Sancho-Rodriguez, L. (Lidia)

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    11C-methionine PET/CT in assessment of multiple myeloma patients: comparison to 18F-FDG PET/CT and prognostic value evaluation
    (2022) Guillén-Valderrama, E.F. (Edgar Fernando); Marcos-Jubilar, M. (María); Sancho-Rodriguez, L. (Lidia); Prieto-Azcárate, E. (Elena); Alfonso-Piérola, A. (Ana); Garcia-Velloso, M. J. (María José); Rodriguez-Otero, P. (Paula); Rosales, J.J. (Juan José); Nuñez-Cordoba, J.M. (Jorge M.); San-Miguel, J.F. (Jesús F.); Morales-Lozano, M. I. (Mª Isabel)
    Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[11C]- methionine (MET), suggest higher sensitivity than 18F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of 1FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37-83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.
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    11C-Methionine PET/CT in Assessment of Multiple Myeloma Patients: Comparison to 18F-FDG PET/CT and Prognostic Value
    (MDPI, 2022) Sin Autoridad; Rodriguez-Otero, P. (Paula); Sancho-Rodriguez, L. (Lidia); Nuñez-Cordoba, J.M. (Jorge M.); Prieto, E. (Elena); Marcos-Jubilar, M. (María); Rosales, J.J. (Juan José); Alfonso-Piérola, A. (Ana); Guillén-Valderrama, E.F. (Edgar Fernando); San-Miguel, J.F. (Jesús F.); Garcia-Velloso, M. J. (María José)
    Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[11C]- methionine (MET), suggest higher sensitivity than 18F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of 1FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37–83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.
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    3D voxel-based dosimetry to predict contralateral hypertrophy and an adequate future liver remnant after lobar radioembolization
    (Springer, 2021) Grisanti-Vollbracht, F. (Fabiana); Prieto, E. (Elena); Bastidas, J.F. (Juan Fernando); Sancho-Rodriguez, L. (Lidia); Rodrigo, P. (Pablo); Beorlegui, C. (Carmen); Iñarrairaegui, M. (Mercedes); Bilbao-Jaureguízar, J. (José Ignacio); Sangro, B. (Bruno); Rodriguez-Fraile, M. (Macarena)
    Introduction: Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. Materials and methods: Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2–5 (T2), and 6–12 months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. Results: Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30 Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30 Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). Conclusion: NTL-Dmean and NTL exposed to ≥ 30 Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30 Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.
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    Diagnostic accuracy of visual analysis versus dual time-point imaging with 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules with low uptakePrecisión diagnóstica del análisis visual frente al protocolo de imagen tardía con 18F-FDG PET/TC para la caracterización de nódulos pulmonares indeterminados con baja captación
    (Elsevier, 2021) Grisanti-Vollbracht, F. (Fabiana); Zulueta, J. (Javier); Rosales, J.J. (Juan José); Sin Autoridad; Sancho-Rodriguez, L. (Lidia); Lozano, M.D. (María Dolores); Mesa-Guzmán, M.A. (Miguel Alejandro); Garcia-Velloso, M. J. (María José)
    Objective: To determine the accuracy of visual analysis and the retention index (RI) with dual-time point 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules (IPN) with low FDG uptake. Materials and methods: A retrospective analysis was performed on 43 patients (28 men, 64 ± 11 years old, range 36–83 years) referred for IPN characterization with 18F-FDG-PET/CT and maximum standard uptake value ≤2.5 at 60 min post-injection (SUVmax1). Nodules were analyzed by size, visual score for FDG uptake on standard (OSEM 2,8) and high definition (HD) reconstructions, SUVmax1, SUVmax at 180 min post-injection (SUVmax2), and RI was calculated. The definitive diagnosis was based on histopathological confirmation (n = 28) or ≥2 years of follow-up. Results: Twenty-four nodules (56%) were malignant. RI ≥ 10% on standard reconstruction detected 18 nodules that would have been considered negative using the standard SUVmax ≥ 2.5 criterion for malignancy. RI ≥ 10% had a sensitivity, specificity, PPV, NPV and accuracy of 75%, 73.7%, 78.3%, 70%, and 74.4%, respectively, while for FDG uptake > liver on HD these were 79.1%, 63.2%, 73.1%, 70.6%, and 72.1%, respectively. SUVmax1 ≥ 2, SUVmax2 > 2.5 and FDG uptake > liver on standard reconstruction had a PPV of 100%. FDG uptake > mediastinum on HD had a NPV of 100%. Conclusions: RI ≥ % was the most accurate criterion for malignancy, followed by FDG uptake > liver on HD reconstruction. On standard reconstruction, SUVmax1 ≥ 2 was highly predictive of malignancy, as well as SUVmax2 > 2.5 and FDG uptake > liver. FDG uptake < mediastinum on HD was highly predictive of benign nodules.
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    A proof-of-concept study of the in-vivo validation of a computational fluid dynamics model of personalized radioembolization
    (2021) Antón, R. (Raúl); Antoñana, J. (Javier); Aramburu-Montenegro, J. (Jorge); Ezponda, A. (Ana); Prieto, E. (Elena); Andonegui-Isasa, A. (Asier); Ortega, J. (Julio); Vivas, I. (Isabel); Sancho-Rodriguez, L. (Lidia); Sangro, B. (Bruno); Bilbao-Jaureguízar, J. (José Ignacio); Rodriguez-Fraile, M. (Macarena)
    Radioembolization (RE) with yttrium-90 (90Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six 90Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by 90Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual 90Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict 90Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.
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    The Pattern of Progression Defines Post-progression Survival in Patients with Hepatocellular Carcinoma Treated with SIRT
    (Springer, 2020) de la Torre-Aláez, M. (Manuel Antonio); Sin Autoridad; Casadei-Gardini, A. (Andrea); Lorente-Bilbao, J.I. (José Ignacio); Rodriguez-Fraile, M. (Macarena); Sancho-Rodriguez, L. (Lidia); D'Avola, D. (Delia); Herrero, J.I. (José Ignacio); Iñarrairaegui, M. (Mercedes); Sangro, B. (Bruno)
    Purpose In patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib, post-progression survival (PPS) is marked by the pattern of progression. Our aim was to assess the influence of the pattern of progression to selective internal radiotherapy (SIRT) in PPS among patients with HCC. Methods A retrospective analysis of patients treated with SIRT between 2003 and 2015 was conducted, excluding those with a single nodule < 5 cm or with metastases. Four patterns of progression to SIRT were defined: target tumour growth, non-target tumour growth, new intrahepatic disease, and new extrahepatic disease. PPS was calculated from the time of progression based on RECIST 1.1 criteria. Results Out of the 102 patients who met the selection criteria, 76 progressed after a median follow-up of 15 months. Median PPS was 6.5 months (95% CI 3.8–9.3 months). Patients who progressed at pre-existing lesions had a better PPS (median 12.5 months) than those who progressed with new lesions inside or outside the liver (median 4.2 months) (p = 0.02). In a Cox model adjusted by liver function and systemic inflammation, the pattern of progression had a hazard ratio of 1.64 (95% CI 0.92–2.93; p = 0.093). Conclusion In a cohort of HCC patients treated with SIRT, the pattern of progression associated with worst survival was the development of new intrahepatic lesions or extrahepatic metastases.
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    18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) predictive score for complete resection in primary cytoreductive surgery
    (2022) Boria, F. (Félix); Chiva, L. (Luis); Sin Autoridad; Gutierrez, M. (Monica); Sancho-Rodriguez, L. (Lidia); Alcázar, A. (Andrés); Zapardiel, I. (Ignacio)
    Objective To assess the value of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan, combined with clinical variables, in predicting complete cytoreduction in selected patients with advanced ovarian cancer. Methods We carried out a multicenter, observational, retrospective study evaluating patients who underwent primary cytoreductive surgery for advanced ovarian cancer in two Spanish centers between January 2017 and January 2022. Inclusion criteria were histological confirmation of invasive epithelial ovarian carcinoma; preoperative International Federation of Gynecology and Obstetrics (FIGO) stage III or IV; upfront cytoreductive surgery; and 18F-FDG PET/CT performed 1 month prior to surgery. A modified 18F-FDG PET/CT peritoneal cancer index score was calculated for all patients. Clinical variables and preoperative 18F-FDG PET/CT findings were analyzed and a multivariate model was constructed. A predictive score based on the odds ratio of the variables was calculated to determine patient selection. Results A total of 45 patients underwent primary cytoreductive surgery. Complete resection was achieved in 36 (80%) patients. On multivariate analysis, two clinical variables (age ≥58 years and American Society of Anesthesiology score ≥3) and two preoperative 18F-FDG PET/CT scan findings (presence of extra-abdominal lymph node involvement and modified peritoneal cancer index value of 6 or more) were associated with gross residual disease. For this multivariate model predictive of non-complete cytoreduction, the area under the curve was 0.881. A predictive value of ≥5 was the most predictive cut-off for gross residual disease. Complete resection rate was 91.7% in patients with a score of ≤4 and 33.3% in patients with a score of ≥5 points on the predictive score. Conclusions In selected patients, a predictive score value ≥5 may be consider as a cut-off point for triaging patients to diagnostic laparoscopy before the primary surgery or neoadjuvant chemotherapy.
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    Evaluation of the role of thyroid scintigraphy in the differential diagnosis of thyrotoxicosis
    (Wiley, 2020) Perdomo-Zelaya, C.M. (Carolina M.); Sin Autoridad; Sancho-Rodriguez, L. (Lidia); Paricio, J.J. (J. J.); Lozano, M.D. (María Dolores); Higuera, M. (Magdalena) de la; Arbizu, J. (Javier); Galofre, J.C. (Juan Carlos)
    Objective: A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH-R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third-generation TRAb are not available. First-generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first-generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first-generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism. Methods: We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first-generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis. Results: Seventy-three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves’ disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%). Conclusions: Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first-generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first-generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.