1–4 was higher in Asian than Dutch data (66.2 and 49.6 per cent; P = 0.004). The ypN1–3 rate was 44.4 per cent in the Asian and 33.1 per cent in the Dutch data set. Clear margins were achieved in 92.5 per cent of Asian and 95.5 per cent of Dutch patients. Conclusion Regional differences in responses to CROSS nCRT for oesophageal cancer were apparent, the origin of which will need evaluation.

Contains fulltext : 291108.pdf (Publisher’s version ) (Open Access) Active surveillance may be a safe and effective treatment in oesophageal cancer patients with a clinically complete response after neoadjuvant chemoradiotherapy (nCRT). In the NOSANO-study we gained insight in patients' motive to opt for either an experimental treatment called active surveillance or for standard immediate surgery. Both qualitative and quantitative analyses methods were used. Forty patients were interviewed about their treatment preference, 3 months after completion of nCRT (T1). Data were recorded, transcribed verbatim and analysed according to the principles of grounded theory. In addition, at T1 and T2 (12 months after completion of nCRT) questionnaires on health-related quality of life, coping, anxiety and decisional regret (only T2) were administered. Interview data analyses resulted in a conceptual model with 'dealing with threat of cancer' as the central theme. Patients preferring active surveillance tend to cope with this threat by confiding in their bodies and good outcomes. Their mind-set is one of 'enjoy life now'. Patients preferring surgery tend to cope by minimizing uncertainty and eliminating the source of cancer. Their mind-set is one of 'don't give up, act now'. Furthermore, questionnaire results showed that patients with a preference for standard surgery had a lower quality of life. Patient preferences are individualized and thus difficult to predict. Our model can help healthcare professionals to determine patient preferences for treatment. Coping style and mind-set seem to be determining factors here.

Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24-71) (8/17), specificity of 85% (95% CI 42-99) (6/7), positive predictive value (PPV) of 89% (95% CI 51-99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17-67) (6/15) for detecting major residual disease (10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6-51) (3/14), specificity of 100% (95% CI 56-100) (7/7), PPV of 100% (95% CI 31-100) (3/3), and NPV of 39% (95% CI 18-64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Optimal surgical treatment for Siewert type II esophagogastric junction adenocarcinoma is debated. The aim of this study was to compare transhiatal extended gastrectomy (TEG) and transthoracic esophagectomy (TTE). Patients with Siewert type II tumors who underwent a resection by TEG or TTE in two centers (Erasmus University Medical Center, Rotterdam, and University of Verona) between 2014 and 2019 were identified. To limit selection bias, patients were matched for baseline characteristics and compared with a multivariable logistic regression model. Some 159 patients treated by TEG (60 patients, 37.7%) or TTE (99 patients, 62.3%) were included. Patients in the TEG group were older, had less tumor invasion of the esophagus, and were more often excluded from neoadjuvant therapy. Post-operative morbidity was comparable (P = 0.88), while 90-day mortality was higher after TEG (90-day mortality 10.0% in TEG group vs. 2.0% in TTE group P = 0.01). R0 resection was achieved in 83.3% of patients after TEG and in 97.9% after TTE (P

Purpose: There is a lack of prospective studies evaluating the effects of body composition on postoperative complications after gastrectomy in a Western population with predominantly advanced gastric cancer. Methods: This is a prospective side study of the LOGICA trial, a multicenter randomized trial on laparoscopic versus open gastrectomy for gastric cancer. Trial patients who received preoperative chemotherapy followed by gastrectomy with an available preoperative restaging abdominal computed tomography (CT) scan were included. The CT scan was used to calculate the mass (M) and radiation attenuation (RA) of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). These variables were expressed as Z-scores, depicting how many standard deviations each patient’s CT value differs from the sex-specific study sample mean. Primary outcome was the association of each Z-score with the occurrence of a major postoperative complication (Clavien-Dindo grade ≥ 3b). Results: From 2015 to 2018, a total of 112 patients were included. A major postoperative complication occurred in 9 patients (8%). A high SM-M Z-score was associated with a lower risk of major postoperative complications (RR 0.47, 95% CI 0.28–0.78, p = 0.004). Furthermore, high VAT-RA Z-scores and SAT-RA Z-scores were associated with a higher risk of major postoperative complications (RR 2.82, 95% CI 1.52–5.23, p = 0.001 and RR 1.95, 95% CI 1.14–3.34, p = 0.015, respectively). VAT-M, SAT-M, and SM-RA Z-scores showed no significant associations. Conclusion: Preoperative low skeletal muscle mass and high visceral and subcutaneous adipose tissue radiation attenuation (indicating fat depleted of triglycerides) were associated with a higher risk of developing a major postoperative complication in patients treated with preoperative chemotherapy followed by gastrectomy.

Background Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. Methods This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. Results Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. Conclusion A long-term symptom burden is common after oesophageal cancer surgery.

Active surveillance for patients with esophageal cancer and a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) is being studied. Active surveillance requires accurate clinical response evaluations. 18F-FDG PET/CT might be able to detect local tumor recurrence after nCRT as soon as the esophagus recovers from radiationinduced esophagitis. The aims of this study were to assess the value of serial 18F-FDG PET/CT scans for detecting local recurrence in patients beyond 3 mo after nCRT and to determine when radiation-induced esophagitis has resolved. Methods: This retrospectivemulticenter study included patients who had cCR after nCRT, who initially declined surgery, and who subsequently underwent active surveillance. Clinical response evaluations included 18F-FDG PET/CT, endoscopic biopsies, and endoscopic ultrasound with fine-needle aspiration at regular intervals. SUVmax normalized for lean body mass (SULmax) was measured at the primary tumor site. The percentage change in SULmax (D%SULmax) between the last follow-up scan and the scan at 3 mo after nCRT was calculated. Tumor recurrence was defined as biopsy-proven vital tumor at the initial tumor site. Results: Of 41 eligible patients, 24 patients had recurrent disease at a median of 6.5 mo after nCRT and 17 patients remained cancer free during a median follow-up of 24 mo after nCRT. Five of 24 patients with tumor recurrence had sudden intense SULmax increases of greater than 180%. In 19 of 24 patients with tumor recurrence, SULmax gradually increased (median D%SULmax, 118%), whereas SULmax decreased (median D%SULmax, -12%) in patients with ongoing cCR (P , 0.001, independent-samples t test). In patients with ongoing cCR, SULmax was lowest at 11 mo after nCRT. Conclusion: Serial 18F-FDG PET/CT might be a useful tool for detecting tumor recurrence during active surveillance. In patients with ongoing cCR, the lowest SULmax was reached at 11 mo after nCRT, suggesting that radiation-induced esophagitis had mostly resolved by that time. These findings warrant further evaluation in a larger cohort.

Over one-quarter of patients would choose not to undergo standard oesophagectomy again, at least 1 year after they underwent neoadjuvant chemoradiotherapy and standard oesophagectomy. These patients had worse short- and long-term health-related quality of life (HRQoL) than patients who chose standard oesophagectomy. Considering both treatments, 5-year survival and long-term HRQoL were considered most important factors by individual patients.

Objective The aim of this study was to perform a meta-analysis on the accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) for detecting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. Summary of background data After nCRT, one-third of patients have a pathologically complete response in the resection specimen. Before an active surveillance strategy could be offered to these patients, clinically complete responders should be accurately identified. Methods Embase, Medline, Cochrane, and Web-of-Science were searched until February 2018 for studies on accuracy of endoscopic biopsies, EUS, or PET(-CT) for detecting locoregional residual disease after nCRT for squamous cell- or adenocarcinoma. Pooled sensitivities and specificities were calculated using random-effect meta-analyses. Results Forty-four studies were included for meta-analyses. For detecting residual disease at the primary tumor site, 12 studies evaluated endoscopic biopsies, 11 qualitative EUS, 14 qualitative PET, 8 quantitative PET using maximum standardized uptake value (SUVmax), and 7 quantitative PET using percentage reduction of SUVmax (%ΔSUVmax). Pooled sensitivities and specificities were 33% and 95% for endoscopic biopsies, 96% and 8% for qualitative EUS, 74% and 52% for qualitative PET, 69% and 72% for PET-SUVmax, and 73% and 63% for PET-%ΔSUVmax. For detecting residual nodal disease, 11 studies evaluated qualitative EUS with a pooled sensitivity and specificity of 68% and 57%, respectively. In subgroup analyses, sensitivity of PET-%ΔSUVmax and EUS for nodal disease was higher in squamous cell carcinoma than adenocarcinoma. Conclusions Current literature suggests insufficient accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) as single modalities for detecting residual disease after nCRT for esophageal cancer.

Background Active surveillance has been proposed for patients with oesophageal cancer in whom there is a complete clinical response after neoadjuvant chemoradiotherapy (nCRT). However, endoscopic biopsies have limited negative predictive value in detecting residual disease. This study determined the location of residual tumour following surgery to improve surveillance and endoscopic strategies. Methods The present study was based on patients who participated in the prospective preSANO trial with adenocarcinoma or squamous cell carcinoma of the oesophagus or oesophagogastric junction treated in four Dutch hospitals between 2013 and 2016. Resection specimens and endoscopic biopsies taken during clinical response evaluations after nCRT were reviewed by two expert gastrointestinal pathologists. The exact location of residual disease in the oesophageal wall was determined in resection specimens. Endoscopic biopsies were assessed for the presence of structures representing the submucosal layer of the oesophageal wall. Results In total, 119 eligible patients underwent clinical response evaluations after nCRT followed by standard surgery. Residual tumour was present in endoscopic biopsies from 70 patients, confirmed on histological analysis of the resected organ. Residual tumour was present in the resection specimen from 27 of the other 49 patients, despite endoscopic biopsies being negative. Of these 27 patients, residual tumour was located in the mucosa in 18, and in the submucosa beneath tumour‐free mucosa in eight. One patient had tumour in muscle beneath tumour‐free mucosa and submucosa. Conclusion Most residual disease after nCRT missed by endoscopic biopsies was located in the mucosa. Active surveillance could be improved by more sampling and considering submucosal biopsies., Remnant cancer missed by endoscopic biopsies was located in the mucosa in two‐thirds of patients with residual disease after neoadjuvant chemoradiotherapy (nCRT). One‐third of patients had residual disease in the submucosa underneath a tumour‐free mucosa. The yield of biopsies in active surveillance after nCRT could be improved by sampling larger areas of oesophageal mucosa and using biopsies targeting the submucosa. What lies beneath

Objective To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. Background Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. Patients and methods Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. Results A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ± 0.02 and 0.82 ± 0.09 respectively. Conclusion Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

Objective:This study compared outcomes of patients with esophageal cancer and clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) undergoing active surveillance or immediate surgery. Background:Since nearly one-third of patients with esophageal cancer show pathologically complete response after nCRT according to CROSS regimen, the oncological benefit of immediate surgery in cCR is topic of debate. Methods:Patients with cCR based on endoscopic biopsies and endoscopic ultrasonography with fine-needle aspiration initially declining or accepting immediate surgery after nCRT were identified between 2011 and 2018. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), rate and timing of distant dissemination, and postoperative outcomes. Results:Some 98 patients with cCR were identified: 31 in the active surveillance- and 67 in the immediate surgery group with median followup of survivors of 27.7 and 34.8 months, respectively. Propensity score matching resulted in 2 comparable groups (n = 29 in both groups). Patients undergoing active surveillance or immediate surgery had a 3-year OS of 77% and 55% (HR 0.41; 95% CI 0.14-1.20, P = 0.104), respectively. The 3-year PFS was 60% and 54% (HR 1.08; 95% CI 0.44-2.67, P = 0.871), respectively. Patients undergoing active surveillance or immediate surgery had a comparable distant dissemination rate (both groups 28%), radical resection rate (both groups 100%), and severity of postoperative complications (Clav- ien-Dindo grade ≥ 3: 43% vs 45%, respectively). Conclusion:In this retrospective study, OS and PFS in patients with cCR undergoing active surveillance or immediate surgery were not significantly different. Active surveillance with postponed surgery for recurrent disease was not associated with a higher distant dissemination rate or more severe adverse postoperative outcomes.

Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20 and 50% of patients having a pathological complete response (pCR). Disease, however, still recurs in 20–30% of these patients. The aim of this study was to assess the pattern of recurrence in patients with pCR after nCRT and surgery. Methods All patients with pCR after neoadjuvant chemoradiotherapy and surgery included in the phase II and III ChemoRadiotherapy for Oesophageal followed by Surgery Study (CROSS) trials (April 2001—March 2009) and after the CROSS trials (September 2009—October 2017) were identified. The site of recurrence was compared to the applied radiation and surgical fields. Outcomes were median time to recurrence, overall and progression-free survivals. Results A total of 141 patients with a median follow-up of 100 (interquartile range [IQR] 64–134) months were included. Some 29 of 141 patients (21%) developed recurrence. Of these, four (14%) had isolated locoregional recurrence, 15 (52%) distant recurrence only and ten (34%) had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five were within the radiation field, seven outside the radiation field and two at the border. Median (IQR) time to recurrence was 24 (10–62) months. The 5-year overall survival was 74% and recurrence-free survival 70%. Conclusion Despite good overall survival, recurrence still occurred in 21% of patients. Most recurrences were distant, outside the radiation and surgical fields.

To compare complications following totally minimally invasive (TMIE), laparoscopically assisted (hybrid) and open Ivor Lewis esophagectomy in patients with esophageal cancer. Three randomized trials have reported benefits for minimally invasive esophagectomy. Two studies compared TMIE versus open esophagectomy and another compared hybrid versus open Ivor Lewis esophagectomy. Only small retrospective studies compared TMIE with hybrid Ivor Lewis esophagectomy. Methods Data were used from the International Esodata Study Group assessing patients undergoing TMIE, hybrid or open Ivor Lewis esophagectomy. Primary outcome was pneumonia, secondary outcomes included incidence and severity of anastomotic leakage, (major) complications, length of stay, escalation of care and 90-day mortality. Data were analyzed using multivariate multilevel models. Results In total, 4733 patients were included in this study (TMIE:1472, hybrid:1364 and open:1897). Patients undergoing TMIE had lower incidence of pneumonia compared to hybrid (10.9% vs 16.3%, Odds Ratio (OR):0.56, 95%CI: 0.40–0.80) and open esophagectomy (10.9% vs 17.4%, OR:0.60, 95%CI: 0.42–0.84) and had shorter length of stay (median 10 days (IQR 8–16)) compared to hybrid (14 (11–19), p = 0.041) and open esophagectomy (11 (9–16), p = 0.027). Patients undergoing TMIE had higher rate of anastomotic leakage compared to hybrid (15.1% vs 10.7%, OR:1.47, 95%CI: 1.01–2.13) and open esophagectomy (7.3%, OR:1.73, 95%CI: 1.26–2.38). No differences were reported between hybrid and open esophagectomy. Conclusion Compared to hybrid and open Ivor Lewis esophagectomy, TMIE resulted in a lower pneumonia rate, a shorter hospital length of stay but a higher anastomotic leakage rate. The impact of these individual complications on survival and long-term quality of life should be further investigated.

Active surveillance after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal cancer is currently topic of investigation. In a discrete choice experiment, patients’ preferences can be quantified by asking patients to state their preference over hypothetical treatment alternatives. The aim of the present study was to assess patients’ preferences for either active surveillance or standard esophagectomy in patients who underwent neoadjuvant chemoradiotherapy followed by surgery without signs of recurrence. Methods A discrete choice experiment was performed in esophageal cancer patients who underwent neoadjuvant chemoradiotherapy followed by standard esophagectomy at least one year earlier. Patients completed a questionnaire consisting of eighteen choice sets considering active surveillance or standard esophagectomy. Treatment alternatives were characterized by attributes with varying attribute levels hypothesized to influence treatment choice: five-year survival, short-term and long-term health related quality of life (HRQOL), annual number of diagnostics required and the risk that esophagectomy is still necessary later in time. The importance of attributes and willingness to trade-off 5-year survival for other attributes were assessed using panel latent class model. Results A total of 107 patients were consecutively included, of whom 100 (93%) responded between August 2018 and October 2020. Regardless of the attribute levels, 28 patients preferred active surveillance and 28 patients preferred standard esophagectomy. When considering both treatments, five-year survival and long-term HRQOL were considered most important attributes. Patients were willing to trade-off 5.4% five-year overall survival to obtain a better long-term HRQOL. Conclusion At least one year after neoadjuvant chemoradiotherapy and esophagectomy, over a quarter of patients would choose not to undergo standard esophagectomy again, regardless of the attribute levels. Patients were willing to trade-off five-year survival chance in order to achieve an HRQOL which was much better than their own situation. When considering both treatments, five-year survival and long-term HRQOL were the most important determinants in the choice for treatment.

The need for standard surgical resection in esophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) is subject of debate. Possibly, active surveillance (AS) is an option for patients with a clinically complete response (cCR), in whom no vital tumor cells are detected after nCRT. In a large Dutch multicenter randomized trial (SANO trial), standard surgery is compared to AS in patients with a cCR. Within this trial, we performed a side-study on patient treatment preferences. Methods Esophageal cancer patients, who declined participation in the SANO-trial due to a strong treatment preference for either AS or surgery were included. In-depth interviews were held on patient’s motives for their treatment choice. First, personal motives were addressed in an open manner, and later specific topics were addressed: earlier experiences with illness and health care, future health expectations, emotional motives, religious or spiritual believes and values in life. Data was recorded, transcribed verbatim and qualitatively analyzed according to the grounded theory principles. In addition, questionnaires on health literacy, coping, anxiety and decision regret were administered at two time points. Results Forty patients participated: twenty preferred AS and twenty standard surgery. The central principle for all patients is striving for safety while dealing with the threat of cancer. However, patients express different coping strategies in dealing with this threat. Patients preferring AS rely on trusting their bodies and good outcomes, while questioning the need for surgery. Patients preferring surgery try to minimize insecurity by eliminating the source of the cancer, while arguing that chances for undergoing surgery are high anyway. Interestingly, for either treatment option comparable arguments were used, with the most striking one of wishing ‘not to become a patient’. Conclusion Patients’ preferences in the treatment of esophageal cancer are determined by the way they cope with the threat of cancer. Since the arguments given for either AS or standard surgery can be comparable or even similar, the need for healthcare professionals to discuss what truly matters to their patients is of high importance. Subsequently, attuning to the personal needs of esophageal cancer patients will benefit the decision making process on future treatment.

Standard treatment for locally advanced oesophageal cancer is neoadjuvant chemoradiotherapy (nCRT), plus surgery 6-8 weeks later. Time to surgery (TTS) after nCRT seems safe up to 12 weeks, and possibly improves patient condition and pathological response. However, it is unknown whether prolonged TTS is safe in patients with residual disease. The aim of this study was to investigate whether prolonged TTS leads to inferior surgical outcomes and survival in patients with residual disease after nCRT. Methods Patients with pathologically confirmed residual disease 4-6 weeks after nCRT who underwent preoperative PET/CT and surgery were selected from the preSANO-trial and SANO-trial. Patients were stratified by TTS ≤12 weeks versus TTS >12 weeks after completion of nCRT. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), peroperative unresectability, microscopically radical resections (R0), tumour regression grade (TRG), postoperative complications and risk of distant dissemination. Effects of TTS on OS, PFS and distant dissemination were analysed with Cox regression, adjusted for Charlson comorbidity index (CCI) at baseline, as well as WHO performance score and weight loss after nCRT. Results Forty-two patients were included in the TTS >12 weeks and 132 patients in the TTS ≤12 weeks group. Median follow-up was 20.6 months (IQR 16.1-30.3). Adjusted hazard ratios for OS and PFS were 0.50 (95% CI: 0.24-1.02) and 0.47 (95% CI: 0.25-0.91), respectively, in favour of TTS >12 weeks. Patients with TTS >12 weeks had more postoperative complications (89% vs 72%, p = 0.049), but comparable peroperatively unresectable tumours (11.9% vs. 3.8%, p = 0.11), R0-resections (89% vs 87%, p = 0.89), and TRG-scores (p = 0.97) compared to patients with TTS ≤12 weeks. Patients with TTS >12 weeks showed less distant dissemination (HR 0.40, 95% CI: 0.18-0.88). Conclusion Prolonged TTS beyond 12 weeks in patients with clinically proven residual disease after nCRT did not have a negative effect on OS and on PFS, but was correlated with an increase in postoperative complications. The (non-significantly) better survival outcomes for TTS >12 weeks may be explained by the fact that patients had a lower risk of developing distant dissemination, which may reflect improved selection prior to surgery.

Esophagectomy is the cornerstone of intentionally curative treatment in patients with locally advanced esophageal cancer. Neoadjuvant treatments have been introduced to minimize the risk of development of locoregional- and/or distant recurrences. Chemotherapy is used based on the results of the MAGIC- and the OEO2-trials and chemoradiotherapy became part of standard treatment after the publication of the CROSS-trial. Although several studies have compared the efficacy of neoadjuvant chemotherapy and chemoradiotherapy, no robust evidence on the optimal neoadjuvant treatment has been obtained as yet. Several studies indirectly comparing both modalities suggest a benefit for chemoradiotherapy in the number of pathologically complete responders, radical resection rate and possibly even in overall survival. Large randomized controlled trials like the Neo-AEGIS-, ESOPEC- and NeXT-trials are currently addressing this topic. A relatively new aspect of esophageal cancer treatment is the administration of monoclonal antibodies. Several monoclonal antibodies have been tested in, mostly, advanced esophageal cancer treatment. Cetuximab has also been tested as addition to neoadjuvant- and definitive treatment in patients with locally advanced esophageal cancer, showing mixed results. This review aims at providing an overview of the currently available neoadjuvant treatments in esophageal cancer.

Background Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20–50 per cent of patients having a pathological complete response (pCR). Disease, however, still recurs in 20–30 per cent of these patients. The aim of this study was to assess the pattern of recurrence in patients with a pCR after nCRT and surgery. Methods All patients with a pCR after nCRT and surgery included in the phase II and III CROSS (ChemoRadiotherapy for Oesophageal followed by Surgery Study) trials (April 2001 to December 2008) and after the CROSS trials (September 2009 to October 2017) were identified. The site of recurrence was compared with the applied radiation and surgical fields. Outcomes were median time to recurrence, and overall and progression-free survival. Results A total of 141 patients with a median follow-up of 100 (i.q.r. 64–134) months were included. Some 29 of 141 patients (20,6 per cent) developed recurrence. Of these, four had isolated locoregional recurrence, 15 had distant recurrence only, and ten had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five had recurrence within the radiation field, seven outside the radiation field, and two at the border. Median time to recurrence was 24 (10–62) months. The 5-year overall survival rate was 74 per cent and the recurrence-free survival rate was 70 per cent. Conclusion Despite good overall survival, recurrence still occurred in 21 per cent of patients. Most recurrences were distant, outside the radiation and surgical fields., Although patients with a pathological complete response after neoadjuvant chemoradiotherapy and surgery have a good prognosis, recurrence still develops in 21 per cent. Most recurrences were either distant or located outside the radiation and surgical field, which stresses the need for more effective systemic therapy.

The buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy (PEG). Hereby the internal PEG bumper is overgrown by hypertrophic gastric mucosa and embedded into the gastric wall. Most often an endoscopic approach to remove the bumper is successful. If not, an operative removal of the plate is necessary. In this paper, we present a case of a patient in whom a BBS was diagnosed. Besides the therapeutic options to treat a BBS, in this paper we want to focus on the prevention of this complication. Consideration needs to be given as to how long after the procedure should it be loosened to prevent BBS. The distance a PEG tube is advanced and whether it should be rotated is crucial in order to prevent BBS.

Item does not contain fulltext BACKGROUND: Esophagectomy is a technically challenging procedure, associated with significant morbidity. The introduction of minimally invasive esophagectomy (MIE) has reduced postoperative morbidity. OBJECTIVE: Although the short-term effect on complications is increasingly being recognized, the impact on long-term survival remains unclear. This study aims to investigate the association between postoperative complications following MIE and long-term survival. METHODS: Data were collected from the EsoBenchmark Collaborative composed by 13 high-volume, expert centers routinely performing MIE. Patients operated between June 1, 2011 and May 31, 2016 were included. Complications were graded using the Clavien-Dindo (CD) classification. To correct for short-term effects of postoperative complications on mortality, patients who died within 90 days postoperative were excluded. Primary endpoint was 5-year overall survival. RESULTS: A total of 915 patients were included with a mean follow-up time of 30.8 months (standard deviation 17.9). Complications occurred in 542 patients (59.2%) of which 50.2% had a CD grade ≥III complication [ie, (re)intervention, organ dysfunction, or death]. The incidence of anastomotic leakage (AL) was 135 of 915 patients (14.8%) of which 84 patients were classified as a CD grade ≥III. Multivariable analysis showed a significantly deteriorated long-term survival in all patients with AL [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.25-2.24]. This inverse relation was most distinct when AL was scored as a CD grade ≥III (HR 1.83, 95% CI 1.30-2.58). For all other complications, no significant association with long-term survival was found. CONCLUSION: The occurrence and severity of AL, but not overall complications, after MIE negatively affect long-term survival of esophageal cancer patients.

Aims: The role of resection remains debated in cases of metastatic gastric carcinoma (mGC). Some mGCs are technically resectable. At the population level, the real-world application of resection for mGC remains largely unclear in most Western countries. This large, population-based international investigation aimed to reveal the resection patterns and trends for mGC and the treatment-associated factors in Europe and the US. Methods: Data on cases with microscopically-confirmed primary invasive stomach carcinoma with distant metastasis were obtained from the nationwide cancer registries of the Netherlands, Belgium, Norway, Sweden, Estonia, and Slovenia and the US Surveillance, Epidemiology, and End Results-18 database. We calculated age-standardized rates of primary cancer-directed resection and assessed resection trends using linear regression. We investigated associations of treatment with patient and cancer factors using multivariable-adjusted log-binomial regression. Results: Among 133,321 patients with gastric cancer, overall, 40,215 cases with mGC diagnosed between 2003–2017 were investigated. Age-standardized resection rates significantly declined over time in the US, Belgium, Sweden, and Norway (by 5–14%). Resection rates greatly differed from 5% to 16% in 2013–2014. Cases with older ages, cardia tumors, or tumors involving adjacent structures were significantly less often operated across most countries. Sex was not significantly associated with resection. Across countries the association patterns and strengths differed largely. With multivariable adjustment, resection rates decreased significantly in all countries except Slovenia and Estonia (prevalence ratio per year = 0.90–0.98), and the decreasing trends were consistently observed in various stratifications by age and location. Conclusion: In Europe and the US, resection patterns and trends largely varied across countries for mGCs, which were mostly less often resected in the early 21st century. Various resection-associated factors were shown, with greatly varying association patterns and strengths. Our report could aid to identify discrepancies in clinical practice and highlight the great need for further clarifying the role of resection in mGCs to enhance standardization of care.

Importance: The optimal staging for gastric cancer remains a matter of debate. Objective: To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. Design, Setting, and Participants: This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (=cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. Exposures: All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. Main Outcomes and Measures: The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. Results: Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. Conclusions and Relevance: This study's findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT..

Background The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. Design The SANO trial protocol has been published (10.1186/s12885-018-4034-1). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. Update Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. Conclusion Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care.

Up to 50% of patients with esophageal cancer have a pathologically complete response after neoadjuvant chemoradiotherapy (nCRT) plus surgery. An active surveillance strategy may be feasible in patients with a complete clinical response (cCR) after nCRT. The aim of this study was to perform a meta-analysis using data of individual patients that underwent active surveillance with surgery for recurrent disease versus standard surgery after nCRT. Methods A systematic search was performed in Embase, Medline, Web of Science, Scopus and Cochrane from inception to February 2020. Studies were sought that reported on overall survival and recurrence rates in patients with cCR after nCRT that underwent active surveillance versus standard surgery. Authors were contacted to supply individual patient data. Pooled hazard ratio (HR) comparing survival outcomes and distant dissemination rates (DDR) between patients with cCR undergoing active surveillance or standard surgery were estimated using a random-effect meta-analysis. Cumulative incidence of locoregional recurrences in active surveillance were assessed using a Cox Frailty model. Results Seven studies including 788 patients (256 active surveillance and 532 surgery) were identified. All authors provided anonymized patient data. Pooled two- and five-year overall-survival was 75% and 58% for active surveillance and 76% and 60% for standard surgery with a pooled HR of 1.04 (95%CI:0.73–1.49) (Figure 1). Two-years DDR was 18% and 19% for active surveillance and standard surgery, respectively (HR 1.10,95%CI:0.75–1.63). Locoregional recurrence rate necessitating esophagectomy in patients undergoing active surveillance was 24% at one year, 33% at two years and 38% at five years. Active surveillance patients undergoing postponed surgery had R0 in 91% of cases. Conclusion Overall survival is comparable in patients undergoing active surveillance with postponed surgery compared to standard surgery after neoadjuvant chemoradiation. Distant dissemination rate is also comparable between both groups. During active surveillance, local regrowths developing after two years are rare. Although these data support an active surveillance strategy, randomized trials have to be completed before an active surveillance strategy can be actively proposed to patients with esophageal cancer.

Currently, trials are investigating active surveillance in esophageal cancer compared to standard esophagectomy after neoadjuvant chemoradiotherapy (nCRT). If non-inferiority is reported, on patients the choice will be imposed choice between active surveillance or immediate esophagectomy. The aim of this study was to identify clinical- and tumor characteristics that are predictive for a worse health-related quality of life (HR-QoL) after esophagectomy. Methods HR-QoL was measured using EORTC-QLQ-C30 and QLQ-OES24 questionnaires prior treatment and three, six, nine and twelve months postoperatively. Subgroups were predefined from patients with different clinical (global HR-QoL, WHO-status) and tumor characteristics (histology, disease stage and location of the tumor). High and low global HR-QoL were defined as global health scores ≥75 and 0.8 considered a large effect. The primary endpoints were physical functioning and eating problems. Secondary endpoints were global HRQOL, fatigue and emotional problems. Exploratory, the effect of age and gender on HR-QoL was assessed. Results In total, 363 patients received HR-QoL questionnaires. Patients who reported a high global HR-QoL prior treatment had a significantly worse deterioration in HR-QoL after esophagectomy than patients who reported a low HR-QoL prior treatment, on all endpoints except for physical functioning. Corresponding Cohen’s d scores were 0.85 for eating problems, −1.25 for global HR-QoL, 0.75 for fatigue and 0.65 for emotional problems. No additional differences between subgroups were identified. All predefined subgroups had impaired HR-QoL up to twelve months postoperatively for both physical functioning and fatigue with a medium to large Cohen’s d effect size. Conclusion Patients reporting high global HR-QoL prior treatent have worse deteriotation in HR-QoL than patients reporting low global HR-QoL prior treatment. No additional characteristics were identified that were predictive for worse HR-QoL after esophagectomy. This emphazises the need for shared-decision making in case active surveillance proves non-inferior compared to standard esophagectomy. All subgroups had deterioration in physical functioning and eating problems up to twelve months postoperatively.

Active surveillance for patients with esophageal cancer and a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) is being studied. Active surveillance requires accurate clinical response evaluations. (18)F-FDG PET/CT might be able to detect local tumor recurrence after nCRT as soon as the esophagus recovers from radiation-induced esophagitis. The aims of this study were to assess the value of serial (18)F-FDG PET/CT scans for detecting local recurrence in patients beyond 3 mo after nCRT and to determine when radiation-induced esophagitis has resolved. Methods: This retrospective multicenter study included patients who had cCR after nCRT, who initially declined surgery, and who subsequently underwent active surveillance. Clinical response evaluations included (18)F-FDG PET/CT, endoscopic biopsies, and endoscopic ultrasound with fine-needle aspiration at regular intervals. SUV(max) normalized for lean body mass (SUL(max)) was measured at the primary tumor site. The percentage change in SUL(max) (Δ%SUL(max)) between the last follow-up scan and the scan at 3 mo after nCRT was calculated. Tumor recurrence was defined as biopsy-proven vital tumor at the initial tumor site. Results: Of 41 eligible patients, 24 patients had recurrent disease at a median of 6.5 mo after nCRT and 17 patients remained cancer free during a median follow-up of 24 mo after nCRT. Five of 24 patients with tumor recurrence had sudden intense SUL(max) increases of greater than 180%. In 19 of 24 patients with tumor recurrence, SUL(max) gradually increased (median Δ%SUL(max), +18%), whereas SUL(max) decreased (median Δ%SUL(max), −12%) in patients with ongoing cCR (P < 0.001, independent-samples t test). In patients with ongoing cCR, SUL(max) was lowest at 11 mo after nCRT. Conclusion: Serial (18)F-FDG PET/CT might be a useful tool for detecting tumor recurrence during active surveillance. In patients with ongoing cCR, the lowest SUL(max) was reached at 11 mo after nCRT, suggesting that radiation-induced esophagitis had mostly resolved by that time. These findings warrant further evaluation in a larger cohort.