Even with negative biopsies, post-immunotherapy scans and scopes can show residual masses or mucin pools that are mistaken for active cancer. This makes determining a true complete clinical response difficult and can lead to unnecessary surgeries where no cancer is found, as these changes can take years to resolve.

Diakonos chose glioblastoma, the deadliest brain cancer, for its first trial. This counterintuitive strategy provided a faster data readout, powerful validation upon success, and a lower regulatory burden from the FDA—all critical advantages for an early-stage company.

After immunotherapy, many colorectal cancer patients have residual nodules on scans that appear to be partial responses. However, ctDNA testing can confirm these are often just scar tissue, not active disease. This provides the confidence to stop therapy at the two-year mark and avoid unnecessary surgeries for what are effectively complete responses.

Glioblastoma isn't a single mass but has finger-like 'tentacles' (diffuse infiltration) extending into brain tissue. It is also genetically and cellularly diverse, meaning a single-pathway drug will inevitably miss many tumor cells, leading to rapid recurrence and treatment failure.

When imaging is ambiguous between radiation necrosis and tumor progression in the brain, a short course of high-dose dexamethasone can serve as a diagnostic tool. Imaging improvement after steroids strongly suggests radionecrosis, potentially avoiding an invasive biopsy.

Patients on niragacestat for desmoid tumors often experience rapid symptom improvement. However, this clinical benefit significantly precedes radiological response (tumor shrinkage on scans), which can take over five months to appear. This disconnect is crucial for managing patient expectations and assessing early treatment efficacy.

Patients showing a near-complete response at the end of a six-month immunotherapy course may still convert to a full complete response two months later without additional treatment. Clinicians should consider 'holding their nerve' and re-evaluating with repeat imaging before altering the treatment plan.

Immunotherapies can be effective even without causing significant tumor shrinkage. Immunocore's drug KimTrack had a low 5-7% objective response rate (ORR) but demonstrated a massive overall survival (OS) benefit, challenging the reliance on traditional chemotherapy metrics for evaluating modern cancer treatments.

Therapies that rewire cancer cells to mature can cause "differentiation syndrome," a flood of immune cells. While a dangerous side effect, it's considered an on-target toxicity, confirming the drug is successfully restoring the cell's lost function and providing a real-time signal of its effectiveness.