Abstract A013: 225Actinium and tandem 177Lutetium/225Actinium - FAPi therapy in medullary thyroid carcinoma
Notice bibliographique
Résumé
Abstract Background Medullary thyroid carcinoma (MTC) has limited systemic options in advanced stages. Cancer-associated fibroblasts in tumor stroma in MTC overexpress fibroblast activation protein (FAP). FAP-targeted radioligand therapy (FAPI RLT) thus offers a novel theranostic approach. Alfa particle emitters like 225Actinium (225Ac) deliver high linear energy transfer (LET) to small, aggressive lesions, potentially improving tumor kill, where as bulkier lesions merit use of beta emitter 177lutetium alone or in tandem with 225Actinium. Methods A retrospective analysis of 31 patients with advanced/metastatic MTC treated FAPI RLT at our center was done. These patients had progressive disease despite exhausting TKI options. Pre therapy 68Ga-FAPI PET/CT demonstrated intense uptake in the lesions. 225Ac-FAPi (DOTAGA.Glu.(FAPi)_2) was administered intravenously (3.5–7.0 MBq (95–190 μCi) per treatment cycle) every 8 to 12 weeks. Patients with bulky disease received tandem therapy (two cycles of 177Lu-FAPi dimer ∼5–6 GBq of 177Lu-FAPi each followed by one cycle of 225Ac-FAPi dimer, with each cycle ∼8 weeks apart). Full blood count, renal, and liver function were obtained prior to each cycle.Treatment response was assessed biochemically (serum calcitonin and CEA) and by 68Gallium FAPI-PET/CT every 2 cycles. Progression-free survival (PFS) and overall survival (OS) were calculated from first FAPI therapy, with a follow-up duration up to 3 years. Adverse events were graded by CTCAE v5.0. Results Among 14(∼45%) MTC patients receiving tandem 177Lu/225Ac-FAPi dimer therapy, 68% patients had ∼ 52 to 67% decline in serum calcitonin and CEA levels while 17(∼55%) patients who received only 225Ac-FAPi dimer therapy demonstrated 46 to 61 % reduction in serum calcitonin and CEA levels. Restaging 68Ga-FAPi PET/CT in showed partial metabolic responses in 62.5% of patients and stable disease in 20% patients. A median PFS of ∼32 months and median OS of ∼37 months was observed. A substantial percentage of treated patients remained progression-free at 3 years post-therapy, though subsequent PFS data are awaited. Treatment was generally well tolerated with grade III hematologic toxicity observed in few patients in tandem therapy group (anemia in ∼4%, thrombocytopenia in ∼6.5%). Overall, side effects were transient and reversible. The safety profile of 225Ac-FAPI and tandem therapy mostly includes CTCAE v5.0 grade 1–2 effects. Conclusion Our study suggests FAPI RLT as an promising salvage option for advanced MTC. A substantial tumor response rate (by biochemical and PET criteria) and median PFS on the order of 2 to 3 years were observed. The safety profile appears favorable, with few low grade toxicities, mainly hematological. We conclude that tandem 177Lu/225Ac-FAPI or 225Ac-FAPI therapy can achieve encouraging disease control in carefully selected FAP-positive MTC patients, with durable PFS and OS benefits and acceptable toxicity. Citation Format: Dr Nitin Gupta. 225Actinium and tandem 177Lutetium/225Actinium - FAPi therapy in medullary thyroid carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr A013.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».