Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy.

BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment. OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin. METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up. RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively. CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.

Surgical treatment of esophago-tracheobronchial fistulas after esophagectomy.

The aim of this study was to evaluate the surgical treatment of esophago-tracheobronchial fistulas (ETBFs) that occurred after esophagectomy with gastric conduit reconstruction in a tertiary referral center for esophageal surgery. All patients who underwent surgical repair for an ETBF after esophagectomy with gastric conduit reconstruction were included in a tertiary referral center. The primary outcome was successful recovery after surgical treatment for ETBF, defined as a patent airway at 90 days after the surgical fistula repair. Secondary outcomes were details on the clinical presentation, diagnostics, and postoperative course after fistula repair. Between 2007 and 2022, 14 patients who underwent surgical repair for an ETBF were included. Out of 14 patients, 9 had undergone esophagectomy with cervical anastomosis and 5 esophagectomy with intrathoracic anastomosis after which 13 patients had developed anastomotic leakage. Surgical treatment consisted of thoracotomy to cover the defect with a pericardial patch and intercostal flap in 11 patients, a patch without interposition of healthy tissue in 1 patient, and fistula repair via cervical incision with only a pectoral muscle flap in 2 patients. After surgical treatment, 12 patients recovered (86%). Mortality occurred in two patients (14%) due to multiple organ failure. This study evaluated the techniques and outcomes of surgical repair of ETBFs following esophagectomy with gastric conduit reconstruction in 14 patients. Treatment was successful in 12 patients (86%) and generally consisted of thoracotomy and coverage of the defect with a bovine pericardial patch followed by interposition with an intercostal muscle.

Laparoscopic ischemic conditioning of the stomach prior to esophagectomy induces gastric neo-angiogenesis.

BACKGROUND: The risk of an anastomotic leakage (AL) following Ivor-Lewis esophagectomy is increased in patients with calcifications of the aorta or a stenosis of the celiac trunc. Ischemic conditioning (ISCON) of the gastric conduit prior to esophagectomy is supposed to improve gastric vascularization at the anastomotic site. The prospective ISCON trial was conducted to proof the safety and feasibility of this strategy with partial gastric devascularization 14 days before esophagectomy in esophageal cancer patients with a compromised vascular status. This work reports the results from a translational project of the ISCON trial aimed to investigate variables of neo-angiogenesis. METHODS: Twenty esophageal cancer patients scheduled for esophagectomy were included in the ISCON trial. Serum samples (n = 11) were collected for measurement of biomarkers and biopsies (n = 12) of the gastric fundus were taken before and after ISCON of the gastric conduit. Serum samples were analyzed including 62 different cytokines. Vascularization of the gastric mucosa was assessed on paraffin-embedded sections stained against CD34 to detect the degree of microvascular density and vessel size. RESULTS: Between November 2019 and January 2022 patients were included in the ISCON Trial. While serum samples showed no differences regarding cytokine levels before and after ISCON biopsies of the gastric mucosa demonstrated a significant increase in microvascular density after ISCON as compared to the corresponding gastric sample before the intervention. CONCLUSION: The data prove that ISCON of the gastric conduit as esophageal substitute induces significant neo-angiogenesis in the gastric fundus which is considered as surrogate of an improved vascularization at the anastomotic site.

Impact of body composition and physical strength changes during chemoradiotherapy on complications and survival after oesophagectomy.

BACKGROUND: The aim of this study was to assess body composition and physical strength changes during neoadjuvant chemoradiotherapy (nCRT) and assess their predictive value for (severe) postoperative complications and overall survival in patients who underwent oesophagectomy for oesophageal cancer. METHODS: Consecutive patients who underwent nCRT and oesophagectomy with curative intent in a tertiary referral center were included in the study. Perioperative data were collected in a prospectively maintained database. The CT images before and after nCRT were used to assess skeletal muscle index (SMI), subcutaneous fat index (SFI), and visceral fat index (VFI). To assess physical strength, handgrip strength (HGS) and the exercise capacity of the steep ramp test (SRT Wpeak) were acquired before and after nCRT. RESULTS: Between 2015 and 2020, 126 patients were included. SMI increased in female subgroups and decreased in male subgroups (35.38 to35.60 cm2/m2 for females, P value 0.048, 46.89 to 45.34 cm2/m2 for males, P value < 0.001). No significant changes in SFI, VFI, HGS, and SRT Wpeak were observed. No predictive value of changes in SMI, HGS, and SRT Wpeak was shown for (severe) postoperative complications and overall survival. CONCLUSIONS: A significant but minimal decrease in SMI during nCRT was observed for males only, it was not associated with postoperative complications or overall survival. Physical strength measurements did not decrease significantly over the course of nCRT. No associations with postoperative complications or overall survival were observed.

Deep learning-based recognition of key anatomical structures during robot-assisted minimally invasive esophagectomy.

OBJECTIVE: To develop a deep learning algorithm for anatomy recognition in thoracoscopic video frames from robot-assisted minimally invasive esophagectomy (RAMIE) procedures using deep learning. BACKGROUND: RAMIE is a complex operation with substantial perioperative morbidity and a considerable learning curve. Automatic anatomy recognition may improve surgical orientation and recognition of anatomical structures and might contribute to reducing morbidity or learning curves. Studies regarding anatomy recognition in complex surgical procedures are currently lacking. METHODS: Eighty-three videos of consecutive RAMIE procedures between 2018 and 2022 were retrospectively collected at University Medical Center Utrecht. A surgical PhD candidate and an expert surgeon annotated the azygos vein and vena cava, aorta, and right lung on 1050 thoracoscopic frames. 850 frames were used for training of a convolutional neural network (CNN) to segment the anatomical structures. The remaining 200 frames of the dataset were used for testing the CNN. The Dice and 95% Hausdorff distance (95HD) were calculated to assess algorithm accuracy. RESULTS: The median Dice of the algorithm was 0.79 (IQR = 0.20) for segmentation of the azygos vein and/or vena cava. A median Dice coefficient of 0.74 (IQR = 0.86) and 0.89 (IQR = 0.30) were obtained for segmentation of the aorta and lung, respectively. Inference time was 0.026 s (39 Hz). The prediction of the deep learning algorithm was compared with the expert surgeon annotations, showing an accuracy measured in median Dice of 0.70 (IQR = 0.19), 0.88 (IQR = 0.07), and 0.90 (0.10) for the vena cava and/or azygos vein, aorta, and lung, respectively. CONCLUSION: This study shows that deep learning-based semantic segmentation has potential for anatomy recognition in RAMIE video frames. The inference time of the algorithm facilitated real-time anatomy recognition. Clinical applicability should be assessed in prospective clinical studies.

Trends in surgical techniques for the treatment of esophageal and gastroesophageal junction cancer: the 2022 update.

The aim of this study was to evaluate the current practice in surgical techniques for esophageal and gastroesophageal junction cancer surgery worldwide and to compare the results to the previous surveys in 2007 and 2014. An online survey was sent out among surgical members of the International Society for Diseases of the Esophagus, the World Organization for Specialized Studies on Disease of the Esophagus, the International Gastric Cancer Association, the Association of Upper Gastrointestinal Surgery of Great Britain and Ireland and Dutch gastroesophageal surgeons via the network of the investigators. In total, 260 surgeons completed the survey representing 52 countries and 6 continents; Europe 56%, Oceania 14%, Asia 14%, South-America 9%, North-America 7%. Of the responding surgeons, 39% worked in a hospital that performed >51 esophagectomies per year. Total minimally invasive esophagectomy was the preferred technique (53%) followed by hybrid esophagectomy (26%) of which 7% consisted of a minimally invasive thoracic phase and 19% of a minimally invasive abdominal phase. Total open esophagectomy was preferred by 21% of the respondents. Total minimally invasive esophagectomy was significantly more often performed in high-volume centers compared with non-high-volume centers (P = 0.002). Robotic assistance was used in 13% during the thoracic phase and 6% during the abdominal phase. Minimally invasive transthoracic esophagectomy has become the preferred approach for esophagectomy. Although 21% of the surgeons prefer an open approach, 26% of the surgeons perform a hybrid procedure which may reflect further transition towards the use of total minimally invasive esophagectomy.

Safety and Feasibility of Robot-Assisted Minimally Invasive Esophagectomy (RAMIE) with Three-Field Lymphadenectomy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Esophageal Cancer and Cervical Lymph Node Metastasis.

BACKGROUND: In the West, patients with cervical lymph node metastasis of resectable esophageal cancer at diagnosis are generally precluded from curative treatment. This study prospectively explored the safety and feasibility of neoadjuvant chemoradiotherapy followed by robot-assisted minimally invasive esophagectomy (RAMIE) with three-field lymphadenectomy for these patients. METHODS: Between 2015 and 2021, patients with resectable thoracic esophageal cancer and cervical lymph node metastasis were recruited nationwide in the Netherlands. Patients without interval metastasis following neoadjuvant chemoradiotherapy and good physical condition underwent RAMIE with bilateral three-field lymphadenectomy. Safety was predefined as ≤50% Clavien-Dindo grade ≥3b postoperative complications. RESULTS: Neoadjuvant chemoradiotherapy was administered to 29 patients (19 (66%) adenocarcinoma and 10 (34%) squamous cell carcinoma). After restaging, nine (31%) patients were excluded (interval metastasis, clinical deterioration, or withdrawn consent). RAMIE was performed in 20 patients (R0-rate 95%). A median of 42 [range 21-71] lymph nodes were resected of which 13 [range 2-35] were cervical. Only 1 (5%) patient had an unexpected contralateral cervical lymph node metastasis. Complications grade ≥3b occurred in 50%. Most frequent complications of any grade were recurrent laryngeal nerve palsy (45%) and pneumonia (40%). Overall survival at 1 year was 85% and quality of life at 6 months was comparable to esophageal cancer patients treated with curative intent. CONCLUSIONS: RAMIE with three-field lymphadenectomy following neoadjuvant chemoradiotherapy for patients with resectable esophageal cancer presenting with cervical lymph node metastasis is feasible in a Western population. Because contralateral cervical metastasis is rare, a unilateral neck dissection would suffice in the majority of cases. CLINICAL TRIAL: gov Identifier: NCT02426879. Dutch trial register Identifier: NTR 4552.

The surgical anatomy of a (robot-assisted) minimally invasive transcervical esophagectomy.

BACKGROUND: Transcervical esophagectomy allows for esophagectomy through transcervical access and bypasses the thoracic cavity, thereby eliminating single lung ventilation. A challenging surgical approach demands thorough understanding of the encountered anatomy. This study aims to provide a comprehensive overview of surgical anatomy encountered during the (robot-assisted) minimally invasive transcervical esophagectomy (RACE and MICE). METHODS: To assess the surgical anatomy of the lower neck and mediastinum, MR images were made of a body donor after, which it was sliced at 24-µm intervals with a cryomacrotome. Images were made every 3 slices resulting in 3.200 images of which a digital 3D multiplanar reconstruction was made. For macroscopic verification, microscopic slices were made and stained every 5 mm (Mallory-Cason). Schematic drawings were made of the 3D reconstruction to demonstrate the course of essential anatomical structures in the operation field and identify anatomical landmarks. RESULTS: Surgical anatomy 'boxes' of three levels (superior thoracic aperture, upper mediastinum, subcarinal) were created. Four landmarks were identified: (i) the course of the thoracic duct in the mediastinum; (ii) the course of the left recurrent laryngeal nerve; (iii) the crossing of the azygos vein right and dorsal of the esophagus; and (iv) the position of the aortic arch, the pulmonary arteries, and veins. CONCLUSIONS: The presented 3D reconstruction of unmanipulated human anatomy and schematic 3D 'boxes' provide a comprehensive overview of the surgical anatomy during the RACE or MICE. Our findings provide a useful tool to aid surgeons in learning the complex anatomy of the mediastinum and the exploration of new surgical approaches such as the RACE or MICE.

Indocyanine green fluorescence in robot-assisted minimally invasive esophagectomy with intrathoracic anastomosis: a prospective study.

Indocyanine green fluorescence angiography (ICG-FA) allows for real-time intraoperative assessment of the perfusion of the gastric conduit during esophagectomy. The aim of this study was to investigate the effect of the implementation of ICG-FA during robot-assisted minimally invasive esophagectomy (RAMIE) with an intrathoracic anastomosis. In this prospective cohort study, a standardized protocol for ICG-FA was implemented in a high-volume center in December 2018. All consecutive patients who underwent RAMIE with an intrathoracic anastomosis were included. The primary outcome was whether the initial chosen site for the anastomosis on the gastric conduit was changed based on ICG-FA findings. In addition, ICG-FA was quantified based on the procedural videos. Out of the 63 included patients, the planned location of the anastomosis was changed in 9 (14%) patients, based on ICG-FA. The median time to maximum intensity at the base of the gastric conduit was shorter (25 s; range 13-49) compared to tip (34 s; range 12-83). In patients with anastomotic leakage, the median time to reach the FImax at the tip was 56 s (range 30-83) compared to 34 s (range 12-66) in patients without anastomotic leakage (p = 0.320). The use of ICG-FA resulted in an adaptation of the anastomotic site in nine (14%) patients during RAMIE with intrathoracic anastomosis. The quantification of ICG-FA showed that the gastric conduit reaches it maximum intensity in a base-to-tip direction. Perfusion of the entire gastric conduit was worse for patients with anastomotic leakage, although not statistically different.

Implementation of the robotic abdominal phase during robot-assisted minimally invasive esophagectomy (RAMIE): results from a high-volume center.

BACKGROUND: Evidence on the added value of robotic-assistance in the abdominal phase during esophagectomy is scarce. In 2003, our center implemented the robotic thoracic phase for esophagectomy. In November 2018 the robot was also implemented in the abdominal phase. The aim of this study was to evaluate the implementation of the abdominal phase during robot-assisted minimally invasive esophagectomy (RAMIE). METHODS: Consecutive patients who underwent full RAMIE with intrathoracic anastomosis for esophageal cancer were included. Patients were extracted from a prospectively maintained institutional database. A cumulative sum (CUSUM) analysis was performed for abdominal operation time and abdominal lymph node yield. Intraoperative, postoperative and oncological outcomes including collected lymph nodes per abdominal lymph node station were reported. RESULTS: Between 2018 and 2021, 70 consecutive patients were included. The majority of the patients had an adenocarcinoma (n = 55, 77%) and underwent neoadjuvant chemo(radio)therapy (n = 65, 95%). The median operative time for the abdominal phase was 180 min (range 110-233). The CUSUM analysis for abdominal operation time showed a plateau at case 22. There were no intraoperative complications or conversions during the abdominal phase. The most common postoperative complications were pneumonia (n = 18, 26%) and anastomotic leakage (n = 14, 20%). Radical resection margins were achieved in 69 (99%) patients. The median total lymph node yield was 42 (range 23-83) and the median abdominal lymph node yield was 16 (range 2-43). The CUSUM analysis for abdominal lymph node yield showed a plateau at case 21. Most abdominal lymph nodes were collected from the left gastric artery (median 4, range 0-20). CONCLUSIONS: This study shows that a robotic abdominal phase was safely implemented for RAMIE without compromising intraoperative, postoperative and oncological outcomes. The learning curve is estimated to be 22 cases in a high-volume center with experienced upper GI robotic surgeons.

Computer-aided anatomy recognition in intrathoracic and -abdominal surgery: a systematic review.

BACKGROUND: Minimally invasive surgery is complex and associated with substantial learning curves. Computer-aided anatomy recognition, such as artificial intelligence-based algorithms, may improve anatomical orientation, prevent tissue injury, and improve learning curves. The study objective was to provide a comprehensive overview of current literature on the accuracy of anatomy recognition algorithms in intrathoracic and -abdominal surgery. METHODS: This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Pubmed, Embase, and IEEE Xplore were searched for original studies up until January 2022 on computer-aided anatomy recognition, without requiring intraoperative imaging or calibration equipment. Extracted features included surgical procedure, study population and design, algorithm type, pre-training methods, pre- and post-processing methods, data augmentation, anatomy annotation, training data, testing data, model validation strategy, goal of the algorithm, target anatomical structure, accuracy, and inference time. RESULTS: After full-text screening, 23 out of 7124 articles were included. Included studies showed a wide diversity, with six possible recognition tasks in 15 different surgical procedures, and 14 different accuracy measures used. Risk of bias in the included studies was high, especially regarding patient selection and annotation of the reference standard. Dice and intersection over union (IoU) scores of the algorithms ranged from 0.50 to 0.98 and from 74 to 98%, respectively, for various anatomy recognition tasks. High-accuracy algorithms were typically trained using larger datasets annotated by expert surgeons and focused on less-complex anatomy. Some of the high-accuracy algorithms were developed using pre-training and data augmentation. CONCLUSIONS: The accuracy of included anatomy recognition algorithms varied substantially, ranging from moderate to good. Solid comparison between algorithms was complicated by the wide variety of applied methodology, target anatomical structures, and reported accuracy measures. Computer-aided intraoperative anatomy recognition is an upcoming research discipline, but still at its infancy. Larger datasets and methodological guidelines are required to improve accuracy and clinical applicability in future research. TRIAL REGISTRATION: PROSPERO registration number: CRD42021264226.

Outcomes of surgical treatment of non-metastatic gastric cancer in patients aged 70 and older: A systematic review and meta-analysis.

The optimal surgical treatment strategy for gastric cancer in older patients needs to be carefully evaluated due to increased vulnerability of older patients. We performed a database search for randomized controlled trials (RCTs) and cohort studies that included patients ≥70 years with potentially resectable stage I-III gastric cancer. Postoperative and survival outcomes were compared between groups undergoing 1) gastrectomy vs conservative treatment (best supportive care or non-operative treatment), 2) minimally invasive (MIG) vs open gastrectomy (OG), or 3) extended vs limited lymphadenectomy. When possible, results were pooled using risk ratios (RR). Thirty-one studies were included. Six retrospective studies compared overall survival (OS) between gastrectomy (N = 2332) and conservative treatment (N = 246). Longer OS was reported in the gastrectomy group in all studies, but study quality was low and meta-analysis was not feasible. Eighteen cohort studies compared MIG (N = 3626) and OG (N = 5193). MIG was associated with fewer complications (pooled RR 0.68, 95% confidence interval 0.54-0.84). OS was not different between the groups. Two RCTs and five cohort studies compared outcomes between extended (N = 709) and limited lymphadenectomy (N = 1323). Complication rates were comparable between the groups. Two cohort studies found longer OS or cancer-specific survival after extended lymphadenectomy. No quality of life (QoL) or functional outcomes were reported. In older patients with gastric cancer, there is low-quality evidence for better OS after gastrectomy vs conservative treatment. Compared to OG, MIG was associated with less postoperative morbidity. The evidence to support extended lymphadenectomy is limited. QoL and functional outcomes should be addressed in future studies.

Endoscopic surgery suturing techniques: a randomized study on learning.

BACKGROUND: Surgeons have widely adopted endoscopic suturing techniques using conventional laparoscopic instruments and the more advanced robotic systems. The FlexDex is a novel articulating laparoscopic needle driver providing enhanced dexterity in laparoscopic surgery. This study evaluates and compares the learning curve of endoscopic suturing with conventional laparoscopy, the FlexDex and robotic suturing in novices. METHODS: Participants performed a minimal invasive suturing task in three different ways in a randomized order: with a conventional laparoscopic needle driver, using the FlexDex needle driver and third, using the Da Vinci Si surgical system. Primary outcome was suturing task time. Secondary outcome parameters were assessment of suturing quality and workload perception. RESULTS: A total of 10 novice participants were included and completed a total of 300 sessions. Median (IQR) suturing time of the first 5 sessions was 231 s (188-291) in the laparoscopic group versus 378 s (282-471) in the FlexDex group versus 189 s (160-247) in the DaVinci Si group. The last 5 sessions showed significant reduction of median suturing time of 143 s (120-190), 232 s (180-265) and 172 s (134-199) respectively. Analysis identified that the learning curve for the laparoscopic needle driver and Da Vinci Si was reached in 5 sessions, compared to 8 sessions for the Flexdex. The laparoscopic needle driver and Da Vinci Si showed a significant shorter median suturing time compared to the FlexDex (p = 0.00). The FlexDex quality assessment scores were significantly lower compared to the laparoscopic (p = 0.00) and robotic (p = 0.00) scores and perceived workload remains high for the FlexDex users. CONCLUSIONS: Ex vivo endoscopic suturing with the FlexDex demonstrated a prolonged learning curve compared to laparoscopic and robotic suturing. The learning curve of the FlexDex is fundamentally different from conventional laparoscopic and robotic instruments. This study provides further insights in the implementation and training of endoscopic suturing techniques.

The ISCON-trial protocol: laparoscopic ischemic conditioning prior to esophagectomy in patients with esophageal cancer and arterial calcifications.

BACKGROUND: Anastomotic leakage is the most important surgical complication following esophagectomy. A major cause of leakage is ischemia of the gastric tube that is used for reconstruction of the gastrointestinal tract. Generalized cardiovascular disease, expressed by calcifications of the aorta and celiac axis stenosis on a pre-operative CT scan, is associated with an increased risk of anastomotic leakage. Laparoscopic ischemic conditioning (ISCON) aims to redistribute blood flow and increase perfusion at the anastomotic site by occluding the left gastric, left gastroepiploic and short gastric arteries prior to esophagectomy. This study aims to assess the safety and feasibility of laparoscopic ISCON in selected patients with esophageal cancer and concomitant arterial calcifications. METHODS: In this prospective single-arm safety and feasibility trial based upon the IDEAL recommendations for surgical innovation, a total of 20 patients will be included recruited in 2 European high-volume centers for esophageal cancer surgery. Patients with resectable esophageal carcinoma (cT1-4a, N0-3, M0) with "major calcifications" of the thoracic aorta accordingly to the Uniform Calcification Score (UCS) or a stenosis of the celiac axis accordingly to the modified North American Symptomatic Carotid Endarterectomy Trial (NASCET) score on preoperative CT scan, who are planned to undergo esophagectomy are eligible for inclusion. The primary outcome variables are complications grade 2 and higher (Clavien-Dindo classification) occurring during or after laparoscopic ISCON and before esophagectomy. Secondary outcomes include intra- and postoperative complications of esophagectomy and the induction of angiogenesis by biomarkers of microcirculation and redistribution of blood flow by measurement of indocyanine green (ICG) fluorescence angiography. DISCUSSION: We hypothesize that in selected patients with impaired vascularization of the gastric tube, laparoscopic ISCON is feasible and can be safely performed 12-18 days prior to esophagectomy. Depending on the results, a randomized controlled trial will be needed to investigate whether ISCON leads to a lower percentage and less severe course of anastomotic leakage in selected patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03896399 . Registered 4 January 2019.

Impact of nationwide centralization of oesophageal, gastric, and pancreatic surgery on travel distance and experienced burden in the Netherlands.

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 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.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus minimally invasive esophagectomy for resectable esophageal adenocarcinoma, a randomized controlled trial (ROBOT-2 trial).

BACKGROUND: For patients with esophageal adenocarcinoma or cancer of the gastroesophageal junction, radical esophagectomy with 2-field lymphadenectomy is the cornerstone of the multimodality treatment with curative intent. Both conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE) were shown to be superior compared to open transthoracic esophagectomy considering postoperative complications. However, no randomized comparison exists between MIE and RAMIE in the Western World for patients with esophageal adenocarcinoma. METHODS: This is an investigator-initiated and investigator-driven multicenter randomized controlled parallel-group superiority trial. All adult patients (age ≥ 18 and ≤ 90 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 218) with resectable esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction are randomized to either RAMIE (n = 109) or MIE (n = 109). The primary outcome of this study is the total number of resected abdominal and mediastinal lymph nodes specified per lymph node station. CONCLUSION: This is the first randomized controlled trial designed to compare RAMIE to MIE as surgical treatment for resectable esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction in the Western World. The hypothesis of the proposed study is that RAMIE will result in a higher abdominal and mediastinal lymph node yield specified per station compared to conventional MIE. Short-term results and the primary endpoint (total number of resected abdominal and mediastinal lymph nodes per lymph node station) will be analyzed and published after discharge of the last randomized patient within this trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04306458 . Registered 13th March 2020, https://clinicaltrials.gov/ct2/show/NCT04306458; Date of first enrolment 18.01.2021; Target sample size 218; Recruitment status: Recruiting; Protocol version 2; Issue date 10.03.2020; Rev. 02.02.2021; Authors ET, PCvdS, PPG.

Prognostic value of patient-reported quality of life for survival in oesophagogastric cancer: analysis from the population-based POCOP study.

BACKGROUND: Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. METHODS: Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. RESULTS: In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. CONCLUSION: In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models.

CTV-to-PTV margin assessment for esophageal cancer radiotherapy based on an accumulated dose analysis.

PURPOSE: This study aimed to assess the smallest clinical target volume (CTV) to planned target volume (PTV) margins for esophageal cancer radiotherapy using daily online registration to the bony anatomy that yield full dosimetric coverage over the course of treatment. METHODS: 29 esophageal cancer patients underwent six T2-weighted MRI scans at weekly intervals. An online bone-match image-guided radiotherapy treatment of five fractions was simulated for each patient. Multiple conformal treatment plans with increasing margins around the CTV were created for each patient. Then, the dose was warped to obtain an accumulated dose per simulated fraction. Full target coverage by 95% of the prescribed dose was assessed as a function of margin expansion in six directions. If target coverage in a single direction was accomplished, then the respective margin remained fixed for the subsequent dose plans. Margins in uncovered directions were increased in a new dose plan until full target coverage was achieved. RESULTS: The smallest set of CTV-to-PTV margins that yielded full dosimetric CTV coverage was 8 mm in posterior and right direction, 9 mm in anterior and cranial direction and 10 mm in left and caudal direction for 27 out of 29 patients. In two patients the curvature of the esophagus considerably changed between fractions, which required a 17 and 23 mm margin in right direction. CONCLUSION: Accumulated dose analysis revealed that CTV-to-PTV treatment margins of 8, 9 and 10 mm in posterior & right, anterior & cranial and left & caudal direction, respectively, are sufficient to account for interfraction tumor variations over the course of treatment when applying a daily online bone match. However, two patients with extreme esophageal interfraction motion were insufficiently covered with these margins and were identified as patients requiring replanning to achieve full target coverage.

Supervised exercise after oesophageal cancer surgery: the PERFECT multicentre randomized clinical trial.

BACKGROUND: This study investigated whether a supervised exercise programme improves quality of life (QoL), fatigue and cardiorespiratory fitness in patients in the first year after oesophagectomy. METHODS: The multicentre PERFECT trial randomly assigned patients to an exercise intervention (EX) or usual care (UC) group. EX patients participated in a 12-week moderate- to high-intensity aerobic and resistance exercise programme supervised by a physiotherapist. Primary (global QoL, QoL summary score) and secondary (QoL subscales, fatigue and cardiorespiratory fitness) outcomes were assessed at baseline, 12 and 24 weeks and analysed as between-group differences using either linear mixed effects models or ANCOVA. RESULTS: A total of 120 patients (mean(s.d.) age 64(8) years) were included and randomized to EX (61 patients) or UC (59 patients). Patients in the EX group participated in 96 per cent (i.q.r. 92-100 per cent) of the exercise sessions and the relative exercise dose intensity was high (92 per cent). At 12 weeks, beneficial EX effects were found for QoL summary score (3.5, 95 per cent c.i. 0.2 to 6.8) and QoL role functioning (9.4, 95 per cent c.i. 1.3 to 17.5). Global QoL was not statistically significant different between groups (3.0, 95 per cent c.i. -2.2 to 8.2). Physical fatigue was lower in the EX group (-1.2, 95 per cent c.i. -2.6 to 0.1), albeit not significantly. There was statistically significant improvement in cardiorespiratory fitness following EX compared with UC (peak oxygen uptake (1.8 ml/min/kg, 95 per cent c.i. 0.6 to 3.0)). After 24 weeks, all EX effects were attenuated. CONCLUSIONS: A supervised exercise programme improved cardiorespiratory fitness and aspects of QoL. TRIAL REGISTRATION: Dutch Trial Register NTR 5045 (www.trialregister.nl/trial/4942).