Periodic Reporting for period 1 - CAST (Active Monitoring of Cancer As An Alternative To Surgery)
Berichtszeitraum: 2019-11-01 bis 2021-10-31
What is the problem/issue being addressed: CAST is to implement a paradigm change for a novel approach in deciding if cancer surgery is needed. Therefore, our aim will be to clinically translate innovative new monitoring technologies from the industry. This will provide better patient selection and increase the surveillance window to allow for better treatment options over time and avoid surgery. This will involve developing new ‘watch and wait’ strategies to study the behaviour of the cancer so that any risks can be minimized. This would lead to a better clinical outcome and quality of life (QOL) for the patient and maximize the benefits of an active monitoring policy for both the patient and the healthcare system.
Why is it important for society: i) Better understand the importance of watch and wait and to estimate the risks to either perform or not to perform cancer surgery; ii) Address how the implementation of a more patient-tailored approach in cancer treatment may be utilised; iii) Address how the implementation of novel monitoring technologies for the surgeon may be utilised to open-up a risk-free window of opportunity for active surveillance; and iv) Even if surgery is determined to be needed, what are the alternative interventions to preserve the quality of life in patients.
What are the overall objectives: i) A consensus for full implementation of watch and wait for different cancers involving shared databases, training facilities and determined best practice for patient management; ii) Beyond state of art technologies, including camera systems, hardware and liquid biopsies, that will allow better prognosis and management of patients; and iii) Improved methods for the localised delivery of immunotherapy or radiotherapy.
Why is it important for society: i) Better understand the importance of watch and wait and to estimate the risks to either perform or not to perform cancer surgery; ii) Address how the implementation of a more patient-tailored approach in cancer treatment may be utilised; iii) Address how the implementation of novel monitoring technologies for the surgeon may be utilised to open-up a risk-free window of opportunity for active surveillance; and iv) Even if surgery is determined to be needed, what are the alternative interventions to preserve the quality of life in patients.
What are the overall objectives: i) A consensus for full implementation of watch and wait for different cancers involving shared databases, training facilities and determined best practice for patient management; ii) Beyond state of art technologies, including camera systems, hardware and liquid biopsies, that will allow better prognosis and management of patients; and iii) Improved methods for the localised delivery of immunotherapy or radiotherapy.
The project started successfully but experienced very soon considerable delays due to the COVID-19 pandemic. Hiring of staff was delayed due to travel restrictions. Research could initially not at all be performed due to measures to work from home, limited access to lab space, and worldwide problems in availability of lab consumables. Fortunately, the project is now fully started and for all problems solutions have been found that comply with the aims of the project.
Where the trainings can be done on-line, this is now being scheduled and implemented. On-site and hand-on sessions are being delayed till next spring or summer due to the current pandemic travel and social distancing restrictions.
For all 15 Early Stage Researchers (PhD candidates) research plans have been formulated and progress has been made.
1) High-tech cameras that can detect near-infrared light have been tested by making an accurate assessment of the bowel of pigs. The near-infrared fluorescent peptide EMI-137 is being validated in the laboratory for being able to bind to rectum tumours that have been resected in a routine rectal cancer operation. The use of this and other markers to detect residual tumour inside the patient during or before an operation are under research.
2) Nanoparticles are very small particles that can bind to tumour cells and can also be loaded with a drug or other substances, like a dye. Physical and chemical properties of our nanoparticles were determined. Our current results suggest that a specific formulation of these nanoparticles, produced by us, can specifically target tumours and produces strong near-Infrared light signals in rectal cancer tumours. This will show the tumour better than currently used imaging methods. Studies to optimise 3-dimensional microscopy methods to image rectum cancer have been started with different types of highly advanced microscopy methods (Light Sheet Microscopy, Confocal microscopy and 2-Photon microscopy).
3) Blood samples of patients with rectal cancer are assessed for the presence of tumour cells and techniques to do this kind of research are being improved.
4) Results of the RAPIDO study (focussed on the effect of preoperative therapy) are further extended. Images of the tumour made by MRI before and after preoperative therapy are collected and will be assessed. Results from several clinical studies are being reviewed to decide which chemo-radiotherapy schedule would be most profitable for which patient. Many different patient characteristics are considered, in relation with the standard long-course chemoradiation, a short-course external radiotherapy with chemotherapy, or contact radiation therapy.
5) Immunotherapy is a type of cancer treatment that helps the immune system to fight cancer, using drugs that activate the immune system. Under research is weather the nanoparticles developed as mentioned above can deliver such immune agents at the tumour site.
6) Three Early Stage Researchers are investigating newly developed clinical procedures, best practises and the use of artificial intelligence. With this knowledge standardized procedures are going to be formulated and optimised for current and future doctors.
7) The rectal cancer disappears completely after chemo- and/or radiotherapy in 15-33% of the patients. It is studied in the project if it can be predicted for which patients, it is safe to be included in a Wait and Watch strategy and skip or postpone surgery. Results from the projects described above will be needed to perform this research.
8) The overall aim of the study is to implement a more personalised treatment for rectal cancer patients.
Both the scientific community and the general public are being informed about the CAST project through our website, social media and at local and international conferences. The LUMC has installed a management team to coordinate all actions. Research done within CAST is being performed at the participating sites according to the ethical requirements, like animal welfare and privacy laws.
The COVID- pandemic caused delays, but the project is making good progress. Therefore, it can be expected that the different approaches and results of CAST will large have impact on the treatment of rectal cancer in the near future.
Where the trainings can be done on-line, this is now being scheduled and implemented. On-site and hand-on sessions are being delayed till next spring or summer due to the current pandemic travel and social distancing restrictions.
For all 15 Early Stage Researchers (PhD candidates) research plans have been formulated and progress has been made.
1) High-tech cameras that can detect near-infrared light have been tested by making an accurate assessment of the bowel of pigs. The near-infrared fluorescent peptide EMI-137 is being validated in the laboratory for being able to bind to rectum tumours that have been resected in a routine rectal cancer operation. The use of this and other markers to detect residual tumour inside the patient during or before an operation are under research.
2) Nanoparticles are very small particles that can bind to tumour cells and can also be loaded with a drug or other substances, like a dye. Physical and chemical properties of our nanoparticles were determined. Our current results suggest that a specific formulation of these nanoparticles, produced by us, can specifically target tumours and produces strong near-Infrared light signals in rectal cancer tumours. This will show the tumour better than currently used imaging methods. Studies to optimise 3-dimensional microscopy methods to image rectum cancer have been started with different types of highly advanced microscopy methods (Light Sheet Microscopy, Confocal microscopy and 2-Photon microscopy).
3) Blood samples of patients with rectal cancer are assessed for the presence of tumour cells and techniques to do this kind of research are being improved.
4) Results of the RAPIDO study (focussed on the effect of preoperative therapy) are further extended. Images of the tumour made by MRI before and after preoperative therapy are collected and will be assessed. Results from several clinical studies are being reviewed to decide which chemo-radiotherapy schedule would be most profitable for which patient. Many different patient characteristics are considered, in relation with the standard long-course chemoradiation, a short-course external radiotherapy with chemotherapy, or contact radiation therapy.
5) Immunotherapy is a type of cancer treatment that helps the immune system to fight cancer, using drugs that activate the immune system. Under research is weather the nanoparticles developed as mentioned above can deliver such immune agents at the tumour site.
6) Three Early Stage Researchers are investigating newly developed clinical procedures, best practises and the use of artificial intelligence. With this knowledge standardized procedures are going to be formulated and optimised for current and future doctors.
7) The rectal cancer disappears completely after chemo- and/or radiotherapy in 15-33% of the patients. It is studied in the project if it can be predicted for which patients, it is safe to be included in a Wait and Watch strategy and skip or postpone surgery. Results from the projects described above will be needed to perform this research.
8) The overall aim of the study is to implement a more personalised treatment for rectal cancer patients.
Both the scientific community and the general public are being informed about the CAST project through our website, social media and at local and international conferences. The LUMC has installed a management team to coordinate all actions. Research done within CAST is being performed at the participating sites according to the ethical requirements, like animal welfare and privacy laws.
The COVID- pandemic caused delays, but the project is making good progress. Therefore, it can be expected that the different approaches and results of CAST will large have impact on the treatment of rectal cancer in the near future.
Due to the COVID-19 related project delay we cannot report on progress beyond state of the art at this time. The expected results and potential impacts remain as described in the Description of Action of the Grant Agreement. This will be part of the next report.