Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of... Show moreIntroduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome. Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting. Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795. Show less
BackgroundThis study assesses the incidence of gastrointestinal symptoms in the first year after resection of esophageal or gastric cancer and its association with health-related quality of life ... Show moreBackgroundThis study assesses the incidence of gastrointestinal symptoms in the first year after resection of esophageal or gastric cancer and its association with health-related quality of life (HRQoL), functioning, work productivity, and daily activities.Patients and MethodsPatients diagnosed with esophageal or gastric cancer between 2015 and 2021, who underwent a resection, and completed & GE; 2 questionnaires from the time intervals prior to resection and 0-3, 3-6, 6-9, and 9-12 months after resection were included. Multivariable generalized linear mixed models were used to assess changes in gastrointestinal symptoms over time and the impact of the number of gastrointestinal symptoms on HRQoL, functioning, work productivity, and daily activities for patients who underwent an esophagectomy or gastrectomy separately.ResultsThe study population consisted of 961 (78.8%) and 259 (21.2%) patients who underwent an esophagectomy and gastrectomy, respectively. For both groups, the majority of gastrointestinal symptoms changed significantly over time. Most clinically relevant differences were observed 0-3 after resection compared with prior to resection and included increased diarrhea, appetite loss, and eating restrictions, and specifically after esophagectomy dry mouth, trouble with coughing, and trouble talking. At 9-12 after resection one or more severe gastrointestinal symptoms were reported by 38.9% after esophagectomy and 33.7% after gastrectomy. A higher number of gastrointestinal symptoms was associated with poorer functioning, lower HRQoL, higher impairment in daily activities, and lower work productivity.ConclusionsThis study shows that gastrointestinal symptoms are frequently observed and burdensome after esophagectomy or gastrectomy, highlighting the importance to address these sequelae for high quality survivorship. Show less
Veen, A. van der; Ramaekers, M.; Marsman, M.; Brenkman, H.J.F.; Seesing, M.F.J.; Luyer, M.D.P.; ... ; LOGICA Study Grp 2023
Background Laparoscopic gastrectomy could reduce pain and opioid consumption, compared to open gastrectomy. However, it is difficult to judge the clinical relevance of this reduction, since these... Show moreBackground Laparoscopic gastrectomy could reduce pain and opioid consumption, compared to open gastrectomy. However, it is difficult to judge the clinical relevance of this reduction, since these outcomes are reported in few randomized trials and in limited detail.Methods This secondary analysis of a multicenter randomized trial compared laparoscopic versus open gastrectomy for resectable gastric adenocarcinoma (cT1-4aN0-3bM0). Postoperative pain was analyzed by opioid consumption in oral morphine equivalents (OME, mg/day) at postoperative day (POD) 1-5, WHO analgesic steps, and Numeric Rating Scales (NRS, 0-10) at POD 1-10 and discharge. Regression and mixed model analyses were performed, with and without correction for epidural analgesia.Results Between 2015 and 2018, 115 patients in the laparoscopic group and 110 in the open group underwent surgery. Some 16 patients (14%) in the laparoscopic group and 73 patients (66%) in the open group received epidural analgesia. At POD 1-3, mean opioid consumption was 131, 118, and 53 mg OME lower in the laparoscopic group, compared to the open group, respectively (all p < 0.001). After correcting for epidural analgesia, these differences remained significant at POD 1-2 (47 mg OME, p = 0.002 and 69 mg OME, p < 0.001, respectively). At discharge, 27% of patients in the laparoscopic group and 43% patients in the open group used oral opioids (p = 0.006). Mean highest daily pain scores were between 2 and 4 at all PODs, < 2 at discharge, and did not relevantly differ between treatment arms.Conclusion In this multicenter randomized trial, postoperative pain was comparable between laparoscopic and open gastrectomy. After laparoscopic gastrectomy, this was generally achieved without epidural analgesia and with fewer opioids. Show less
Hermus, M.; Wilk, B.J. van der; Chang, R.; Dekker, J.W.T.; Coene, P.P.L.O.; Nieuwenhuijzen, G.A.P.; ... ; Kranenburg, L.W. 2023
BackgroundThis study explores patients' need for information and support in deciding on esophageal cancer treatment, when experimental active surveillance and standard surgery are both feasible.... Show moreBackgroundThis study explores patients' need for information and support in deciding on esophageal cancer treatment, when experimental active surveillance and standard surgery are both feasible. MethodsThis psychological companion study was conducted alongside the Dutch SANO-trial (Surgery As Needed for Oesophageal cancer). In-depth interviews and questionnaires were used to collect data from patients who declined participation in the trial because they had a strong preference for either active surveillance (n = 20) or standard surgery (n = 20). Data were analyzed using both qualitative and quantitative techniques. ResultsPatients prefer to receive information directly from their doctors and predominantly rely on this information to make a treatment decision. Other information resources are largely used to confirm their treatment decision. Patients highly value support from their loved ones and appreciate emphatic doctors to actively involve them in the decision-making process. Overall, patients' needs for information and support during decision-making were met. ConclusionsThe importance of shared decision-making and the role doctors have in this process is underlined. The role of doctors is essential at the initial phase of decision-making: Once patients seem to have formed their treatment preference for either active surveillance or surgery, the influence of external resources (including doctors) may be limited. Show less
Nordkamp, S.; Piqeur, F.; Berg, K. van den; Tolenaar, J.L.; Hellemond, I.E.G. van; Creemers, G.J.; ... ; Burger, J.W.A. 2023
Background: For patients with locally recurrent rectal cancer, it is an ongoing pursuit to establish factors predicting or improving oncological outcomes. In locally advanced rectal cancer, a pCR... Show moreBackground: For patients with locally recurrent rectal cancer, it is an ongoing pursuit to establish factors predicting or improving oncological outcomes. In locally advanced rectal cancer, a pCR appears to be associated with improved outcomes. The aim of this retrospective cohort study was to compare the oncological outcomes of patients with locally recurrent rectal cancer with and without a pCR.Methods: Patients who underwent neoadjuvant treatment and surgery for locally recurrent rectal cancer with curative intent between January 2004 and June 2020 at a tertiary referral hospital were analysed. Primary outcomes included overall survival, disease-free survival, metastasis-free survival, and local re-recurrence-free survival, stratified according to whether the patient had a pCR.Results: Of a total of 345 patients, 51 (14.8 per cent) had a pCR. Median follow-up was 36 (i.q.r. 16-60) months. The 3-year overall survival rate was 77 per cent for patients with a pCR and 51.1 per cent for those without (P < 0.001). The 3-year disease-free survival rate was 56 per cent for patients with a pCR and 26.1 per cent for those without (P < 0.001). The 3-year local re-recurrence-free survival rate was 82 and 44 per cent respectively (P < 0.001). Surgical procedures (for example soft tissue, sacrum, and urogenital organ resections) and postoperative complications were comparable between patients with and without a pCR.Conclusion: This study showed that patients with a pCR have superior oncological outcomes to those without a pCR. It may therefore be safe to consider a watch-and-wait approach in highly selected patients, potentially improving quality of life by omitting extensive surgical procedures without compromising oncological outcomes. Show less
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... Show moreObjective: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 <0.001), median lymph node harvest increased from 15 to 19 (P <0.001), and median survival increased from 35 to 41 months (P = 0.027). 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. Show less
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... Show moreObjective. 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. Show less
Veen, A. van der; Meulen, M.P. van der; Seesing, M.F.J.; Brenkman, H.J.F.; Haverkamp, L.; Luyer, M.D.P.; ... ; Laparoscopic Vs Open Gastrectomy G 2022
IMPORTANCE Laparoscopic gastrectomy is rapidly being adopted worldwide as an alternative to open gastrectomy to treat gastric cancer. However, laparoscopic gastrectomy might be more expensive as a... Show moreIMPORTANCE Laparoscopic gastrectomy is rapidly being adopted worldwide as an alternative to open gastrectomy to treat gastric cancer. However, laparoscopic gastrectomy might be more expensive as a result of longer operating times and more expensive surgical materials. To date, the cost-effectiveness of both procedures has not been prospectively evaluated in a randomized clinical trial. OBJECTIVE To evaluate the cost-effectiveness of laparoscopic compared with open gastrectomy. DESIGN, SETTING, AND PARTICIPANTS In this multicenter randomized clinical trial of patients undergoing total or distal gastrectomy in 10 Dutch tertiary referral centers, cost-effectiveness data were collected alongside a multicenter randomized clinical trial on laparoscopic vs open gastrectomy for resectable gastric adenocarcinoma (cT1-4aN0-3bM0). A modified societal perspective and 1-year time horizon were used. Costs were calculated on the individual patient level by using hospital registry data and medical consumption and productivity loss questionnaires. The unit costs of laparoscopic and open gastrectomy were calculated bottom-up. Quality-adjusted life-years (QALYs) were calculated with the EuroQol 5-dimension questionnaire, in which a value of 0 indicates death and 1 indicates perfect health. Missing questionnaire data were imputed with multiple imputation. Bootstrapping was performed to estimate the uncertainty surrounding the cost-effectiveness. The study was conducted from March 17, 2015, to August 20, 2018. Data analyses were performed between September 1, 2020, and November 17, 2021. INTERVENTIONS Laparoscopic vs open gastrectomy. MAIN OUTCOMES AND MEASURES Evaluations in this cost-effectiveness analysis included total costs and QALYs. RESULTS Between 2015 and 2018, 227 patients were included. Mean (SD) age was 67.5 (11.7) years, and 140 were male (61.7%). Unit costs for initial surgery were calculated to be euro8124 (US $8087) for laparoscopic total gastrectomy, euro7353 (US $7320) for laparoscopic distal gastrectomy, euro6584 (US $6554) for open total gastrectomy, and euro5893 (US $5866) for open distal gastrectomy. Mean total costs after 1-year follow-up were euro26 084 (US $25 965) in the laparoscopic group and euro25 332 (US $25 216) in the open group (difference, euro752 [US $749; 3.0%]). Mean (SD) QALY contributions during 1 year were 0.665 (0.298) in the laparoscopic group and 0.686 (0.288) in the open group (difference, -0.021). Bootstrapping showed that these differences between treatment groups were relatively small compared with the uncertainty of the analysis. CONCLUSIONS AND RELEVANCE Although the laparoscopic gastrectomy itself was more expensive, after 1-year follow-up, results suggest that differences in both total costs and effectiveness were limited between laparoscopic and open gastrectomy. These results support centers' choosing, based on their own preference, whether to (de)implement laparoscopic gastrectomy as an alternative to open gastrectomy. Show less
Objective: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery. Background: Survival of recurrent esophageal cancer is usually... Show moreObjective: 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. Show less
Hermus, M.; Wilk, B.J. van der; Chang, R.T.H.; Collee, G.; Noordman, B.J.; Coene, P.P.L.O.; ... ; Kranenburg, L.W. 2022
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... Show moreActive 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. Show less
Pape, M.; Vissers, P.A.J.; Bertwistle, D.; McDonald, L.; Slingerland, M.; Mohammad, N.H.; ... ; Verhoeven, R.H.A. 2022
Background: Real-world data on treatment and outcomes in patients with synchronous metastatic disease compared with patients with metachronous metastatic disease in esophagogastric cancer have not... Show moreBackground: Real-world data on treatment and outcomes in patients with synchronous metastatic disease compared with patients with metachronous metastatic disease in esophagogastric cancer have not been published before. The aim of our study was to explore treatment, overall survival (OS), and time to treatment fialure (TTF) in patients with synchronous and metachronous metastatic esophagogastric adenocarcinoma. Methods: Patients with synchronous metastatic disease (2015-2017) and patients with metachronous metastatic disease initially treated with curative intent for nonmetastatic disease (2015-2016) were selected from the Netherlands Cancer Registry. OS and TTF were assessed from metastatic diagnosis for patients with synchronous, early metachronous (<= 6 months) or late metachronous (>6 months) metastatic disease using Kaplan-Meier curves with two-sided log-rank test. Results: Median OS was 4.2, 2.1, and 4.4 months in patients with synchronous, early metachronous, and late metachronous metastatic disease, respectively (p < 0.001). The proportion of patients receiving systemic treatment was 41.3%, 21.5%, and 32.5% for synchronous, early metachronous, and late metachronous metastatic disease, respectively (p = 0.001). Among patients receiving systemic treatment, median OS was 8.8, 4.5, and 9.1 months (p < 0.001) and median TTF was 6.1, 3.8, and 5.7 months (p < 0.001) in synchronous, early metachronous, and late metachronous metastatic disease, respectively. Conclusion: Patients with early metachronous metastatic disease have a worse survival compared with patients with synchronous or late metachronous metastatic disease. These patients less often receive systemic treatment, and even when treated, survival is worse compared with patients with synchronous or late metachronous metastatic disease, suggesting a more aggressive tumor behavior. Show less
Background: This study aims to assess the impact of nationwide centralization of surgery on travel distance and travel burden among patients with oesophageal, gastric, and pancreatic cancer... Show moreBackground: This study aims to assess the impact of nationwide centralization of surgery on travel distance and travel burden among patients with oesophageal, gastric, and pancreatic cancer according to age in the Netherlands. As centralization of care increases to improve postoperative outcomes, travel distance and experienced burden might increase. Materials and methods: All patients who underwent surgery between 2006 and 2017 for oesophageal, gastric and pancreatic cancer in the Netherlands were included. Travel distance between patient's home address and hospital of surgery in kilometres was calculated. Questionnaires were used to assess experienced travel burden in a subpopulation (n = 239). Multivariable ordinal logistic regression models were constructed to identify predictors for longer travel distance. Results: Over 23,838 patients were included, in whom median travel distance for surgical care increased for oesophageal cancer (n = 9217) from 18 to 28 km, for gastric cancer (n = 6743) from 9 to 26 km, and for pancreatic cancer (n = 7878) from 18 to 25 km (all p < 0.0001). Multivariable analyses showed an increase in travel distance for all cancer types over time. In general, patients experienced a physical and social burden, and higher financial costs, due to traveling extra kilometres. Patients aged >70 years travelled less often independently (56% versus 68%), as compared to patients aged <= 70 years. Conclusion: With nationwide centralization, travel distance increased for patients undergoing oesophageal, gastric, and pancreatic cancer surgery. Younger patients travelled longer distances and experienced a lower travel burden, as compared to elderly patients. Nevertheless, on a global scale, travel distances in the Netherlands remain limited. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
BACKGROUND\nMETHODS\nRESULTS\nCONCLUSION\nGuidelines recommending antibiotic prophylaxis at emergency cholecystectomy for cholecystitis were based on low-quality evidence. The aim of this trial was... Show moreBACKGROUND\nMETHODS\nRESULTS\nCONCLUSION\nGuidelines recommending antibiotic prophylaxis at emergency cholecystectomy for cholecystitis were based on low-quality evidence. The aim of this trial was to demonstrate that omitting antibiotics is not inferior to their prophylactic use.\nThis multicentre, randomized, open-label, non-inferiority clinical trial randomly assigned adults with mild-to-moderate acute calculous cholecystitis (immediate cholecystectomy indicated) to 2 g cefazolin administered before incision or no antibiotic prophylaxis. The primary endpoint was a composite of all postoperative infectious complications in the first 30 days after surgery. Secondary endpoints included all individual components of the primary endpoint, other morbidity, and duration of hospital stay.\nSixteen of 226 patients (7.1 per cent) in the single-dose prophylaxis group and 29 of 231 (12.6 per cent) in the no-prophylaxis group developed postoperative infectious complications (absolute difference 5.5 (95 per cent c.i. -0.4 to 11.3) per cent). With a non-inferiority margin of 10 per cent, non-inferiority of no prophylaxis was not proven. The number of surgical-site infections was significantly higher in the no-prophylaxis group (5.3 versus 12.1 per cent; P = 0.010). No differences were observed in the number of other complications, or duration of hospital stay.\nOmitting antibiotic prophylaxis is not recommended. Show less
Eyck, B.; Lanschot, J.J.B. van; Hulshof, M.C.C.M.; Wilk, B.J. van der; Shapiro, J.; Hagen, P. van; ... ; CROSS Study Grp 2021
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... Show morePURPOSE 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. Show less
Eyck, B.; Wilk, B.J. van der; Noordman, B.J.; Wijnhoven, B.P.L.; Lagarde, S.M.; Hartgrink, H.H.; ... ; SANO Study Grp 2021
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... Show moreBackground: 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 (https://doi.org/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 6months 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. Show less
Stroes, C.I.; Schokker, S.; Creemers, A.; Molenaar, R.J.; Hulshof, M.C.C.M.; Woude, S.O. van der; ... ; Laarhoven, H.W.M. van 2020
PURPOSE Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit... Show morePURPOSE Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC.PATIENTS AND METHODS Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as >= 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score-matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses.RESULTS Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score-matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [F-18]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor-bound protein 7 (Grb7) -positive tumors at baseline demonstrated significantly better survival (P = .007) or treatment response (P = .016), respectively.CONCLUSION Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively. (C) 2019 by American Society of Clinical Oncology Show less
This multicentre pilot study investigated the role of peroperative carcinoembryonic antigen (CEA)-specific fluorescence imaging during cytoreductive surgery-hyperthermic intraperitoneal... Show moreThis multicentre pilot study investigated the role of peroperative carcinoembryonic antigen (CEA)-specific fluorescence imaging during cytoreductive surgery-hyperthermic intraperitoneal chemotherapy surgery in peritoneal metastasized colorectal cancer. A correct change in peritoneal carcinomatosis index (PCI) owing to fluorescence imaging was seen in four of the 14 included patients. The use of SGM-101 in patients with peritoneally metastasized colorectal carcinoma is feasible, and allows intraoperative detection of tumour deposits and alteration of the PCI. Augmented reality guidance Show less
Vos-Geelen, J. de; Geurts, S.M.E.; Putten, M. van; Valkenburg-van Iersel, L.B.J.; Grabsch, H.I.; Mohammad, N.H.; ... ; Lemmens, V.E.P.P. 2019
BACKGROUNDThe management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical... Show moreBACKGROUNDThe management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation (CRT) have been implemented. The trends in (non-)surgical treatment and its impact on overall survival (OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer, it is therefore essential to gain more insight through real-life studies.AIMTo establish trends in treatment and OS in patients with proximal esophageal cancer.METHODSIn this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics.RESULTSIn total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%, 23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval (CI): 6.4-8.1] in 1989-1994 to 9.5 mo (95%CI: 8.1-10.8) in 2010-2014 (logrank P < 0.001). In non-metastatic disease, 5-year OS rates improved from 5% (95%CI: 3%-7%) in 1989-1994 to 13% (95%CI: 9%-17%) in 2010-2014 (logrank P < 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo (95%CI: 2.5-5.1) in 1989-1994, and 5.1 mo (95%CI: 4.3-5.9) in 2010-2014 (logrank P = 0.26).CONCLUSIONOS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time. Show less
Werf, L.R. van der; Eshuis, W.J.; Draaisma, W.A.; Etten, B. van; Gisbertz, S.S.; Harst, E. van der; ... ; Dutch Upper Gastrointestinal Canc 2019
Background Radical gastrectomy is the cornerstone of the treatment of gastric cancer. For tumors invading the pancreas, en-bloc partial pancreatectomy may be needed for a radical resection. The aim... Show moreBackground Radical gastrectomy is the cornerstone of the treatment of gastric cancer. For tumors invading the pancreas, en-bloc partial pancreatectomy may be needed for a radical resection. The aim of this study was to evaluate the outcome of gastrectomies with partial pancreatectomy for gastric cancer.Methods Patients who underwent gastrectomy with or without partial pancreatectomy for gastric or gastro-oesophageal junction cancer between 2011 and 2015 were selected from the Dutch Upper GI Cancer Audit (DUCA). Outcomes were resection margin (pR0) and Clavien-Dindo grade >= III postoperative complications and survival. The association between partial pancreatectomy and postoperative complications was analyzed with multivariable logistic regression. Overall survival of patients with partial pancreatectomy was estimated using the Kaplan-Meier method.Results Of 1966 patients that underwent gastrectomy, 55 patients (2.8%) underwent en-bloc partial pancreatectomy. A pR0 resection was achieved in 45 of 55 patients (82% versus 85% in the group without additional resection, P = 0.82). Clavien-Dindo grade = III complications occurred in 21 of 55 patients (38% versus 17%, P < 0.001). Median overall survival [95% confidence interval] was 15 [6.8-23.2] months. For patients with and without perioperative systemic therapy, median survival was 20 [12.3-27.7] and 10 [5.7-14.3] months, and for patients with pR0 and pR1 resection, it was 20 [11.8-28.3] and 5 [2.4-7.6] months, respectively.Conclusions Gastrectomy with partial pancreatectomy is not only associated with a pR0 resection rate of 82% but also with increased postoperative morbidity. It should only be performed if a pR0 resection is feasible. Show less
