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Department of Surgery, Utrecht University Medical Center, Utrecht University, Utrecht, the NetherlandsDepartment of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, the Netherlands
Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, United KingdomInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
† OMEC contributors: Camiel Rosman, Heide Rütten, Elske C. Gootjes, Francine E.M. Vonken, Jolanda M. van Dieren, Marieke A. Vollebergh, Maurice van der Sangen, Geert-Jan Creemers, Thomas Zander, Hans Schlößer, Stefano Cascinu, Elena Mazza, Roberto Nicoletti, Anna Damascelli, Najla Slim, Paolo Passoni, Andrea Cossu, Francesco Puccetti, Lavinia Barbieri, Lorella Fanti, Francesco Azzolini, Federico Ventoruzzo, Antoni Szczepanik, Laura Visa, Anna Reig, Tom Roques, Mark Harrison, Bogumiła Ciseł, Agnieszka Pikuła, Magdalena Skórzewska, Hanne Vanommeslaeghe, Elke Van Daele, Piet Pattyn, Karen Geboes, Eduard Callebout, Suzane Ribeiro, Peter van Duijvendijk, Cathrien Tromp, Meindert Sosef, Fabienne Warmerdam, Joos Heisterkamp, Joos Heisterkamp, Almudena Vera, Esther Jordá, Fernando López-Mozos, Maria C. Fernandez-Moreno, Maria Barrios-Carvajal, Marisol Huerta, Wobbe de Steur, Irene Lips, Marc Diez, Sandra Castro, Robert O'Neill, Daniel Holyoake, Ulrich Hacker, Timm Denecke, Thomas Kuhnt, Albrecht Hoffmeister, Regine Kluge, Tilman Bostel, Peter Grimminger, Václav Jedlička, Jan Křístek, Petr Pospíšil, Anne Mourregot, Clotilde Maurin, Naureen Starling, Irene Chong, Jelle P. Ruurda, Stella Mook, Nadia Haj Mohammad.
OMEC working group
Footnotes
† OMEC contributors: Camiel Rosman, Heide Rütten, Elske C. Gootjes, Francine E.M. Vonken, Jolanda M. van Dieren, Marieke A. Vollebergh, Maurice van der Sangen, Geert-Jan Creemers, Thomas Zander, Hans Schlößer, Stefano Cascinu, Elena Mazza, Roberto Nicoletti, Anna Damascelli, Najla Slim, Paolo Passoni, Andrea Cossu, Francesco Puccetti, Lavinia Barbieri, Lorella Fanti, Francesco Azzolini, Federico Ventoruzzo, Antoni Szczepanik, Laura Visa, Anna Reig, Tom Roques, Mark Harrison, Bogumiła Ciseł, Agnieszka Pikuła, Magdalena Skórzewska, Hanne Vanommeslaeghe, Elke Van Daele, Piet Pattyn, Karen Geboes, Eduard Callebout, Suzane Ribeiro, Peter van Duijvendijk, Cathrien Tromp, Meindert Sosef, Fabienne Warmerdam, Joos Heisterkamp, Joos Heisterkamp, Almudena Vera, Esther Jordá, Fernando López-Mozos, Maria C. Fernandez-Moreno, Maria Barrios-Carvajal, Marisol Huerta, Wobbe de Steur, Irene Lips, Marc Diez, Sandra Castro, Robert O'Neill, Daniel Holyoake, Ulrich Hacker, Timm Denecke, Thomas Kuhnt, Albrecht Hoffmeister, Regine Kluge, Tilman Bostel, Peter Grimminger, Václav Jedlička, Jan Křístek, Petr Pospíšil, Anne Mourregot, Clotilde Maurin, Naureen Starling, Irene Chong, Jelle P. Ruurda, Stella Mook, Nadia Haj Mohammad.
† OMEC contributors: Camiel Rosman, Heide Rütten, Elske C. Gootjes, Francine E.M. Vonken, Jolanda M. van Dieren, Marieke A. Vollebergh, Maurice van der Sangen, Geert-Jan Creemers, Thomas Zander, Hans Schlößer, Stefano Cascinu, Elena Mazza, Roberto Nicoletti, Anna Damascelli, Najla Slim, Paolo Passoni, Andrea Cossu, Francesco Puccetti, Lavinia Barbieri, Lorella Fanti, Francesco Azzolini, Federico Ventoruzzo, Antoni Szczepanik, Laura Visa, Anna Reig, Tom Roques, Mark Harrison, Bogumiła Ciseł, Agnieszka Pikuła, Magdalena Skórzewska, Hanne Vanommeslaeghe, Elke Van Daele, Piet Pattyn, Karen Geboes, Eduard Callebout, Suzane Ribeiro, Peter van Duijvendijk, Cathrien Tromp, Meindert Sosef, Fabienne Warmerdam, Joos Heisterkamp, Joos Heisterkamp, Almudena Vera, Esther Jordá, Fernando López-Mozos, Maria C. Fernandez-Moreno, Maria Barrios-Carvajal, Marisol Huerta, Wobbe de Steur, Irene Lips, Marc Diez, Sandra Castro, Robert O'Neill, Daniel Holyoake, Ulrich Hacker, Timm Denecke, Thomas Kuhnt, Albrecht Hoffmeister, Regine Kluge, Tilman Bostel, Peter Grimminger, Václav Jedlička, Jan Křístek, Petr Pospíšil, Anne Mourregot, Clotilde Maurin, Naureen Starling, Irene Chong, Jelle P. Ruurda, Stella Mook, Nadia Haj Mohammad.
47 tumour boards of cancer expert centers discussed 15 real-life clinical cases.
•
A consensus on definitions of oligometastatic oesophagogastric cancer was found.
•
However, high practice variability in treatment strategies exists.
•
This practice variability could potentially impact on quality of care.
Abstract
Background
Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking.
Objective
To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe.
Material and methods
European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (<50%), fair (50%–75%), or consensus (≥75%).
Results
A total of 47 MDTs across 16 countries fully discussed the cases (96%). Oligometastatic disease was considered in patients with 1–2 metastases in either the liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue or bone (consensus). At follow-up, oligometastatic disease was considered after a median of 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen (consensus). If at restaging after a median of 18 weeks of systemic therapy the number of lesions progressed, this was not considered as oligometastatic disease (fair agreement). There was no consensus on treatment strategies for oligometastatic disease.
Conclusion
A broad consensus on definitions of oligometastatic oesophagogastric cancer was found among MDTs of oesophagogastric cancer expert centres in Europe. However, high practice variability in treatment strategies exists.
Oligometastatic disease is defined as an intermediate state between loco-regional and systemic disease and reflects a potentially distinct and favourable tumour biology [
]. Consequently, local treatment for oligometastatic disease (e.g. metastasectomy or stereotactic body radiation therapy (SBRT)) could improve overall survival (OS) [
]. A recent randomised controlled trial (RCT) has shown improved OS after SBRT for oligometastatic prostate-, lung- or colorectal cancer as compared with systemic therapy alone or observation [
Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study.
]. In addition, another recent RCT has shown improved OS after SBRT and palliative standard-of-care treatment for oligometastatic non-small cell lung cancer (NSCLC) as compared with palliative standard-of-care treatment alone [
Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial.
The RENAISSANCE (AIO-FLOT5) trial: Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III tri.
ECOG-ACRIN Cancer Research Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body.
Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction.
Guo W. PD-1 Antibody Combined With Modified FLOT Regimen in the Treatment ofUnresectable Locally Advanced or Limited Metastatic Gastric Cancer. ClinicaltrialsGov/NCT04510064 2021.
The RENAISSANCE (AIO-FLOT5) trial: Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III tri.
ECOG-ACRIN Cancer Research Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body.
Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction.
Guo W. PD-1 Antibody Combined With Modified FLOT Regimen in the Treatment ofUnresectable Locally Advanced or Limited Metastatic Gastric Cancer. ClinicaltrialsGov/NCT04510064 2021.
The RENAISSANCE (AIO-FLOT5) trial: Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III tri.
ECOG-ACRIN Cancer Research Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body.
Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction.
Guo W. PD-1 Antibody Combined With Modified FLOT Regimen in the Treatment ofUnresectable Locally Advanced or Limited Metastatic Gastric Cancer. ClinicaltrialsGov/NCT04510064 2021.
Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: The AIO-FLOT3 trial.
]. However, interpretation and comparison of individual studies are hampered by different clinical definitions of oligometastatic disease, heterogeneity in case mix, selection bias, and various treatment strategies probably due to a lack of international consensus and guidelines.
A comprehensive definition of oligometastatic disease is necessary to initiate studies on the benefit of treatment strategies in this group of patients. For this purpose, the OligoMetastatic Esophagogastric Cancer (OMEC) consortium was established. OMEC is a consortium of 50 oesophagogastric cancer expert centers in Europe and is endorsed by the European Organisation for Research and Treatment of Cancer (EORTC), European Society for Radiotherapy and Oncology (ESTRO), European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), European Society for Diseases of the Esophagus (ESDE), the European chapter of the International Gastric Cancer Association (IGCA) and the Dutch Upper GI Cancer Group (DUCG). The OMEC project aims to develop a European consensus definition for oligometastatic oesophagogastric cancer in organs, as well as extra-regional lymph nodes. Peritoneal disease was not included in the OMEC project, as this is a distinct entity that has already received much attention with hyperthermic intraperitoneal chemotherapy (HIPEC) as the main treatment [
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: Final results of a phase III randomized clinical trial.
Patients with Peritoneal Carcinomatosis from Gastric Cancer Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Is Cure a Possibility?.
]. The OMEC-project consists of 5 studies and includes a systematic review and meta-analysis on oligometastatic oesophagogastric cancer (OMEC-1), the distribution of real-life clinical cases (OMEC-2), Delphi consensus rounds (OMEC-3), the publication of a multidisciplinary European consensus statement on oligometastatic oesophagogastric cancer (OMEC-4) and, finally, a prospective study for oligometastatic oesophagogastric cancer (OMEC-5).
The current study (OMEC-2) was conducted to assess the definitions and treatment strategies for oligometastatic disease used in daily practice across multidisciplinary tumour boards (MDTs) in Europe. Decision-making on definition and treatment is based on various variables, such as the organ involved, extra-regional lymph node metastases [
Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: The AIO-FLOT3 trial.
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial.
HER2/neu (ERBB2) expression and gene amplification correlates with better survival in esophageal adenocarcinoma 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis.
The RENAISSANCE (AIO-FLOT5) trial: Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III tri.
Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: The AIO-FLOT3 trial.
]. The assessment of (dis)agreement in definition and management can be used to define oligometastatic oesophagogastric cancer and to identify the currently used treatment options [
]. Therefore, oesophagogastric cancer expert centres were requested to discuss 15 real-life clinical cases in their MDT to assess the agreement in definition and treatment strategies for oligometastatic oesophagogastric cancer across MDTs in Europe.
2. Material and methods
This study was approved by the institutional review board of the UMC Utrecht, and the need for informed consent was waived for this study. This study has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans and is in line with the Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals. The methodology of this study was comparable with a simulated multidisciplinary expert opinion study on oligometastatic non-small cell lung cancer by the EORTC Lung Cancer Group [
A search was performed of real-life patients with distant metastases from oesophagogastric cancer with adenocarcinoma or squamous cell carcinoma histology. Distant metastasis was limited to either a distant organ or 1–2 extra-regional lymph node stations (according to TNM 8th edition) [
]. All patients were in good clinical condition with few to no comorbidities and were discussed at the MDT of the UMC Utrecht or Amsterdam UMC, both in The Netherlands, between 2015 and 2020. The cases varied in terms of 1. Location of metastatic lesions (e.g. liver or lung); 2. Number of metastatic lesions (one or two); 3. Timing of detection (synchronous, interval [i.e. detected at restaging after neoadjuvant treatment before surgery], or metachronous); 4. Primary tumour treatment status (surgery with or without neoadjuvant chemoradiotherapy, definitive chemoradiotherapy or no primary tumour treatment); 5. Histology (adenocarcinoma or squamous cell carcinoma), HER2 Neu status (positive, negative or mixed [i.e. the difference in the HER2 Neu status between the metastasis and the primary tumour]) and microsatellite stability; and 6. Response to systemic therapy at restaging. The response to systemic therapy at restaging was categorised into no progression (i.e. complete or partial response, or stable disease), progression in size only of the metastatic lesion(s) (i.e. ≥20% growth in size), or progression in the number of lesions. The response to systemic therapy at restaging was classified according to response evaluation criteria in solid tumours (RECIST 1.1) [
The 15 real-life clinical cases were provided to 49 European oesophagogastric cancer experts on 23rd March 2020 using an online tool (Castor EDC). These experts were either identified by EORTC, ESTRO, ESMO, ESSO, ESDE, IGCA or DUCG or identified by a systemic review of first or last authors of published RCTs related to oesophagogastric cancer between 2015 and 2020.
2.3 Discussion of clinical cases
The experts were required to host a local MDT with at least a surgical oncologist, medical oncologist, and radiation oncologist present to discuss the 15 real-life clinical cases before 1st August 2020. The case information consisted of 1. The patient history (including primary tumour stage and treatment), 2. The current problem (including location and size of distant metastasis), 3. Pathology of the primary tumour and metastasis (including histology, HER2Neu status, and microsatellite stability), and 4. Imaging of the primary tumour and metastasis (18F-fluorodeoxyglucose positron emission tomography [18F-FDG PET], computed tomography [CT], or magnetic resonance imaging [MRI]). The experts were not aware of the actual diagnosis or treatment of the real-life clinical cases.
Fig. 1 shows an example of a real-life clinical case provided to the expert. The first question for this case was: ‘Does the MDT consider this patient to have oligometastatic disease?’ If the answer was ‘no’, the questions for this specific case stopped. If the answer was ‘yes’, subsequent questions were asked regarding the treatment for the oligometastasis. The case continued only if the answer was ‘systemic therapy followed by restaging to consider local treatment’ (Fig. 2). At restaging, the case information consisted of: 1. The current problem at restaging (including the response of the primary tumour and metastasis to systemic therapy) and 2. Restaging imaging of the primary tumour and metastasis (18F FDG PET/CT, MRI, or CT). Next, the following question was asked: ‘Does the MDT consider this patient to have oligometastatic disease at restaging?’ If the answer was ‘no’, questions for this specific case stopped. If the answer was ‘yes’, subsequent questions were asked regarding the treatment for the oligometastasis. If all the questions were completed, the next case was presented (built-in data verification tool).
Fig. 1Baseline information of real-life clinical case #3 included in this survey.
The primary outcome of this study was the agreement across MDTs in Europe on the definition of oligometastatic oesophagogastric cancer at diagnosis and after systemic therapy (‘not oligometastatic disease’ versus ‘oligometastatic disease’). The secondary outcome of this study was the agreement across MDTs in Europe on treatment strategies for oligometastatic oesophagogastric cancer. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (e.g. metastasectomy, SBRT, or other local oligometastasis-directed treatment), systemic therapy followed by restaging to consider local treatment for oligometastatic disease, or systemic therapy alone (without considering local treatment for oligometastasis later).
2.5 Statistical analysis
Regarding the primary and secondary outcome, the agreement across MDTs was either scored as absent/poor (<50% agreement), fair (50%–75% agreement) or consensus (≥75% agreement), comparable with recent studies on the definition of oligometastatic disease for other tumours [
Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation.
]. According to a recent systemic review, the most common definition for consensus was per cent agreement, with 75% being the median threshold to define consensus among 25 studies [
A total of 47 MDTs across 16 countries in Europe fully discussed the cases (response rate: 96%). The hospital type was university medical center in 79%, comprehensive cancer center in 15%, and community medical center in 6%. Centers were generally high-volume (i.e. 91% of centers performed >30 oesophagectomies or gastrectomies per year). Besides a medical oncologist, surgical oncologist, and radiation oncologist, the following specialities were present at the MDT meetings: a radiologist in 60%, a gastroenterologist in 49%, a pathologist in 40%, and a nuclear medicine physician in 28%. Table 2 shows the characteristics of the participating MDTs.
Table 2Characteristics of the participating multidisciplinary tumour boards.
Oligometastatic disease was considered when one or two metastases in either liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue, or bone were present (consensus). In addition, oligometastatic disease was considered at restaging after median 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen (consensus). If at restaging after systemic therapy the number of lesions increased, this was not considered as oligometastatic disease (fair agreement).
The definition of oligometastatic disease was not limited to one lesion, as one lesion or two lesions were considered oligometastatic (consensus). Moreover, the definition of oligometastatic disease was not limited to a specific primary tumour treatment status, as a resected or definitively irradiated primary tumour with a subsequent complete response was considered oligometastatic (consensus). Also, the definition of oligometastatic disease was not limited to a specific histology or HER2Neu status, as either HER2Neu positive, HER2Neu mixed or HER2Neu negative tumour, or with squamous cell carcinoma histology were considered oligometastatic (consensus). Finally, the definition of oligometastatic disease was not limited to a particular timing of detection, as synchronous, interval, or metachronous metastasis were considered oligometastatic (consensus). Table 3 shows the agreement across MDTs on the definition of oligometastatic oesophagogastric cancer.
Table 3Agreement in definitions of oligometastatic oesophagogastric cancer
Table 3Agreement in definitions of oligometastatic oesophagogastric cancer
3.3 Restaging of oligometastatic disease
18F-FDG PET/CT imaging was used for restaging after systemic therapy in patients with either lung, retroperitoneal lymph node, adrenal gland, soft tissue, or bone oligometastasis (consensus). For patients with liver oligometastasis, either MRI or 18F-FDG PET/CT imaging was used for restaging after systemic therapy (fair agreement). Table 4 shows the agreement in restaging modalities for oligometastatic oesophagogastric cancer.
Table 4Agreement in restaging modalities for oligometastatic oesophagogastric cancer
Table 4Agreement in restaging modalities for oligometastatic oesophagogastric cancer
3.4 Treatment strategies for oligometastatic disease
No consensus on treatment strategies for oligometastatic oesophagogastric cancer was identified across presented cases. However, if the number of lesions increased at restaging after a median of 18 weeks of systemic therapy, consensus was reached that systemic therapy should be continued (rather than local treatment for oligometastasis). Upfront local treatment for oligometastatic disease was recommended with a fair agreement for soft tissue oligometastasis, a resected or definitively irradiated primary tumour or with interval or metachronous HER2Neu negative oligometastasis. Systemic therapy followed by restaging to consider local treatment for oligometastatic disease was recommended with fair agreement for HER2Neu positive or HER2Neu mixed tumours. Local treatment for oligometastatic disease after a median of 18 weeks of systemic therapy was recommended with a fair agreement when no progression (i.e. partial or complete response or stable disease) or progression in size only of the oligometastatic lesion(s) was seen at restaging. Table 5 shows the agreement in treatment strategies for oligometastatic oesophagogastric cancer across MDTs.
Table 5Agreement in treatment strategies for oligometastatic disease
Table 5Agreement in treatment strategies for oligometastatic disease
4. Discussion
This is the first study investigating the agreement in the definition and treatment of oligometastatic oesophagogastric cancer in European expert centers. Consensus (i.e. ≥75% agreement) across MDTs was reached that the term oligometastatic disease was appropriate across presented cases with oesophagogastric cancer with one or two metastases in either liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue, or bone. In addition, the term oligometastatic disease remained appropriate at restaging after a median of 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen. However, in contrast to the consensus on the definition of oligometastatic disease, we found no consensus (i.e. <75% agreement) across MDTs regarding the treatment strategies that should be followed in the case of oligometastatic disease. In fact, a considerable variation in treatment approaches for oligometastatic oesophagogastric cancer across European oesophagogastric cancer expert centers was exposed. This lack of consensus on treatment strategies can partly be explained by the lack of evidence-based guidelines to guide treatment decision-making and the lack of completed RCTs for oligometastatic oesophagogastric cancer.
If oligometastatic disease was no longer considered at restaging after systemic therapy (i.e. the number of lesions increased), a consensus was reached that presented cases should not receive local treatment for oligometastatic disease but rather subsequent systemic therapy. The administration of systemic therapy followed by restaging allows for the identification of patients with (suspected) oligometastatic disease at baseline but with an actual biologically aggressive tumour who might not benefit from local treatment for oligometastatic disease [
The RENAISSANCE (AIO-FLOT5) trial: Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III tri.
ECOG-ACRIN Cancer Research Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body.
]. In both trials, including patients with synchronous oligometastatic gastric or oesophagogastric cancer, local treatment for the primary tumour and metastases will be performed at restaging after systemic therapy in patients with a partial or complete response. However, this study identified a fair agreement (i.e. 50-75% agreement) across MDTs that local treatment for oligometastatic disease was also appropriate at restaging after median 18 weeks of systemic therapy when progression in size only of the oligometastatic lesion(s) was seen.
Despite the potential advantage of the administration of systemic therapy first to identify patients who benefit the most from local treatment for oligometastatic disease, which is incorporated in several ongoing RCTs for oligometastatic oesophagogastric cancer and German S3 guidelines [
The RENAISSANCE (AIO-FLOT5) trial: Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III tri.
ECOG-ACRIN Cancer Research Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body.
Guo W. PD-1 Antibody Combined With Modified FLOT Regimen in the Treatment ofUnresectable Locally Advanced or Limited Metastatic Gastric Cancer. ClinicaltrialsGov/NCT04510064 2021.
Nguyen Q-N. Chemotherapy with or without radiation or surgery in treating participants with oligometastatic esophageal or gastric cancer. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03161522. Accessed July 11, 2019.
], upfront local treatment for oligometastatic disease was recommended with a fair agreement across MDTs for presented cases with soft tissue oligometastasis, a resected or a definitively irradiated primary tumour, metachronous or interval HER2neu negative oligometastasis. The use of upfront local treatment for oligometastatic disease in these presented cases might be explained by the timing of detection of the oligometastasis (metachronous) and thus after previous systemic therapy for the primary tumour.
A consensus statement for the definition and treatment strategies of oligometastatic oesophagogastric cancer could reduce practice variability, increase the quality of care and offer all patients the optimal treatment approach for oligometastatic disease [
Optimization of transmural care by implementation of an online expert panel to assess treatment strategy in patients suffering from colorectal cancer liver metastases: A prospective analysis.
]. The findings of this study (OMEC-2), together with a systematic review on the definition of oligometastatic oesophagogastric cancer (OMEC-1), will be used for a multidisciplinary consensus statement on the definition and treatment of oligometastatic oesophagogastric cancer (OMEC-4). This consensus statement will result in a prospective study for oligometastatic oesophagogastric cancer (OMEC-5).
Strengths of this study include the excellent response rate of 96%, the use of real-life clinical cases, and the distribution of these real-life clinical cases to MDTs of oesophagogastric cancer expert centers in Europe, resulting in real-life multidisciplinary (dis)agreement. Therefore, this study provides a largely unbiased reflection of clinical practice and excellent generalisability. However, a limitation was that this study could not address the causes of (dis)agreement, and these causes will be investigated in subsequent steps of the OMEC project.
In conclusion, 47 multidisciplinary tumour boards of European oesophagogastric cancer expert centers fully discussed 15 real-life clinical cases. A multidisciplinary consensus was identified on the definition of oligometastatic oesophagogastric cancer at diagnosis and after systemic therapy. However, no consensus and even high practice variability in treatment decision-making for oligometastatic disease was established. This practice variability could potentially impact on quality of care. The findings of this study and a systematic review on the definition of oligometastatic oesophagogastric cancer will be used for a consensus statement on the diagnosis and treatment of oligometastatic oesophagogastric cancer in the OMEC project.
Funding
Not applicable.
Data sharing
The data that support the findings of this study are available from the corresponding author, upon reasonable request.
Credit author statment
Conceptualisation: Tiuri Kroese, Peter van Rossum, Richard van Hillegersberg, Hanneke van Laarhoven.
Data curation: all authors.
Formal analysis: Tiuri Kroese, Peter van Rossum, Richard van Hillegersberg, Hanneke van Laarhoven.
Funding acquisition: NA.
Investigation: all authors.
Methodology: Tiuri Kroese, Peter van Rossum, Richard van Hillegersberg, Hanneke van Laarhoven.
Project administration: Tiuri Kroese, Peter van Rossum, Richard van Hillegersberg, Hanneke van Laarhoven.
Resources: NA.
Software: Tiuri Kroese, Peter van Rossum, Richard van Hillegersberg, Hanneke van Laarhoven.
Supervision: Peter van Rossum, Richard van Hillegersberg, Jelle Ruurda, Hanneke van Laarhoven.
Validation: all authors.
Visualisation: Tiuri Kroese, Peter van Rossum, Richard van Hillegersberg, Hanneke van Laarhoven.
Roles/Writing - original draft: Tiuri Kroese, Peter van Rossum, Richard van Hillegersberg, Hanneke van Laarhoven.
Writing - review and editing: all authors.
Conflict of interest statement
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Gani reports a research collaboration and travel expenses from Elekta outside the submitted work; Dr. Hawkins reports grants from NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust, outside the submitted work; Dr. Smyth reports personal fees from AMAL Therapeutics, Astellas Pharma, AstraZeneca, Beigene, Five Prime Therapeutics, Merck, Pfizer, Roche, Servier and Zymeworks and institutional funding for clinical trials research from Astra Zeneca, Astellas, Basilea, BMS, Daiichi Sankyo, Roche, Macrogenics and MSD. Dr. Moehler reports grants and non-financial support from EORTC, grants and non-financial support from AIO, grants and non-financial support from German Cancer Aid, grants and non-financial support from BMBF, during the conduct of the study; personal fees from Falk Foundation, personal fees from Lilly, grants and personal fees from MSD, personal fees from Roche, grants and personal fees from Pfizer, grants, personal fees and non-financial support from Amgen, grants, personal fees and non-financial support from Bristol-Myers Squibb, grants and personal fees from Merck Serono, personal fees from MCI Group, personal fees from Taiho, outside the submitted work; Dr. van Laarhoven reports other from BMS, other from Lilly, other from MSD, other from Nordic Pharma, other from Servier, other from Bayer, outside the submitted work; the other authors have nothing to disclose.
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