Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioblastoma

Glioma

Central Nervous System Neoplasms

Nervous System Neoplasms

Astrocytoma

Ependymoma

Oligodendroglioma

Gliosarcoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Anaplastic Ependymoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Temozolomide is administered according to standard of care practice guidelines. Dosing may be modified at the discretion of the treating investigator.

temozolomide

Imaging biomarker analysis

Radiation is administered to the tumor plus edema with a 1-2 centimeter margin for a total dose of 60 Gy in 30 fractions.

Photon Radiation Therapy

Elizabeth Gerstner, MD

RATIONALE: Diagnostic procedures, such as MRI, may help in learning how well radiation therapy and chemotherapy work in killing tumor cells and allow doctors to plan better treatment.

PURPOSE: This clinical trial is studying MRI scans to see how well they evaluate the effects of radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma multiforme or anaplastic glioma.

OBJECTIVES:

Primary

* To quantitatively compare the relative cerebral blood volume/flow, mean transit time, and mean vessel diameter as measured by perfusion-weighted MRI before, during, and after chemoradiotherapy in patients with newly diagnosed glioblastoma multiforme.
* To measure the permeability-surface area product on a voxel-by-voxel basis before, during, and after chemoradiotherapy in these patients.
* To measure the full water self-diffusion tensor on a voxel-by-voxel basis before, during, and after chemoradiotherapy in these patients.
* To compare the tensor fractional anisotropy before, during, and after chemoradiotherapy in these patients.
* To compare the relative regional concentrations of choline, N-acetyl-asparate, and myoinositol as measured by magnetic resonance spectroscopy before, during, and after chemoradiotherapy to interrogate cell membrane turnover, neuronal integrity, and glial reactions.
* To test the affects of a short period of 100% oxygen inhalation on imaging of tumor and surrounding tissue regions of interest, specifically cerebral blood volume changes in each area as compared to room air.

Secondary

* To collect blood and urine samples for correlation analysis between imaging changes, molecular markers (including genetic markers), and clinical outcome of glioblastoma multiforme (phenotypic information).
* To correlate blood and urine biomarkers and blood genetic markers with tumor expression of these markers.

OUTLINE: Patients undergo radiotherapy once daily 5 days a week for 6 weeks. Patients also receive oral temozolomide once daily 7 days a week during radiotherapy. After completion of chemoradiotherapy, patients receive oral temozolomide once daily for 5 days. Treatment with temozolomide repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo MRI, including perfusion- and diffusion-weighted MRI, diffusion tensor imaging, and magnetic resonance spectroscopy prior to initiation of chemoradiotherapy, once weekly during chemoradiotherapy, and then monthly until tumor progression or until completion of 6 courses of post chemoradiotherapy.

After completion of study treatment, patients are followed annually.

MRI Scans in Evaluating the Effects of Radiation Therapy and Chemotherapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Glioma

Quantitative Assessment of the Early and Late Effects of Radiation and Chemotherapy on Glioblastoma Using Multiple MRI Techniques

Relative cerebral blood volume (rCBV) is the blood volume in the region of interest (ROI) divided by the blood volume in the symmetrical region on the other side of the normal brain (control region). CBV was assessed using spin-echo post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. The baseline value was measured twice (representing baseline 1 and 2) to make sure that the value was reproducible and to account for any variation attributable to measurement variation.

CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide

Relative cerebral blood flow (rCBF) is the blood flow rate (the volume of blood passing through the specified are over a specified period of time) in the region of interest (ROI) divided by the blood flow rate in the symmetrical region on the other side of the normal brain (control region). CBF was assessed using spin-echo post-contrast T1-weighted images. CBF was assessed using spin-echo post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. The baseline value was measured twice (representing baseline 1 and 2) to make sure that the value was reproducible and to account for any variation attributable to measurement variation.

CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide

Mean transit time (MTT) corresponds to the average time, in seconds, that red blood cells spend within a determinate volume of capillary circulation.

Permeability-surface Area Product (Ktrans). Ktrans reflects the efflux rate of contrast from blood plasma into the tissue extravascular extracellular space (EES). Ktrans was assessed using post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point.

CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide

Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue. ADC was assessed using post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point.

CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide

Fractional anisotropy (FA) is a measure of the directionality of the molecular motion of water.

National Cancer Institute (NCI)

Massachusetts General Hospital

Adverse event data were not collected as a part of this study

temozolomide: Temozolomide is administered according to standard of care practice guidelines. Dosing may be modified at the discretion of the treating investigator.

Imaging biomarker analysis: MRI

Photon Radiation Therapy: Radiation is administered to the tumor plus edema with a 1-2 centimeter margin for a total dose of 60 Gy in 30 fractions.

Temozolomide and Radiation Therapy

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

The Karnofsky Performance Status is a measure of patients' general well-being and activities of daily living. The score ranges from 0 to 100, higher scores indicating a patient is better able to carry out daily activities.

Karnofsky Performance Status

One participant withdrew consent after baseline and was excluded from the analysis set

Dr. Elizabeth Gerstner

Baseline 1

Baseline 2

Week 1 CRT

Week 2 CRT

Week 3 CRT

Week 4 CRT

Week 5 CRT

Week 6 CRT

Pre-C1 TMZ

Pre-C2 TMZ

Pre-C3 TMZ

Pre-C4 TMZ

Pre-C5 TMZ

Pre-C6 TMZ

Post-TMZ

One participant withdrew consent after baseline and was excluded from the analysis set. The number of patients evaluated decreased over time due to participants experiencing disease progression and discontinuing from the study

Relative Cerebral Blood Volume as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy

Relative Cerebral Blood Flow as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy

Vessel Diameter as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy

Mean Transit Time as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy

Permeability-surface Area Product Before, During, and After Chemoradiotherapy

Apparent Diffusion Coefficient Before, During, and After Chemoradiotherapy

Tensor Fractional Anisotropy Before, During, and After Chemoradiotherapy

Relative Regional Concentrations of Choline, N-acetyl-asparate, and Myoinositol as Measured by Magnetic Resonance Spectroscopy Before, During, and After Chemoradiotherapy to Interrogate Cell Membrane Turnover, Neuronal Integrity, and Glial Reactions

Affects of a Short Period of 100% Oxygen Inhalation on Imaging of Tumor and Surrounding Tissue Regions of Interest, Specifically Cerebral Blood Volume Changes in Each Area as Compared to Room Air

Overall Study

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Fibrosis

Breast Diseases

Skin Diseases

Participants will be randomized 1:1 to XRT group and stratified by receipt of chemotherapy and cardiac risk factors and will complete:

* Cardiac MRI and blood tests within 1 month prior to start of radiation therapy.
* Radiation therapy 1x daily for 5 days over 1 week.
* End of radiation therapy visit with blood tests.
* 6 month follow up visit with cardiac MRI, blood tests, questionnaires, and photographic imaging.
* 12 month follow up visit with questionnaires and photographic imaging.

Accelerated Proton Beam Radiation Therapy (PBT)

Accelerated Photon Radiation Therapy (XRT)

Rachel Jimenez, MD

This research is being done to see if proton beam radiation therapy (PBT) results in fewer changes to a participant's heart measured with MRI-imaging than conventional or "photon" radiation therapy (XRT) for participants with non-metastatic left sided breast cancer.

The names of the two study groups in this research study are:

* Proton Radiation Therapy (PBT)
* Conventional or "Photon" Radiation Therapy (XRT)

This is a randomized phase II trial comparing participants with stage II-III breast cancer treated with accelerated Proton Beam Radiation Therapy (PBT) versus accelerated conventional photon radiation therapy (XRT) inclusive of the regional lymph nodes.

Participants will be randomized into one of two study groups: proton beam radiation therapy versus photon radiation therapy. Randomization means that participants are put into a group by chance.

Study procedures includes screening for eligibility, study treatment visits, Cardiac Magnetic Resonance Imaging (MRI), blood tests, and questionnaires.

The National Cancer Institute, American Society of Clinical Oncology, and Claflin Grant are supporting this research by providing funding for the research study.

All women of all races and ethnic groups are eligible for this trial.

Ultrahypofractionation and Normal Tissue Toxicity

Proton Versus Photon Ultrahypofractionated Radiation Therapy and Its Impact on Normal Tissue

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The primary outcome is to determine whether participants who receive accelerated PBT show no increase in myocardial fibrosis on Cardiac MRI (CMR) compared to an estimated 4% increase in extracellular matrix volume fraction (ECV) in participants who receive accelerated XRT. CMR will be performed using a 3T system (Skyra, Siemens). The T1 phase on MRI will be used to measure ECV.

GLS will be measured using feature tracking from the Steady-state free precession (SSFP) MRI cine images (Medis Suite, Leiden).

Cardiac Biomarkers will be measured using enzyme-linked immunoassay (ELISA).

Assessed by photographic imaging of the breast, chest wall and reconstructed breast, the Breast Q: Mastectomy Module (Postoperative) 2.0, the Breast Q: Reconstruction Module (Postoperative) 2.0, and the Breast-Q: Breast Conserving Therapy Module (Postoperative) 2.0 questionnaires which are rigorous patient-report outcome measures. Modules grade Quality of Life (QOL) and Satisfaction Domains related to post-operative care and experiences. All BREAST-Q scales are transformed into scores that range from 0-100. T. A higher score means greater satisfaction or better QOL (depending on the scale).

Assessed by the Thoracic Focused Assessment with Sonography for Trauma, Triage, and Tracking (TFAST), the Penn Shoulder Scale (PSS), and the Disabilities of the Arm, Shoulder and Hand (DASH) Shoulder Function Scale. TFAST is an objective and highly reproducible functional assessment tool of the arm and shoulder. The PSS is a patient-reported outcome tool which provides a shoulder-specific metric and distinguishes between finer levels of functioning. Scores range from 0 to 100 with a score of 100 indicating low pain, high satisfaction, and high function. DASH is a 30-item, validated, patient-reported scale that captures upper extremity functionality and mobility and maintains high construct validity and responsiveness in the breast cancer population. Questions are graded on a Likert scale with scores ranging from "1" Strongly Disagree to "5" Strongly Agree, where a cumulative score of 0 is graded no disability and 100 is most severe disability.

American Society of Clinical Oncology

Principal Investigator

Proton radiation therapy daily (Monday through Friday) for six weeks. This is a single arm study.

Once daily, Monday through Friday, for 6 weeks.

Proton Radiation Therapy

Helen A. Shih, MD, MS, MPH

In this research study, we are looking to study the side effects from the use of proton radiation in treating people with low-grade gliomas that are recommended radiation treatment. We expect response of the tumors to be the same with proton radiation as compared to standard 3D conformal radiation therapy, but also expect less side effects from radiation.

* Participants will receive radiation therapy for 6 weeks, given in daily doses, Monday through Friday, for a total of 30 treatments.
* A medical history and physical examination will be performed prior to the start of radiation treatment, weekly during the 6 weeks of radiation and after the finish of radiation performed at 3 and 6 months and then annually for 5 years.
* Hormonal function tests will be taken prior to the start of radiation treatment and after the finish of radiation treatment at 3 and 6 months, and annually for five years to assess the participants hormonal functions as they relate to the pituitary gland's function.
* A brain MRI will be performed prior to the start of radiation treatment and then performed at 3 and 6 months after radiation treatment then annually for 5 years.
* A neurocognitive exam will be performed prior to the start of radiation therapy, a limited exam 6 months after the completion of radiation therapy, and a complete exam annually for 5 years.
* Quality of Life and Emotional Well-Being Questionnaires will be done before radiation begins, 2 months after radiation treatment, 6 months after radiation treatment and then annually for 5 years.

Late Effects of Proton Radiation Therapy in Patients With Low-Grade Glioma

Clinical and/or radiographic assessments Percentages were estimated by Kaplan Meier

Percentages were estimated by Kaplan Meier

Attending Radiation Oncologist

All 20 baseline participants were included in analysis.

Helen A. Shih, MD

Number of Participants With Late Effects > 3 Months Post RT

1 Year

3 Year

5 Year

Percentage of Participants With Progression Free Survival

Percentage of Participants With Overall Survival

Proton Radiation Therapy daily (Monday through Friday) for six weeks. This is a single arm study.

Recurrence

Diffuse Intrinsic Pontine Glioma

Brain Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Stem Neoplasms

Infratentorial Neoplasms

Starting dose of 24 Gray (Gy) in 2 Gy fractions.

Radiation Therapy

Susan L. McGovern, MD

The goal of this clinical research study is to find a safe dose of radiation that can be given to patients with brainstem glioma who have already received radiation therapy.

You will receive photon radiation therapy. This type of radiation is similar to the radiation you have already had. Conformal radiotherapy or intensity modulated radiotherapy (IMRT) will be used to try to treat the tumor while affecting as little of the surrounding normal tissue as possible.

Radiation Therapy Administration:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of radiation therapy based on when you join this study. Three (3) dose levels of radiation therapy will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will be randomly assigned (as in the roll of dice) to one of the dose levels, and the assignment will also depend on how the previous participants have done. Participants will not be assigned to one of the higher 2 of the 3 dose levels unless the lower dose level is found to be tolerable. The first and second groups will receive 12 treatments and the third group will receive 14 treatments (Monday through Friday for about 2½ weeks). Your doctor will tell you how many treatments you will receive.

You may be given drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

Study Visits:

About 2-4 days before you start radiation therapy, you will have a simulation. During the simulation session, a mask will be made of your face and head to keep you still. You will also have a computed tomography (CT) scan. This process allows the radiation planning to take place. Sedation by an anesthesiologist (anesthesia doctor) will be used if needed for young children to allow the radiotherapy to be delivered safely.

One (1) time a week for 3 weeks, and then 1 time a month (30 days +/- 10 days) for 2 months or unless the disease gets worse:

* You will have a neurological exam.
* Your performance status will be recorded.
* You will fill out the quality-of-life questionnaire.
* You will be asked about any side effects you may have had.

You will have a magnetic resonance imaging (MRI) scan of the brain within 1 month after joining the study.

Length of Treatment:

You may continue receiving radiation therapy for 12 or 14 treatments. You will no longer be able to receive radiation therapy if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Follow-up Visits:

One (1) month after you finish radiation therapy, at 6-8 weeks, then every 2-3 months after that from then on, you will have an MRI scan to check the status of the disease. The MRI scan will include advanced imaging to learn if the tumor has come back or if there is brain tissue damage from the radiation. With this type of imaging, a temporary infusion line with a bigger than standard size needle will be inserted to your vein if you do not already have a power port-a-cath in place. This may take between 20-30 minutes.

This is an investigational study. Radiation therapy in this study is delivered using FDA-approved and commercially available methods. It is investigational to find the best dose of radiation therapy to use for repeat radiation therapy.

Up to 30 participants will be enrolled in this study.

Diffuse Intrinsic Pontine Glioma (DIPG) Reirradiation (ReRT)

Phase I/II Study of Reirradiation of Recurrent or Progressive Brainstem Glioma

Optimal dose level among three RT dose levels, defined in terms of the biologically equivalent dose (BED). The BED is given by the formula BED = (Total Dose)\*(1 + d/3), denoting d = dose/fraction, with the constant 3 corresponding to brain tissue.

M.D. Anderson Cancer Center

Meningioma

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Standard radiation therapy: 55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week.

63 CGE in 35 treatments of 1.8 CGE given once a day, for five days of each week.

55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week. Treatment based upon a treatment planning CT.

Standard Treatment

Higher Dose

Helen A Shih, MD

The purpose of this study is to determine the best radiation dose for participants with meningioma that has grown back after previous surgery, or which the surgeon has been unable to remove completely. This research study is designed to determine whether a higher dose of radiation will decrease the likelihood that the tumor will grow back, compared to the probability of re-growth that occurs after standard radiation doses.

* After initial interview and physical examination, an immobilization device (head mask, neck support, back support, etc.) will be made for the participant. A treatment planning CT will be performed and a radiation treatment plan will be based on this CT scan.
* The radiation dose will usually be given once a day, five days per week. The radiation treatment will take between 7 and 8 1/2 weeks, including treatment planning.
* Treatment doses will vary, and the dose each participant will receive will be made on the basis of random assignment. Participants will either receive the usual dose of 55.8 CGE in 31 treatments or 1.8 CGE, or 63 CGE in 35 treatments of 1.8 CGE.

Proton/Photon Rt - Benign Meningiomas(P92-13)

Prospective Study Of Patients With Recurrent Or Incomplete Excised Benign Intercranial Meningiomas For The Evaluation Of Treatment Result With Combined Proton And Photon Irradiation To Doses 55.8 Or 63.0 CGE

The number of participants surviving at the given time point. Progression free survival (PFS) is measured from the starting date of radiation therapy and analyzed by intention to treat. PFS is measured until the earlier, date of death or development of radiologic progression, and is otherwise censored at the last follow-up for progression-free patients still alive.

The number of participants that experienced the specified acute toxicities (any grade) as assessed by Radiation Therapy Oncology Acute Morbidity Scoring Criteria. Acute toxicities were assessed from the start of treatment through day 90 of treatment.

The number of participants that experienced the specified late toxicities (any grade) as assessed by Radiation Therapy Oncology Group Late Effects Scale.

The number of participants with local failure. Local failure is defined as radiologic progression seen on follow-up scans showing tumor margin(s) extending in any direction at least five mm beyond that seen on baseline scans.

Prinicipal Investigator

Patients were assessed for adverse events with Radiation Therapy Oncology Group Common Toxicity Criteria. Patients were assessed weekly during the course of treatment. Post treatment, participants were evaluated for interval history and neurological function routinely at one month, every three months during the first year, four month intervals during the second year, twice yearly through year 5, and then yearly for the remainder of follow-up.

Standard radiation therapy: 55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week.

Standard Treatment: 55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week.

Treatment based upon a treatment planning CT.

63 CGE in 35 treatments of 1.8 CGE given once a day, for five days of each week.

Higher Dose: 55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week. Treatment based upon a treatment planning CT.

Higher Dose Treatment

Total

Sphenoid wing

Cavernous sinus

Sella/Parasella

Cerebellar pontine angle

Clival/prepontine space

Olfactory groove

Optic canal

Tentorium

Tumor Location

Smoker

Non-smoker

Unknown

Smoking Status

Hypertension

Diabetes mellitus

Hyperlipidemia

Coronary artery disease

One or more of the above

Co-morbidities

Sub-Total Resection, postoperative

Recurrent Disease

Radiation Indication

Gross Tumor Volume

Clinical Target Volume

Nina Sanford, MD

Null hypothesis: Progression free survival is not significantly different by dose level in the overall cohort.

Null hypothesis: Progression free survival is not significantly different by dose level in the subgroup receiving treatment due to a sub-total resection

Null hypothesis: Progression free survival is not significantly different by dose level in the sub-group receiving treatment due to recurrent disease

Entire Cohort: 5 Years

Entire Cohort: 10 Years

Entire Cohort: 15 Years

Subtotal Resection: 5 Years

Subtotal Resection: 10 Years

Subtotal Resection: 15 Years

Recurrent Disease: 5 Years

Recurrent Disease: 10 Years

Recurrent Disease: 15 Years

Progression free survival in the entire cohort and by radiation indication sub-groups

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MRI Scans in Evaluating the Effects of Radiation Therapy and Chemotherapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Glioma	NCT00756106	Brain and Centr...	temozolomide Imaging biomark... Photon Radiatio...	18 Years -	Massachusetts General Hospital
Ultrahypofractionation and Normal Tissue Toxicity	NCT05912231	Breast Cancer Breast Cancer F... Breast Cancer S... Breast Cancer S... Myocardial Fibr...	Accelerated Pro... Accelerated Pho...	18 Years -	Massachusetts General Hospital
Late Effects of Proton Radiation Therapy in Patients With Low-Grade Glioma	NCT00681473	Low Grade Gliom...	Proton Radiatio...	18 Years -	Massachusetts General Hospital
Diffuse Intrinsic Pontine Glioma (DIPG) Reirradiation (ReRT)	NCT01469247	Brain Cancer	Radiation Thera...	- 17 Years	M.D. Anderson Cancer Center
MRI Scans in Evaluating the Effects of Radiation Therapy and Chemotherapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Glioma	NCT00756106	Brain and Centr...	temozolomide Imaging biomark... Photon Radiatio...	18 Years -	Massachusetts General Hospital
Proton/Photon Rt - Benign Meningiomas(P92-13)	NCT02947984	Benign Meningio...	Standard Treatm... Higher Dose	18 Years -	Massachusetts General Hospital
Proton/Photon Rt - Benign Meningiomas(P92-13)	NCT02947984	Benign Meningio...	Standard Treatm... Higher Dose	18 Years -	Massachusetts General Hospital
Dose Escalated Proton Beam Therapy or Photon Therapy for Esophageal Cancer	NCT03234842	Esophageal Canc...	Proton Beam The... Photon Radiatio... Chemotherapy	18 Years -	University of Florida

Spots Global Cancer Trial Database for photon radiation therapy