Brain Metastases, Small Cell Lung Cancer
Conditions
Keywords
Small Cell Lung Cancer, Brain Metastases, Brain metastasis, Lung cancer, Stereotactic radiation, Stereotactic radiosurgery, SRS, Stereotactic, Radiation, Quality of life, Neurocognitive, Neurocognition
Brief summary
This research study is studying stereotactic radiation (focused/pinpoint radiation that targets each individual tumor but not the surrounding brain) instead of whole-brain radiation (radiation targeting the entire brain) as a possible treatment for patients with small cell lung cancer and 1-10 brain metastases. The intervention involved in this study is: -Stereotactic (focused, pinpoint) radiation
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational treatment, in this case stereotactic radiation, to learn whether this treatment works in treating a specific disease. "Investigational" means that the treatment is being studied. In patients with a limited number of brain metastases (spread of a cancer that started outside of the brain to the brain itself) the standard radiation option is stereotactic radiation, which involves using a high dose of radiation that only targets the specific metastases that are visible on imaging of the brain, not the whole brain itself. However, studies evaluating the role of stereotactic radiation to treat brain metastases generally excluded patients with small cell lung cancer. Therefore, among patients with small cell lung cancer and brain metastases, the typical treatment that has been offered is whole brain radiation. However, whole brain radiation has deleterious associated side effects including significant fatigue and permanent memory/attention problems. The investigators are studying whether stereotactic radiation can be effectively utilized for patients with small cell lung cancer and brain metastases in order to avoid such side effects.
Interventions
RADIATIONStereotactic Radiation
Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have a biopsy-proven tumor consistent with small cell lung cancer and intracranial lesions radiographically consistent with or pathologically proven to be brain metastases. Patients who have undergone prior systemic therapy are eligible. Patients who have undergone resection of one or more brain metastases but who have not yet started adjuvant radiotherapy are eligible for the study. * 1-10 definitive intracranial lesions must be present on MRI of the brain. * Age \>=18 years at diagnosis of brain metastases.
Exclusion criteria
* Participants who have undergone prior radiation for brain metastases. * Participants who have received prophylactic cranial radiation for prevention of brain metastases * Participants who cannot receive gadolinium * Participants with stage IV-V chronic kidney disease or end stage renal disease * Participants with widespread, definitive leptomeningeal disease * Participants with a maximum tumor diameter exceeding 5 cm (if not resected) * Participants with \>6 definitive lesions consistent with brain metastases * Participants with inadequate mental capacity to complete quality of life questionnaires
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurologic Mortality | 12 months | Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic progressive disease). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | Until death or loss to follow up, up to 24 months | Death from any cause cumulative incidence estimate assessed at 1 year and 2 year |
| Quality of Life as Assessed by Patient Questionnaire | Until death or loss to follow up, up to 24 months | Questionnaire - MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) |
| Neurocognitive Function: Verbal Learning and Memory | 12 months | Hopkins Verbal Learning Test -Revised (HVLT-R). Scores are transformed into Z scores. |
| Neurocognitive Function: Visual Attention and Task Switching | 12 months | Trail Making Test Part A and B (TMT). Scores are transformed into Z scores. |
| Neurocognitive Function: Verbal Fluency | 12 months | Controlled Oral Word Association Test (COWAT). Scores are transformed into Z scores. |
| Neurocognitive Function: Cognitive Impairment | 12 months | Mini Mental Status Examination (MMSE). Scored 0 to 30. Higher scores indicate better cognitive function |
| Ability to Complete Activities of Daily Living | Until death or loss to follow up, up to 24 months | Questionnaire - EQ-5D. A patient reported quality of life questionnaire |
| Performance Status | Until death or loss to follow up, up to 24 months | Karnofsky performance status. Scale ranges from 0 to 100, with higher scores indicating better function. |
| One and Two Year Incidence of New Brain Metastases | Until death or loss to follow up, up to 24 months | 1 and 2 year estimates of first appearance of new brain metastases (on radiographic assessment) |
| Incidence of Existing Brain Metastases | Until death or loss to follow up, up to 24 months | Per patient radiographic assessment of first event of local recurrence in the brain metastases treated with radiation on trial. One- and 2-Year estimates. |
| Incidence of Development of Radiographic Radiation Necrosis | Until death or loss to follow up, up to 24 months | Per patient radiographic assessment of first event of radiation necrosis in the brain metastases treated with radiation on trial. One- and 2-Year cumulative incidence estimates. |
| Incidence of Development of Leptomeningeal Disease | Until death or loss to follow up, up to 24 months | Per patient radiographic assessment of first event of leptomeningeal disease. One- and 2-Year estimates. |
| Incidence of Salvage Craniotomy | Until death or loss to follow up, up to 24 months | Per patient clinical assessment of first use of neurosurgical resection / craniotomy as salvage therapy in metastases treated with radiation on trial. One- and 2-Year estimates. |
| Incidence of Additional CNS-directed Radiotherapeutic Treatments (Stereotactic Radiation) After the Initial Course | Until death or loss to follow up, up to 24 months | Per patient clinical assessment of first use of salvage brain-directed stereotactic radiation. 1- and 2-Year estimates. |
| Incidence of Seizures | Until death or loss to follow up, up to 24 months | Per patient clinical assessment of first post-treatment seizure as assessed during routine study visits and via medical record review. 1 and 2-Year estimates. |
| Incidence of Symptomatic Radiation Necrosis | Until death or loss to follow up, up to 24 months | Per patient assessment of first event of symptomatic radiation necrosis in the brain metastases treated with radiation on trial. 1- and 2-Year estimates. |
| Incidence of Neurologic Death at 2 Years | 2-years | Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic progressive disease). |
| Incidence of Additional CNS-directed Radiotherapeutic Treatments (Whole Brain Radiation) After the Initial Course | Until death or loss to follow up, up to 24 months | Per patient clinical assessment of first use of salvage whole brain radiation. One- and 2-Year estimates. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAyal A Aizer, MD
Brigham and Women's Hospital
Participant flow
Recruitment details
Participants were recruited at Brigham and Women's Hospital / Dana-Farber Cancer Institute as well as at Beth Israel Deaconess Medical Center, Milford Regional Medical Center, and South Shore Health. All patients were assessed for eligibility before being approached by their treating physician regarding participation in the study. Study enrollment occurred between February 2018 and April 2023.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 68 Years |
| Dexamethasone Use No | 83 Participants |
| Dexamethasone Use Yes | 17 Participants |
| Distant Extracranial Metastases No | 57 Participants |
| Distant Extracranial Metastases Yes | 43 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Intracranial Resection Prior to Study Registration No | 84 Participants |
| Intracranial Resection Prior to Study Registration Yes | 16 Participants |
| Karnofsky Performance Status <70 | 6 Participants |
| Karnofsky Performance Status 70-80 | 48 Participants |
| Karnofsky Performance Status 90-100 | 40 Participants |
| Karnofsky Performance Status Unknown | 6 Participants |
| Neurologic Symptoms at Diagnosis No | 32 Participants |
| Neurologic Symptoms at Diagnosis Yes | 68 Participants |
| Number of Brain Metastases | 2 Metastases |
| Primary Site of Malignancy Extrathoracic Primary | 4 Participants |
| Primary Site of Malignancy SCLC Primary | 96 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 89 Participants |
| Seizures at Diagnosis No | 96 Participants |
| Seizures at Diagnosis Yes | 4 Participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 45 Participants |
| Size of Largest Brain Metastasis | 12 millimeters |
| Smoking Status Current | 12 Participants |
| Smoking Status Never | 11 Participants |
| Smoking Status Prior | 77 Participants |
| Systemic Therapy for Metastatic Disease Prior to Study Registration No | 17 Participants |
| Systemic Therapy for Metastatic Disease Prior to Study Registration Yes | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 84 / 100 |
| other Total, other adverse events | 94 / 100 |
| serious Total, serious adverse events | 9 / 100 |
Outcome results
None listed