About a year into treatment, I got a message from Fred’s wife. They were planning his retirement party. Thirty-seven years of teaching health and fitness. She wanted to make sure he’d be up for it, that it wouldn’t be too much.
He was 14 months out from a glioblastoma diagnosis.
He went to the party.
GBM is not a diagnosis I soften. It is IDH-wildtype, WHO grade 4, and it carries a median overall survival of roughly 14 to 16 months on the Stupp protocol — temozolomide plus radiation, then adjuvant TMZ. Roughly one in three patients are gone within a year. The ones who do better almost always have one thing in common: MGMT promoter methylation. When that gene is methylated, the tumor can’t repair the DNA damage temozolomide inflicts. The drug actually works.
Fred’s MGMT was hypermethylated at over 80%. That matters. It is not a guarantee, but it is the single most favorable prognostic marker in newly diagnosed GBM, and it changes how aggressively I approach the integrative protocol. There is more to work with.
He came to me a few weeks after a near-total resection of a large left frontal mass. The tumor sat directly at Broca’s area. He had expressive aphasia. He could understand everything, but the words wouldn’t come out right. He was a health and fitness teacher. Words were his work.
He had just started chemoradiation. I had about six weeks to get a protocol in place before the real work of adjuvant chemotherapy began.
What we built, and why
The integrative protocol in GBM has to do several things at once: sensitize the tumor to chemotherapy, support the immune system, reduce cerebral edema without relying entirely on dexamethasone, and maintain whatever neurological function is still intact. These are not independent goals. The biology connects them.
Curcumin was the first layer. The preclinical evidence in GBM is more substantial than most people realize. Curcumin sensitizes GBM cells to temozolomide by generating reactive oxygen species and simultaneously suppressing phosphorylated AKT and mTOR, two pathways GBM uses to evade cell death. In U87-MG cell lines and xenograft models, the combination outperformed TMZ alone. I started Fred at 1200 mg twice daily with meals and held it there through the radiation phase.
Trametes versicolor (turkey tail) at 1500 mg twice daily, away from food. The goal here is NK cell activation and white blood cell support during chemotherapy. TMZ is myelosuppressive. Turkey tail’s polysaccharopeptide fraction has immunomodulatory properties that have been studied in breast cancer patients during treatment, and the in vitro data on NK cell potentiation is solid. In the context of GBM, where the tumor actively suppresses local immunity, this is not a small consideration.
1:1 THC:CBD at 50 mg twice daily. I want to be precise about the intent here. This was not about antitumor effects — the data in humans is not there yet for that framing. The goal was quality of life, specifically his aphasia. Cannabinoids are neuroprotective and anti-inflammatory in the CNS. There is also a signal worth paying attention to: a GW Pharmaceuticals phase 2 study showed an 83% one-year survival rate in the 1:1 THC:CBD plus TMZ group versus 53% in the TMZ-only control, with median survival of 662 days versus 369. That data needs replication in a larger trial before I lead with it, but it informed the decision to include it. The dose was reasonable, titrated slowly, and unlikely to cause harm. I made that framing explicit to Fred and his wife.
Boswellia extract was the intervention I was most confident would affect his outcomes positively. His neuro-oncologist at Swedish had given his the same recommendation. Boswellic acids reduce cerebral edema (there is a longitudinal pilot study in GBM patients specifically showing this) and the mechanism is COX and 5-LOX inhibition at the tumor margin. It is important that your Boswellia supplement contains AKBA (3-O-acetyl-11-keto-β-boswellic acid) as it is the most potent anti-inflammatory compound found in Boswellia serrata. I started him at 1200 mg daily and titrated to 3800 mg as tolerated. Several months in, imaging showed improvement in cerebral edema. He was tolerating ~3g twice daily without issue. This matters because every milligram of dexamethasone he doesn’t need is a win. Steroids cause weight gain, dysglycemia, immune suppression, and bone loss, and getting a GBM patient off them is almost always the right direction.
Ketogenic diet and 14-hour intermittent fasting for metabolic pressure on the tumor. GBM is highly glycolytic. Restricting glucose while elevating ketones exploits the Warburg effect and is the most evidence-informed dietary intervention we have in gliomas. The systematic review by Sargaço et al. supports its safety and feasibility. I referred him to oncology-specialized dietitians for support because this transition during active treatment requires guidance.
What actually happened
Nothing went smoothly. It never does with GBM.
His aphasia improved completely after surgery, then came back two weeks later. We navigated steroid tapers repeatedly; every time we got him below 2 mg dexamethasone, his speech worsened. A few months into adjuvant chemotherapy, imaging showed significant cystic expansion at the resection site. His neurosurgeon placed an Ommaya reservoir. Shortly after, he was diagnosed with a pulmonary embolism and started anticoagulation. The same month, he got COVID-19. We added nattokinase, liposomal lactoferrin, and L-arginine plus vitamin C for the post-COVID syndrome.
He went to Italy for three weeks and had a wonderful time sans his medical team.
When he came back, we added two more interventions. Low dose naltrexone at 4.5 mg four nights per week for immune modulation, endorphin upregulation, and its antiproliferative effects, which have been documented since the 1980s. He tolerated it well. His aphasia improved and his right motor function improved on it. I believe LDN belongs in most integrative oncology protocols for its safety profile alone. The risk-benefit here is not complicated.
All in all, Fred was doing relatively well. He and his wife were still taking short trips and spending time together. At one visit, they were both quieter than usual. His wife finally said they had a question neither of them wanted to say out loud. Since the start of treatment, they had not been able to be intimate. Fred was experiencing erectile dysfunction.
Tadalafil is an intervention that isn’t often discussed in GBM care but I think it belongs in the conversation. Male GBM patients on chronic dexamethasone are at high risk for steroid-induced hypogonadism and erectile dysfunction. This is rarely addressed, even though it directly affects quality of life and relationship functioning during an already devastating illness. Tadalafil (a PDE5 inhibitor) addresses this while offering a mechanistic bonus: preclinical data shows PDE5 inhibitors reduce myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment. MDSCs are one of GBM's primary tools for evading immune destruction, they suppress T-cell and NK-cell activity locally. By reducing MDSC burden, tadalafil may help the immune system regain ground. The evidence here is early and mostly preclinical, but the drug while closely monitored is safe, the QoL rationale is clear, and the potential anti-tumor immune benefit makes it a reasonable addition in male GBM patients on steroids. I discuss it with every eligible patient.
After some tinkering with the dose, Fred was able to achieve and maintain an erection. His life went on.
Valganciclovir came last. The Stragliotto data out of Sweden is hard to ignore: in newly diagnosed GBM patients receiving valganciclovir as an add-on, median OS was 24.1 months versus 13.3 months in controls. The 2-year survival rate was 49.8% versus 17.3%. The proposed mechanism involves cytomegalovirus, which is found in GBM tissue in a high percentage of tumors and is thought to drive tumor-promoting inflammation. Though his tumor was not tested for CMV, his serum titers were suggestive for CMV reactivation. The data needs a prospective randomized trial to be definitive, but it is safe, it has a plausible mechanism, and the survival signal is large enough that I discuss it with every GBM patient.
By the one-year mark, Fred was on 1.5 mg of dexamethasone, down from 10 mg at his worst. He was having what his wife described as “really good weeks.” He was answering in short sentences on our telehealth visits. But recent imaging was suggestive of progression at the posterior rim, and the central portion of the lesion appeared non-viable on PET. His neuro-oncologist was following closely.
One year after diagnosis, he had his retirement party.
What I want clinicians and patients to take from this
GBM is MGMT-stratified medicine whether we acknowledge it or not. If your patient is newly diagnosed, the first question is: what is the methylation status, and what is the percentage? That shapes the whole protocol.
The integrative approach in GBM is not about replacing Stupp, it is about making Stupp work better, protecting neurological function, getting patients off steroids faster, and giving the immune system something to work with. Every intervention in Fred’s protocol has a rationale and a reference. None of it is universally reproducible, and not all of it has RCT-level evidence in humans. I say that clearly to every patient.
Something else happens when a diagnosis carries a prognosis this heavy. Providers get focused on the protocol, the next scan, the next decision point, and the rest of the person quietly disappears from the conversation. No one asked Fred about sex. No one asked his wife. Two people in a long marriage navigating something unsurvivable, and that part of their life had simply stopped. It took them months to bring it up, and only because there was enough trust in the room to ask. The retirement party, the trip to Italy, the quiet question about intimacy, these are not detours from the clinical work. They are the clinical work. When we stop seeing the person behind the diagnosis, we lose the most important information: what they are still living for, and what they need to keep living well.
What I believe, based on years of working in this space: the integrative layer matters. Whether it is curative or contributory or simply supportive, I cannot tell you from a single case. What I can tell you is that Fred made it to his retirement party, he felt as well as he could have during it. He also felt the uttermost love and support and devastation that happens when you are in his position.
Fred lived with GBM for two and a half years. Not long before he died, he was reminiscing and told me he was disappointed I had missed his retirement party, and that he expected me at his second — his memorial service. He passed at home surrounded by his family.
I went to the party.
Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.
She provides medical care for Washington residents and offers global health coaching.
To schedule a free 15-minute consult, visit drkseniamalarkey.com
Interesting how many of these compounds have CNS/BBB relevance — it makes the combination feel very GBM-specific. I suspect these are also an important backbone in other cancers where brain mets are a risk (such as HER2 breast cancer).
I’m also curious about the valganciclovir angle: do you see a role for CMV targeting beyond GBM, especially in patients with high IgG, or is that context-dependent?
I recently wrote a deeper dive on Turkey Tail and its immune effects if helpful:
https://thecancerstrategist.substack.com/p/how-a-strange-mushroom-became-one