Anlotinib for Metastatic Progressed Pheochromocytoma and Paraganglioma: A Retrospective Study of Real-World Data.

Introduction: Pheochromocytomas (PCC) and paragangliomas (PGL) (collectively PPGL) are a type of rare hypervascular neuroendocrine tumors that are very challenging to treat. This study aimed to determine the efficacy and safety of the multi-tyrosine kinase inhibitor anlotinib for the treatment of locally advanced or metastatic (LA/M) PPGL. Methods: A total of 37 eligible patients with unresectable or progressive LA/M PPGL were enrolled. Of them, 27 patients received anlotinib alone (n = 19) or in combination (n = 8) with radionuclide therapies, including peptide receptor radionuclide therapy (PRRT) and iodine 131 meta-iodobenzylguanidine (131I-MIBG). The primary endpoints included objective response rate (ORR), defined as partial response (PR) or complete response (CR), and disease-control rate, defined as PR, CR, or stable disease (SD). The secondary endpoints were progression-free survival (PFS), duration of response, and drug safety. Results: In the efficacy evaluation for all 27 patients, the ORR was 44.44% (95% CI: 24.4%-64.5%) and disease-control rate was 96.29% (95% CI: 88.7%-100%). Twelve cases (44.44%) achieved PR, 14 (51.85%) SD. The median PFS was 25.2 months (95% CI: 17.2 months to not reached). PFS was shorter in the anlotinib monotherapy group than in the group receiving anlotinib in combination with radionuclide therapy (P = .2). There were no serious treatment-related AEs. Conclusion: Anlotinib monotherapy or in combination with radionuclide therapies shows promising efficacy and safety for the treatment of LA/M PCC and PGL. Multi-tyrosine kinase inhibitors might represent a novel therapeutic strategy for patients with PPGL; however, large-scale prospective randomized, blinded, controlled clinical research studies are required.

Distinguishing benign and malignant thyroid nodules using plasma trimethylamine N-oxide, carnitine, choline and betaine.

PURPOSE: Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, and its precursors (carnitine, choline, betaine) have not been fully examined in relation to thyroid cancer (TC) risk. The aim of this study was to assess the value of TMAO and its precursors in diagnosis of benign and malignant thyroid nodules. METHODS: In this study, high-performance liquid chromatography-tandem mass spectrometry was utilized to measure the levels of plasma TMAO and its precursors (choline, carnitine, and betaine) in 215 TC patients, 63 benign thyroid nodules (BTN) patients and 148 healthy controls (HC). The distribution of levels of TMAO and its precursors among the three groups were compared by the Kruskal-Wallis test. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the sensitivity, specificity, and the predictive accuracy of single and combined biomarkers. RESULTS: In comparison to HC, TC showed higher levels of TMAO and lower levels of its precursors (carnitine, choline, and betaine) (all P < 0.001). Plasma choline (P < 0.01) and betaine (P < 0.05) were declined in BTN than HC. The levels of carnitine (P < 0.001) and choline (P < 0.05) were significantly higher in BTN than that in TC group. Plasma TMAO showed lower levels in TC with lymph node metastasis (101.5 (73.1-144.5) ng/ml) than those without lymph node metastasis (131 (84.8-201) ng/ml, P < 0.05). Combinations of these four metabolites achieved good performance in the differential diagnosis, with the area under the ROC curve of 0.703, 0.741, 0.793 when discriminating between TC and BTN, BTN and HC, TC and HC, respectively. CONCLUSION: Plasma TMAO, along with its precursors could serve as new biomarkers for the diagnosis of benign and malignant thyroid nodules.

177 Lu-DOTATATE Therapy: Effects of Water Intake and Drinking Duration on Patient Peripheral Dose Equivalent Rates.

ABSTRACT: This study investigated the amount and duration of water consumption in neuroendocrine tumor patients after receiving 177 Lu-DOTATATE radionuclide therapy. We recruited 39 patients with neuroendocrine tumors, all of whom were treated with 177 Lu-DOTATATE radionuclide while in the nuclear medicine ward of a tertiary hospital in Nanjing from January 2021 to April 2022. We conducted a cross-sectional survey to investigate their drinking times, water consumption, and urine volumes at 0 min, 30 min, 60 min, 2 h, 24 h, and 48 h after radionuclide treatment. At each timepoint, their radiation dose equivalent rates were monitored at 0 m, 1 m, and 2 m from the middle abdomen. f at 24 h were significantly lower than those at 0 min, 30 min, 60 min, and 2 h (all p < 0.05). The dose equivalent rates at 48 h were significantly lower than those at 24 h (all p < 0.05). At 1 m or 2 m from the patient, the dose equivalent rate gradually decreased at all six timepoints and was significantly different between groups ( P < 0.05). To achieve lower radiation doses, there was a correlation with 24 h water consumption (P < 0.05) but no correlation with 48 h water consumption (P > 0.05); there were lower peripheral dose equivalents for patients when 24 h water consumption was no less than 2,750 mL. Patients with neuroendocrine tumors should drink at least 2,750 mL of water 24 h after treatment with 177 Lu-DOTATATE radionuclides. Drinking water in the first 24 h after treatment is more critical to reduce the peripheral dose equivalent, which can accelerate the reduction of peripheral radiation dose equivalent in early patients.

Cervical lymph node metastasis prediction of postoperative papillary thyroid carcinoma before 131I therapy based on clinical and ultrasound characteristics.

Background: The status of lymph nodes is crucial to determine the dose of radioiodine-131(131I) for postoperative papillary thyroid carcinoma (PTC). We aimed to develop a nomogram for predicting residual and recurrent cervical lymph node metastasis (CLNM) in postoperative PTC before 131I therapy. Method: Data from 612 postoperative PTC patients who underwent 131I therapy from May 2019 to December 2020 were retrospectively analyzed. Clinical and ultrasound features were collected. Univariate and multivariate logistic regression analyses were performed to determine the risk factors of CLNM. Receiver operating characteristic (ROC) analysis was used to weigh the discrimination of prediction models. To generate nomograms, models with high area under the curves (AUC) were selected. Bootstrap internal validation, calibration curves and decision curves were used to assess the prediction model's discrimination, calibration, and clinical usefulness. Results: A total of 18.79% (115/612) of postoperative PTC patients had CLNM. Univariate logistic regression analysis found serum thyroglobulin (Tg), serum thyroglobulin antibodies (TgAb), overall ultrasound diagnosis and seven ultrasound features (aspect transverse ratio, cystic change, microcalcification, mass hyperecho, echogenicity, lymphatic hilum structure and vascularity) were significantly associated with CLNM. Multivariate analysis revealed higher Tg, higher TgAb, positive overall ultrasound and ultrasound features such as aspect transverse ratio ≥ 2, microcalcification, heterogeneous echogenicity, absence of lymphatic hilum structure and abundant vascularity were independent risk factors for CLNM. ROC analysis showed the use of Tg and TgAb combined with ultrasound (AUC = 0.903 for "Tg+TgAb+Overall ultrasound" model, AUC = 0.921 for "Tg+TgAb+Seven ultrasound features" model) was superior to any single variant. Nomograms constructed for the above two models were validated internally and the C-index were 0.899 and 0.914, respectively. Calibration curves showed satisfied discrimination and calibration of the two nomograms. DCA also proved that the two nomograms were clinically useful. Conclusion: Through the two accurate and easy-to-use nomograms, the possibility of CLNM can be objectively quantified before 131I therapy. Clinicians can use the nomograms to evaluate the status of lymph nodes in postoperative PTC patients and consider a higher dose of 131I for those with high scores.

Development and validation of 68Ga-PSMA-11 PET/CT-based radiomics model to detect primary prostate cancer.

BACKGROUND: This study aimed to develop a novel analytic approach based on a radiomics model derived from 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT for predicting intraprostatic lesions in patients with prostate cancer (PCa). METHODS: This retrospective study included consecutive patients with or without PCa who underwent surgery or biopsy after 68Ga-PSMA-11 PET/CT. A total of 944 radiomics features were extracted from the images. A radiomics model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm with tenfold cross-validation in the training set. PET/CT images for the test set were reviewed by experienced nuclear medicine radiologists. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated for the model and radiologists' results. The AUCs were compared. RESULTS: The total of 125 patients (86 PCa, 39 benign prostate disease [BPD]) included 87 (61 PCa, 26 BPD) in the training set and 38 (61 PCa, 26 BPD) in the test set. Nine features were selected to construct the radiomics model. The model score differed between PCa and BPD in the training and test sets (both P < 0.001). In the test set, the radiomics model performed better than the radiologists' assessment (AUC, 0.85 [95% confidence interval 0.73, 0.97] vs. 0.63 [0.47, 0.79]; P = 0.036) and showed higher sensitivity (model vs radiologists, 0.84 [0.63, 0.95] vs. 0.74 [0.53, 0.88]; P = 0.002). CONCLUSION: Radiomics analysis based on 68Ga-PSMA-11 PET may non-invasively predict intraprostatic lesions in patients with PCa.

177Lu-PSMA-I&T Radioligand Therapy for Treating Metastatic Castration-Resistant Prostate Cancer: A Single-Centre Study in East Asians.

Purpose: There is increasing evidence for convincing efficacy and safety of 177Lu-labled prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) for metastatic castration-resistant prostate cancer (mCRPC). However, data are not available regarding the feasibility of 177Lu-labled PSMA-targeted RLT in East Asians. The present study summarized the first experience with 177Lu-PSMA-I&T therapy for mCRPC in China. Methods: Forty consecutive patients with mCRPC were enrolled from December 2019 to September 2021. Eligible patients received 177Lu-PSMA-I&T RLT at intervals of 8-12 weeks. Toxicity was assessed based on standardized physicians' reports and the Common Toxicity Criteria for Adverse Events criteria. Response to PRLT was evaluated according to the changes of prostate specific antigen (PSA) response and imaging response. Quality of life (QOL), Karnofsky performance status (KPS) and pain (visual analogue scale, VAS) were also evaluated. The impacts of baseline parameters on the therapeutic effects were explored by univariate and multivariate logistic regression analyses. Results: All patients underwent a total of 86 cycles of 177Lu-PSMA-I&T (range: 1-5 cycles) with dosages of 3.70-14.43GBq per cycle, with a median of 8 months followed up. Six patients (15%) developed mild reversible xerostomia during follow-up, and 28 patients (70%) experienced grade 1-4 bone marrow dysfunction. Changes in PSA were assessed after therapy, accompanied by the partial response (PR) in 25 patients (62.5%), the stable disease (SD) in 5 patients (12.5%), and the progressive disease (PD) in 10 patients (25%), respectively. QOL, KPS (%) and VAS scores were improved significantly due to treatment (P<0.05). Overweight and elevated AST, ALP, and LDH were associated with poor outcomes. Conclusions: 177Lu-PSMA-I&T achieves the favourable response and well tolerance in mCRPC, which associates with not only PSA decline but also with tumor remission including lymphadenopathy and bone metastasis. We also find that patients with overweight and high AST, ALP, and LDH should be cautious to undergo the PRLT. Large-cohort studies are warranted to confirm the initial findings and elucidate the survival benefit of the treatment.

Drivers' visual load at different time periods in entrance and exit zones of extra-long tunnel.

OBJECTIVE: As the number of tunnels and traffic accidents increase, it is necessary to study the drivers' visual characteristic in the tunnels. Considering that freeway tunnels have limited space and narrow sight zone, drivers usually have a short visual blind zone and visual shock when entering and exiting the tunnels. This study aims to investigate the characteristics of drivers' visual load in the entrance and exit zones of extra-long tunnels, and to provide a theoretical basis for the traffic safety prevention and control measures of the engineering design. METHODS: 20 drivers were enrolled to conduct real vehicle tests in the Guizhou Sifangdong Tunnel at different time periods (daytime, twilight, and nighttime). The drivers' pupil area was collected by an eye tracker. The maximum transient vibration value (MTVV) of the pupil area was selected as the index of visual load. In addition, the changing characteristics of visual load in the entrance and exit zones were examined. Using ANOVA, the significant difference of visual load in different zones and at different time periods were performed. Accordingly, the overall drivers' visual load in the entrance and the exit zones were compared. Exponential function models of the MTVV value and the speed of pupil area change were constructed, where the pattern of mutual influence was examined. RESULTS: The changing pattern of the drivers' visual load at different time periods in the entrance and exit zones were markedly different. The comparison of the overall visual load was as follows: exit zones at nighttime > entrance zones at nighttime > entrance zones at twilight > exit zones at twilight ≈ entrance zones at daytime ≈ exit zones at daytime. Moreover, the MTVV value positively correlated with the speed of the pupil area change. Finally, this study proposes an evaluation standard of visual comfort based on the speed of the pupil area change. CONCLUSION: This study highlights the driving risk in extra-long tunnel. These findings could provide a basis for studying the setting method of visual guidance facilities in entrance and exit zones of extra-long tunnel. Also, this study could provide a theoretical basis for the evaluation of drivers' visual load in the tunnel.