Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Breast Neoplasms

Neoplasm Metastasis

Brain Neoplasms

Breast Diseases

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Conventional whole-brain radiotherapy for brain metastases from breast cancer with dose of 37.5 Gy in 15 fractions.

Hippocampal-sparing whole brain radiotherapy is performed using modern intensity-modulated radiotherapy (IMRT) technique to avoid conformally the hippocampal neural stem-cell structure during WBRT. Prescription dose is 37.5 Gy in 15 fractions.

whole brain radiotherapy

Zheng Jiang

Bing Sun, M.D.

Based on evidence that radiation-induced damage to the hippocampus plays a considerable role in neurocognitive decline after cranial irradiation, hippocampal-sparing whole brain radiation therapy (HS-WBRT) has been proposed. This study will investigate the neurocognitive function and prognosis between HS-WBRT and conventional WBRT for the treatment of brain metastases from breast cancer.

Hippocampal-sparing Whole Brain Radiotherapy for Brain Metastases From Breast Cancer

Whole Brain Irradiation With Hippocampal Sparing for Brain Metastases From Breast Cancer: Neurocognitive Function and Prognosis Analysis

delayed recall using Hopkins Verbal Learning Test

Affiliated Hospital to Academy of Military Medical Sciences

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Small Cell Lung Carcinoma

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Irradiation HA-PCI concomitant to the second cycle of CHT and to tRT for patients with LD SCLC

25 Gy in 10 daily factions, five times a week

Irradiation: HA-PCI

Francesca Caparrotti, MD

The main objective of this trial is to assess NCF after early HA-PCI concomitant to the second cycle of CHT and to tRT for patients with LD SCLC.

About 15% of all lung cancers are small cell lung cancer (SCLC). SCLC is a high-grade, neuroendocrine carcinoma of the lung. Limited disease (LD) SCLC is confined to the hemithorax of origin, the mediastinum, or the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port. About 30% of all SCLC are LD at diagnosis. The median overall survival (OS) in LD SCLC is approximately 20 months, with an expected 5-year survival of less than 15%.

SCLC is characterized by rapid growth and early dissemination. The standard treatment of LD SCLC involves multimodality therapy with concurrent thoracic radiotherapy (tRT) and chemotherapy (CHT) with cisplatin and etoposide.

Recurrence in the brain is usually the primary site of treatment failure in SCLC and is associated with significant morbidity; and consequently often the cause of death. Occult early dissemination of SCLC has frequently occurred prior to the time of diagnosis. In patients with brain metastasis two randomized trials showed an overall 5-year rate of brain metastasis of 59% without prophylactic cranial irradiation (PCI) compared to 43% with PCI. However the rate of brain metastasis with PCI is still very high.

About 50% of patients with SCLC will develop brain metastases some time during the course of their disease. Therefore PCI is recommended in case of good response to CHT and tRT. PCI has shown to improve overall survival in patients with LD who have achieved a complete or partial remission after initial chemoradiotherapy. CHT might achieve insufficient drug levels in the brain. Therefore, an up-front PCI could treat occult brain metastases at a preclinical state and may increase the permeability of the blood-brain barrier for CHT products.

When evaluating PCI it is important to weigh the reduced incidence of brain metastases against the potential risk of deficits resulting from the treatment itself, including deteriorations in neurocognitive functions (NCF) or quality of life (QoL).

A possibility to reduce long-term neurocognitive effects due to PCI is the sparing of the hippocampus. Recent technological advancements in radiation oncology delivery enable the avoidance of the hippocampus. A PCI with hippocampus avoidance (HA-PCI) can reduce memory loss due to radiation.

Prospective neurocognitive testing has been increasingly used in trials for patients with CNS tumors and in patients with brain metastases in order to determine the risks versus benefits of different treatment approaches. For this trial, the choice for NCF assessments follows the recommendation provided by Meyers and Brown (2006). This neurocognitive battery for the use in multinational drug trials with neurocognitive endpoints consists of four standardized psychometric instruments, i.e. the Hopkins Verbal Learning Test, the Controlled Oral Word Association Test (COWAT) and the Trail Making Part A and Part B (TMT A/B). These tests have been shown to be sensitive to the neurotoxic effects of cancer treatment in clinical trials and cover several cognitive functions (memory, verbal fluency, visual-motor speed, executive function). In addition, published normative data are available that take into account age, and where appropriate, education and sex. To minimize the effects of repeated administration alternate forms can be used and test administration is highly standardized. The same battery of tests has been used in trials conducted by the Radiation Therapy Oncology Group (RTOG) (e.g. Wolfson 2011), and one or several of these three tests were applied in most of the studies mentioned above. Using the same tests across trials is important in order to be able to compare results of different trials. It has been shown that performing a cognitive test battery consisting of five cognitive tests (and a QoL assessment) in a multi-site trial and cooperative group setting (i.e. a RTOG trial) in patients with brain metastases is feasible.

NCF can be affected by a number of factors such as the volume of brain metastases, disease progression, other treatments (e.g. surgery, chemo- or endocrine therapy), medications and psychological factors such as anxiety and distress. These factors should be considered when evaluating the actual neurocognitive effect of concomitant CHT, tRT and PCI.

Rationale for performing the trial PCI is part of the standard treatment of LD SCLC as the rate of developing brain metastases is very high and PCI has shown to increase overall survival. PCI is given to patients presenting a good response to CHT and tRT. However the overall 5-year rate of brain metastasis with PCI is still very high.

As long as safety data are lacking on PCI administered concurrently with CHT and tRT, PCI is given after the end of CHT in the clinical practice. Therefore the aim of this phase II trial is to evaluate to what extent early HA-PCI given concomitant to CHT and tRT impairs NCF and whether this neurotoxicity can be considered acceptable to evaluate this question in a phase III trial.

Early Hippocampal Avoidance Prophylactic Cranial Irradiation in Patients With LD SCLC

Early Prophylactic Cranial Irradiation With Hippocampal Avoidance in Patients With Limited Disease Small-cell Lung Cancer. A Multicenter Phase II Trial

NCF at 6 months after end of HA-PCI treatment measured by Hopkins Verbal Learning Test Revised (HVLT-R), Controlled Oral Word Association (COWAT) and Trail Making Test Part A and B (TMT A/B). A neurocognitive decline is defined as a decrease of one standard error of measurement (SEM) in any of the four NCF tests.

Neurotoxicity according to NCI CTCAE version 4.0

Swiss Group for Clinical Cancer Research

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Behaviors and Mental Disorders

Recurrence

Melanoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Second Primary

Quality of Life

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

* MRI will be performed prior to radiation is administered
* A hippocampal sparing approach will be used when possible
* Dose will be 30 Gy in 10 fractions

* MRI will be performed prior to radiation is administered
* Radiation will be given in 1-5 fractions (dose depends on the size of the tumor that will be treated)

Treatment of the whole brain with radiation. When possible the hippocampus will be spared from radiation.

Whole brain radiation

Focused radiation to each individual brain metastasis without treatment of the remainder of the brain.

Stereotactic radiation (SRS)

Ayal Aizer, MD

Ivy Ricca, BA

Ayal Aizer, MD MHS

This research study is studying two different types of radiation as treatment for brain metastases (tumors in the brain that spread from a cancer that originated elsewhere in the body)

This research study is a Phase III clinical trial. Phase III clinical trials examine the safety and effectiveness of a treatment, often comparing it to another known treatment. In this case, the investigators are specifically looking at differences between two forms of radiation treatment in terms of subsequent quality of life.

In this research study, the investigators are comparing stereotactic (focused, pinpoint) radiation (in which each tumor is narrowly targeted) against whole brain radiation (radiation targeting the entire brain) in the treatment of brain metastases. Currently whole brain radiation is the standard option for patients with 5-20 brain metastases. Stereotactic radiation is the standard option for patients with 1-4 brain metastases. Among patients with 1-4 brain metastases, recently published studies suggest that stereotactic radiation results in fewer neurologic side effects than whole brain radiation. It also yields better quality of life in this population. It remains unknown whether stereotactic radiation improves quality of life in patients with 5-20 brain metastases relative to whole brain radiation. In this study, the investigators seek to determine which of the two methods of study treatment results in a better subsequent quality of life for patients with 5-20 brain metastases.

Hippocampal Sparing Whole Brain Radiation Versus Stereotactic Radiation in Patients With 5-20 Brain Metastases: A Phase III, Randomized Trial

Hippocampal Sparing Whole Brain Radiation Versus Stereotactic Radiation (SRS) in Patients With 5-20 Brain Metastases: A Phase III, Randomized Clinical Trial

Questionnaire - MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT)

Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic)

Radiographic assessment of first appearance of new brain metastases

Radiographic assessment of first local recurrence in the 5-20 brain metastases that were initially treated with radiation

Radiographic assessment of first appearance of radiation necrosis

Radiographic assessment of first appearance of leptomeningeal disease

Clinical assessment of first use of neurosurgical resection as salvage therapy

Clinical assessment of first use of salvage brain-directed radiation

Clinical assessment of first post-treatment seizure as assessed during routine study visits and via medical record review

Questionnaire - Karnofsky performance status

Brigham and Women's Hospital

Dana-Farber Cancer Institute

Principal Investigator

Hippocampal avoiding Whole brain radiation therapy (HA-WBRT) with volumetric modulated arc therapy (VMAT) with a simultaneously integrated boost (SIB) to each brain metastasis

Single session or hypofractionated stereotactic radiosurgery (SRS) of multiple brain metastases

Hippocampal avoiding Whole brain radiation therapy (HA-WBRT) with volumetric modulated arc therapy (VMAT) with a prescribed dose of 30Gy in 12 fractions, 2.5Gy per fraction and a simultaneously integrated boost (SIB) to each brain metastasis of 51Gy to 95% of PTV in 12 Fractions, 4.25Gy per fraction.

Hippocampal Avoiding Whole Brain Radiation Therapy with Simultaneous Integrated Boost

Single session or hypofractionated stereotactic radiosurgery (SRS) of multiple brain metastases. Single session SRS will be delivered in 18 to 22Gy to the tumour encompassing 80% Isodose. Hypofractionated stereotactic radiosurgery (HfSRS) will be delivered in 5 sessions of 6Gy each to the tumour encompassing 80% isodose.

Single session or hypofractionated stereotactic radiosurgery

Julian Mangesius, MD

Ute Maria Ganswindt, MD, PhD

This study compares the effectiveness and safety of two radiation treatment techniques for patients with multiple brain metastases.

For patients suffering from multiple brain metastases whole brain radiation therapy still constitutes a standard therapy. However, because of the risk of neurocognitive side effects as well as reduced local tumor control, employment of stereotactic radiosurgery (SRS) is becoming more common. The disadvantage of SRS alone may be poor intracranial tumor control because of frequent appearance of new distant brain metastases after therapy. In recent years hippocampal avoidance whole brain therapy has been shown to minimize treatment related side effects while reducing the rate of distant intracranial failure.

In this study patients will be randomized to receive either hippocampal avoidance whole brain radiation therapy with integrated tumor boost (HA-WBRT+SIB) or stereotactic radiosurgery. The investigators hypothesize that HA-WBRT+SIB can improve intracranial tumor control compared to stereotactic radiosurgery, while avoiding additional neurocognitive side effects.

HA-WBRT vs SRS in Patients With Multiple Brain Metastases

Hippocampal Avoidance Whole Brain Radiotherapy (HA-WBRT) and Stereotactic Radiosurgery (SRS) in Patients With Multiple Brain Metastases

survival with freedom from both local and distant intracranial progression, measured in months from end of treatment until progression or death, assessed in follow-up imaging (MRI, FET-PET)

Change of z-scores of VLMT (Verbaler Lern- und Merkfähigkeitstest) to baseline examination

Change of z-scores of COWAT (controlled oral word association test) to baseline examination

Change of z-scores of TMT (trail making test) to baseline examination

rate of progression of treated metastases assessed in follow-up imaging (MRI, FET-PET)

Change in Quality of Life Score of EORTC QLQ-C30 (Quality of life core module) relative to baseline

Change in Quality of Life Score of QLQ-BN20 (quality of life brain cancer module) relative to baseline

Medical University Innsbruck

Patients with lung cancer and brain metastases undergo HA-WBRT-SIB using image-guided radiotherapy, receiving a total dose of 30-36 Gy delivered in 18-20 fractions to the whole brain (CTV), while the dose to the GTV is boosted to 44 Gy-52 Gy in 18-20 fractions, ﬁve times a week. The optimal mean dose (Dmean) to the bilateral hippocampus should optimally be ≤ 8 Gy, with a mandatory maximum dose (Dmax) to the hippocampus not exceeding 10 Gy; the preferred Dmean to the hippocampus PRV should optimally be ≤ 9 Gy, while the mandatory Dmax to the hippocampus PRV should be ≤ 12 Gy. The HVLT-R immediate recall scores are obtained at baseline and 1, 3, and 6 months after treatment.

A total dose of 30-36 Gy delivered in 18-20 fractions to the whole brain (CTV), while the dose to the GTV were boosted to 44 Gy-52 Gy in 18-20 fractions, ﬁve times a week.

HA-WBRT-SIB

HA-WBRT-SIB for Brain Metastasis of Lung Cancer

Hippocampal Avoidance Whole Brain Irradiation With Simultaneous Integrated Boost for the Treatment of Lung Cancer Brain Metastases：A Prospective Phase II Study

the time from the end of brain radiotherapy to death from any cause

the time from the end of brain radiotherapy to tumor progression or death from any cause

the time from the end of brain radiotherapy to intracranial tumor progression or death from any cause

The HVLT scores were calculated as the sum of trials 1, 2, and 3

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hippocampal-sparing Whole Brain Radiotherapy for Brain Metastases From Breast Cancer	NCT03002532	Breast Cancer M... Brain Metastase...	whole brain rad...	18 Years - 75 Years	Affiliated Hospital to Academy of Military Medical Sciences
Early Hippocampal Avoidance Prophylactic Cranial Irradiation in Patients With LD SCLC	NCT02058056	Small-Cell Lung...	Irradiation: HA...	18 Years - 75 Years	Swiss Group for Clinical Cancer Research
Hippocampal Sparing Whole Brain Radiation Versus Stereotactic Radiation in Patients With 5-20 Brain Metastases: A Phase III, Randomized Trial	NCT03075072	Brain Metastase...	Whole brain rad... Stereotactic ra...	18 Years - 80 Years	Dana-Farber Cancer Institute
HA-WBRT vs SRS in Patients With Multiple Brain Metastases	NCT04277403	Brain Metastase...	Hippocampal Avo... Single session ...	18 Years -	Medical University Innsbruck
HA-WBRT-SIB for Brain Metastasis of Lung Cancer	NCT06289023	Lung Neoplasm Brain Metastase... Simultaneous In... Hippocampal Avo... Cognitive Funct...	HA-WBRT-SIB	18 Years - 75 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences
HA-WBRT vs SRS in Patients With Multiple Brain Metastases	NCT04277403	Brain Metastase...	Hippocampal Avo... Single session ...	18 Years -	Medical University Innsbruck

Spots Global Cancer Trial Database for hippocampal avoidance