RT Journal Article SR Electronic T1 Optimal [18F]FDG PET/CT Cutoff for Pathologic Complete Response in HER2-Positive Early Breast Cancer Patients Treated with Neoadjuvant Trastuzumab and Pertuzumab in the PHERGain Trial JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 708 OP 713 DO 10.2967/jnumed.123.266384 VO 65 IS 5 A1 Gebhart, Geraldine A1 Keyaerts, Marleen A1 Guiot, Thomas A1 Flamen, Patrick A1 Ruiz-Borrego, Manuel A1 Stradella, Agostina A1 Bermejo, Begoña A1 Escriva-de-Romani, Santiago A1 Calvo Martínez, Lourdes A1 Ribelles, Nuria A1 Fernandez-Abad, María A1 Albacar, Cinta A1 Colleoni, Marco A1 Garrigos, Laia A1 Atienza de Frutos, Manuel A1 Dalenc, Florence A1 Prat, Aleix A1 Marmé, Frederik A1 Schmid, Peter A1 Kerrou, Khaldoun A1 Braga, Sofia A1 Gener, Petra A1 Sampayo-Cordero, Miguel A1 Cortés, Javier A1 Pérez-García, José Manuel A1 Llombart-Cussac, Antonio YR 2024 UL http://jnm.snmjournals.org/content/65/5/708.abstract AB The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)–positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [18F]FDG PET/CT. [18F]FDG PET/CT responders were defined as patients with an SUVmax reduction (ΔSUVmax) of at least 40% in all of their target lesions after 2 cycles of trastuzumab and pertuzumab (HP) (with or without endocrine therapy). In total, 227 of 285 patients (80%) included in the HP arm showed a predefined metabolic response and received a total of 8 cycles of HP (with or without endocrine therapy). Pathologic complete response (pCR), defined as ypT0/isN0, was achieved in 37.9% of the patients. Here, we describe the secondary preplanned analysis of the best cutoff of ΔSUVmax for pCR prediction. Methods: Receiver-operating-characteristic analysis was applied to look for the most appropriate ΔSUVmax cutoff in HER2-positive early breast cancer patients treated exclusively with neoadjuvant HP (with or without endocrine therapy). Results: The ΔSUVmax capability of predicting pCR in terms of the area under the receiver-operating-characteristic curve was 72.1% (95% CI, 65.1–79.2%). The optimal ΔSUVmax cutoff was found to be 77.0%, with a 51.2% sensitivity and a 78.7% specificity. With this cutoff, 74 of 285 patients (26%) would be classified as metabolic responders, increasing the pCR rate from 37.9% (cutoff ≥ 40%) to 59.5% (44/74 patients) (P < 0.01). With this optimized cutoff, 44 of 285 patients (15.4%) would avoid chemotherapy in either the neoadjuvant or the adjuvant setting compared with 86 of 285 patients (30.2%) using the original cutoff (P < 0.001). Conclusion: In the PHERGain trial, an increased SUVmax cutoff (≥77%) after 2 cycles of exclusive HP (with or without endocrine therapy) achieves a pCR in the range of the control arm with chemotherapy plus HP (59.5% vs. 57.7%, respectively), further identifying a subgroup of patients with HER2-addicted tumors. However, the original cutoff (≥40%) maximizes the number of patients who could avoid chemotherapy.