Pre-Op SRS Before Surgery for Brain Metastases

Overseen By Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Disqualifiers: Prior WBRT, Tumor ≥5 cm, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether administering a special type of radiation, called stereotactic radiosurgery (SRS), before surgery can better control brain tumors that have spread from other parts of the body. Researchers aim to determine if this approach can facilitate complete tumor removal and reduce the risk of tissue damage and disease spread. Suitable participants have a solid tumor that has metastasized to the brain and plan to undergo surgery to remove at least one of these tumors. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that pre-operative stereotactic radiosurgery is safe for brain metastases?

Research has shown that pre-operative stereotactic radiosurgery (SRS) is generally safe for people with brain metastases. In one study, 88% of patients completed both the SRS and surgery without issues. Another study found that SRS before surgery did not cause additional surgical problems and was well-tolerated by patients.

Pre-operative SRS also effectively manages brain tumors. It helps control tumors without increasing the risk of side effects, such as the need for steroids. Although researchers continue to study the best timing for radiation treatment, this approach has been safely used in other situations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard approach of treating brain metastases with surgery followed by Stereotactic Radiosurgery (SRS), this new treatment method flips the order by delivering SRS before surgery. Researchers are excited about this trial because pre-operative SRS might better target cancer cells, potentially leading to improved outcomes and reduced risk of tumor spread during surgery. Additionally, by administering the radiation upfront, there might be fewer complications related to wound healing, which is a common concern with post-operative radiation. This innovative timing could offer a more effective and safer option for patients with brain metastases.

What evidence suggests that pre-operative stereotactic radiosurgery is effective for brain metastases?

Research has shown that using a special type of radiation treatment called stereotactic radiosurgery (SRS) before surgery can help control brain tumors. Participants in this trial will receive SRS, which studies have found can lower the risk of cancer spreading to the brain's protective layers from 27.1% to 7.4%. This treatment also helps prevent tumor recurrence and may reduce the need for steroids, often used to manage brain swelling. Overall, early evidence suggests this approach could be a promising option for treating brain tumors that have spread. ^{1 2 3 6 7}

Who Is on the Research Team?

Rodney E Wegner, MD

Principal Investigator

AHN Radiation Oncology

Are You a Good Fit for This Trial?

This trial is for adults with solid tumor brain metastases who can consent to treatment, have a Karnofsky Performance Status of ≥70 (meaning they are able to care for themselves), and agree to use contraception. They must be planning surgery for at least one brain metastasis smaller than 5 cm. Those with serious medical or psychiatric illnesses, prior whole-brain radiation, or pregnant women cannot participate.

Inclusion Criteria

My cancer has spread to my brain.

I had a brain MRI less than a month before starting brain SRS.

I have had radiation therapy for brain cancer before.

Exclusion Criteria

I need assistance with my daily activities.

I have had whole brain radiation therapy or stereotactic radiosurgery on the main tumor.

Patients must not have a serious medical or psychiatric illness that would in the opinion of the treating physician prevent informed consent or completion of protocol treatment, and/or follow-up visits

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stereotactic Radiosurgery (SRS)

Participants undergo stereotactic radiosurgery using the Elekta Gamma Knife Icon, treated in once daily or every other day 15 minute fractions of 9 Gy for a total dose of 27 Gy in 3 doses

1 week

3 visits (in-person)

Surgical Resection

Routine surgical resection of the brain metastasis is performed within two weeks after completion of SRS

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with MRIs performed and quality of life questionnaires completed

2 years

Regular visits (in-person) every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Pre-operative Stereotactic Radiosurgery

Trial Overview The study tests if performing stereotactic radiosurgery (SRS) before surgical removal of the brain tumor improves chances of complete removal without recurrence and reduces risks like tissue breakdown at the tumor site and leptomeningeal disease development.

How Is the Trial Designed?

Group I: Pre-Operative Stereotactic Radiosurgery (SRS) Experimental Treatment 1 Intervention

Subjects are treated using the standard of care SRS to a total dose of 24-27 Gray (Gy) in 3 fractions with a once daily fractionation or every other day at treating physician discretion. The preferred dose will be 27 Gy, with ability to drop dose down to 24 Gy if normal tissue constraints cannot be met. It should be noted, that while the dosing remains within standard of care, the timing of the radiation (pre-operative) is still not considered standard of care but is supported by emerging data as described in the study background. Additional metastatic lesions may be treated using SRS according to institutional practices. The radiation dose prescribed to the non-index lesions is at the discretion of the treating physicians. Surgical resection will be performed within 2 weeks of completion of SRS.

Who Is Running the Clinical Trial?

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Lead Sponsor

Trials

52

Recruited

13,000+

Elekta Limited

Industry Sponsor

Trials

13

Recruited

8,900+

Published Research Related to This Trial

Moderately dosed stereotactic radiosurgery (SRS) for one to four brain metastases showed a median overall survival of 7.5 months, with high local brain control rates of 87% at 6 months and 79% at 12 months, indicating its efficacy in treating limited brain metastases.

The study suggests that initial SRS alone can be a safe treatment option, as only 22% of patients required additional whole-brain radiotherapy, and significant predictors of survival included the time between the primary diagnosis and brain metastases, as well as the volume of the treated metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. Meisner, J., Meyer, A., Polivka, B., et al.[2021]

Pre-operative stereotactic radiosurgery (SRS) for brain metastases significantly reduces dose exposure to healthy brain tissue compared to post-operative SRS, with a median volume receiving 28 Gy being lower in the pre-operative setting (6.79 ccm) than in the extended field post-operative setting (10.79 ccm).

The study found that the morphology of the resection cavity post-surgery differs significantly from the original lesion, which could complicate treatment planning; thus, pre-operative SRS may provide better delineation and treatment planning advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases-Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept. El Shafie, RA., Tonndorf-Martini, E., Schmitt, D., et al.[2020]

In a study of 174 patients treated with stereotactic radiosurgery (SRS) for brain metastases, those who underwent surgery after SRS experienced significant improvements in quality of life, with 50% showing better performance scores post-surgery.

Patients who had surgery after SRS had a median overall survival of 11 months, with longer survival observed in those with radiation necrosis, suggesting that SRS can effectively manage symptoms and improve outcomes when followed by surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative Resection of Metastatic Brain Tumors Previously Treated by Stereotactic Radiosurgery. Jeon, YS., Koh, YC., Song, SW., et al.[2020]

Preoperative stereotactic radiosurgery (SRS) in 117 patients with brain metastases showed excellent local control of tumor cavities with a low risk of radiation necrosis (4.8%) and leptomeningeal disease recurrence (4.3%), suggesting it is a safe and effective treatment option.

The study found that subtotal resection of tumors significantly increased the risk of local recurrence and worsened overall survival, highlighting the importance of achieving gross total resection for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative stereotactic radiosurgery before planned resection of brain metastases: updated analysis of efficacy and toxicity of a novel treatment paradigm. Prabhu, RS., Miller, KR., Asher, AL., et al.[2021]

Postoperative stereotactic radiosurgery (SRS) improves local control of brain metastases and preserves neurocognitive function compared to whole brain radiation therapy, but local recurrence rates can still be as high as 40% within a year.

Preoperative SRS may enhance tumor control by targeting intact metastases, potentially reducing the risk of intra-operative tumor cell seeding and leptomeningeal disease, while also lowering the likelihood of symptomatic radiation necrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Stereotactic Radiosurgery for Brain Metastases. Routman, DM., Yan, E., Vora, S., et al.[2020]

In a study of 404 patients with brain metastases, preoperative stereotactic radiosurgery (SRS) showed low rates of cavity local recurrence (13.7%) and adverse radiation effects (7.4%), indicating it is a safe option before surgical resection.

The median overall survival for patients receiving preoperative SRS was 17.2 months, with factors like systemic disease status and extent of resection significantly influencing survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases. Prabhu, RS., Akinyelu, T., Vaslow, ZK., et al.[2023]

This multicenter, randomized controlled trial aims to determine whether preoperative stereotactic radiosurgery (SRS) is more effective than postoperative SRS in managing resectable brain metastases, involving 88 patients over three years.

The primary goal is to assess local control of the tumors at 12 months, while secondary outcomes will evaluate overall survival, recurrence rates, neurocognitive effects, and adverse events like radiation necrosis, addressing a significant gap in current treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, multicenter, randomized controlled trial of preoperative versus postoperative stereotactic radiosurgery for patients with surgically resectable brain metastases. Das, S., Faruqi, S., Nordal, R., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38728761/

safe, effective, and decreases steroid dependency Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of ...

2. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00169-1/fulltext

Preoperative Stereotactic Radiosurgery for Brain Metastases In the expanded analysis, preoperative SRS significantly reduced rates of nLMD (7.4% vs 27.1%, P = .002), while rates of classical LMD (4.2% vs 4.5%) and local ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39279766/

A single-arm phase 2 trial outcome analysis (NCT03398694) Our data confirms superior local control in patients who received preoperative SRS when compared to historical controls.

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2835449

Therapy, Safety, and Logistics of Preoperative vs ... Of these, 70 patients (84%) had 1 to 4 brain metastases at enrollment, 11 (13%) had 5 to 10 lesions, and 2 (2%) had more than 10 lesions. In the ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001691

Preoperative Stereotactic Radiosurgery for Brain Metastases In the expanded analysis, preoperative SRS significantly reduced rates of nLMD (7.4% vs 27.1%, p=0.002), while rates of cLMD (4.2% vs 4.5%) and ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625026975

Analysis of the Safety Cohort of a Phase II Study ... Pre-operative SRS followed by neurosurgical resection for patients with resectable brain metastases was deemed safe with no excess surgical morbidity. The ...

7. redjournal.org redjournal.org/article/S0360-3016(23)05424-X/fulltext

MD Anderson Phase III Randomized Preoperative ... The majority of patients (83%) had 1-4 brain mets on their baseline MRI and 91% subsequently had a single lesion resected. Seventy-nine patients completed both ...