Novel Technologies Augment the Evolution of Minimally Invasive Brain Tumor Surgery

Neurosurgery is being transformed by minimally invasive techniques, such as port-based surgeries and laser strategies, alongside fluorescent guidance for more aggressive tumor resection and the use of advanced brachytherapy to provide immediate, targeted radiation therapy, according to Gabriel Zada, MD.

“I’m optimistic,” Zada said in an interview with OncLive^® during Brain Tumor Awareness Month, which is observed annually in May. “What a time to be in this specialty, where things are exponentially advancing with artificial intelligence and drug options and immunotherapy options. I think we’re close to finding—we don’t use the word cure lightly in brain tumors—but I would say definitive treatments. Making some of these tumors or cancers more chronic diseases rather than terminal diseases is where we’re headed, and that’s exciting. I think in the next 5 to 10 years, we’re going to get there.”

In the interview, Zada discussed advanced surgical techniques for brain cancer, highlighting minimally invasive options like endonasal and eyebrow incisions, port-based surgeries, and laser interstitial thermal therapy (LITT). He also explained how 5-ALA, which is FDA-approved for use in patients with high-grade glioma (HGG), aids in tumor resection by fluorescing tumors under blue light. Furthermore, he dove into the details of GammaTiles, which are used for HGG and brain metastases to provide immediate radiation therapy benefits.

Zada is director of the University of Southern California (USC) Brain Tumor Center at Keck Medicine of USC in Los Angeles.

OncLive: What are some of the most common minimally invasive brain tumor surgical techniques, and in what instances might each of them be used?

Zada: Not every tumor that needs surgery is amenable to a minimally invasive option. A lot of them require traditional craniotomy or [other traditional] approaches. But among the minimally invasive ones, which a subset [of tumors are eligible for], sometimes we can use small incisions, openings, natural corridors to remove the tumors. Occasionally, that can be done through [an area] like through the nose to reach various tumors, or through an eyebrow incision.

When we’re dealing with tumors in deep brain or cortical locations, or in the ventricles, we now have the options of port-based surgeries as well, which look like little syringes that we can navigate to the tumor and safely resect deeper tumors. Another minimally invasive option is LITT, which we use now for many recurrent tumors. That’s where we go in and ablate the tumor under real-time MRI thermometry guidance. That’s a great option for patients because it can induce the immune system to fire up as well. There are some other minimally invasive options, but in cases where those can’t be done, we still resort to traditional craniotomy, which are sometimes done with mapping techniques or awake craniotomies.

How does 5-ALA work to guide certain brain tumor surgeries?

5-ALA has been a huge addition to what we do as surgeons. It’s FDA approved now; [the US] followed suit after Europe had [5-ALA] approved.¹ It’s primarily used for HGG, but that’s also evolving. There are emerging data [with 5-ALA] for meningiomas as well; those are going to be published from a trial we were part of.

We give the oral drug a couple hours before surgery, and it’s metabolized by the tumor differently than the normal brain into protoporphyrin IX. When we look at the tumor with a special blue light, the tumor fluoresces a hot pink color, but the normal brain does not, and that selectivity allows us to be more aggressive in getting more of the tumor out. Reaching certain thresholds of resection is associated with progression-free survival [PFS] and [overall survival] benefits.

That has to be balanced with safety, so we always use techniques like motor mapping or speech mapping to preserve critical areas. On the other end, we try to be as aggressive as possible in removing these tumors. [5-ALA has] been a breakthrough, especially for HGG and now meningiomas and selected brain metastases. [We do not use it] as much in low-grade glioma, but there are evolving roles as we learn more about it.

How do GammaTiles work in brain tumor management?

GammaTiles are a form of brachytherapy, which has been around for approximately a century and is making a resurgence now because of emerging data and the GammaTile, which is leading that effort. These are small tiles with embedded radiation beads in them. We can trim them, and we use a certain amount after we remove a tumor to line the cavity of the tumor to provide immediate radiation benefit, rather than having to wait often several weeks until the patient’s incision is healed and they undergo whatever therapy or rehab they need to do; it gives a kickstart to the radiation process.

We were using it initially for salvage cases of HGG, metastases, and meningiomas that had failed initial surgery, radiation, or chemotherapy. However, in the past 1 to 2 years, there have been randomized trials investigating the upfront use of GammaTile for HGG and brain metastases compared with deferred radiation alone. There seems to be a PFS benefit there. Some of those data are out of The University of Texas MD Anderson Cancer Center in Houston, and some of it is out of the Barrow Neurological Institute in Phoenix, Arizona, but [USC has] been part of [some of] these trials and offers GammaTiles.^2,3 We’re using them a lot more as we learn the indication.

[GammaTiles are] a viable salvage and probably upfront technique that we now offer. For surgeons, this is great, because historically all we could do is remove a tumor, and we felt a little helpless because we know there’s sometimes residual tumor there. This allows us to offer [treatment] immediately at that time of surgery that patients appreciate as well.

What is your process for leveraging multidisciplinary collaboration during GammaTile use?

This applies beyond GammaTile. Our weekly tumor board is the core of everything we do. We work closely as a team here with radiation oncology, neuro-oncology, and other specializations: neuropathology, neuroradiology, etc. Treatment decisions are all made in a multidisciplinary fashion.

We get a ton of community referrals for cases that have been treated in the community and have recurred, progressed, or failed. [Referring physicians] send [these patients to USC] as a quaternary care center. We review every case, determine which patients are candidates [for GammaTile] how many tiles they would need, and what other therapies [they may need].

We have GammaTiles, but we’re weighing these with other clinical trials, immunotherapies, laser therapies, and additional surgery. There are many potential treatment options for patients now. We evaluate all those as a team.

GammaTile is often one we use, but it’s not the only one. [Patients will often be evaluated by surgeons], and then they’ll see radiation oncology right away for a separate consultation. The tiles are available in approximately 2 days now; it is great that they’ve improved that turnaround, so things are moving quickly now if a patient needs additional care.

References

1. Hadjipanayis CG, Stummer W. 5-ALA and FDA approval for glioma surgery. J Neurooncol. 2019;141(3):479-486. doi:10.1007/s11060-019-03098-y
2. Beckham TH, Cha EE, Rooney MK, et al. Cesium-131 collagen tile brachytherapy for salvage of recurrent intracranial metastases. J Neurooncol. 2025;175(1):165-174. doi:10.1007/s11060-025-05113-x
3. Nakaji P, Smith K, Youssef E, et al. Resection and surgically targeted radiation therapy for the treatment of larger recurrent or newly diagnosed brain metastasis: results from a prospective trial. Cureus. 2020;12(11):e11570. doi:10.7759/cureus.11570