A low total metabolic tumor volume independently predicts for a longer time to first treatment in initially observed, low tumor burden follicular lymphoma.

Watchful waiting is an acceptable management strategy for advanced-stage, low tumor burden (LTB) patients with follicular lymphoma (FL). However, the prediction of how long this treatment-free observation period will last remains imperfect. We explored whether total metabolic tumor volume (TMTV) and other positron emission tomography parameters were predictive of time to first treatment (TTFT). We analyzed 97 grade 1-3A advanced-stage LTB FL patients and found that a high TMTV was associated with other tumor burden features at diagnosis. Patients with a TMTV above our established cutoff of 50 mL had a significantly shorter median duration of observation (2.6 vs. 8.8 years; p = 0.001). At 5 years, 77% of patients with a high TMTV and 46% of patients with a low TMTV required treatment. In the multivariable analysis, a high TMTV was the only independent factor predicting TTFT (hazard ratio = 2.09; p = 0.017). Overall, TMTV is a strong predictor of the duration of observation in LTB FL patients. Upon validation of our cutoff in external series and standardization of the methodology, the TMTV could become an additional factor to consider deferring or initiating treatment in otherwise LTB patients.

Predictive factors of preoperative sentinel lymph node detection in intermediate and high-risk endometrial cancer.

BACKGROUND: In endometrial cancer (EC), sentinel lymph node (SLN) mapping has emerged as an alternative to systematic lymphadenectomy. Little is known about factors that might influence SLN preoperative detection. The aim of our study was to evaluate the clinical and technical variables that may influence on the success of SLN detection in preoperative lymphatic mapping in patients with intermediate and high-risk EC when performing transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR). METHODS: Between March 2006 and March 2017, we prospectively enrolled patients with histologically confirmed EC with intermediate or high-risk of lymphatic involvement. All women underwent SLN detection by using TUMIR approach. After radiotracer injection, pelvic and abdominal planar and SPECT/CT images were acquired to obtain a preoperative lymphoscintigraphic mapping. Pattern of drainage was registered and analyzed to identify the factors directly involved in drainage. Sonographer learning curves to perform TUMIR approach were created following Cumulative Sum and Wright methods. Univariate and multivariate analyses were performed using logistic regression. RESULTS: During study period, 123 patients were included. SLN preoperative detection rate was 70.7%. Age under 75 years at diagnosis (P<0.01), radiotracer injection above 4 mL -high-volume- (P<0.01), and tumoral size below 2 cm (P=0.04) were associated with higher SLN preoperative detection rate. Twenty-five procedures were necessary to attain an adequate performance in TUMIR approach. CONCLUSIONS: The higher SLN preoperative detection rate in women with intermediate and high-risk endometrial cancer after TUMIR approach was related with younger age, smaller tumors and high-volume injection of radiotracer. Sonographers are required to perform 25 procedures before acquiring an expertise in radiotracer injection.

Comparison of [18F]fluorocholine PET/CT with [99mTc]sestamibi and ultrasonography to detect parathyroid lesions in primary hyperparathyroidism: a prospective study.

Background: Primary hyperparathyroidism is a common endocrine disorder produced by the increase of parathyroid hormone (PTH) due to a benign adenoma of a single parathyroid gland, or as multiple gland hyperplasia, or as a rare malignant tumor. Preoperative imaging scans are frequently necessary for the minimally invasive parathyroidectomies to identify the location of enlarged parathyroid glands and to design the procedure. Methods: The diagnostic reliability of [18F]fluorocholine positron emission tomography/computed tomography (FCH PET/CT), [99mTc]sestamibi [multiplexed ion beam imaging (MIBI)] and cervical ultrasonography was analyzed in 37 patients diagnosed with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. The three preoperative imaging techniques were correlated with intraoperative and histopathological findings as well as changes in biochemical parameters (serum PTH and calcium levels). Statistical analysis was carried out with SPSS version 24.0. Results: In 30 of 37 patients (81.1%), FCH PET/CT correctly localized the pathological gland. In 3 cases of ectopic adenomas, the accuracy of the techniques was 100% (3/3) for FCH PET/CT, 66.7% (2/3) for MIBI, and 33.3% (1/3) for neck ultrasonography. Neither neck ultrasonography nor MIBI were able to locate pathological parathyroid glands in those patients with multiglandular disease, while FCH PET/CT correctly located one patient (1/3, 33.3%) with two adenomas and 3 patients (3/6, 50.0%) with hyperplasia. The three imaging techniques, FCH PET/CT, MIBI and neck ultrasound yielded a sensitivity of 92.1%, 57.9% and 32.4%, a positive predictive value of 94.6%, 84.6% and 78.6%, and a diagnostic accuracy of 96.4%, 85.7% and 79.0%, respectively. Conclusions: In this group of patients diagnosed with primary hyperparathyroidism, FCH PET/CT was superior to MIBI and neck ultrasound in detecting adenomas, particularly in the presence of ectopic glands or multiglandular disease.

Role of a portable gamma-camera with optical view for margins assessment of pulmonary nodules resected by radioguided surgery.

PURPOSE: Radioguided occult lesion localization (ROLL) of pulmonary nodules is an alternative to hook-wire. Both required of a histological margin assessment. The activity emerging from the radiotracer allows to obtain an intraoperative scintigraphic image of the surgical specimen by a portable gamma-camera (PGC) fitted with an optical view, which provides information about the localization of the nodule in relation to the margins. The aim of this study was to evaluate the intraoperative use of a PGC for margin assessment of pulmonary nodules. METHODS: ROLL technique was used in 38 nodules (36 pulmonary, 1 chest wall, and 1 pleural nodules). A PGC intraoperative image of the surgical specimen was obtained in 32. Scintigraphic results were compared to the histological assessment. Other factors, such as nodule size, distance from the pleural surface, or distance covered by the needle, were considered as possible factors for non-centered lesions. RESULTS: PGC images showed that the lesion was in contact with the margins in 8/32 cases and centered in 24. In all cases in which the lesion was considered as centered by the PGC, the margins were free of involvement (NPV 100%), although the PPV is low. CONCLUSIONS: The use of a PGC for margin assessment after pulmonary nodule resection is feasible and provides a high NPV in our series. In addition, the short intraoperative time required for its use makes the PGC a useful tool for providing supplementary information to histopathologic results. Further studies from different surgical teams are required for an external validation.

Mutational Landscape and Tumor Burden Assessed by Cell-free DNA in Diffuse Large B-Cell Lymphoma in a Population-Based Study.

PURPOSE: We analyzed the utility of cell-free DNA (cfDNA) in a prospective population-based cohort to determine the mutational profile, assess tumor burden, and estimate its impact in response rate and outcome in patients with diffuse large B-cell lymphoma (DLBCL). EXPERIMENTAL DESIGN: A total of 100 patients were diagnosed with DLBCL during the study period. Mutational status of 112 genes was studied in cfDNA by targeted next-generation sequencing. Paired formalin-fixed, paraffin-embedded samples and volumetric PET/CT were assessed when available. RESULTS: Appropriate cfDNA to perform the analyses was obtained in 79 of 100 cases. At least one mutation could be detected in 69 of 79 cases (87%). The sensitivity of cfDNA to detect the mutations was 68% (95% confidence interval, 56.2-78.7). The mutational landscape found in cfDNA samples was highly consistent with that shown in the tissue and allowed genetic classification in 43% of the cases. A higher amount of circulating tumor DNA (ctDNA) significantly correlated with clinical parameters related to tumor burden (elevated lactate dehydrogenase and ß2-microglobulin serum levels, advanced stage, and high-risk International Prognostic Index) and total metabolic tumor volume assessed by PET/CT. In patients treated with curative intent, high ctDNA levels (>2.5 log hGE/mL) were associated with lower complete response (65% vs. 96%; P < 0.004), shorter progression-free survival (65% vs. 85%; P = 0.038), and overall survival (73% vs. 100%; P = 0.007) at 2 years, although it did not maintain prognostic value in multivariate analyses. CONCLUSIONS: In a population-based prospective DLBCL series, cfDNA resulted as an alternative source to estimate tumor burden and to determine the tumor mutational profile and genetic classification, which have prognostic implications and may contribute to a future tailored treatment.

Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure.

AIMS: The addition of an aldosterone receptor antagonist on top of current optimal therapy (based on angiotensin II inhibition) has demonstrated an important clinical benefit in heart failure patients with systolic dysfunction. Whether this finding also applies to heart failure patients with preserved systolic function is unknown. Therefore, we have studied the effect of adding eplerenone to standard pharmacological heart failure therapy (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and diuretic and ß-blocker) in the progression of heart failure in spontaneously hypertensive heart failure (SHHF) rats. METHODS AND RESULTS: Two-month-old SHHF rats were randomized to receive no treatment (SHHF group), a standard heart failure therapy (quinapril-torasemide-carvedilol; ST-SHHF group), or the combination of eplerenone and standard heart failure therapy (Eple+ST-SHHF group) for 20 months. Untreated SHHF was characterized by progressive left ventricular hypertrophy, fibrosis, and myocardial contractile and relaxation abnormalities, leading to pulmonary congestion. Despite similar blood pressure control, the addition of eplerenone to standard heart failure therapy further prevented left ventricular hypertrophy, contractile and relaxation alterations, and pulmonary congestion than standard heart failure therapy alone. ST-SHHF and Eple + ST-SHHF rats showed similar inhibition of structural extracellular matrix proteins collagen I, collagen III and fibronectin and metalloproteinase (MMP)-2, MMP-7, MMP-12, and MMP-13. However, only the coadministration of eplerenone with standard heart failure therapy normalized the expression of matricellular proteins thrombospondin 1, tenascin C, periostin, and secreted protein acidic rich in cysteine/osteonectin to values comparable to normotensive rats. CONCLUSION: In a hypertensive heart failure rat model, the addition of eplerenone to conventional heart failure therapy further improves cardiac structural and functional parameters, delaying the progression of heart failure. These beneficial effects of eplerenone were associated with normalization of matricellular protein expression.