Función pronóstica de los parámetros derivados de FDG PET en la estadificación preoperatoria del cáncer de endometrio / Prognostic role of FDG PET-derived parameters in preoperative staging of endometrial cancer

Objetivo: Investigar el papel pronóstico preoperatorio de la PET/TC con 18F-FDG en pacientes con carcinoma de endometrio (CE). Material y métodos: Se realizó PET/TC con 18F-FDG en 57 pacientes para el estudio preoperatorio del CE. Se evaluaron los valores de captación estandarizados máximos y medios (SUVmax, media), volumen tumoral metabólico (MTV) y glicólisis de lesión total (TLG) de tumores primarios, a diferentes umbrales de 40%, 50%, 60% (40-50-60), comparándose con las características anatomopatológicas. Se evaluó el rendimiento diagnóstico de los parámetros PET (categorizados por análisis ROC) en la discriminación de la enfermedad de bajo y mediano riesgo y el papel pronóstico en la supervivencia (supervivencia global-OS, supervivencia libre de enfermedad-SSE). Resultados: Los TLG40-50-60 categorizados fueron los únicos parámetros relacionados con FIGO estadio I versus II-III-IV (p = 0,0035 para todos). Los puntos de corte para la estratificación del riesgo fueron 83,69, 61,81 y 41,32, respectivamente (sensibilidad: 60%; especificidad, 71,43% para todos los parámetros. El estadio patológico 1 (pT1) del tumor primario se predijo con MTV60 y TLG40-50 (p = 0,0328, 0,0240 y 0,0147, respectivamente). Los umbrales óptimos fueron 7,795, 99,55 y 77,58, respectivamente (sensibilidad: 38,46%, 53,85% y 53,85%, respectivamente; especificidad: 88,64%, 79,55% y 81,82%, respectivamente). SUVmax y SUVmean40-50-60 fueron los únicos parámetros que discriminaron el subtipo endometrioide del no endometrioide. La sensibilidad fue del 64,86% y 62,16% para SUVmax y SUVmean50-60, y 62,16% para SUVmean40; la especificidad fue del 70% para todos los parámetros. La SG media (DE) fue del 79,77% (3,34%) y la SSE media fue del 77,89% (3,73%). El tipo de tumor fue la única variable significativamente asociada a la SG (p = 0,0486). TLG50 > 77,58 cm3 fue la única variable asociada a un mayor riesgo de recaída (p = 0,0472). Conclusión: TLG40-50-60 y MTV60 de EC primaria tienen valor pronóstico para discriminar FIGO y estadificación patológica. Estos resultados sugieren un posible papel de estos parámetros en la predicción de la agresividad de la CE, mejorando así la caracterización preoperatoria del cáncer de endometrio

Purpose: To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). Methods: 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40-50-60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival -OS; disease free survival - DFS) was evaluated. Results: The categorized TLG40-50-60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40-50-60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50-60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). Conclusion: TLG40-50-60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer

Prognostic role of FDG PET-derived parameters in preoperative staging of endometrial cancer. / Función pronóstica de los parámetros derivados de FDG PET en la estadificación preoperatoria del cáncer de endometrio.

PURPOSE: To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). METHODS: 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40-50-60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival -OS; disease free survival - DFS) was evaluated. RESULTS: The categorized TLG40-50-60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40-50-60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50-60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). CONCLUSION: TLG40-50-60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer.

FDG PET-derived parameters as prognostic tool in progressive malignant pleural mesothelioma treated patients.

PURPOSE: The value of FDG PET-derived parameters in predicting overall survival (OS), local relapse-free survival (LRFS) and distant relapse-free survival (DRFS) in treated patients with malignant pleural mesothelioma (MPM) was evaluated. METHODS: This retrospective evaluation included 55 MPM patients treated between March 2006 and February 2015 with FDG PET/CT-guided salvage helical tomotherapy (HTT) after previous surgery plus chemotherapy. Univariate Cox regression analysis was performed to assess the impact of the following FDG PET-derived parameters: biological target volume (BTV), mean and maximum standardized uptake values (SUVmean/max), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured using different uptake thresholds (40%, 50% and 60%). Logistic regression was then performed to identify the best FDG PET-derived parameters for selecting patients with poorer survival. RESULTS: The median OS was 9.1 months (range 0.0 - 69.6 months) after the end of HTT; 54/55 patients were dead at the last follow-up. BTV and TLG40, TLG50 and TLG60 were the most significant predictors of OS (p < 0.005). The median OS was 4.8 months in patients with MTV60 >5 cm3 and TLG40 >334.4, compared with 13.8 months and 16.1 months in patients with smaller values, respectively. The median LRFS and DRFS were 6.2 months (range 1.2 - 39.4 months) and 6.5 months (0.0 - 66.4 months), respectively. TLG40, TLG50 and TLG60 were significantly correlated with LRFS (p < 0.015). Median DRFS was 6.4 months in patients with MTV40 >39.6 cm3 and 6.2 months in patients with TLG40 >334.4, compared with 17 months and 18.8 months in patients with smaller values. BTV, TLG40 and MTV40 were also found to be good predictors in patients with poor OS/LRFS/DRFS (median survival times less than the median values). CONCLUSION: FDG PET-derived parameters effectively discriminated patients with a poor prognosis and may be helpful in the selection of MPM patients for salvage HTT.

Muscle-specific Drp1 overexpression impairs skeletal muscle growth via translational attenuation.

Mitochondrial fission and fusion are essential processes in the maintenance of the skeletal muscle function. The contribution of these processes to muscle development has not been properly investigated in vivo because of the early lethality of the models generated so far. To define the role of mitochondrial fission in muscle development and repair, we have generated a transgenic mouse line that overexpresses the fission-inducing protein Drp1 specifically in skeletal muscle. These mice displayed a drastic impairment in postnatal muscle growth, with reorganisation of the mitochondrial network and reduction of mtDNA quantity, without the deficiency of mitochondrial bioenergetics. Importantly we found that Drp1 overexpression activates the stress-induced PKR/eIF2α/Fgf21 pathway thus leading to an attenuated protein synthesis and downregulation of the growth hormone pathway. These results reveal for the first time how mitochondrial network dynamics influence muscle growth and shed light on aspects of muscle physiology relevant in human muscle pathologies.

Imaging biomarkers in prostate cancer: role of PET/CT and MRI.

Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed.

(11)C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients.

PURPOSE: To evaluate, in prostate cancer (PCa) patients the potential of (11)C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. METHODS: We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on (11)C-choline PET/CT only at the LN site. (11)C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. RESULTS: PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. CONCLUSION: (11)C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated (11)C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate.