Magnus Nilsson

Gastric cancer (GC) is the 4th most common cause of cancer deaths globally. Peritoneal metastases (PM) occur in 50% of patients with GC and is associated with dismal prognosis and very poor quality of life (QoL) due to progressive ascites, bowel obstruction and abdominal pain. Systemic chemotherapy has low efficacy and severe toxicity in patients with PM. Objective responses is achieved in a mere 30% of cases, and this comes with a high cost in terms of toxicity and compromised QoL.Intraperitoneal (IP) chemotherapy (IPC) with paclitaxel has been tested in GC patients with PM in trials in Asia, showing significantly improved overall survival (OS) and low toxicity in an asian population, and is now routinely used in some Asian countries. To date no randomised controlled trial (RCT) has addressed IPC in peritoneally metastasized GC in a Western population and in combination with western standard of care treatment regimes.We will now perform a European multicentric randomised phase III trial, IPa-Gastric, comparing IP paclitaxel, administered through an indwelling peritoneal catheter connected to a subcutaneous port, together with standard systemic therapy (ST) versus standard ST alone. In total 262 patients with peritoneally metastasised GC will be enroled. The primary endpoint is overall survival, and the main secondary endpoint is QoL. The short-term aim is to establish IP paclitaxel with standard ST as new standard of care for GC with PM in Western populations.

In many European countries the recent rise in incidence of esophageal adenocarcinoma (EAC) is without precedent. EAC is notorious for its highly aggressive biological behavior leading to invasive disease and early metastases. The only way to reduce mortality is through treatment in early stage of the cancer. EAC has a well recognized premalignant precursor lesion identified as esophageal metaplasia, or Barrett’s Esophagus (BE), which offers important opportunities for treatment in early stages of cancer which may reach 5 years survival rates up to 80%. However, these patients need to be monitored constantly for timely intervention in case of disease recurrence or metastases. The problem is that after endoscopic treatment up to 30% of cases will develop recurring cancers or even present with metastases, which requires additional endoscopic treatments or surgery. Currently it is impossible to predict which of the treated BE patients with will have stable disease and which will recur or progress to invasive cancer. As a consequence all treated patients need to remain in frequent endoscopic surveillance. This leads to over-treatment of a large group of BE patients and under-treatment of those with more aggressive disease. There is a low cost effectiveness of endoscopic therapies, low quality of life of patients and poor satisfaction of care providers. An accurate risk stratification method for early AEC in BE patients is therefore an unmet clinical need. The ambition of the ENDEAVOR consortium is to implement an innovative risk stratification method, which encompasses minimally invasive cell collection supplemented by single cell genomic analysis to address this specific need. Taking into account patient characteristics, gender dimensions, an optimal model model will be tested in a randomized controlled prospective trial. Future implementation of this method will reduce health care costs, increase quality of life and satisfaction of health care providers. This action is part of the Cancer Mission cluster of projects on Diagnostics and Treatment (diagnostics).

There are two types of esophageal cancer, adenocarcinoma and squamous cell carcinoma. Curative treatment for adenocarcinoma is based on surgery to remove the esophagus after chemotherapy or combined treatment with chemotherapy and radiation, so-called chemoradiotherapy (CRT). In the case of squamous cell carcinoma, the most established treatment is surgery after pre-treatment with CRT, but in this type of esophageal cancer there is also an option to treat with CRT for curative purposes, then given in a higher dose and with careful follow-up afterwards, with the possibility of surgery in cases where the tumor does not disappear completely or return locally. In the randomized study NeoRes 2, we investigate for adenocarcinoma of the esophagus whether an extended wait of 10-12 weeks between completed CRT and surgery, compared to the usual wait of 4-6 weeks, results in better tumor response, less risk of residual tumor tissue and better recovery before surgery . In the randomized study NEEDS, we investigate for squamous cell carcinoma of the esophagus whether CRT followed by careful controls, and surgery only when needed, provides similar survival but with a better quality of life, compared to today's standard treatment with CRT followed by mandatory surgery. For esophageal adenocardinomas, a randomized trial demonstrating oncologic benefits and better quality of life after delayed surgery would be of great value as many patients are not recovered and ready for major surgery within the conventional time frame of 4-6 weeks. In the case of squamous cell carcinoma, the vast majority of patients today routinely undergo surgery after CRT. However, the operation causes a lifelong reduction in the quality of life. If CRT with surgery only when really needed for local tumor control were to be shown to provide as good a survival rate as routine surgery, then it is likely to become the new standard treatment worldwide.

Cancer of the esophagus has poor prognosis. The best chance of being cured has patients who are first treated with chemotherapy, or a combination of chemotherapy and radiotherapy, and then operated. However, it is not entirely clear which pretreatment is better, chemotherapy alone or combination of chemotherapy and radiation. It is also not clear how long you should wait with surgery after pretreatment with chemotherapy and radiation. Previous preliminary data suggest that you can get better treatment effect if you wait much longer with the surgery than is normal today. This research project consists of two studies in which we each draw two different treatment options. In study 1, we draw between giving pretreatment with chemotherapy alone and giving pretreatment with combination of chemotherapy and radiation. In study 2, all patients receive combination therapy with chemotherapy and radiation, but instead we draw between waiting 4-6 weeks with the operation, which is common today, and waiting 10-12 weeks, which in preliminary, unlisted studies, shown promising results with better shrinkage effect on the tumor. I hope with this research can contribute with well-founded knowledge about how to pre-treat with chemotherapy and radiation before surgery of esophageal cancer in as efficient and safe manner as possible. In the first study, we hope to answer the question whether radiation has a place in the pretreatment or not, which most previous data suggests, but this study could ultimately determine. In the second study, we hope to get an answer to the question of how long one should wait for surgery of esophageal cancer after pretreatment with chemotherapy and radiation.

Cancer of the esophagus has poor prognosis. The best chance of being cured has patients who are first treated with chemotherapy, or a combination of chemotherapy and radiotherapy, and then operated. However, it is not entirely clear which pretreatment is better, chemotherapy alone or combination of chemotherapy and radiation. It is also not clear how long you should wait with surgery after pretreatment with chemotherapy and radiation. Previous preliminary data suggest that you can get better treatment effect if you wait much longer with the surgery than is normal today. This research project consists of two studies in which we each draw two different treatment options. In study 1, we draw between giving pretreatment with chemotherapy alone and giving pretreatment with combination of chemotherapy and radiation. In study 2, all patients receive combination therapy with chemotherapy and radiation, but instead we draw between waiting 4-6 weeks with the operation, which is common today, and waiting 10-12 weeks, which in preliminary, unlisted studies, shown promising results with better shrinkage effect on the tumor. I hope with this research can contribute with well-founded knowledge about how to pre-treat with chemotherapy and radiation before surgery of esophageal cancer in as efficient and safe manner as possible. In the first study, we hope to answer the question whether radiation has a place in the pretreatment or not, which most previous data suggests, but this study could ultimately determine. In the second study, we hope to get an answer to the question of how long one should wait for surgery of esophageal cancer after pretreatment with chemotherapy and radiation.

Cancer of the esophagus has poor prognosis. The best chance of being cured has patients who are first treated with chemotherapy, or a combination of chemotherapy and radiotherapy, and then operated. However, it is not entirely clear which pretreatment is better, chemotherapy alone or combination of chemotherapy and radiation. It is also not clear how long you should wait with surgery after pretreatment with chemotherapy and radiation. Previous preliminary data suggest that you can get better treatment effect if you wait much longer with the surgery than is normal today. This research project consists of two studies in which we each draw two different treatment options. In study 1, we draw between giving pretreatment with chemotherapy alone and giving pretreatment with combination of chemotherapy and radiation. In study 2, all patients receive combination therapy with chemotherapy and radiation, but instead we draw between waiting 4-6 weeks with the operation, which is common today, and waiting 10-12 weeks, which in preliminary, unlisted studies, shown promising results with better shrinkage effect on the tumor. I hope with this research can contribute with well-founded knowledge about how to pre-treat with chemotherapy and radiation before surgery of esophageal cancer in the most effective and safe way possible. In the first study, we hope to answer the question whether radiation has a place in the pretreatment or not, which most previous data suggests, but this study could ultimately determine. In the second study, we hope to get an answer to the question of how long one should wait for surgery of esophageal cancer after pretreatment with chemotherapy and radiation.

Cancer of the esophagus has poor prognosis. The best chance of being cured has patients who are first treated with chemotherapy, or a combination of chemotherapy and radiotherapy, and then operated. However, it is not entirely clear which pretreatment is better, chemotherapy alone or combination of chemotherapy and radiation. It is also not clear how long you should wait with surgery after pretreatment with chemotherapy and radiation. Previous preliminary data suggest that you can get better treatment effect if you wait much longer with the surgery than is normal today. This research project consists of two studies in which we each draw two different treatment options. In study 1, we draw between giving pretreatment with chemotherapy alone and giving pretreatment with combination of chemotherapy and radiation. In study 2, all patients receive combination therapy with chemotherapy and radiation, but instead we draw between waiting 4-6 weeks with the operation, which is common today, and waiting 10-12 weeks, which in preliminary, unlisted studies, shown promising results with better shrinkage effect on the tumor. I hope with this research can contribute with well-founded knowledge about how to pre-treat with chemotherapy and radiation before surgery of esophageal cancer in the most effective and safe way possible. In the first study, we hope to answer the question whether radiation has a place in the pretreatment or not, which most previous data suggests, but this study could ultimately determine. In the second study, we hope to get an answer to the question of how long one should wait for surgery of esophageal cancer after pretreatment with chemotherapy and radiation.

Cancer of the esophagus has poor prognosis. The best chance of being cured has patients who are first treated with chemotherapy, or a combination of chemotherapy and radiotherapy, and then operated. However, it is not entirely clear which pretreatment is better, chemotherapy alone or combination of chemotherapy and radiation. It is also not clear how long you should wait with surgery after pretreatment with chemotherapy and radiation. Previous preliminary data suggest that you can get better treatment effect if you wait much longer with the surgery than is normal today. This research project consists of two studies in which we each draw two different treatment options. In study 1, we draw between giving pretreatment with chemotherapy alone and giving pretreatment with combination of chemotherapy and radiation. In study 2, all patients receive combination therapy with chemotherapy and radiation, but instead we draw between waiting 4-6 weeks with the operation, which is common today, and waiting 10-12 weeks, which in preliminary, unlisted studies, shown promising results with better shrinkage effect on the tumor. I hope with this research can contribute with well-founded knowledge about how to pre-treat with chemotherapy and radiation before surgery of esophageal cancer in the most effective and safe way possible. In the first study, we hope to answer the question whether radiation has a place in the pretreatment or not, which most previous data suggests, but this study could ultimately determine. In the second study, we hope to get an answer to the question of how long one should wait for surgery of esophageal cancer after pretreatment with chemotherapy and radiation.