How do you manage glioblastoma presenting with leptomeningeal dissemination?

Hospice is a very legitimate option. As physicians, we recommend this far too infrequently.

In an older person with poor PS who is not symptomatic from the leptomeningeal disease, they are still more likely to suffer from their primary tumor so I think it is reasonable to just ignore it.

I think performance status and prognosis (age, MGMT) are critical. One could argue for a trial of TMZ alone in an MGMT-methylated poor PS patient. For "better" prognosis patients, I have used a whole brain of 40 Gy/20 with SIB 50 Gy/20 to the contrast-enhancing portion of the tumor as an aggressive palliative dose for someone with symptomatic leptomeningeal disease, young person with excellent PS and asymptomatic from leptomeningeal disease, or GBM in the setting of gliomatosis cerebri (in that case it is not whole brain but T2+1 cm margin). It is...

Have a serious discussion about prognosis, getting affairs in order, and end-of-life care.

All patients with Glioblastoma should have a frank discussion about end-of-life care, health care proxy designation, and advance directives within the first 2-3 visits. I generally have such discussions on the first MRI following chemoradiation therapy, since this is a window of opportunity to think clearly about the answers with less time pressure and when things are generally stable.

Leptomeningeal dissemination has important additional clinical implications, although the literature indicating worse prognosis is mixed, given the overall terrible prognosis of GBM. However, care should be taken to identify all sites of CSF dissemination, including an MRI of the total spine with contrast for symptom palliation. Notably, the incidence of hydro...

Considered initially a rare complication in gliomas, the incidence of LMD is estimated at 4%, reaching 25% on postmortem neuropathological evaluation. There is no standard-of-care treatment for LMS in patients with GBM, although multiple groups have proposed several therapeutic options (e.g., methotrexate, cytarabine, thiotepa, and/or nimustine) with limited efficacy. The life expectancy is estimated to be 2-5 months.

If the LMD is limited, I would try to include that portion of the brain included in the primary radiation field approach; if diffuse, I'd just treat the contrast-enhancing portion with an abbreviated course of RT then consider using Optune (Novocure) along with temozolamide depending on age, KPS and whether the primary focus o...

I'd be eager to hear from other neuro-oncologists on this but generally, in my practice, similar to without LMD. Our chemotherapeutic agents are BBB penetrants, and IT cytotoxic chemotherapy only penetrates a couple of millimeters (so would not address the parenchymal disease). Having said this, I'm aware of some retrospective data from China on IT MTX with systemic therapy and of a few oncologists across the US who have offered a similar strategy. For me, the risks/benefits balance and where the data is currently is such that I have not recommended it. Another consideration is that I find LP usually is negative on cytology, which I was taught as this is more of a subependymal/subpial process rather than free-floating cells, as in systemic ...

Also depends on the molecular profile of the GBM. If there is a suitable molecular target, then low threshold to move from TMZ/radiation onto targeted therapy.

As others have pointed out, many different approaches to this rare presentation of glioblastoma. Leptomeningeal dissemination is more common later in the disease course of glioblastoma, particularly after surgical manipulation. An approach we have used for patients with good performance status presenting with leptomeningeal dissemination on presentation is biopsy followed by CSI to 30 Gy with concurrent and adjuvant temozolomide +/- Avastin. A boost can be considered depending on the primary site of disease and how well the patient tolerates CSI. As with any malignant leptomeningeal dissemination, patients are at risk of developing hydrocephalus and may need to have a shunt placed.

Leptomeningeal dissemination would require enlarging the radiation field to cover the disseminated area.