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

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

The patients will receive particle radiotherapy before operation,and then radical hysterectomy, removal of pelvic lymph nodes and abdominal aorta lymph nodes would be conducted. Besides ovary reservation would be made according to the individual situation. Concurrent radiation and chemotherapy would be performed according to the clinical situation.

The patients will receive NACT before operation,and then radical hysterectomy, removal of pelvic lymph nodes and abdominal aorta lymph nodes would be conducted. Besides ovary reservation would be made according to the individual situation. Concurrent radiation and chemotherapy would be performed according to the clinical situation.

Xioaqing Guo, PhD

Na Liu, PhD

Locally advanced cervical cancer (LACC) refers to the clinically cervical visible lesion with a diameter of \> 4 cm, which has been considered as a high risk of early cervical cancer for a long time. Because of local bulk lesion of LACC, the risk of radical hysterectomy is pretty high and the radical effect commonly does not meet the satisfactory. Therefore, 1-3 course of neoadjuvant chemotherapy (NACT) were carried out before operation. However, nearly 20% of patients are not sensitive to NACT. Therefore NACT did not bring any benefits to radical surgery even to some extent delayed the treatment.

Traditional radiotherapy is also commonly used in the treatment of LACC, however ovarian function would be permanently destroyed especially for young patients, additionally radioactive complications to adjacent organs of cervical such as vagina, bladder and rectal also commonly happened, moreover sexual dysfunction after radiotherapy significantly affect the life quality of young patients.

Particle radiotherapy developed recently, has the advantages of short course of treatment and mild side effects, due to its special working mechanism, Bragg effect. So the amount of radiation in the tumor tissue is very extremely high, and in the adjacent tissue is quiet low, therefore the organs at risk were protected by avoiding unnecessary damage.

Based on these, we proposed the application of particle radiotherapy in LACC pre-operation, and comprehensively evaluated recent curative effect, complications and long-term follow-up between particle radiotherapy and NACT. Furthermore, the clinical significance and long-term application prospects about particle therapy were objectively assessed.

Observation and Evaluation of Short-term Curative Effect of Local Advanced Cervical Cancer Treated With Particle Radiotherapy Versus Neoadjuvant Chemotherapy

Shanghai First Maternity and Infant Hospital

RenJi Hospital

Shanghai Proton and Heavy Ion Center

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

According to the radiation plan using protons or carbon ions (between 25 and a maximum of 40 Gy). Planning Target Volume 1 : 25 Gy (Relative Biological Effectiveness) in 5 fractions of 5 Gy (Relative Biological Effectiveness) Planning Target Volume 2 : A simultaneous integrated boost (SIB) will be delivered to the Planning Target Volume 2: 40 Gy (Relative Biological Effectiveness) in 5 fractions of 8 Gy (Relative Biological Effectiveness).

According to the radiation plan (between 25 and a maximum of 40 Gy). Planning Target Volume 1 : 25 Gy (Relative Biological Effectiveness) in 5 fractions of 5 Gy (Relative Biological Effectiveness) Planning Target Volume 2 : A simultaneous integrated boost (SIB) will be delivered to the Planning Target Volume 2: 40 Gy (Relative Biological Effectiveness) in 5 fractions of 8 Gy (Relative Biological Effectiveness).

Particle-therapy using protons or carbon ions

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

Piero Fossati, M.D.

This is an interventional, single-arm, open-label study with high dose short course radiotherapy for patients with locally advanced pancreatic cancer.

This is an interventional, open label, trial of definitive hypofractionated radiotherapy for patients with locally advanced pancreatic cancer.

Within this study radiotherapy shall be delivered with active scanning particle-therapy using proton- or carbon ions radiotherapy.

Particle therapy will be performed with a simultaneous integrated boost (SIB) treating a larger target volume, including elective lymph node stations and neural plexus, at a lower dose and boosting macroscopic disease.

The investigator will explore the efficacy of these treatment in a real world scenario in which patients are allowed to receive standard systemic treatment and standard surgical treatment (if conversion to resectability is achieved).

However, and in order to record and to gain better understanding of the influence of systemic therapies on the outcomes parameters of this study, patients will be sub-stratified in 3 groups: i) patients receiving FOLFIRINOX, ii) patients receiving Gemcitabine + Nanoparticle Albumin Bound Paclitaxel (NAB-Paclitaxel), iii) patients receiving other systemic therapies or not receiving antineoplastic systemic therapy.

Radiotherapy for Locally Advanced Pancreatic Carcinomas (Phase II Trial)

Phase II Trial of Hypo-fractionated Highly Conformal Radiotherapy for Locally Advanced Pancreatic Carcinomas

Rate of locoregional tumor control at two year will be evaluated radiologically.

This endpoint will be measured with the actuarial approach.

This endpoint will be measured with the actuarial approach. It will be assessed as the union of locoregional control and survival. Patient with loco regional recurrence will be considered failures. Deceased patient will also be considered failures. Patient lost to follow-up without evidence of locoregional recurrence will be censored. Distant metastasis and peritoneal carcinosis will be irrelevant respect to this endpoint.

This endpoint will be measured with the actuarial approach. All deaths will be considered failures, patient lost to follow-up will be censored.

This endpoint will be scored as gross rate. The investigator will measure the number of patients experiencing at least one toxicity \>= Grade 4 and \>= Grade 5 and the number of events \>= Grade 4 and \>= Grade 5. The crude number will be divided by the total number of patients treated.

Quality of life will be measured with Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) before radiation therapy and at each follow-up. The FACT-Hep has 27 (+ a subscale with 18 additional) questions, each of which is answered using a 5-point Likert scale ranging from 0 (Not at all) to 4 (Very much). Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored. Questions measure the respondents' health state over the last 7 days in four subscales: Physical Well-Being (7 questions), Social/Family Well-Being (7 questions), Emotional Well-Being (6 questions), and Functional Well-being (7 questions). This disease-specific version of the FACT-Hep contain these four core subscales, with additional (18) questions appended to address disease-specific factors.

The higher the score the better the Quality of Life.

Quality of life will be measured with EORTC Quality of Life Questionnaire-C30 before radiation therapy and at each follow-up.

Questionnaire developed to assess the quality of life of cancer patients. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Quality of life will be measured with Brief Pain Inventory before radiation therapy and at each follow-up.

The Brief Pain Inventory (BPI) is a measurement tool for assessing clinical pain.The interference items were now presented with 0-10 scales, with 0=no interference and 10=interferes completely.

The number of events, their grade and their time course will be measured.

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.

The Princess Margaret Cancer Foundation

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Patients will receive particle radiotherapy in arm up position. Radiation: adjuvant hypofractionated intensity-modulated proton radiotherapy; For patients received modified radical mastectomy, Clinical Target Volume (CTV) 1: chest wall ± regional lymph drainage area, 40.05Gy (RBE) in 15 fractions with proton radiotherapy; For patients received lumpectomy, CTV1: whole breast ± regional lymph drainage area, 40.05 Gy (RBE) in 15 fractions with proton radiotherapy; CTVtb: tumor bed SIB（simultaneous integrated boost） to 48 Gy (RBE) in 15 fractions with proton radiotherapy.

Patients will receive particle radiotherapy in arm down position. Radiation: adjuvant hypofractionated intensity-modulated proton radiotherapy; For patients received modified radical mastectomy, CTV1: chest wall ± regional lymph drainage area, 40.05Gy (RBE) in 15 fractions with proton radiotherapy; For patients received lumpectomy, CTV1: whole breast ± regional lymph drainage area, 40.05 Gy (RBE) in 15 fractions with proton radiotherapy; CTVtb: tumor bed SIB to 48 Gy (RBE) in 15 fractions with proton radiotherapy.

In order to explore the accuracy of breast cancer patients' treatment positions and its impact on dose of the new fixation device in two different fixed positions of arm up and arm down, optimize the position fixed equipment and methods of particle radiotherapy for breast cancer, and then establish the precision process of particle radiotherapy for breast cancer under the guidance of multimodal images.

Fixed positions of arm down and arm up

Jingfang Zhao

Ping Li

The optical body surface image (C-RAD) was used to guide and track the change of positions, and multimodal images (including 2D X-ray images, CT images and PET-CT images) were used to verify the treatment positions. In order to explore the accuracy of breast cancer patients' treatment positions and its impact on dose of the new fixation device in two different fixed positions of arm up and arm down, optimize the position fixed equipment and methods of particle radiotherapy for breast cancer, and then establish the precision process of particle radiotherapy for breast cancer under the guidance of multimodal images. In a word, this is a dosimetry and prospective Phase II randomized clinical study of the accuracy of multi-modal guided particle radiotherapy for postoperative breast cancer with different arm position.

PET-CT: Positron Emission Tomography - Computed Tomography CT: Computed Tomography

Prospective Study of Particle Radiotherapy for Breast Cancer With Different Arm Position

Prospective Phase II Randomized Clinical Study of the Accuracy of Multi-modal Guided Particle Radiotherapy for Postoperative Breast Cancer With Different Arm Position

The optical body surface image (C-RAD) was used to guide and track the change of positions, and multimodal images (including 2D X-ray images, CT images and PET-CT images) were used to verify the treatment positions. In order to explore the accuracy of breast cancer patients' treatment positions and its impact on dose of the new fixation device in two different fixed positions of arm up and arm down, optimize the position fixed equipment and methods of particle radiotherapy for breast cancer, and then establish the precision process of particle radiotherapy for breast cancer under the guidance of multimodal images.

Acute toxicities assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03

Late toxicities assessed by Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European organization for research and treatment of cancer (EORTC)

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
Observation and Evaluation of Short-term Curative Effect of Local Advanced Cervical Cancer Treated With Particle Radiotherapy Versus Neoadjuvant Chemotherapy	NCT03225443	Uterine Cervica... Locally Advance...		-	Shanghai First Maternity and Infant Hospital
Radiotherapy for Locally Advanced Pancreatic Carcinomas (Phase II Trial)	NCT05191940	Pancreas Cancer	Particle-therap... Blood sampling Magnetic resona... Computertomogra... 18-F-FluorDesox...	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
Prospective Study of Particle Radiotherapy for Breast Cancer With Different Arm Position	NCT05878678	Breast Cancer	Fixed positions...	18 Years - 80 Years	Shanghai Proton and Heavy Ion Center
Radiotherapy for Locally Advanced Pancreatic Carcinomas (Phase II Trial)	NCT05191940	Pancreas Cancer	Particle-therap... Blood sampling Magnetic resona... Computertomogra... 18-F-FluorDesox...	18 Years -	EBG MedAustron GmbH
Observation and Evaluation of Short-term Curative Effect of Local Advanced Cervical Cancer Treated With Particle Radiotherapy Versus Neoadjuvant Chemotherapy	NCT03225443	Uterine Cervica... Locally Advance...		-	Shanghai First Maternity and Infant Hospital
Radiotherapy for Locally Advanced Pancreatic Carcinomas (Phase II Trial)	NCT05191940	Pancreas Cancer	Particle-therap... Blood sampling Magnetic resona... Computertomogra... 18-F-FluorDesox...	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 particle radiotherapy