Glucagon-like Peptide-1 Receptor Agonists-A Potential New Medication for Pediatric Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children in the US and, if untreated, may progress to end-stage liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown improvement in MASLD markers in adults with type 2 diabetes mellitus (T2DM). Currently, there is a lack of medications available for the treatment of pediatric MASLD. We aimed to provide preliminary data on the effects of GLP-1 RAs on markers of MASLD in a retrospective study, in an effort to bridge this gap in the pharmacotherapies available. Nine patients from a T2DM clinic who met the following inclusion criteria were included in this study: patients diagnosed with pre-diabetes or T2DM, prescribed a GLP-1 RA in the prior 12 months, and having alanine aminotransferase (ALT) elevated to twice the upper limit of the normal range, indicating evidence of MASLD. The average change between baseline and the first measurement after starting a GLP-1 RA was calculated for ALT, hemoglobin A1c, and BMI. ALT decreased by an average of 98 points. A1c decreased by an average of 2.2 points. BMI decreased by an average of 2.4 points. There was greater reduction in ALT and A1c compared to BMI, suggesting that improvement in MASLD may be independent of weight loss. This is a preliminary study that shows potential, and prospective studies are needed to evaluate the effects of GLP-1 RAs in the management of pediatric MASLD.

Frequency and Severity of Hypothyroidism During TKI Therapy in the Pediatric and Young Adult Population.

Tyrosine kinase inhibitors that target vascular endothelial growth factor receptor [VEGFR-TKI] are a class of targeted therapies approved for treatment of several malignancies and are increasingly used in the pediatric population. Development of hypothyroidism during VEGFR-TKI therapy is well described in adults; however, there are no available data in children. Importantly, hypothyroidism during childhood can negatively impact growth and neurodevelopment. This retrospective study is the first to document frequency and severity of VEGFR-TKI induced hypothyroidism in pediatric and young adult patients. Patients included were ≤25 years of age and treated with at least one VEGFR-TKI between 2010 and 2018 at Cincinnati Children's Hospital Medical Center. After review of clinical and demographic data, 69 patients were identified. Of these, 19 (27.5%) developed thyroid dysfunction defined as Thyroid-stimulating hormone≥5 mIU/mL during therapy. Twelve of those patients had overt hypothyroidism with documentation of low free thyroxine and/or levothyroxine initiation. Mean exposure time to VEGFR-TKI before thyroid dysfunction was 2.8 (0.5-10.4) months. These results suggest moderate risk of developing thyroid dysfunction during VEGFR-TKI therapy in pediatric and young adult patients. Baseline thyroid hormone screening should be performed and repeated frequently during the first year of therapy in the pediatric population.

Improving Malignancy Prediction in AUS/FLUS Pediatric Thyroid Nodules with the Aid of Ultrasound.

INTRODUCTION: The standard workup of thyroid nodules concerning for malignancy includes fine-needle aspiration (FNA). In 2015, the American Thyroid Association (ATA) guidelines for the management of pediatric thyroid nodules recommended that all nodules with a Bethesda III cytology undergo surgical resection. OBJECTIVES: To correlate a Bethesda III cytology with histologic and clinical outcomes to determine the relevance of the ATA recommendations, and to evaluate whether Thyroid Imaging Reporting and Data System (TI-RADS) scoring could identify Bethesda III nodules at a lower risk of malignancy. METHODS: A retrospective chart review of patients who had undergone thyroid nodule FNA from 2008 to 2018 was performed. Malignancy rates were determined for each Bethesda category. The reference standard was histopathology or 2-year follow-up of imaging outcomes for nonoperative cases. Ultrasound exams of Bethesda III nodules were reviewed and TI-RADS scores assigned. RESULTS: A total of 143 FNA samples from 128 patients were identified. The mean age was 14.9 years (range 7-22). Twenty-two (15%) of the FNA samples were Bethesda III; the malignancy rate was 38%. A TI-RADS score was assigned in 20 of the 22 Bethesda III nodules. ROC analysis found an optimal cut-off for malignancy prediction of ≥7 points (risk category TR5). The negative predictive value was 85.7% (95% CI 35.9-99.6) and the positive predictive value was 83.3% (95% CI 57.2-98.2). CONCLUSION: Although, at baseline, thyroid nodules with a Bethesda III classification carry a moderate risk of malignancy in the pediatric population, TI-RADS scoring can identify nodules with a lower risk within this group. If validated by larger studies, this can inform decision making and reduce unneeded surgery.

Analysis of stereotactic radiation vs. wedge resection vs. wedge resection plus Cesium-131 brachytherapy in early stage lung cancer.

PURPOSE: The purpose of the study was to evaluate the outcomes for wedge resection (WR), WR plus brachytherapy (WRB), or stereotactic body radiation therapy (SBRT) for early stage non-small lung cancer. METHODS AND MATERIALS: Retrospectively collected data of patients treated with WR, WRB, or SBRT (1993-2012). Cesium-131 (Cs131) used in WRB group in patients with close or positive margins based on surgical assessment. Kaplan-Meier survival analysis, log-rank test used to compare disease-free survival/overall survival between different groups. Multivariable analysis, using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, gender, and treatment procedure on disease-free survival. RESULTS: A total of 272 patients were included in the study (123 WR, 52 WR+Cs-131, 97 SBRT). Cs-131 was used with WRs that the surgeons deemed high risk. Local control (LC) was similar in the three groups and was achieved in 92.2% for WR group vs. 96.2% for WR+Cs-131 and 95.5% for SBRT (p = 0.60). On multivariate analysis, although females showed a higher LC, neither LC nor distant metastasis were associated with age or gender (p = 0.65 and p = 0.41, respectively). Five-year overall survival was 100% in the WR+B group, 97.7% in the WR group, and 89.6% in the SBRT group (p = 0.02). Toxicity was similar in the three groups. CONCLUSION: WR, WR+ Cs-131, or SBRT are all excellent treatment options for patients with early stage non-small cell lung cancer that are not candidates for lobectomy. For high risk WRs, we favor use of Cesim-131 brachytherapy. Until a prospective randomized comparative study is done to evaluate the best treatment approach for early stage NSCLC, treatment selection should be based on a multidisciplinary team approach.

Comparison of primary radiation versus robotic surgery plus adjuvant radiation in high-risk prostate cancer: a single center experience.

OBJECTIVE: The objective of this study was to compare robotic-prostatectomy plus adjuvant radiation therapy (RPRAT) versus primary RT for high-risk prostate cancer (HRPCa). MATERIALS AND METHODS: A retrospective chart review was performed for the HRPCa patients treated in our institution between 2000 and 2010. One hundred and twenty-three patients with high-risk disease were identified. The Chi-square test and Fisher's exact test were used to compare local control and distant failure rates between the two treatment modalities. For prostate-specific antigen comparisons between groups, Wilcoxon rank-sum test was used. RESULTS: The median follow-up was 49 months (range: 3-138 months). Local control, biochemical recurrence rate, distant metastasis, toxicity, and disease-free survival were similar in the two groups. CONCLUSIONS: Primary RT is an excellent treatment option in patients with HRPCa, is equally effective and less expensive treatment compared with RPRAT. A prospective randomized study is required to guide treatment for patients with HRPCa.

Cesium-131 brachytherapy in high risk and recurrent head and neck cancers: first report of long-term outcomes.

PURPOSE: The feasibility and efficacy of re-irradiation using contemporary radiation techniques to treat recurrent head and neck cancer has been demonstrated but the role of brachytherapy is unclear. Here we describe the use of (131)Cs brachytherapy with concurrent salvage surgery in 18 patients. MATERIAL AND METHODS: Eligible patients underwent maximal gross resection of the tumor with implantation of brachytherapy seeds delivering a minimum dose of 80 Gy to the tumor bed. Rates of overall survival, locoregional progression free survival, disease-free survival, and radiation-induced toxicity were analyzed. RESULTS: Retrospective Kaplan-Meier analysis shows median overall survival was 15 months and disease free survival was 12 months. Two patients developed grade 3 toxicity; all other complications were grade 1-2 with no grade 4 or 5 complications. CONCLUSIONS: Compared to prior literature, our study shows comparable rates of survival with a decreased rate of radiation-induced toxicity.

Comparing outcomes in poorly-differentiated versus anaplastic thyroid cancers treated with radiation: a surveillance, epidemiology, and end results analysis.

PURPOSE: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are considered the most aggressive cancers of the head and neck. The aim of the study was to evaluate and compare survival outcomes in PDTC and ATC in a large population-based cohort. MATERIALS AND METHODS: Patients with PDTC and ATC diagnosed from 1973 to 2008 were obtained from Surveillance, Epidemiology, and End RESULTS database. Kaplan-Meier survival analysis and log-rank analyses were performed to evaluate (1) The effect of histology on cause-specific survival (CSS) and (2) the influence of factors such as treatment, treatment sequence, race, sex, and age on CSS. Multivariate analysis was performed to assess the independent effect of these factors on CSS. RESULTS: A total of 1352 patients with PDTC and ATC were identified. PDTC constituted 52.4% of patients versus 47.6% for ATC. Median CSS was similar in the two histology groups (P = 0.14). Both PDTC and ATC patients receiving radioisotopes showed a significantly better CSS compared to external beam radiation (P < 0.0001). PDTC and ATC Patients receiving radiation prior to surgery demonstrated a significantly lower CSS compared to patients receiving radiation postoperatively (P < 0.0001). Female gender and black/nonwhite race tended to improve CSS in PDTC and ATC patients (P = 0.29 and P = 0.03, for gender and race, respectively). However, multivariate analysis revealed only type of radiation treatment and age to be independently associated with CSS. CONCLUSION: This is the first large population-based study evaluating PDTC and ATC outcomes in patients who received radiation treatment. Radioisotope use and timing of radiotherapy (postoperative vs. preoperative) were associated with improved CSS in both histologies.

Role of radiation therapy for renal tumors.

Renal cell carcinoma (RCC) is an aggressive malignancy that carries a poor prognosis, especially in patients presenting with advanced stage. Primary treatment for localized RCC is surgical resection however, a significant number of patients still develop locoregional and distant metastasis after curative resection. In metastatic disease, radiation therapy (RT) has been used for palliation routinely for brain and other extracranial lesions with respectable response rates. However, RT for primary RCC has questionable benefit. In this article, the authors discuss the evidence with regards to the role of RT in primary RCC either as a primary treatment, adjuvant treatment, or preoperatively to improve resection outcomes. In addition, novel RT techniques such as stereotactic body radiation therapy and its use in RCC management are also addressed. Finally, the authors discuss the techniques and doses of RT for primary RCC.

Stereotactic body radiation therapy (SBRT) for early stage lung cancer delivers clinically significant radiation to the draining lymph nodes.

BACKGROUND: To evaluate clinically significant radiotherapy (RT) dose to draining lymph nodes (LN) in patients treated with SBRT. FINDINGS: Early stage non-small cell lung cancer patients treated with SBRT were selected for analysis. Patients received SBRT if they were not considered eligible for surgical resection. RT plans for 29 patients (32 lesions) were analyzed. For each patient, ipsilateral and contralateral levels 2, 3, 4, 5, 6, 7 and ipsilateral hilar LN stations were contoured. Dose volume histograms and dosimetric coverage of each lymph node region were obtained for each patient. There were 14 males and 15 females. Median age was 75 (range 60-89). Clinically significant RT was received at the corresponding draining lymph node station depending on the primary tumor location. Friedman's non-parametric test revealed a statistically significant difference in RT dose to LN stations depending on the location of the tumor (p<0.0001). CONCLUSION: SBRT for early stage lung cancer results in significant RT dose to the draining LN. This RT dose may be sufficient to eliminate subclinical microscopic disease despite being a highly conformal treatment. Prospective studies are needed to evaluate if SBRT is comparable to lobectomy plus mediastinal lymph node dissection as a treatment option.

Stereotactic body radiation therapy (SBRT) for early stage lung cancer delivers clinically significant radiation to the draining lymph nodes.

BACKGROUND: To evaluate clinically significant radiotherapy (RT) dose to draining lymph nodes (LN) in patients treated with SBRT. FINDINGS: Early stage non-small cell lung cancer patients treated with SBRT were selected for analysis. Patients received SBRT if they were not considered eligible for surgical resection. RT plans for 29 patients (32 lesions) were analyzed. For each patient, ipsilateral and contralateral levels 2, 3, 4, 5, 6, 7 and ipsilateral hilar LN stations were contoured. Dose volume histograms and dosimetric coverage of each lymph node region were obtained for each patient. There were 14 males and 15 females. Median age was 75 (range 60-89). Clinically significant RT was received at the corresponding draining lymph node station depending on the primary tumor location. Friedman's non-parametric test revealed a statistically significant difference in RT dose to LN stations depending on the location of the tumor (p<0.0001). CONCLUSION: SBRT for early stage lung cancer results in significant RT dose to the draining LN. This RT dose may be sufficient to eliminate subclinical microscopic disease despite being a highly conformal treatment. Prospective studies are needed to evaluate if SBRT is comparable to lobectomy plus mediastinal lymph node dissection as a treatment option.

Radiation therapy for early stage lung cancer.

Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In addition, the toxicity profiles are quite favorable. In addition to stereotactic radiation, advances in brachytherapy techniques have enabled high local control rates in operable patients who receive sublobar resections due to compromised pulmonary function. Isotopes that have been used include iodine-125, palladium-103, and cesium-131. In this review article, the role of radiation therapy in treatment of lung cancer, patient selection, outcomes, toxicity and recent technological advancements are discussed. The radiation therapy techniques described in this article are also being used in the management of locally advanced lung cancers.