A Neuroendocrine Tumor With One Lesion That Won't Take Up the Tracer It Needs To
The therapy that works best for this tumor type only works on the parts of the tumor still displaying the target it depends on — and one lesion, for reasons nobody can fully explain, isn't.
S.E., a 60-year-old woman, has kept the books for her family's small chain of dry cleaners for over thirty years and jokes that she found her midgut neuroendocrine tumor "the boring way" — an incidental finding on a CT scan ordered for unrelated back pain four years ago, well before any symptom of her own made her suspicious. She has been on high-dose octreotide since diagnosis, with stable disease for three years before this year's surveillance imaging showed clear growth in three liver metastases, alongside mild new flushing episodes suggesting early carcinoid physiology breaking through her somatostatin analog control. Gallium-68 DOTATATE PET, repeated as part of progression workup, showed strong somatostatin receptor avidity in two of the three growing lesions — and notably weak, near-background uptake in the third, a 3cm segment VI liver lesion that is otherwise indistinguishable on CT from its two avid neighbors.
NETTER-1 established Lutetium Lu 177 dotatate as superior to high-dose octreotide for progressive, somatostatin-receptor-positive midgut neuroendocrine tumors, with a substantial progression-free survival benefit — but the therapy works by delivering targeted radiation through the same receptor PET imaging is used to visualize, meaning a lesion without meaningful receptor expression receives little to no therapeutic radiation dose regardless of how well the rest of the tumor responds. Everolimus, validated in RADIANT-4 for progressive gastrointestinal and lung neuroendocrine tumors, works through a distinct mechanism entirely independent of somatostatin receptor status, treating all of S.E.'s disease uniformly regardless of which lesions do or don't light up on PET. Her one receptor-poor lesion is small enough to be easy to overlook next to two more dramatic, avid ones — and specific enough, in what it implies about treating her disease as a single uniform target, to be the actual crux of today's decision. Her Ki-67 of 4% marks the disease overall as well-differentiated, which is ordinarily what predicts receptor expression in the first place — so whether the near-background lesion represents dedifferentiation that grading has not yet caught, or simply heterogeneity in a low-grade tumor, is a question her own numbers raise and cannot answer.
Neuroendocrine tumor board, reviewing PET and CT together
Two of her three progressing lesions are strongly SSTR-avid, and NETTER-1 (Strosberg et al., NEJM 2017) showed a substantial progression-free survival benefit for PRRT over continued high-dose octreotide in exactly this population. Some degree of intra-patient receptor heterogeneity is common, and I don't think one smaller, weakly-avid lesion should override treating the majority of her disease with the therapy that's shown the biggest benefit here.
I want to be precise about what "some heterogeneity is common" means here — we're not inferring possible heterogeneity from indirect data, we're looking directly at a PET scan showing near-background uptake in a specific, measurable lesion. PRRT delivers its radiation dose through that exact receptor. Proceeding with PRRT means proceeding knowing one lesion will likely receive little therapeutic benefit, not hoping it might. Everolimus, validated in RADIANT-4, doesn't depend on receptor status at all — it would at least engage all three lesions, even if less dramatically in the avid ones.
I'm not disputing PRRT's benefit in avid disease — I'm disputing treating a documented, imaged gap as background noise rather than a real limitation for this specific patient.
There's a way to stop treating this as one-mechanism-must-cover-everything. The receptor-poor lesion is solitary, 3cm, and in a segment that's technically accessible for radiofrequency ablation. Ablate that lesion directly, and give PRRT for the two avid ones where it has the strongest evidence. That addresses each lesion according to what actually works on it, rather than asking either systemic option to be the single answer for genuinely heterogeneous disease.
Agreed: PRRT for the two SSTR-avid liver lesions, with radiofrequency ablation of the receptor-poor segment VI lesion performed before the first PRRT cycle, addressing each lesion according to its own demonstrated biology rather than treating the disease as a single uniform target.
The medical oncologist's underlying concern — that PRRT alone would have knowingly left one lesion undertreated — was resolved by the ablation plan rather than by switching to everolimus outright, and everolimus was recorded explicitly as the next planned option if either the treated or ablated site progresses further.