Post-therapy Evaluation Research Articles

Genetic Predisposition to Sarcoma: What Should Clinicians Know?

Pathogenic germline variants in the setting of several associated cancer predisposition syndromes (CPS) may lead to the development of sarcoma. We would consider testing for a CPS in patients with a strong family history of cancer, multiple primary malignancies, and/or pediatric/adolescent/young adult patients diagnosed with other malignancies strongly associated with CPS. When a CPS is diagnosed in a patient with sarcoma, additional treatment considerations and imaging options for those patients are required. This applies particularly to the use of radiation therapy, ionizing radiation with diagnostic imaging, and the use of alkylating chemotherapy. As data and guidelines are currently lacking for many of these scenarios, we have adopted a shared decision-making process with patients and their families. If the best chance for cure in a patient with CPS requires utilization of radiation therapy or alkylating chemotherapy, we discuss the risks with the patient but do not omit these modalities. However, if there are treatment options that yield equivalent survival rates, yet avoid these modalities, we elect for those options. Considering staging imaging and post-therapy evaluation for sarcoma recurrence, we avoid surveillance techniques that utilize ionizing radiation when possible but do not completely omit them when their use is indicated.

Dual-Energy CT in Oncologic Imaging.

Dual-energy CT (DECT) is an innovative technology that is increasingly widespread in clinical practice. DECT allows for tissue characterization beyond that of conventional CT as imaging is performed using different energy spectra that can help differentiate tissues based on their specific attenuation properties at different X-ray energies. The most employed post-processing applications of DECT include virtual monoenergetic images (VMIs), iodine density maps, virtual non-contrast images (VNC), and virtual non-calcium (VNCa) for bone marrow edema (BME) detection. The diverse array of images obtained through DECT acquisitions offers numerous benefits, including enhanced lesion detection and characterization, precise determination of material composition, decreased iodine dose, and reduced artifacts. These versatile applications play an increasingly significant role in tumor assessment and oncologic imaging, encompassing the diagnosis of primary tumors, local and metastatic staging, post-therapy evaluation, and complication management. This article provides a comprehensive review of the principal applications and post-processing techniques of DECT, with a specific focus on its utility in managing oncologic patients.

Efficacy of hippotherapy simulator exercise program in patients with stroke: a randomized single-blind clinical trial

ABSTRACT Objectives The aim of this study was to investigate the effect of hippotherapy simulator on balance, postural control, mobility, functional capacity and independence level in people with stroke. Methods This study involved 26 people with stroke aged 18–65, who were randomly assigned to a Hippotherapy Simulator Group (HSG; n = 13) and a Conventional Exercise Group (CEG; n = 13). Patients underwent assessments using the Berg Balance Scale (BBS), Postural Assessment Scale for Stroke (PAS-S), Timed Up and Go Test (TUG), Rivermead Mobility Index (RMI), 2-Minute Walking Test (2-MWT), and Barthel Daily Living Activity Index (BI) to evaluate balance, postural control, mobility, functional capacity, and independence before and after treatment. In the HSG, participants received 30 sessions of conventional exercises and hippotherapy simulator – a mechanical and robotic equipment with a dynamic saddle simulating horse movement – exercises over 6 weeks. Meanwhile, the CEG underwent 30 sessions of conventional exercises alone for 6 weeks. Results In the post-therapy evaluation between groups, BBS (p = 0.004) and 2-MWT (p < 0.001) scores were higher in HSG compared to CEG. However, no statistically significant difference was found between the two groups in terms of PAS-S, RMI, TUG and BI scores (p > 0.05). Statistically significant differences were found between BBS, PAS-S, RMI, TUG, BI and 2-MWT scores before and after treatment in both groups (p < 0.05). Conclusions Hippotherapy simulator can be added to conventional exercises to improve balance and functional capacity in people with stroke.

Improving swallowing function in a child with cerebral palsy: A single case study on the efficacy of intervention strategies

The study explored the efficacy of Oromotor exercises and proprioceptive neuromuscular facilitation (PNF) to improve swallowing abilities pre- and post-behavioral intervention in a child with cerebral palsy (CP). A 4-year-old female child diagnosed with global developmental delay secondary to spastic quadriplegic CP and poor feeding skills was taken up for study. Oro-motor stimulation and PNF with taste, temperature, and texture were used. Therapy was given twice a week for 30 min. Pre- and post-intervention, a detailed Oro motor and feeding evaluation was performed. Post-therapy evaluation revealed significant increase in body weight, oromotor movements, International Dysphagia Diet Standardization Initiative, Eating Drinking Ability Classification System level, frequency of water, and meal intake. The intense application of oromotor and PNF stimulation seemed to have effected significant improvements in feeding and swallowing abilities which translated to increased weight and positive parental feedback. This might have been responsible for positive outcomes seen in the present study as well.

Preclinical and Clinical Use of Indigenously Developed 99mTc-Diethylenetriaminepentaacetic Acid-Bis-Methionine: l-Type Amino Acid Transporter 1-Targeted Single Photon Emission Computed Tomography Radiotracer for Glioma Management.

A new era in tumor classification, diagnosis, and prognostic evaluation has begun as a consequence of recent developments in the molecular and genetic characterization of central nervous system tumors. In this newly emerging era, molecular imaging modalities are essential for preoperative diagnosis, surgical planning, targeted treatment, and post-therapy evaluation of gliomas. The radiotracers are able to identify brain tumors, distinguish between low- and high-grade lesions, confirm a patient's eligibility for theranostics, and assess post-radiation alterations. We previously synthesized and reported the novel l-type amino acid transporter 1 (LAT-1)-targeted amino acid derivative in light of the use of amino acid derivatives in imaging technologies. Further, we have developed a single vial ready to label Tc-lyophilized kit preparations of diethylenetriaminepentaacetic acid-bis-methionine [DTPA-bis(Met)], also referred to as methionine-diethylenetriaminepentaacetic acid-methionine (MDM) and evaluated its imaging potential in numerous clinical studies. This review summarizes our previous publications on 99mTc-DTPA-bis(Met) in different clinical studies such as detection of breast cancer, as a prognostic marker, in detection of recurrent/residual gliomas, for differentiation of recurrent/residual gliomas from radiation necrosis, and for comparison of 99mTc-DTPA-bis(Met) with 11C-L-methionine (11C-MET), with relevant literature on imaging modalities in glioma management.

Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort.

Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively. The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection.

Radiation dose to the cochlea and its association with sensorineural hearing loss in head and neck cancer-A prospective study

AimTo determine the effect of cochlear dose on sensorineural hearing loss in patients with head and neck cancer treated by radiotherapy and chemoradiotherapy. Materials and methodA two-year longitudinal study was conducted on 130 subjects with various head and neck malignancies who were receiving radiotherapy or chemoradiation. 56 patients received only radiotherapy while 74 patients received concurrent chemoradiation five days a week at a dose of 66–70 Gy. They were categorized as having a radiation dose to the cochlea of <35 Gy, <45 Gy or >45 Gy. Pre- and post-therapy audiological evaluation was done using a Pure-tone audiogram, distortion product otoacoustic emission, and impedence. Hearing thresholds were measured at frequencies up to 16,000 Hz. ResultsOut of 130 patients 56 received RT alone and 74 received CTRT. There was statistically significant (p value <0.005) difference in Pure-tone audiometry assessment in both the RT and CTRT groups between subjects who received more than and <45 Gy of radiation to the cochlea. There was no significant difference in distortion product otoacoustic emission assessment between patients who received >45 Gy and <45 Gy radiation to the cochlea. Comparison between subjects who received radiation dose of <35 Gy and >45 Gy revealed significant results in the degree of hearing loss (p value <0.005). ConclusionWe observed that patients who received >45 Gy of radiation had more sensorineural hearing loss compared to patients who received <45 Gy. A cochlear dose of <35 Gy is associated with significantly lower hearing loss compared to higher doses. We would like to conclude by emphasizing the importance of regular audiological assessments prior to and post radiotherapy and chemoradiotherapy, with regular follow-ups encouraged over a longer period to improve the quality of life in patients with head and neck malignancy.

Imaging Recommendations for Diagnosis, Staging, and Management of Esophageal Cancer

AbstractEarly staging and treatment initiation affect prognosis of patients with esophageal and esophagogastric junction cancer; hence, it is imperative to have knowledge of proper choice of imaging modality for staging of these patients, to effectively convey relevant imaging findings to the treating physician/surgeon. It is also essential to be aware of pertinent imaging findings that need to be conveyed to the treating physician/surgeon at staging, and after treatment, including post-therapy complications (if any), so as to provide timely management to such patients. In this article, we have provided imaging guidelines for diagnosis, staging, post-therapy response evaluation, follow-up, and assessment of post-therapy complications of esophageal and esophagogastric junction cancer in a systematic manner. Besides, risk factors and clinical workup have also been elucidated. We have also attached comprehensive staging and post-therapy contrast-enhanced computed tomography and fluorodeoxyglucose-positron emission tomography/computed tomography-based synoptic reporting formats “ECI-RADS” and “pECI-RADS,” respectively, for esophageal and esophagogastric junction cancer in the supplement, for effective communication of imaging findings between a radiologist and the treating physician/surgeon.

Speech and swallowing rehabilitation of post-partial mandibulectomy: a case report

&lt;p class="abstract"&gt;Squamous cell carcinomas of the oral cavity require multiple treatment approaches such as chemotherapy, radiotherapy, and surgical treatment. Glossectomy and mandibulectomy are the most common surgical treatment procedures for oral carcinoma with pre-, and post-surgical chemo-radiotherapy depending on the stage of cancer. The patients with glossectomy and mandibulectomy are at risk of developing a wide range of impairments in speech and swallowing functions due to surgical procedures and post chemo-radiation therapy (trismus and xerostomia). The present case report describes a 52-year-old male who had a history of oral squamous cell carcinoma and underwent wide excision of maxillar and mandibular regions who presented with severe speech and swallowing impairments. On examination of speech and swallowing functions, the patient exhibited oral dysphagia of moderate severity and poor speech intelligibility. The patient had undergone 50 speech and swallow therapy sessions over two months duration and post-therapy evaluation showed improvements in speech and swallowing functions. The patient had exhibited improvements in quality of life on various physical and functional domains post-rehabilitation. However, the improvements were limited due to the presence of trismus and hypernasality due to maxillar resection. This case report describes the importance of speech and swallowing rehabilitation to improve the post-surgical impairments in speech and swallowing functions and also the overall quality of life of patients with oral cancers.&lt;/p&gt;

Metabolic Imaging in B-Cell Lymphomas during CAR-T Cell Therapy.

Simple SummaryChimeric antigen receptor–engineered T cells are an innovative therapy in hematologic malignancies, especially in patients with refractory/relapsed B-cell lymphomas. Few studies have analyzed the role of [18F]FDG PET/CT in this field; this review aims to illustrate the literature data and the major findings related to [18F]FDG PET/CT use during CAR-T cell therapy in B-cell lymphomas, focusing on the prognostic value of metabolic parameters, as well as on response assessment. Furthermore, this work shows in detail the specific adverse events during CAR-T cell therapy and the role of [18F]FDG PET/CT imaging in their occurrence.Chimeric antigen receptor–engineered (CAR) T cells are emerging powerful therapies for patients with refractory/relapsed B-cell lymphomas. [18F]FDG PET/CT plays a key role during staging and response assessment in patients with lymphoma; however, the evidence about its utility in CAR-T therapies for lymphomas is limited. This review article aims to provide an overview of the role of PET/CT during CAR-T cell therapy in B-cell lymphomas, focusing on the prognostic value of metabolic parameters, as well as on response assessment. Data from the literature report on the use of [18F]FDG PET/CT at the baseline with two scans performed before treatment started focused on the time of decision (TD) PET/CT and time of transfusion (TT) PET/CT. Metabolic tumor burden is the most studied parameter associated with disease progression and overall survival, making us able to predict the occurrence of adverse effects. Instead, for post-therapy evaluation, 1 month (M1) PET/CT seems the preferable time slot for response assessment and in this setting, the Deauville 5-point scale (DS), volumetric analyses, SUVmax, and its variation between different time points (∆SUVmax) have been evaluated, confirming the usefulness of M1 PET/CT, especially in the case of pseudoprogression. Additionally, an emerging role of PET/CT brain scans is reported for the evaluation of neurotoxicity related to CAR-T therapies. Overall, PET/CT results to be an accurate method in all phases of CAR-T treatment, with particular interest in assessing treatment response. Moreover, PET parameters have been reported to be reliable predictors of outcome and severe toxicity.

The effect of hyperbaric oxygen therapy on cognition, performance, proteomics, and telomere length-The difference between zero and one: A case report.

IntroductionHyperbaric oxygen (HBO2) therapy has recently been suggested for the treatment of different brain injuries as well as for physical and cognitive enhancement. The author recently carried out a self-experiment to obtain objective information on the effects of HBO2 therapy on neurocognition, cardiopulmonary function, neuroimaging and its effect on novel biomarkers such as telomere length and proteomics. In the following case report, the author will present and discuss the results and the differences between zero and one.MethodsThis is a personal case report on a single subject, myself, who underwent a protocol of 60 daily HBO2 therapy sessions within 3 months. Pre- and post-therapy objective evaluation measured included computerized cognitive assessment, brain imaging, cardiopulmonary exercise test, physical assessments and blood tests including telomere length and proteomics.ResultsNeurocognitive results showed a 3.1–3.8% improvements in global cognitive function as well as all other cognitive function domains. In the perfusion MRI, there was a relative increase ranging from 43.3 to 52.3% in cerebral perfusion in various areas subserving memory, coordination, and visual motor cortex function. Similar improvements in cerebral perfusion were seen in the SPECT scans, which ranged from 8.79 to 16.12% increased perfusion in the temporal pole and entorhinal cortex subserving memory, as well as in the subcallosal area and lingual gyrus. MRI-DTI showed prominent increases in fractional anisotropy in several white matter areas including 9% in the body of the corpus callosum, 16.85% in for the fornix and 22.06% in the tapetum. In the physical domains, there were improvements in both anaerobic threshold, exercise endurance, muscle strength, gait speed and grip strength in the 7–15% range. The telomeres length was doubled and clusters of inflammatory proteins dropped around the 40th session and remained low at the 60th session.ConclusionThe difference between zero and one in this single case study of HBO2 therapy confirmed improvement in objective biomarkers which measured cognition, memory, brain processing speed, athletic performance and neuroimaging modalities measuring cerebral perfusion, blood flow and tractography. Additional studies with larger sample size and randomized clinical trials using similar biomarkers are needed to confirm the results and to delineate the longevity of these improvements.

Un adénocarcinome mucineux non kystique (carcinome colloïde) du pancréas de découverte fortuite à la TEP-TDM au 18F-FDG : à propos d’un cas

Colloid carcinoma (CC) of the pancreas, also known as mucinous noncystic carcinoma, is a rare histological variant of pancreatic cancer which had been included in the past under the category of ordinary ductal carcinoma, a tumor with a dismal prognosis, or was frequently misdiagnosed as mucinous cystadenocarcinoma. As CC has a better prognosis than pancreatic ductal carcinoma, early detection of CC by 18 FDG PET SCAN is of great value for the therapeutic management of patients. We report the case of a 66-year-old patient who underwent 18 FDG PET SCAN as part of a post-therapy evaluation of a moderately differentiated carcinoma of the stomach treated with surgery and chemotherapy, in whom a hypermetabolic focus of the body of the pancreas was discovered incidentally. The anathomopathological diagnosis was in favor of a low-grade mucinous noncystic carcinoma of the pancreas. Thus, 18 FDG PET SCAN allowed the discovery of an infraradiological CC synchronous with a gastric adenocarcinoma and provided information on its metabolic activity as well as locoregional and distant staging, which are important prognostic markers and which could improve the therapeutic management of the patient.

The Role of Whole- Body Diffusion Imaging with Background Signal Suppression (DWBS) in comparison with PET/CT in assessment of lymphoma patients

Abstract Background Malignant lymphomas [Hodgkin lymphomas (HL) and non-Hodgkin lymphoma (NHL)] rank third in incidence, of all childhood cancers, Moreover, in adolescents (aged 15-19 years) the malignant lymphomas are the leading cause of cancer. Furthermore, as with many other cancers, the likelihood of an individual being diagnosed with lymphoma increases markedly with age, with the median age at diagnosis being 67 years. Aim of the Work To compare between F-18-FDG PET-CT and whole-body diffusion-weighted imaging MR protocol (DWIBS) for initial staging and post chemotherapy evaluation in patients with pathologically proven lymphoma (Hodgkin and Non-Hodgkin). Patients and Methods The study is conducted on 32 patients with pathologically proven lymphoma to perform 18-F-FDG PET/CT either for pre-treatment initial staging or for evaluation of response to chemotherapy. A total of 22 had HD (69%) and 10 had NHL (31%). Staging PET/CT and WB-MRI/DWIBS were done at time of diagnosis in 19 of the 32 patients (59.4%), where immediate post-therapy PET/CT and WB-MRI-DWIBS were performed 13 patients (40.6%). Accuracy measures were calculated for PET CT and DWIBS. Results Accuracy measures confirm the higher sensitivity and specificity of PET-CT over DWIBS. Results for F-18 FDG PET/CT were clearly superior with statistically higher sensitivity, specificity, accuracy, PPV &amp; NPV (96.3%, 99.16%, 98.43%, 97.5% and 98.75%) compared to (83.95%, 97.91%, 94.38%, 93.15% and 94.74%) for DWIBS results respectively. Conclusion F-18-FDG PET-CT remains a cornerstone in the evaluation of malignant lymphoma patients; it has significant higher sensitivity, specificity and overall accuracy compared to WB-MRI/DWIBS in HL and NHL patients, either in initial staging or in post therapy evaluation. WB-MRI/DWIBS in HL and NHL patients, either in initial staging or in post therapy evaluation. WB-MRI/DWIBS despite of its relatively longer acquisition time may provide a complementary tool for FDG PET CT.

Bortezomib Combined with Mitoxantrone, Vincristine, Peg-Asparaginase and Dexamethasone for Children with Relapsed Acute Lymphoblastic Leukemia

Introduction: Outcomes for children or adolescents with relapsed or refractory acute lymphoblastic leukemia (ALL) are poor, especially for those who experience a second or greater relapse. Novel treatments are needed, however the addition of newer medications to standard therapy is problematic due to the risk of additional toxicities in this high risk population. Mitoxantrone was shown to be superior to idarubicin for patients with a first ALL relapse when combined with vincristine, PEG-asparaginase and dexamethasone and is now frequently used in the treatment of relapsed ALL. Bortezomib is a proteasome inhibitor that has shown activity in relapsed ALL when given in combination with reinduction chemotherapy including doxorubicin. This study evaluates the addition of bortezomib to a reinduction regimen that includes mitoxantrone, dexamethasone, vincristine and PEG-asparaginase for children with relapsed or refractory ALL.Methods: Children ages 0-18 who had experienced one or more relapse of ALL were included in the analysis. Treatment included bortezomib 1.3 mg/m2/dose IV on days 1, 4, 8 and 11, dexamethasone 10 mg/m2/dose PO BID on days 1-5 and 15-19, mitoxantrone 10 mg/m2/dose IV on days 1 and 2, PEG-asparaginase 2500 units/m2/dose on days 3 and 17, vincristine 1.5 mg/m2/dose (max dose: 2 mg) IV on days 1, 8, 15 and 22 and intrathecal methotrexate (standard age based dosing) on days 1 and 8. Erwinase was used for patients with hypersensitivity to PEG-asparaginase and triple intrathecal chemotherapy with hydrocortisone, cytarabine and methotrexate was allowed for patients with active CNS disease. It was recommended that all patients remain hospitalized until count recovery and that all patients receive prophylactic broad-spectrum antibiotic and antifungal prophylaxis while neutropenic.Results: The treatment was administered to 10 children, ages ranging from 11 months to 18 years. Nine patients had precursor B-cell ALL and 1 had T-cell ALL. Nine patients had bone marrow disease and one patient had extramedullary disease in the parotid and submandibular glands along with bone marrow MRD. Patients had between 1 and 4 (median: 2) prior remissions, 2 patients were refractory to their previous therapy and 5 patients had received a prior allogeneic hematopoietic stem cell transplant. There was 1 treatment related death from a presumed pulmonary fungal infection. Of the 9 patients that had a post therapy evaluation, 8 (89%) were in complete remission with less than 5% blasts and 2 (22%) were MRD negative by flow cytometry. One patient was in remission but MRD positive after treatment, declined any further therapy, became MRD negative and maintained a complete remission for 7 months before eventually experiencing a relapse. Of the children that responded to treatment, 2 remain in remission at 2 and 14 months from the completion of therapy and 6 patients have had at least one relapse. Including all patients that were treated, 8 (80%) remain alive with a median follow-up of 21 months. Grade 3 or higher infections were noted in 7 (70%) patients and 2 patients required PICU admission and ventilator support. Two patients had grade 4 pulmonary toxicity, one associated with MRSA sepsis and the other of unclear etiology 25 days following the last bortezomib dose. No patient had ≥ grade 2 neurotoxicity associated with treatment. Event free and overall survival of this cohort at 12 months were 35% and 79%, respectively.Conclusions: The addition of bortezomib to intensive multiagent reinduction chemotherapy including mitoxantrone was feasible and did not result in unexpected toxicity in a heavily pretreated patient cohort. The combination treatment resulted in complete morphologic remission for the majority of patients. The incorporation of bortezomib with reinduction chemotherapy including mitoxantrone warrants further evaluation in the treatment of relapsed ALL in children. DisclosuresAugust:Novartis Pharmaceuticals Corporation: Consultancy.

Diagnostic, Therapeutic and Evolutionary Peculiarities of Spinal Trauma in Children in Sub-Saharan Africa: Experience of Senegal

Introduction: Spinal trauma in children is rare, accounting for 1 and 10% of all spinal traumas. They constitute an entity in their own right due to the injuries they cause. Difficulties (diagnostic) and modalities (therapeutic), different from those of adults the growth of children. The lack of studies in Sub-Saharan Africa leads us to carry out this study focused on the traumatic spine of the child. Patients and Methods: Over a period of 8 and a half years from January 2012 to June 2020, we retrospectively studied 44 cases involving 4 Senegalese hospitals, 3 of which were in the capital and 1 in the province, including children up to the age of 16 who had suffered spinal trauma. Results: Forty-four children were retained, a frequency of 7.11%, with an average age of 10.5 years; sex ratio: 1.6. The most frequent aetiologies were: falls (from trees, from buildings): 41%; play accidents and accidents on public roads: 20.4% each. The average consultation time was 31.3 days. 34% of the patients were ASIA E patients. The majority of patients had performed a spine CT scan as an imaging examination, i.e. 95.4%. The most common site of injury was cervical with 61.3%. The most frequent lesions were: fractures, fracture-luxations and dislocations with 27.3%, 25% and 25% respectively. Five patients had associated lesions, i.e. 11.3% (4 head traumas, 9.1% and 1 pelvic trauma, 1.9). Most of the treatment was surgical (43% orthopaedic, 38.6%) and functional (16%). The post-therapy neurological evaluation (ASIA - backward step) was: A: 25%; B: 2.3%; C: 7%; D: 13.7%; E: 52.3%. We noted 3 deaths and 4 patients were re-operated. There were no consolidation complications such as pseudoarthrosis. Conclusion: Trauma to the spine in children, like any bone trauma, responds well to orthopaedic treatment. Deaths are often related to upper cervical spine injuries or occur in the context of polytrauma. Follow-up should be carried out over several years to detect possible complications at an early stage. Delays in treatment due to the difficulties of punctual medicalised transport remain the challenge to be met in our environment.

1687. Omadacycline in Female Adults With Acute Pyelonephritis: Results from a Randomized, Double-Blind, Adaptive Phase 2 Study

BackgroundOmadacycline (OMC) is a novel intravenous (IV) and oral aminomethylcycline, approved in the USA for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in adults. We present data from a randomized, adaptive dose–response phase 2 study of OMC in adult females with acute pyelonephritis (AP).MethodsFemales aged ≥ 18 y with acute uncomplicated pyelonephritis were initially randomized to 1 of 4 once-daily regimens of OMC vs once-daily standard regimen of IV-to-oral levofloxacin (LEV) (total therapy: 7–10 days) (NCT03757234); the randomization algorithm was subsequently adapted by the data monitoring committee (DMC; blinded to the investigators) following interim analyses of efficacy in the microbiological-intent-to-treat (micro-ITT) population (Table 1). Efficacy was assessed for noninferiority according to investigator’s assessment of clinical response (IACR) and microbiological response at post-therapy evaluation (PTE; Day 21) and end of therapy (EOT). Treatment-emergent adverse events (TEAEs) were assessed. Results were reviewed by the DMC.Table 1 Results201 patients were randomized. Baseline characteristics were similar across groups (Table 2). Among patients with an identified pathogen, the most common species was E. coli. For IACR at both EOT and PTE, no OMC group met noninferiority to LEV (Figure 1), as the lower limit of the 95% CI for the treatment difference exceeded −10% (range −12.4% to −34.8%). Responses at PTE were consistent with those at EOT. Microbiological responses in each OMC group were generally lower than LEV. OMC was well tolerated; 36.2% and 32.4% of OMC- and LEV-treated patients had ≥ 1 TEAE. The most frequently reported TEAEs (≥ 5%) in the OMC the LEV groups, respectively, were headache (10.2% vs 6.8%), asymptomatic bacteriuria (6.3% vs 1.4%), diarrhea (2.4% vs 6.8%), and nausea (5.5% vs 6.8%).Table 2 Figure ConclusionIn this adaptive, phase 2 study, clinical success was high for both groups, although no OMC group met criteria for noninferiority to levofloxacin in AP, potentially due to pharmacokinetic/pharmacodynamic drivers of efficacy for AP. Omadacycline was well tolerated, with a safety profile consistent with its current labeling. Further evaluation is warranted to further understand the outcomes of this study.DisclosuresJ. Scott Overcash, MD, FACEP, Paratek Pharmaceuticals, Inc. (Scientific Research Study Investigator) Evan Tzanis, BS, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Amy Manley, BS, Paratek Pharmaceuticals, Inc. (Employee) Courtney Kirsch, BS, Paratek Pharmaceuticals, Inc. (Employee) Alisa W. Serio, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Tiffany White, PhD, ContraFact Corporation (Consultant, (ended Feb 2020))Facile Therapeutics (Consultant)Paratek Pharmaceuticals, Inc. (Employee) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Surya Chitra, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Paul B. Eckburg, MD, AN2 Therapeutics (Consultant)Bugworks Research (Consultant)Curza (Advisor or Review Panel member)Paratek Pharmaceuticals, Inc. (Consultant)SNIPR Biome (Consultant)Spero Therapeutics (Consultant)

F18-FET PET in pediatric brain tumors: integrative analysis of image derived parameters and clinico-pathological data.

F18-FET PET has an established diagnostic role in adult brain gliomas. In this study we analyzed image derived static and dynamic parameters with available conventional MRI, histological, clinical and follow-up data in assessment of pediatric brain tumor patients at different stages of the disease. Forty-four pediatric patients with median age 7 years, diagnosed with brain tumors and underwent forty-seven 18F-FET PET scans either initially (20 scans) or post-therapy (27 scans) were enrolled. Standardized analysis of summed FET PET images early from 10-20 min and late from 30-40 min post-injection were used for static (mean and maximum tumor to brain ratio [TBR] and biological tumor volume [BTV]) parameters evaluation as well as the time activity curve [TAC]. Nineteen out of 20 initially assessed patients had pathologically and/or clinico-radiologically proven neoplastic lesions and one patient had pathologically proven abscess. Receiver operator curve (ROC) marked early TBR max 2.95, early TBR mean 1.76, late TBR max 2.5 and late TBR mean 1.74 as discriminator points with diagnostic accuracy reaching 90% when TBR max was combined with dynamic parameters. Significant association was found between initial FET scans, early and late BTV and event free survival (EFS) (P value=0.042 and 0.005 respectively). In post-therapy assessment, the diagnostic accuracy of conventional MRI was 81.48% when used alone and 96.30% when combined with F18-FET PET scan findings. A cutoff point of 3.2 cm3 for late BTV, in post-therapy scans, was successfully marked as a predictor for therapy response (P value 0.042) and was significantly associated with EFS (P value 0.002). In FET-avid / MRI non-enhancing lesions, early TBR max was able to detect highly malignant processes (high-grade tumors in initial scans and residue/recurrence in post-therapy scans) with 80% sensitivity and 100% specificity when cutoff value of 2.25 was used (P value=0.024). In patients with FET-avid brainstem lesions, whether enhancing or non-enhancing in MRI scans, 81.8% were associated with high risk diagnoses and 68.2% of them were associated with poor therapy outcome. The degree of FET uptake matched tumor-grading, but did not show significant association with OS or EFS (P value>0.05). F18-FET PET seems to be an evolving pediatric neuro-imaging technique with valuable diagnostic and prognostic information at initial and post-therapy evaluation.

134-OR: Effects of PCSK9 Inhibitors on Glucose Metabolism and ß-Cell Function in Humans

PCSK9 inhibitors are monoclonal antibodies effective in reducing LDL-C and cardiovascular events by neutralizing circulating PCSK9. Since PCSK9 is also expressed in other organs, including pancreas, studies on PCSK9 KO mice, have shown impaired insulin secretion. Other murine models in which PCSK9 was silenced only in the liver (mimicking the action of PCSK9i) had normal glucose metabolism. The aim of our study was to evaluate the effect of PCSK9 inhibitors on glucose metabolism and beta cell function in humans. 11 nondiabetic subjects candidate for PCSK9i therapy were enrolled in the study. All subjects underwent an OGTT at baseline and after 6 months of therapy, at which point surrogate insulin sensitivity indices were obtained (Matsuda; OGIS). During OGTT, insulin secretion parameters were derived from C-peptide levels by deconvolution; we evaluated basal insulin secretion rate, total insulin secretion rate and β-cell glucose sensitivity, for 6 of the 11 enrolled subjects. All patients showed a 53.3% reduction in LDL cholesterol after 6 months of therapy; the mean LDL-C baseline level (B) was 202.5 ± 45 mg/dl, while mean LDL-C post therapy (PT) value was 94.6 ± 27 mg/dl. Glycemic and insulinemic curves showed no significant differences between baseline and follow-up. Matsuda index (B 4.1 ± 1, PT 3.4 ± 0.7 mL min-1kg-1) and OGIS (B 396.9 ± 32, PT 386.2 ± 28 ml min-1m-2), showed no differences between baseline and post-therapy evaluation. There were no significant differences in insulin secretion parameters: basal insulin secretion rate (B 63.7 ± 34, PT 66.4 ± 23 pmol min-1m-2), total insulin secretion rate (B 48.7 ± 17, PT 46.9 ± 16, nmol m-2) and β-cell glucose sensitivity (B 117.5 ± 69, PT 141.2 ± 47 pmol min-1m-2mM-1) obtained from c-peptide deconvolution. Our study, although preliminary and in a small sample of patients, suggests that PCSK9is does not cause alterations in glucose metabolism and beta cell function. Further studies and a longer follow-up may provide us with further data to confirm our observations. Disclosure S. Moffa: None. T. Mezza: None. C. Cefalo: None. F. Cinti: None. G. Sorice: None. F. Impronta: None. U. Capece: None. A. Mari: Consultant; Self; Lilly Diabetes. Research Support; Self; Boehringer Ingelheim International GmbH. A. Giaccari: Speaker’s Bureau; Self; Amgen, AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi-Aventis.

Imaging of Wilms tumor: an update.

Wilms tumor is the most common pediatric renal tumor, accounting for approximately 7% of all childhood cancers. Imaging plays an important role in the detection, staging, post-therapy evaluation and surveillance of Wilms tumor. Wilms tumor can be detected during surveillance of a known cancer predisposition or after a child presents with symptoms. In this manuscript we describe an evidence-based approach to the initial evaluation of Wilms tumor using current guidelines from the Children's Oncology Group (COG). We illustrate the COG staging system for pediatric renal tumors and highlight key imaging findings that are critical for surgical management. We also discuss the controversies regarding detection and significance of <5-mm pulmonary nodules at initial staging. And finally, we present some thoughts regarding surveillance of Wilms tumor, where overall survival has now approached 90%.

FDG PET/CT Evaluation of Pediatric Patients With Yolk Sac Tumor

OBJECTIVE. The objective of our study was to evaluate the clinical utility of FDG PET/CT in staging and restaging pediatric patients with yolk sac tumor (YST). MATERIALS AND METHODS. We retrospectively reviewed the data from 31 pediatric patients with pathologically confirmed YST who underwent 34 PET/CT studies for the purpose of staging or restaging. The PET/CT studies were read by two nuclear medicine doctors in consensus. Histopathology combined with clinical and imaging follow-up was taken as the reference standard. The results of PET/CT were also compared with conventional imaging and α-fetoprotein (AFP) levels when available. RESULTS. Of the total 34 studies, six were performed for initial staging and the other 28 for posttherapy evaluation. FDG PET/CT was true-positive in all six staging studies, detected only a few more metastatic foci than conventional imaging, and changed the therapeutic regimen in none of the six patients. Nevertheless, PET/CT showed high accuracy in the restaging group, with a sensitivity of 100% and specificity of 85.7%. The treatment regimen was changed in 46.4% of the patients in the restaging group according to the PET/CT study. In addition, PET/CT had higher accuracy than AFP levels in YST restaging. Overall, the per-study performance of PET/CT was a sensitivity of 100%, specificity of 85.7%, positive predictive value of 90.9%, and negative predictive value of 100%. CONCLUSION. FDG PET/CT was only slightly superior to conventional imaging in staging YST in pediatric patients. However, PET/CT of posttherapy patients with YST showed high diagnostic accuracy and had a great impact on therapeutic management.