Patterns of microbial growth in urine cultures in a pediatric hematology/oncology unit over a one-year period: a single institution study

Background: Urinary tract infections (UTIs) may present with nonspecific symptoms and without any definitive clinical signs other than fever, hence may be missed without a routine urine analysis. We retrospectively evaluated all cases of culture-positive urine infections in pediatric oncology patients in our center during the year 2015. Methods: We assessed all positive urine culture incidents for pediatric patients receiving treatment and/or follow-up at our center during 2015. Analysis was performed on patients with regards to clinical, microbiology and pertinent lab findings as well as associated risk factors. Results: There were 151 episodes of documented positive urine cultures among 73 patients. Majority of positive urine cultures were found in solid tumor patients (41%), followed by hematological malignancies (26%). Most organisms detected were gram-negative organisms (84%), with E.coli being the most frequent (51%). Forty percent of bacteria were resistant to standard broad-spectrum antibiotics, with the majority being extended-spectrum beta-lactamase-producing. Most of these infections occurred in patients receiving prophylactic antibiotics (46 out of 50). Approximately two thirds of patients were not febrile on the day of culture (64%) and almost half of the reported episodes were associated with urinary symptoms. Pyuria, leukocyte esterase and nitrites were positive in 39%, 51% and 19% of samples, respectively. Conclusions: Positive urine culture in children with cancer may not be associated with urinalysis abnormalities, particularly in patients with neutropenia. When selecting empiric treatment for cancer patients with UTIs, one should take into consideration the institutional patterns for resistance and use of prophylactic antibiotics. Keywords: Urinary tract infection, Genitourinary, Urine culture, Pediatric hematology/oncology, Neutropenia, Prophylactic antibiotic

Evaluation of improved attenuation correction in whole-body PET/MR on patients with bone metastasis using various radiotracers

Purpose!#!This study evaluates the quantitative effect of improved MR-based attenuation correction (AC), including bone segmentation and the HUGE method for truncation correction in PET/MR whole-body hybrid imaging specifically of oncologic patients with bone metastasis and using various radiotracers.!##!Methods!#!Twenty-three patients that underwent altogether 28 whole-body PET/MR examinations with findings of bone metastasis were included in this study. Different radiotracers (!##!Results!#!Overall, 69 bone lesions were detected and evaluated. The mean increase in relative difference over all 69 lesions in SUV!##!Conclusion!#!Improved MR-based AC, including bone segmentation and HUGE truncation correction in whole-body PET/MR on patients with bone lesions and using various radiotracers, is important to ensure best possible diagnostic image quality and accurate PET quantification. The HUGE method for truncation correction based on MR worked robust and results in realistic body contouring, independent of the radiotracers used

Equivalent tumor detection for early and late FAPI-46 PET acquisition

Introduction!#!Positron emission tomography (PET) using small ligands of the fibroblast activation protein (FAP) was recently introduced. However, optimal uptake time has not been defined yet. Here, we systematically compare early (~ 10 min p.i.) and late (~ 60 min p.i.) FAPI-46 imaging in patients with various types of cancer.!##!Methods!#!This is a retrospective single-institutional study. Imaging was performed at the Essen University Hospital, Germany. A total of 69 patients who underwent dual time-point imaging for either restaging (n = 52, 75%) or staging (n = 17, 25%) of cancer were included. Patients underwent PET with two acquisitions: early (mean 11 min, SD 4) and late (mean 66 min, SD 9). Mean injected activity was 148 MBq (SD 33).!##!Results!#!In total, 400 lesions were detected in 69 patients. Two of 400 (0.5%) lesions were only seen in early time-point imaging but not in late time-point imaging. On a per-patient level, there was no significant difference between SUV!##!Conclusion!#!In conclusion, early (~ 10 min p.i.) versus late (~ 60 min p.i.) FAPI-46 imaging resulted in equivalent lesion uptake and tumor detection. For improved feasibility and scan volume, we implement early FAPI-46 PET in future clinical and research protocols

Phase 3 multicenter randomized trial of PSMA PET/CT prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: study protocol.

BackgroundDefinitive radiation therapy (dRT) is an effective initial treatment of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). PSMA PET/CT is superior to standard of care imaging (CT, MRI, bone scan) for detecting regional and distant metastatic PCa. PSMA PET/CT thus has the potential to guide patient selection and the planning for dRT and improve patient outcomes.MethodsThis is a multicenter randomized phase 3 trial (NCT04457245). We will randomize 312 patients to proceed with standard dRT (control Arm, n = 150), or undergo a PSMA PET/CT scan at the study site (both 18F-DCFPyL and 68Ga-PSMA-11 can be used) prior to dRT planning (intervention arm, n = 162). dRT will be performed at the treating radiation oncologist facility. In the control arm, dRT will be performed as routinely planned. In the intervention arm, the treating radiation oncologist can incorporate PSMA PET/CT findings into the RT planning. Androgen deprivation therapy (ADT) is administered per discretion of the treating radiation oncologist and may be modified as a result of the PSMA PET/CT results. We assume that approximately 8% of subjects randomized to the PSMA PET arm will be found to have M1 disease and thus will be more appropriate candidates for long-term systemic or multimodal therapy, rather than curative intent dRT. PET M1 patients will thus not be included in the primary endpoint analysis. The primary endpoint is the success rate of patients with unfavorable IR and HR PCa after standard dRT versus PSMA PET-based dRT. Secondary Endpoints (whole cohort) include progression free survival (PFS), metastasis-free survival after initiation of RT, overall survival (OS), % of change in initial treatment intent and Safety.DiscussionThis is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa who receive dRT. In this trial the incorporation of PSMA PET/CT may improve the success rate of curative intent radiotherapy in two ways: to optimize patient selection as a biomarker and to personalizes the radiotherapy plan.Clinical trial registrationUCLA IND#147591 ○ Submission: 02.27.2020 ○ Safe-to-proceed letter issued by FDA: 04.01.2020 UCLA IRB #20-000378 ClinicalTrials.gov Identifier NCT04457245 . Date of Registry: 07.07.2020. Essen EudraCT 2020-003526-23

Anti-hormonal maintenance treatment with the CDK4/6 inhibitor ribociclib after 1st line chemotherapy in hormone receptor positive / HER2 negative metastatic breast cancer: A phase II trial (AMICA)

Purpose: This phase II study evaluated the impact of adding ribociclib to maintenance endocrine therapy (ET) treatment of physicians’ choice following the first palliative chemotherapy in pre- and post-menopausal women with hormone receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (mBC). Patients and methods: The initial randomized study design was later amended into a single-arm study, and all subsequent patients received ribociclib and ET. The primary end point was locally assessed progression-free survival (PFS). Secondary end points included overall survival (OS), clinical benefit rate (CBR), safety, compliance, and quality of life (QoL). Results: A total of 43 patients received ribociclib + ET and 10 patients received ET only. Median PFS was 12.4 months [95% CI 8.7–24.4] for patients who received ribociclib + ET and 4.75 months [95% CI 1.0–10.3] for those who received ET only. Median OS was not reached for patients who received ribociclib + ET, and 28 (65.1%) patients experienced clinical benefit [95% CI 49.1–79.0]. For patients who received ribociclib + ET, grade 3–4 hematological adverse events (AEs) occurred in 25 (58.1%) patients, and grade 3–4 non-hematological AEs occurred in 17 (39.5%) patients. During the study, 15 patients died – 14 of whom due to tumor-related reasons, and one patient due to pneumonia, which was not treatment-related. Conclusion: The results of the AMICA study show a promising efficacy and safety of maintenance treatment with ribociclib added to ET after at least stable disease following the first metastatic chemotherapy in patients with HR+/HER2-mBC. Trial registration: Anti-hormonal Therapy With Ribociclib in HR-positive/HER2- Negative Metastatic Breast Cancer (AMICA), NCT03555877, https://clinicaltrials.gov/ct2/show/NCT03555877