Symptoms and General Pathology

All Conditions

Hypoxia

All Drugs and Chemicals

Micronutrients

Mineral

Fluorodeoxyglucose F18

Copper

Radiopharmaceuticals

Trace Elements

Copper Supplement

3 fractions of 12 Gy Relative Biological Effectiveness (RBE)

Partial radiotherapy targeting the hypoxic tumor segment

Particle radiotherapy

For treatment planning as well as for follow-up radiological tumor assessment.

Magnetic resonance imaging

Computertomography

For the definition of the hypoxic tumor segment in treatment planning.

Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) Positron Emission Tomography-Computer Tomography (64Cu-ATSM-PET-CT)

For follow-up radiological tumor assessment.

18-F-FluorDesoxyGlukose Positron Emission Tomography-Computer Tomography (18F-FDG-PET-CT)

Evaluation before treatment-start, during treatment and follow-up period.

Blood sampling

Slavisa Tubin, M.D.

Eugen B. Hug, Univ. Prof.

This study uses a novel, recently developed unconventional radiotherapy technique which consists of three high-dose fractions directed to special segments of unresectable bulky tumors.

This is a mono-centric, prospective, two-arms, feasibility study in which the investigator will enroll up to 22 patients with locally advanced or metastatic cancers with at least one bulky (≥6cm) lesion. This study uses a novel, recently developed unconventional radiotherapy technique, consisting of a short course (3 fractions) high dose partial irradiation targeting exclusively the hypoxic segment of unresectable bulky tumors while sparing the peritumoral immune microenvironment for induction of immune-mediated tumoricidal bystander and abscopal effects.

The present study will explore the potential biological and physical advantages of particle-based radiotherapy to deliver a highly conformal radiation dose to the hypoxic tumor segment defined by using hypoxia-specific Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) Positron Emission Tomography-Computer Tomography (64Cu-ATSM PET-CT) and dynamic contrast enhanced Magnetic Resonance Tomography imaging. Based on tumor location, volume and risk factors related to nearby organs at risk, patients will be divided in the "high-dose" or "reduced-dose" group which will be treated with different dose-schedules according to risk factors.

Additionally, radiotherapy will be administered at the precise timing, determined individually for each patient, based on the serially mapped homeostatic immune fluctuations by monitoring blood levels of the inflammatory markers. The objective is to synchronize the radiation treatment with the favorable, most reactive anti-tumor immune response phase, in order to break tumor´s immune-tolerance locally and systemically.

Particle-based Partial Tumor Irradiation of Unresectable Bulky Tumors

Particle-based Partial Tumor Irradiation Targeting Hypoxic Segment and Sparing the Peritumoral Immune Microenvironment for Unresectable Bulky Tumors

Bystander (local, at the level of the partially treated bulky tumor) response rate defined as at least a 30% regression of the unirradiated tumor tissue.

Feasibility of patient recruitment, treatment and follow-up rates.

Defined as the time from treatment until the time of death from any cause.

Defined as the time from treatment until the time of local disease progression.

Defined as the time from treatment until the time of distant disease progression.

Defined as the proportion of metastatic patients that exhibited an abscopal effect versus the total number of metastatic patients allocated to the treatment.

Proportion of patients who will achieve a partial or complete relief at different time-points.

Toxicity assessment according to NCI CTCAE v5.0

The feasibility of PARTICLE-PATHY and to it related TIMING will be defined by the proportion of patients allocated to this treatment who received it within dosimetric constraints after being able to define the immune-cycle periodicity and to synchronize radiotherapy with it versus the total number of patients allocated to the treatment.

Two key cytokines, Interleukin-2 (IL-2) and Interferon Gamma (INFg), will be serially assessed at baseline and after each radiotherapy treatment, in order to determine their potential role in modulating the immune response in relation to the bystander/abscopal effects.

Medical University of Vienna

Landesklinkum Wiener Neustadt

Klinik Ottakring

EBG MedAustron GmbH

Simulation CTs of up to ten patients with bulky (\>6cm) tumors will be selected. This will be used for optimization of contouring and planning strategy.

Ten patients with bulky tumors (\>6cm) recommended to receive RT with CT and MRI planning will be accrued. MRI DCE sequence (20-30mins) will be added if not requested for clinical use. They will be treated with standard clinical plans. Every effort will be made to include equal numbers of patients (2-3) from head and neck, thorax, abdomen and pelvis. Planning images will be used for the purpose of dosimetric comparison between SBRT-PATHY and CARBON-PATHY radiation plans.

SBRT-PATHY and CARBON-PATHY planning is performed for study purposes only. Patients will be treated according to standard radiotherapy as per institutional policies.

The planning images (CT, MRI) will be anonymized and used for planning purposes only.

Planning CT, MRI

Rebecca Wong, MBChB, FRCPC, MSc, Prof.

This study uses a novel unconventional radiotherapy technique, consisting of high dose PArtial Tumor irradiation targeting exclusively the HYpoxic segment of unresectable bulky tumors delivered either with photons (SBRT-PATHY) or with carbon-ions (CARBON-PATHY) while sparing the peritumoral immune microenvironment (PIM).

This study will be conducted as a two phase study. Phase A is a retrospective study. Up to 10 patients with bulky (\>6cm tumors) previous planned with planning CT with IV contrast will be selected for planning and dosimetry comparison. This is performed to optimize the contouring and planning procedures. Phase B is a prospective study. Ten patients with bulky (\>6cm tumor) requiring radiotherapy, with planning CT and MR with IV contrast will be accrued. Every effort will be made to include equal numbers of patients (2-3) from head and neck, thorax, abdomen and pelvis. Their images will be used for planning and dosimetry comparison.

Patients will be treated according to clinical plans. The study plans will not be used for treatment. Treatment plans for Photon delivery (SBRT-PATHY) and Carbon delivery (CARBON-PATHY) to deliver 30 Gy in three fractions will be planned to be delivered to the BTV will be performed. SBRT-PATHY plans will be generated at the Princess Margaret Cancer Center (PMCC, Toronto, Canada) while CARBON-PATHY plans will be generated at the MedAustron Center for Particle Therapy and Research (W. Neustadt, Austria).

The objective is to compare the dosimetric profile achievable using SBRT-PATHY (using photons) and CARBON-PATHY (using carbon-ions) for unresectable bulky tumors and surrounding tissues.

Radiotherapy Treatment Planning Comparison Using SBRT-PATHY (Photons) Versus CARBON-PATHY for Unresectable Bulky Tumors

The objective of phase A is to optimize the target delineation, planning strategy and techniques for SBRT-PATHY at Princess Margaret and CARBON-PATHY at MedAustron.

a prospective identification of 10 patients who are recommended to receive radiotherapy fulfilling the inclusion criteria. SBRT-PATHY and CARBON-PATHY planning is perfomed for study purposes only. A planning comparison between SBRT-PATHY (using photons) and CARBON-PATHY (using carbon-ions) based on dosimetric consideration achieved for the targeted BTV, non-targeted surrounding NTV (normoxic tumor segment), PIM, regional metastases (i.e. local regional involved nodes and distant metastases located within 15 cm cranial caudal to GTV), regional uninvolved lymph nodes and surrounding organs at risk (OAR) will be performed.

The normoxic tumor segment (NTV) will be created by subtracting the BTV from the GTV, representing the remaining peripheral tumor segment outside the BTV.

The OAR will be delineated on MRT images at the level of the treated area. Particularly normal structures involved by or in the close proximity to the tumor such as vessels, nerves, or hollow organs will be contoured. Contours will be checked and refined on the co-registered simulation CT images.

Abscopal tumor site(s), corresponding to radiographic evidence of the regional (for ex. lymph nodes) metastases, will be delineated on whichever images that clearly demonstrate their presence, including simulation CT or MRT.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Particle-based Partial Tumor Irradiation of Unresectable Bulky Tumors	NCT04875871	Cancer	Particle radiot... Magnetic resona... Computertomogra... Copper-64-Diace... 18-F-FluorDesox... Blood sampling	18 Years -	EBG MedAustron GmbH
Radiotherapy Treatment Planning Comparison Using SBRT-PATHY (Photons) Versus CARBON-PATHY for Unresectable Bulky Tumors	NCT06390657	Cancer	Planning CT, MR...	18 Years -	EBG MedAustron GmbH
Radiotherapy Treatment Planning Comparison Using SBRT-PATHY (Photons) Versus CARBON-PATHY for Unresectable Bulky Tumors	NCT06390657	Cancer	Planning CT, MR...	18 Years -	EBG MedAustron GmbH

Spots Global Cancer Trial Database for partial tumor irradiation