Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience.

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study.

Effects of Mild and Moderate Monoclonal Antibody Dose on Inflammation, Bone Loss, and Activation of the Central Nervous System in a Female Collagen Antibody-induced Arthritis Mouse Model.

Induction of severe inflammatory arthritis in the collagen antibody-induced arthritis (CAIA) murine model causes extensive joint damage and pain-like behavior compromising analysis. While mild models are less severe, their reduced, variable penetrance makes assessment of treatment efficacy difficult. This study aimed to compare macroscopic and microscopic changes in the paws, along with central nervous system activation between a mild and moderate CAIA model. Balb/c mice (n=18) were allocated to control, mild, and moderate CAIA groups. Paw inflammation, bone volume (BV), and paw volume (PV) were assessed. Histologically, the front paws were assessed for joint inflammation, cartilage damage, and pre/osteoclast-like cells and the lumbar spinal cord and the periaqueductal gray (PAG) region of the brain for glial reactivity. A moderate CAIA dose induced (1) significantly greater local paw inflammation, inflammatory cell infiltration, and PV; (2) significantly more osteoclast-like cells on the bone surface and within the surrounding soft tissue; and (3) significantly greater glial reactivity within the PAG compared with the mild CAIA model. These findings support the use of a moderate CAIA model (higher dose of monoclonal antibodies with low-dose lipopolysaccharide) to induce more consistent histopathological features, without excessive joint destruction.

Desmoplastic small round cell tumour in the Afro-Caribbean population: case report with imaging findings.

Desmoplastic Small Round Cell Tumour (DSRCT) is a rare malignancy that has only a few cases documented in the literature. We report a case of DSRCT in the abdomen and pelvis that was identified following ultrasound-guided biopsy of one of the numerous liver lesions seen on imaging in a 13-year-old Afro-Caribbean female with increased abdominal girth. The tumour was characterized by all routine imaging modalities available at the time. To our knowledge, this is the first reported and published case in the English speaking Caribbean. In the review of the literature, we correlate the imaging findings with previously reported cases. The diagnosis of DSRCT cannot be made solely using standard imaging techniques, but radiologists should be suspicious of DSRCT as a differential diagnosis in a young patient with increased abdominal girth, multiple liver and peritoneal deposits seen on imaging. Written informed consent for the case to be published (incl. images, case history, and data) was obtained from the parents of this patient for publication of this case report, including accompanying images.

Healthcare-Associated Infections at a Children's Cancer Hospital, 1983-2008.

BACKGROUND: Little is known about the incidence and etiology of healthcare-associated infections in immunosuppressed children. METHODS: Data collected prospectively between 1983 and 2008 were used to analyze changes in the rate, types of infection, and infecting organisms over time in patients treated at a children's cancer hospital. Neutropenia was evaluated as a risk factor. RESULTS: Over the 26-year study period, 1986 healthcare-associated infections were identified during 1653 hospitalizations. The infection rate decreased significantly from 5.6 to 2.0 infections per 100 discharges (P < .01) and from 9.0 to 3.7 infections per 1000 patient-days (P < .01). Bloodstream infections were the most common type of infection (32.7% of all infections). Staphylococci (46.4% of Gram-positive bacteria), Escherichia coli (36.7% of Gram-negative bacteria), and Candida spp. (68.7% of fungi) were the most common pathogens isolated. An absolute neutrophil count (ANC) nadir <100 per mm(3) was significantly associated (P < .0001) with an increased rate of infections compared with higher ANC nadirs. CONCLUSIONS: Despite a steady expansion in hospital capacity and patient encounters over the last 3 decades, rates of healthcare-associated infections decreased significantly at our hospital. These data suggest that sustained decreases in the rate of healthcare-associated infections in immunosuppressed children are possible. An ANC <100 per mm(3) is a risk factor for healthcare-associated infections in this population.

Planning and implementation of an infection control training program for healthcare providers in Latin America.

OBJECTIVE: The lack of well-trained, dedicated infection control personnel prevents optimal control of nosocomial infections in Latin American pediatric oncology centers. We collaboratively planned and implemented a multinational training course in San Salvador, El Salvador, to address this need. METHODS: The course relied on its organizers' experience in training international healthcare providers, the availability of the International Training Center for Nurses, previous infection control collaboration with the Hospital Nacional de Ninos Benjamin Bloom, and resources available at the University of El Salvador. The 4-week course consisted of lecture sessions combined with practical laboratory and hospital experience. RESULTS: Two courses, one conducted in 2005 and one in 2006, trained 44 professionals from 15 Latin American countries. Evaluations showed that course content and teacher performance met the trainees' needs and that all trainees acquired the necessary knowledge and skills. CONCLUSIONS: The course met the need for the training of Latin American infection control practitioners. Our experience can serve as a model for other organizations interested in strengthening infection control and prevention at international sites.

Increased influenza vaccination of healthcare workers at a pediatric cancer hospital: results of a comprehensive influenza vaccination campaign.

A comprehensive influenza vaccination campaign improved vaccination rates among healthcare workers with direct patient care responsibilities from 45% during the 2003-2004 influenza season to 80% during the 2004-2005 season. A strategy of weekly feedback to unvaccinated employees was the most important factor in enhancing the rate of vaccination acceptance and was particularly effective among the nursing staff.

In vivo expression and function of the sodium iodide symporter following gene transfer in the MATLyLu rat model of metastatic prostate cancer.

BACKGROUND: The sodium iodide symporter (NIS) mediates iodide uptake in thyroid follicular cells and provides a mechanism for effective radioiodide treatment of residual, recurrent, and metastatic thyroid cancers. This study investigated the clinical applications of NIS gene transfer for prostate cancer using the MATLyLu metastatic rat model. METHODS: MATLyLu cells expressing NIS were injected subcutaneously in Copenhagen rats, which developed metastases in lymph nodes and lungs. NIS protein expression was evaluated by Western blot and immunohistochemistry, and function was measured by tissue gamma counts and whole-body imaging following radionuclide administration. RESULTS: In vitro radioiodide-concentrating activity was increased up to 72-fold in a mixed population of MATLyLu-hNIS cells. NIS protein expression was confirmed in subcutaneous MATLyLu-hNIS tumors by immunohistochemistry and Western blot. Gamma counts of subcutaneous MATLyLu-hNIS tumors were 23-fold higher than parental MATLyLu tumors and radionuclide uptake in subcutaneous MATLyLu-hNIS tumors and lymph node metastases was visualized by whole-body image analysis. CONCLUSIONS: NIS expression by a proportion of cells in a population was sufficient to confer radionuclide-concentrating function in subcutaneous and metastatic MATLyLu tumors. Ablation of residual normal and neoplastic prostate tissues by radioiodide after prostate-restricted NIS gene transfer might be a novel adjuvant therapy to prostatectomy for the treatment of advanced prostate cancer.