multiple new techniques and software for MR-guided adaptive radiation therapy.

radiotherapy

Marlies Nowee, MD, PhD

Uulke vd Heide, PhD

Radiation therapy is predominantly based on a Computed Tomography (CT) scan obtained during the treatment planning phase. During the course of radiotherapy, however, both the tumor and organs at risk (OAR) are variable in position, shape and size between fractions, and during beam delivery within one treatment fraction. Around the clinical target volume (CTV) a safety margin (Planning Target Volume, PTV) is created to account for these geometric uncertainties to ensure that the tumor receives the prescribed dose.

Direct integration of imaging at the linear accelerator enables daily monitoring of patient positioning, tumor position, and alterations in patient anatomy. Image guided radiotherapy (IGRT) enables the detection and immediate correction of such deviations and increases the precision of delivery.

Adaptive radiotherapy has become an important strategy for serially modifying dose distributions in a manner that can substantially reduce OAR dose and subsequent toxicity, while maintaining adequate target coverage. Current adaptive protocols rely upon a standard CT-based workflow and (cone-beam) CT-based image guidance.

Magnetic Resonance Imaging (MRI) has superior soft-tissue contrast over CT and seems a very promising modality to integrate in the radiation treatment process, facilitating better visualization of the tumor and OAR during treatment.

The proposed protocol aims to determine feasibility of multiple new techniques and software for MR-guided adaptive radiation therapy. For each proposed technique feasibility has to be determined individually. A secondary aim is to prospectively collect data from cohorts of patients treated at the MRL and report on acute toxicity.

By including multiple parallel cohorts, the protocol will accelerate the technical development of MR-guided adaptive radiotherapy and the evidence-based introduction of the MRL into clinical practice.

The MR-Linac Technical Feasibility Protocol

The MR-Linac Technical Feasibility Protocol For Development of MR-guided Adaptive RadiationTherapy

Feasibility of the technical procedure is demonstrated if the technique is successfully applied in 9 out of 10 consecutive patients

Elekta Limited

The Netherlands Cancer Institute

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

MR LINAC

ALISON TREE

Contact Person

Currently radiotherapy for prostate cancer is directed using scans or X-Rays, which ensures the radiotherapy treatment 'hits the target' and avoids the healthy tissues around the prostate. There are two current methods of radiotherapy image guidance- either placing small gold seeds into the prostate and taking XRays or doing a small CT scan of the prostate region each day. Neither of these methods are perfect and have drawbacks and inaccuracies.

The best way to see the prostate is with an MRI scan - this shows the edge of the prostate much more clearly and can even show the area of most aggressive cancer within the prostate. Shortly the investigators will have the ability to use a new machine - an MR-Linac - which combines an MR scanner and a radiotherapy machine.

As well as giving the investigators a clearer picture, and enabling the investigators to keep watching the prostate while the participant has their treatment (not currently possible with standard machines) this new machine will also allow the investigators to change the radiotherapy plan if they can see that the internal anatomy has shifted day to day. Currently the investigators have to give the same radiotherapy plan each day, which means the investigators have to treat a 'safety margin' around to prostate to allow for these day to day anatomy changes (e.g. rectal filling).

The aim of this study is to assess the technical feasibility of delivering radical radiotherapy for prostate cancer using the MR-Linac, including the feasibility of changing the radiotherapy plan on a daily basis to mirror internal anatomy changes. The investigators will recruit 30 patients with localised prostate cancer who need radiotherapy. The team will deliver the same dose in the same number of days i.e. the same as standard radiotherapy. Side effects will also be assessed by physicians and using patient questionnaires.

To assess delivery of prostate IMRT on the MR linac

INVOLVES PROSTATE CANCER PATIENTS SO MUST BE MALE

Prostate Radiotherapy Integrated With Simultaneous MRI (The PRISM Study)

ANONYMISED DATA WILL BE SHARED WITHIN THE ELEKTA CONSORTIUM

The radiotherapy timing sheet will be used to record the length of time for patients to have their MR guided adaptive radiotherapy for each fraction. This information will then inform if treatment can be given in a clinically feasible time frame.

Royal Marsden NHS Foundation Trust

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Pain

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Central Nervous System Depressants

All Drugs and Chemicals

Other Dietary Supplements

Benzocaine

Tannic Acid

mPDAC patients not progressing after 8 weeks of standard of care systemic therapy (SoC-CT: minimum doublet chemotherapy). The primary tumor is treated with SBRT (6.6Gy x 5) on a MR-LINAC in breath-hold technique. For this purpose, daily adaptive planning is performed aiming to maintain stringent dose constraints for organs at risk (duodenum / stomach / bowel / kidney). Chemotherapy will be continued after SBRT.

Continuing SoC-CT (according to clinical routine appr. 2 weeks after the previous cycle) without SBRT.

online adaptive MR-guided hypofractionated stereotactic radiotherapy

SBRT

The chemotherapy is given according to current standard of care, consisting of in minimum doublet - chemotherapy and excluding monotherapy regimens.

SOC chemotherapy

Georg Beyer, Dr.

Ulrike Pflugradt

Maximilian Niyazi, MD, MSc

Juliane Hörner-Rieber, PD Dr.

Matthias Guckenberger, Prof. Dr.

Maximilian Niyazi, Prof. Dr.

The MASPAC trial investigates the added benefit of MR-guided adaptive SBRT of the primary tumor embedded between standard chemotherapy cycles for pain control and prevention of pain in patients with metastatic PDAC (mPDAC).

Patients not progressing after 8 weeks of standard of care systemic therapy (SoC-CT: minimum doublet chemotherapy) will be included and randomized between arm A, receiving MR-guided adaptive SBRT of the primary tumor combined with continuation of SoC-CT, and arm B, continuing SoC-CT without SBRT.

Arm A: The primary tumor is treated with SBRT (6.6 Gy x 5) on a MR-LINAC in breath-hold technique. This scheme was shown to have a reasonable toxicity profile on a conventional LINAC. A low toxicity profile is even more important in patients with metastatic and therefore definitively incurable cancer. Therefore, treatment is performed on a MR-LINAC to deliver high doses to the tumor while keeping the toxicity profile as low as possible. For this purpose, daily adaptive planning is performed aiming to maintain stringent dose constraints for organs at risk (duodenum / stomach / bowel / kidney). Chemotherapy will be continued after SBRT. Arm B: Continuing SoC-CT (according to clinical routine appr. 2 weeks after the previous cycle) without SBRT.

MR-Guided Adaptive SBRT of Primary Tumor for Pain Control in Metastatic PDAC

MR-Guided Adaptive Stereotactic Body Radiotherapy (SBRT) of Primary Tumor for Pain Control in Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - a Randomized, Controlled Clinical Study

Mean Cumulative pain index: AUC of pain scores rated every 4 weeks until death or end of study using numeric rating scale (NRS, 0= no pain, 10 = worst pain) divided by number of multiples of 4 weeks since randomization

Biliary complications defined as cholangitis or post-hepatic cholestasis requiring drainage

Nutritional status measuring bioimpedance-derived phase angle (BIA) every 12 weeks

Treatment toxicity according to CTCAE v5.0

Heidelberg University

University of Zurich

Ludwig-Maximilians - University of Munich

Vice Chair

MR Linac

Robert Huddart

Lorna Bower, BSc

The purpose of PERMIT is to collect information on the treatment of radiotherapy patients using a new radiotherapy machine that includes magnetic Resonance (MR) imaging (MR linac) to guide treatment. The aim is to use this information to support the introduction of MR Linac into clinical practice.

PERMIT will collect details on patients treated on the MR linac plus details on their side effects and other outcomes. This information plus technical and imaging information will be combined with information from other centres using this machine. By doing so this will help us learn how best to use the MR Linac in the future and design new radiotherapy protocols

To assess delivery of radiotherapy on the MR Linac for multiple tumour sites

Prospective Evaluation of Radiotherapy Using Magnetic Resonance Image Guided Treatment

Anonymised data will be shared within the academic and industrial partners. All data sharing would be dependant on appropriate data sharing agreements.

The percentage of treatment fractions delivered successfully on the MR linac, if more than 20 % of patients (depending on treatment site) need to be treated on alternative machine or treatment protocol changed will lead to the MRL protocol at that site to be judged not feasible.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The MR-Linac Technical Feasibility Protocol	NCT04351204	Tumors at All S...	radiotherapy	18 Years -	The Netherlands Cancer Institute
Prostate Radiotherapy Integrated With Simultaneous MRI (The PRISM Study)	NCT03658525	Prostate Cancer	MR LINAC	-	Royal Marsden NHS Foundation Trust
Prostate Radiotherapy Integrated With Simultaneous MRI (The PRISM Study)	NCT03658525	Prostate Cancer	MR LINAC	-	Royal Marsden NHS Foundation Trust
The MR-Linac Technical Feasibility Protocol	NCT04351204	Tumors at All S...	radiotherapy	18 Years -	The Netherlands Cancer Institute
The MR-Linac Technical Feasibility Protocol	NCT04351204	Tumors at All S...	radiotherapy	18 Years -	The Netherlands Cancer Institute
MR-Guided Adaptive SBRT of Primary Tumor for Pain Control in Metastatic PDAC	NCT05114213	Pancreatic Canc...	SBRT SOC chemotherap...	18 Years -	Ludwig-Maximilians - University of Munich
Prospective Evaluation of Radiotherapy Using Magnetic Resonance Image Guided Treatment	NCT03727698	Cancer	MR Linac	5 Years -	Institute of Cancer Research, United Kingdom
The MR-Linac Technical Feasibility Protocol	NCT04351204	Tumors at All S...	radiotherapy	18 Years -	The Netherlands Cancer Institute

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Spots Global Cancer Trial Database for mr linac

Every month we try and update this database with for mr linac cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mr linac cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.