Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Immune System Diseases

Breast Neoplasms

Hypersensitivity

Breast Diseases

Skin Diseases

In cohort A, for patients with high and undetermined risk of fibrosis (bf+), an adaptive BC RT (ETHOS) will be delivered.

In cohort B, for patients with low risk of fibrosis (bf-), an IMRT will be delivered.

• Cohort A: Adaptive RT: PTV = CTV + 2 mm (except for IMC with 5mm), excluding 5mm beneath the skin

Treatment ETHOS radiotherapy

• Cohort B: IMRT: PTV = CTV + 7mm, excluding 5mm beneath the skin

Conventional IMRT

MOUSSION AURORE

BOURGIER CELINE

ARNAUD ANTOINE

* Prospective, open-label, bi-center study, assessing the clinical outcomes of adaptive breast radiotherapy with ETHOS in hypersensitive patients.
* Bi-centric with ETHOS center : ICM (Institut du Cancer de Montpellier) and ISC (Institut Sainte Catherine) Avignon
* 500 patients will be included:
* COHORTE A = Treatment ETHOS RT :46 evaluable patients with high risk of LRR and bf+ risk
* COHORT B = Conventional IMRT : 454 others patients with high risk of LRR and bf- risk

1. Breast cancer (BC) patients with high risk of severe radio-induced side effects

   Severe but also moderate toxicities after curative-intent radiotherapy (RT), such as fibrosis, retraction or telangiectasia can have a negative impact on quality of life and a marked effect on subsequent psychological outcome. A number of factors are known to increase the risk of radiation toxicity including individual radiosensitivity. While toxicity risks for populations of patients are known, the determination of an individual's normal tissue radiosensitivity is seldom possible before treatment.

   Therefore, current practice standards commonly prescribe radiation dose according to clinical scenarios, without regard to the genotype or phenotype of the individual being irradiated.

   In that context, several teams have developed and validated prospectively or retrospectively (a rapid (72 h) radiosensitivity assay based on flow cytometric assessment of radiation-induced CD8 T-lymphocyte apoptosis (RILA).

   An excellent negative predictive value was found in the case of high RILA value and grade 0-1 late toxicity in breast cancers.

   In addition, all severe side-effects (grade ≥2) were observed in patients with low values of RILA.

   Recently, the REQUITE consortium aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy.

   This international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017.

   RILA assay data were available for 1319 patients. More recently, at the last ESTRO Annual Meeting in Milan (April 2019), this Consortium found that low RILA was associated with long-term side effects such breast fibrosis (bf+) after adjuvant BC radiotherapy.

   The median value of RILA was 9.51% in patients with grade ≥2 bf+ (n=17) vs. 17.15% in patients without toxicity (n=631), p=0.003. In the meantime, the German team presented results from a large prospective ISE cohort with a very long-term follow-up (median FU=11.6 years). High RILA values were inversely correlated with the risk of fibrosis (p=0,011) and telangiectasia (p\<0.001). Univariate ROC analysis and multivariate analysis showed higher AUC and c-stat values outside than within the surgical area.

   With a level one of clinical evidence, the RILA assay is recommended by the French guidelines since 2022. The RILA assay has now clear potential to be a useful biomarker for selecting individuals likely to display an increased probability of toxicity to RT. A French Company (NovaGray) now industrializes this assay (NovaGray RILA Breast®).
2. BC patients with high risk of locoregional relapse (LRR)

   Node positive (pN+) patients after breast conserving surgery (BCS) and adjuvant systemic therapies had a high risk of LRR (among 16%) with most of LRR which occurred within 5 years.

   Significant improvements of distant free survival (DFS) were observed in case of regional nodes irradiation in large phase III trials: the EORTC 22922/10925 trial and the MA20 trial. In addition, adjuvant postmastectomy radiotherapy (PMRT) is a standard of care after radical mastectomy in case of nodal involvement as chest wall and regional nodes irradiation reduced both recurrence and breast cancer mortality in particular in BC patients with one to three positive lymph nodes even when systemic therapy was given.

   Therefore, there is a need in those pN+ BC patient's population to well cover planning target volume (PTV) of whole breast (WB) or chest wall (CW) and regional nodes. Intensity-modulated radiotherapy (IMRT) is an appropriate technique to that end.
3. Personalized radiotherapy in BC patients with high risk of LRR and bf+ risk

The present study aimed to assess acute and late toxicities after adaptive radiotherapy ETHOS in high risk of LRR and hypersensitive breast cancer (bf+ BC) patients.

The investigators propose, in high risk of LRR/ bf+ BC patients, to reduce PTVs thanks to ETHOS technology, an adaptive image-guided IMRT radiotherapy.

Usually, PTVs are generated by adding 7 mm-margins around CTVs. By decreasing intrafraction variability, PTV margins could be significantly reduced closed to clinical target volume (CTV). Therefore, target volumes will be significantly reduced.

In an adaptive radiotherapy a new plan is generated every fraction based on the organ and clinical target volume (CTV) delineations of that fraction. With these daily adaptations, inter fractions modifications are taken into account.

The hypothesis is therefore that acute and late RT side effects occurring after ETHOS adaptive RT in bf+ BC patients will not be superior than those obtained after IMRT RT in BC non-hypersensitive patients.

This hypothesis is based on a personalized approach (driven by a predictive assay of late effects to select patients with high and undetermined risk toxicity: for each patient, NovaGray will provide a report including the result of the NovaGray RILA Breast® test as well as a binary risk category (low risk or undetermined risk or high risk).

* COHORTE A = Treatment ETHOS RT :46 evaluable patients with high risk of LRR and bf+ risk
* COHORT B = Conventional IMRT : 454 others patients with high risk of LRR and bf- risk

SAHARA-04 : Adaptive Radiotherapy in Hypersensitive Patients and High Locoregional Risk Breast Cancer With ETHOS Technology

Adaptive Radiotherapy in Hypersensitive Patients and High Locoregional Risk Breast Cancer With ETHOS Technology

A toxicity of grade 2 and more is defined as an observation of grade 2 and more, in case of late toxicities it should be at least confirmed by two consecutive visits.

acute toxicity is defined as side effects observed from the start of RT to 12 weeks post RT, according to NCI-CTCAE v5. Late toxicity is defined as side effects observed from 12 weeks post RT to 3 years post RT, according to NCI-CTCAE v5

score obtained by assessed questionnaires

LRR will be deducted from the local recurrence survival defined as the interval between date of inclusion and the occurrence of local relapse. Patients without relapse at the analysis will be censored at the date of last follow-up

RFS is defined as the interval between date of inclusion and the occurrence of relapse. Patients without relapse at the analysis will be censored at the date of last follow-up

Time to severe RT toxicities is defined as the interval between date of inclusion and the occurrence of radio-induced Gr2+ toxicities (i.e. event). Patients without event at the analysis will be censored at the date of last follow-up.

OS is defined as the interval between date of inclusion and the occurrence of death, due to any cause. Patients alive at the analysis will be censored at the date of last follow-up

Institut du Cancer de Montpellier - Val d'Aurelle

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

In this study, consenting and eligible patients will receive a prescription dose of 55 Gy in 5 fractions delivered on consecutive business days with adaptation based on daily anatomic changes as per clinical standard of care.

Fractions will be delivered on consecutive business days.

Computed tomography-guided stereotactic adaptive radiotherapy

ETHOS is a unique ring-gantry CT-guided linear accelerator notable for having an on-board cone beam CT (CBCT) imaging unit with improved definition and resolution to enable target and organ-at-risk contouring. It also has a dedicated artificial intelligence treatment planning system to allow for online adaptive radiotherapy.

ETHOS

Pamela Samson, M.D., MPHS

Joshua Schiff, M.D.

Eric Laugeman, M.S.

Xiaodong Zhao, Ph.D.

Yi Huang, M.S.

This study will evaluate the impact of CT-guided adaptive stereotactic radiotherapy (CT-STAR) to central and ultra-central early-stage non-small cell lung cancers on grade 3 or greater toxicity. Online adaptive radiation therapy was until recently only done clinically on an integrated MRI-guided system, but recently, Varian Medical Systems has created a CT-guided radiotherapy machine capable of online adaptive radiotherapy (ETHOS). The vast majority of stereotactic body radiotherapy (SBRT) for early-stage lung cancers is performed on a CT-guided machine rather than an MRI-guided machine, necessitating the evaluation of adaptive radiotherapy using ETHOS in this population. Historically, the non-adaptive, stereotactic treatment of central and ultra-central thoracic disease has been associated with unacceptable rates of grade 3+ toxicity. This has resulted in widespread adoption of a hypofractionated, less ablative 8-15 day treatment courses, with a baseline, one-year grade 3+ toxicity rate of 20%. Use of CT-STAR with daily, CT-guided plan adaptation to carefully spare adjacent organs-at-risk (OAR) in this setting may enable safe delivery of a shorter (5 fraction) and more ablative radiotherapy course.

Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (CT-STAR) for the Treatment of Central and Ultra-Central Early-Stage Non-Small Cell Lung Cancer

A Phase I Trial of Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (CT-STAR) for the Treatment of Central and Ultra-Central Early-Stage Non-Small Cell Lung Cancer

Varian Medical Systems

Washington University School of Medicine

Rare Diseases

Small Cell Lung Carcinoma

Small Cell Lung Cancer

-Radiotherapy will consist of stereotactic body therapy, to be given over five fractions, delivered once daily or once every other day for a period of one to two weeks, for a total of five treatments.

Ring-gantry CT-guided radiotherapy unit, pairing a linear accelerator within a ring-gantry imaging unit.

All participants will be initially planned to at least 35 Gy in 5 fractions, subject to hard constraints based on the treatment site.

CT-guided stereotactic adaptive radiotherapy

Motion during radiation therapy can be categorized as inter-fraction (changes in anatomy that occur between treatment days) and intra-fraction (changes that occur during the "beam on" window of treatment delivery). Inter-fraction motion is managed by adaptive radiotherapy (ART), the process of making changes in the treatment plan while the patient remains on the treatment table. This is now a standard-of-care therapy within Washington University's clinic. Intra-fraction motion is managed by gated and non-gated delivery techniques. Varian Medical Systems has integrated the necessary components into a CT-guided radiotherapy device (ETHOS). In the ETHOS, Varian has built a device that integrates on-board cone beam CT imaging capable of delineating target and organ-at-risk positions and a dedicated artificial intelligence-driven treatment planning system for inter-fraction motion management as well as a paired optical surface image guidance system for intra-fraction motion management. Although online ART is a standard-of-care practice in the clinic and has previously been shown to be feasible, use of surface-guidance for intra-fraction gating of abdominal and thoracic SBRT on ETHOS is novel.

Therefore, in this study, the investigators propose to evaluate the feasibility and safety of using a novel surface guidance beam-gating system, incorporated with a CBCT-guided adaptive radiotherapy platform, to manage respiratory motion during delivery of CT-guided stereotactic radiotherapy. To best assess the utility of this technology to manage respiratory motion, the investigators will focus on disease sites that are highly affected by respiratory motion: upper abdominal or lower thoracic malignancies.

Novel Optical Surface Image Guidance System for Beam-Gated Online Adaptive SBRT Delivery in Mobile Lower Lung and Upper Abdominal Malignancies

Pilot Study of a Novel Optical Surface Image Guidance System for Beam-Gated Online Adaptive SBRT Delivery in Mobile Lower Lung and Upper Abdominal Malignancies

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) that will be used for individual participant data meta-analysis.

Success will be defined as delivery of a given treatment fraction in one on-table attempt, without requiring use of a secondary (backup) motion management system, or alternative treatment machine. Unsuccessful delivery of a fraction will be defined as multiple attempts for gating without reproducible positioning, breath-hold, and/or surface guidance feedback, such that the fraction is abandoned.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SAHARA-04 : Adaptive Radiotherapy in Hypersensitive Patients and High Locoregional Risk Breast Cancer With ETHOS Technology	NCT06053086	Breast Cancer	Treatment ETHOS... Conventional IM...	18 Years -	Institut du Cancer de Montpellier - Val d'Aurelle
Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (CT-STAR) for the Treatment of Central and Ultra-Central Early-Stage Non-Small Cell Lung Cancer	NCT05785845	Early Stage Non... Non-small Cell ...	Computed tomogr... ETHOS	18 Years -	Washington University School of Medicine
Novel Optical Surface Image Guidance System for Beam-Gated Online Adaptive SBRT Delivery in Mobile Lower Lung and Upper Abdominal Malignancies	NCT05030454	Any Solid Malig...	ETHOS CT-guided stere...	18 Years -	Washington University School of Medicine
SAHARA-04 : Adaptive Radiotherapy in Hypersensitive Patients and High Locoregional Risk Breast Cancer With ETHOS Technology	NCT06053086	Breast Cancer	Treatment ETHOS... Conventional IM...	18 Years -	Institut du Cancer de Montpellier - Val d'Aurelle

Spots Global Cancer Trial Database for ethos

Every month we try and update this database with for ethos 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.

Spots Global Cancer Trial Database for ethos

Every month we try and update this database with for ethos 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 ethos 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.