Symptoms and General Pathology

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Recurrence

Breast Neoplasms

Disease Attributes

In this cohort, the patients with low risk of recurrence and a low risk of breast toxicity

For this cohort, patients with low risk of recurrence and a high risk of breast toxicity, will receive breast radiotherapy according to the investigator's decision among:

* External partial VMAT: 40 Gy in 15 fractions to the partial breast only (tumorectomy bed).
* Exclusive Brachytherapy: 30.1 Gy in 7 fractions or 32.0 Gy in 8 fractions of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days.
* Whole Breast Normo fractionated IMRT with Fixed Field IMRT Technique: 50 Gy in 25 daily fractions over 5 weeks +/- Sequential (+ 16 Gy/8fr) or SIB (60 Gy/25 fr) treatment for boost if applicable.

For this cohort, patients with high risk of recurrence and a low risk of breast toxicity, will receive whole breast and nodes Hypofractionated VMAT and a localized simultaneous boost according to the HypoG01 schema protocol:

VMAT Technique, 42.3 Gy in 18 fractions on all target volume on 3.5 weeks +/- SIB boost if need (52.2Gy in 18 fractions).

For this cohort, patients with high risk of recurrence and a high risk of breast toxicity, will receive breast radiotherapy based on available clinical trials:

- Whole Breast and Nodes Hypofractionated VMAT with adaptive treatment (margin reduction): HypoG01 Schema with VMAT Technique, 42.3 Gy in 18 fractions on all target volume over 3.5 weeks +/- SIB boost if need (52.2Gy in 18 fr) In case of patient refusal or technique unavailable, a standard treatment available in the center for this indication will be delivered.

IMRT radiotherapy on whole breast according to the investigator's decision among:

* Moderate whole breast hypofractionated RT according to the START B schema with Fixed Field IMRT Technique: 40.05 Gy in 15 daily fractions over 3 weeks and a Sequential boost (+ 16 Gy/8 fr) or (+13.5/5 fr) if applicable.
* Extreme whole breast hypofractionated RT according to :

  * The FAST schema: Once-a-week ultra-HypoRT with Fixed Field IMRT Technique, 28.5 Gy in 5 fractions in 5 weeks
  * The FAST-Forward schema: Very accelerated course of HypoRT with Fixed Field IMRT Technique, 26 Gy in 5 fractions in 5 consecutive days

COHORT A

Breast radiotherapy according to the investigator's decision among:

* External partial VMAT: 40 Gy in 15 fractions to the partial breast only (tumorectomy bed).
* Exclusive Brachytherapy: 30.1 Gy in 7 fractions or 32.0 Gy in 8 fractions of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days.
* Whole Breast Normo fractionated IMRT with Fixed Field IMRT Technique: 50 Gy in 25 daily fractions over 5 weeks +/- Sequential (+ 16 Gy/8fr) or SIB (60 Gy/25 fr) treatment for boost if applicable.

COHORT B

Whole breast and nodes Hypofractionated VMAT and a localized simultaneous boost according to the HypoG01 schema protocol:

VMAT Technique, 42.3 Gy in 18 fractions on all target volume on 3.5 weeks +/- SIB boost if need (52.2Gy in 18 fractions).

COHORT C

Breast radiotherapy based on available clinical trials:

- Whole Breast and Nodes Hypofractionated VMAT with adaptive treatment (margin reduction): HypoG01 Schema with VMAT Technique, 42.3 Gy in 18 fractions on all target volume over 3.5 weeks +/- SIB boost if need (52.2Gy in 18 fr) In case of patient refusal or technique unavailable, a standard treatment available in the center for this indication will be delivered.

COHORT D

MOUSSION AURORE

AZRIA DAVID

MEGE ALICE

BRETON-CALLU CHRISTEL

Our objective is based on a personalized approach of adjuvant breast radiotherapy by selecting patients according to tumor recurrence and toxicity risk.

Breast cancer is the most common cancer in women in the world and remains a major public health burden with 25% of all cancer cases and 15% of all cancer deaths among females1. The Incidence has increased with the introduction of mammography screening and continues to rise, mainly due to population aging; meanwhile, breast cancer survival has significantly improved over the past decades.

Adjuvant radiotherapy (RT) is an essential component of the treatment. After breast surgery for invasive carcinoma, RT is commonly used and delivered without considering the different tumor subtypes, unless the node involvement risk, because it decreases the rate of local recurrence and by this way, specific mortality. The " one size fits all " approach is widely applied, with two main options: breast or chest wall only radiotherapy or breast or chest wall plus nodes radiotherapy. Rare are the centers that discuss IMRT use, external partial breast irradiation, adaptive breast necessity, etc....

1. Breast cancer and loco-regional recurrence risk Ten-year cancer specific survival exceeds 70%, with 89% survival for local and 62% for regional disease1. The risk of recurrence is high during the first two years after the initial diagnosis for patients with hormonal receptor (HR)-negative breast cancer, but rapidly decreases below the recurrence risk of HR-positive tumors2.

   Loco-regional recurrence (LRR) occurs in 5-15% of cases treated with breast conservative surgery (BCS) plus adjuvant radiotherapy (RT) or mastectomy3-5 and is considered an independent poor prognostic factor6. The management of LRR requires a multidisciplinary approach7. Total mastectomy is the standard of care for isolated LRR after BCS. However, secondary BCS ± RT is an alternative approach that could be discussed case by case7.

   Parameters to predict the risk of recurrence are those included in the NHS UK updated PREDICT score such as age, node status, tumor grade, proliferation index, Her2 and hormone receptor expression8.
2. Adjuvant breast radiotherapy and subcutaneous toxicity probability Severe but also moderate toxicities after curative-intent radiotherapy (RT), such as fibrosis, retraction or telangiectasia with poor cosmetic outcome can have a negative impact on quality of life following breast cancer and a marked effect on subsequent psychological outcome. Multiple factors are known to increase the risk of radiation toxicity including individual radiosensitivity9. While the toxicity risks for patients are well-established, determining an individual's normal tissue radiosensitivity is rarely possible before treatment.

   Nevertheless, current practice standards often prescribe radiation dose and volume without regard to individual radiosensitivity.

   In that context, a normal tissue radiosensitivity test that includes a rapid (72h) radiosensitivity assay10 based on flow cytometric assessment of radiation-induced CD8 T-lymphocyte apoptosis (RILA) was developed by Ozsahin et al. A prospective study was conducted to determine whether the RILA assay could help identifying patients at high risk of severe toxicities11. The RILA assay was performed in 399 patients with different cancer types before RT. Findings confirmed that patients who developed severe toxicities displayed a compromised apoptotic response.

   More recently, the RILA assay was validated in a prospective multicenter trial with more than 500 patients with breast cancer12. The negative predictive value for grade ≥2 breast fibrosis was 91% for RILA scores ≥20% and the positive predictive value was 22% for RILA scores \<12% (the overall prevalence of grade ≥2 breast fibrosis was estimated at 14%). For the first time, RILA as a continuous variable was significantly associated with toxicities. Recently, the French results have been validated by a prospective European trial with similar predictive values of the RILA13.

   In the CO-HO-RT trial, the RILA assay was used as the main stratification factor and no late toxicity occurred in patients with a RILA score \>16%14.

   In 2022, the RILA assay was included in the French recommendation (RECORAD) as the only validated predictive test for post-radiotherapy toxicity in a large, multi-center, prospective study15.

   Based on these data, the NovaGray RILA Breast® test has been developed and combine both a biological analysis (radio-induced lymphocyte apoptosis) and an algorithmic analysis.

   The NovaGray RILA Breast is an vitro diagnostic medical device (IVMD) pertaining CE-mark. This prognostic test that assesses the risk of developing grade 2+ breast fibrosis at 36 months following radiotherapy. The test is performed on a blood draw and results are provided within a week, which does not delay the beginning of the radiotherapy.
3. Matrix approach according to tumor recurrence and toxicity risk When using a predictive radiosensitivity test in clinical practice, an alternative treatment must be available to the patient in case of an unfavourable result, i.e. an adjustment in the radiotherapy protocol (change in fractionation or total dose), the addition or elimination of a concomitant treatment (e.g. chemotherapy) or the absolute contraindication to radiotherapy in highly radiosensitive patients for whom the treatment-related risk may be greater than the expected benefit.

Based on tumor control probability (TCP) and normal tissue complication probability (NTCP)15,16, we can group the patients into four situations described below.

1. Clinical situation #1 : High TCP / Low NTCP : COHORT A This circumstance is the optimum situation: a high local control probability and a low risk of developing toxicity. In this situation, the total dose of radiotherapy could be limited to the strict necessity since the probability of tumor control is already high. However, alternative fractionations such as moderate hypofractionation can be proposed to shorten the duration of treatment. In breast cancer, a regimen delivering 42.5 Gy in 16 fractions or 40 Gy in 15 fractions can be offered according to the Canadian or UK regimen, respectively17,18. Recently, hypofractionation regimen are becoming more extreme with shorten fractionation regimen over 5 weeks (FAST protocol19) or over 1 week (FAST-forward protocol20). From a radiobiological and economic standpoint, these short regimens can provide a benefit in terms of quality of life with a lower cost of treatment.

   All of them are now included in the recommendations of the French National Society of Radiation Oncology21 and the French National Cancer Institute (INCa, Cancers du sein - Recommandations et outils d'aide à la pratique (e-cancer.fr)). All are considered as an option in daily clinical practice.
2. Clinical situation #2 : High TCP / High NTCP : COHORT B In this situation, the patient is at risk of developing toxicity, but the probability of tumor control is high16). In those cases, possible alternatives to radiotherapy may be discussed such as surgical treatment alone. In breast cancer, this can mean offering total mastectomy for a small tumor (possibly with immediate breast reconstruction) to postpone the indication of adjuvant radiotherapy. For a tumor with a very favorable prognosis, namely after 65 years old, avoiding radiotherapy after breast surgery may also be an option22. In that case, treatment with partial irradiation of the breast (using external technique or brachytherapy) can also be proposed, to improve the long-term cosmetic results, while ensuring good local control23,24.

   All of them are now included in the recommendations of the French National Society of Radiation Oncology21. All are considered as an option in daily clinical practice.
3. Clinical situation #3 : Low TCP / Low NTCP : COHORT C In that situation, the patient is at low risk of developing toxicity but the probability of tumor control is low16. One of the possibilities is to increase the total dose of radiotherapy, namely with a localized boost within the tumor bed in invasive disease 5 and nodes irradiation according to the HypoG trial (ESTRO - Session Item).

   This treatment is also included in the recommendations of the French National Society of Radiation Oncology21.
4. Clinical situation #4 : Low TCP / High NTCP : COHORT D This is the most unfavourable situation, with a radiation-resistant tumor and a patient with a high risk of developing toxicity. Dose de-escalation cannot be proposed to decrease toxicity in such cases, as the risk of tumor recurrence may be too high. Alternative fractionations, such as hyperfractionation (moderate or high depending on the organs at risk) could however be useful by decreasing the risk of toxicity while retaining a satisfactory level of tumor control. These regimens have not been validated and discussions should be carried out on a case-by-case basis. However, the impact on the decrease of toxicity, especially late-onset toxicity, has yet to be demonstrated. If adjusted radiotherapy regimens are not feasible and standard oncological treatment administered, the radioprotection of normal tissue should be discussed using adaptive techniques as it could decrease the risk of toxicity while maintaining good tumor control.

In this specific COHORT, inclusion in a new clinical trial evaluating adaptive treatment will be proposed to the patient. In case of patient refusal or technique unavailable, a standard treatment available in the center for this indication will be delivered.

* COHORT A = Low risk of recurrence / Low risk of breast toxicity
* COHORT B = Low risk of recurrence / High risk of breast toxicity
* COHORT C = High risk of recurrence / Low risk of breast toxicity
* COHORT D = High risk of recurrence / High risk of breast toxicity

Personalization of Breast Radiotherapy According to Loco-regional Recurrence Risk and Toxicity Probability

Toxicity free survival is defined as the interval between date of inclusion and the occurrence of fibrosis grade 2 or more or radio-induced sarcoma. Patients without event at the analysis will be censored at the date of last follow-up.

according to NCI-CTCAE v5 is defined as side effects observed

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 local 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

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.

Prevalence of Radio-induced Breast Sarcoma at 10 years will be estimated using the Kaplan-Meier method, and then described using rate at 10 years with its associated 95% confidence interval.

Institut du Cancer de Montpellier - Val d'Aurelle

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Hormones

Nivolumab

Immunoglobulins

Cohort A

The aim of this study is to evaluate the safety and efficacy of anti PD-1 antibody with radiation therapy in patients with HER2-negative metastatic breast cancer.

Anti PD-1 Antibody With Radiation Therapy in Patients With HER2-negative Metastatic Breast Cancer

Phase Ib/II Study to Assess Efficacy, Safety & Immunological Biomarker of Anti PD-1 Antibody With Radiation Therapy in Patients With HER2-negative Metastatic Breast Cancer

Kyoto Breast Cancer Research Network

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy

Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy

Cohort B

Kevin R. Shiue, MD

This trial is a pilot, Phase 2, sequential two-cohort study designed to test two de-escalated whole brain radiation therapy (WBRT) dose levels and assess their ability to maintain acceptable in-brain distant control. The WBRT dose would decrease as the study moves forward, both in terms of absolute value and equivalent dose in 2 Gray fractions (EQD2) (as determined by the linear quadratic radiobiological model). The absolute value of the simultaneous integrated boost (SIB) dose will change with each dose level because the number of fractions delivered will depend on the WBRT dose. As such, the SIB dose will be manipulated such that the EQD2 will remain essentially equivalent despite the difference in the number of fractions delivered. This design will ensure that the only variable is the change in WBRT dose.

The concept is that WBRT with SIB would be expected to maximize both local and in-brain distant control as has already been shown in studies exploring WBRT with SRS boost. However, by itself WBRT with SIB does not address the concern over neurocognitive outcomes. Therefore, investigators hypothesize that there is a lower WBRT dose threshold that will maintain acceptable in-brain distant control, particularly in the setting of a SIB to gross lesions to maintain treated lesion control. In addition, lower overall brain dose (including lower hippocampal dose without specific hippocampal avoidance) may potentially improve neurocognitive function. Investigators are also interested in evaluating treated lesion control, overall survival, neurocognitive sequelae of therapy, quality of life, performance status, and adverse effects of therapy. Biomarker identification for potential correlative circulating tumor DNA and microRNA is an exploratory endpoint to generate data for future prospective evaluation.

Primary Objective Evaluate two de-escalated whole brain radiation dose levels (in the setting of simultaneous integrated boost to gross lesions) with respect to in-brain distant control for brain metastases, defined as an in-brain failure rate outside of the planning target volume at 6 months of \< 20%.

Secondary Objectives

1. Evaluate treated lesion control at 6 months for brain metastases in the setting of a predetermined total biologically effective SIB dose as determined by radiographic progression within the planning target volume with fusion and overlay of follow-up MRIs.
2. Evaluate overall survival at 6 months for brain metastases in the setting of WBRT with SIB.
3. Evaluate changes in neurocognitive function after WBRT with SIB in the following domains: verbal learning and memory as assessed by the Hopkins Verbal Learning Test - Revised (HVLT-R).
4. Evaluate changes in health-related quality of life as assessed by the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-Br) after WBRT-SIB for brain metastases.
5. Evaluate changes in performance status as assessed by the Karnofsky Performance Status tool after WBRT-SIB for brain metastases.
6. Evaluate adverse events after WBRT-SIB for brain metastases according to current CTCAE criteria.

Pilot Phase 2 Study Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases

A Pilot Phase 2 Study Evaluating Dose De-escalation in Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases

An actuarial 6-month rate of new parenchymal lesions seen outside the planning target volume of any lesion that received SIB on any post-treatment MRI (in all 3 planes)

An actuarial 6-month rate of any new, recurrent, or progressing (as defined by Response Assessment in Neuro-Oncology Brain Metastases criteria) tumor within the planning target volume on any post-treatment MRI

An actuarial 6-month rate of patients still alive regardless of disease status

Total change in score of neurocognitive tests (Hopkins Verbal Learning Test - Revised, Groton Maze, and Two or One Back Test)

Total change in score of health-related quality of life test (Functional Assessment of Cancer Therapy with Brain Subscale)

Total change in performance status score (Karnofsky)

Adverse effects will be defined per CTCAE

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Personalization of Breast Radiotherapy According to Loco-regional Recurrence Risk and Toxicity Probability	NCT06382818	Breast Cancer	COHORT A COHORT B COHORT C COHORT D	18 Years -	Institut du Cancer de Montpellier - Val d'Aurelle
Anti PD-1 Antibody With Radiation Therapy in Patients With HER2-negative Metastatic Breast Cancer	NCT03430479	Breast Cancer	Cohort A	20 Years -	Kyoto Breast Cancer Research Network
Anti PD-1 Antibody With Radiation Therapy in Patients With HER2-negative Metastatic Breast Cancer	NCT03430479	Breast Cancer	Cohort A	20 Years -	Kyoto Breast Cancer Research Network
Pilot Phase 2 Study Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases	NCT03189381	Brain Metastase...	Cohort A Cohort B	18 Years -	Indiana University

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Spots Global Cancer Trial Database for cohort a

Every month we try and update this database with for cohort a 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 cohort a 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.