In a young patient with recurrent low-grade glioma s/p gross total resection, is there any role for further observation instead of radiation and chemotherapy?

As simple as this question seems to be on the surface, it is actually a very difficult clinical scenario to opine with certainty, primarily because of a lack of data. So, let us address this with each option in mind, weighing the pros and cons:

1. Observation: We do know that in resected patients, radiotherapy over observation prolongs PFS but not OS (older EORTC data), and that RT/PCV prolongs OS over RT alone (RTOG data). This patient, however, is grossly resected, and so we cannot extrapolate the findings mentioned to this patient. Maybe this patient had a subtotal resection, to begin with, and then relapsed and now has a subtotal resection. Personally, I would want to confirm that it is a GTR (detailed evaluation of FLAIR), confirm favorab...

The answer to this question depends on how long it took for the LGG to recur after the first GTR and also on several other criteria such as the size of the recurrence (> or <5 cm), location within the brain (e.g., frontal lobe versus parietal lobe), proximity to eloquent parts of the brain which could be jeopardized by another recurrence, and whether the patient has received chemotherapy after the initial diagnosis.

If the recurrence occurred within a few years from the initial resection, and in light that she is closer to her 40th birthday, I would favor treating her now rather than waiting for another recurrence. Earlier treatment will surely prolong the DFS but not the overall survival based on the prospective study of immediate vs delaye...

Agree with @Dr. First Last and @Dr. First Last's statements. It is a particularly challenging scenario, especially now that we have IDH inhibition available. In a vacuum of clear-cut guidelines, it is worth a discussion with the patient. Not all recurrent low-grade gliomas are created equal. As Dr. Stea said, time to recurrence is a crucial piece of information, as it gives you insight into the "tempo" of the disease. It is worth remembering that the phase 3 INDIGO trial explored the benefit of IDH inhibition with vorasidenib in recurrent low-grade gliomas who had not undergone prior treatment other than surgery and had residual measurable disease, which does not seem to fully apply to this patient as it is a gross total resection. Given th...

I would favor treatment rather than further observation in this patient. The important distinction is that she has already developed a recurrence following her initial GTR and has now required a second resection. To me, this provides an even stronger rationale for chemoradiotherapy rather than waiting for yet another recurrence.

We actually have long-term data from the observation arm of RTOG 9802, which enrolled patients younger than 40 who underwent GTR. Despite a median age of only 30, the median PFS was 6.9 years, and 71% of patients ultimately progressed. Perhaps more concerning, 10- and 15-year OS rates were only 77% and 65%, respectively. Granted, this was a molecularly heterogeneous population, but these are hardly optimal long-term ...

I agree with Dr. @Dr. First Last's considerations. My concerns would weigh on how long it took to recur, as well as the location of the lesion.

A longer interval between the initial resection might lean me towards observation, while a quicker recurrence would prompt treatment. Additionally, if the lesion did recur again, I'd consider how amenable it is to repeat excision. If the lesion is easily resectable, I'd lean towards observation. However, if re-excision would be difficult, treatment is preferred.

These decisions are highly individualized and depend on various factors. Generally, if the lesion causes greater concern for any reason, immediate treatment is more likely favored. I understand these considerations might lack specific guidan...

I approach these patients with my own treatment-related biases to avoid RT for as long as possible, since the risk for late and irreversible adverse effects increases with time. Patients with >10-year survivals are more likely to suffer from RT (RT necrosis, ICH, stroke, or cognitive decline) than those with worse prognoses. As a neuro-oncologist, my bias is the opposite of the radiation oncologists who answered before me.

The facts are not well established because >20-year follow-up is hard to accomplish and oligodendrogliomas are rare. However, patients with good risk factors probably have longer PFS and OS. The longer people live after RT, the greater the risk (Demopoulos et al., PMID 41895745).

Some patients really want to be aggressively...