Site Of Disease Research Articles

Diagnostic Positron Emission Tomography Imaging with Zirconium-89 Desferrioxamine B Squaramide: From Bench to Bedside.

Molecular imaging with antibodies radiolabeled with positron-emitting radionuclides combines the affinity and selectivity of antibodies with the sensitivity of Positron Emission Tomography (PET). PET imaging allows the visualization and quantification of the biodistribution of the injected radiolabeled antibody, which can be used to characterize specific biological interactions in individual patients. This characterization can provide information about the engagement of the antibody with a molecular target such as receptors present in elevated levels in tumors as well as providing insight into the distribution and clearance of the antibody. Potential applications of clinical PET with radiolabeled antibodies include identifying patients for targeted therapies, characterization of heterogeneous disease, and monitoring treatment response.Antibodies often take several days to clear from the blood pool and localize in tumors, so PET imaging with radiolabeled antibodies requires the use of a radionuclide with a similar radioactive half-life. Zirconium-89 is a positron-emitting radionuclide that has a radioactive half-life of 78 h and relatively low positron emission energy that is well suited to radiolabeling antibodies. It is essential that the zirconium-89 radionuclide be attached to the antibody through chemistry that provides an agent that is stable in vivo with respect to the dissociation of the radionuclide without compromising the biological activity of the antibody.This Account focuses on our research using a simple derivative of the bacterial siderophore desferrioxamine (DFO) with a squaramide ester functional group, DFO-squaramide (DFOSq), to link the chelator to antibodies. In our work, we produce conjugates with an average ∼4 chelators per antibody, and this does not compromise the binding of the antibody to the target. The resulting antibody conjugates of DFOSq are stable and can be easily radiolabeled with zirconium-89 in high radiochemical yields and purity. Automated methods for the radiolabeling of DFOSq-antibody conjugates have been developed to support multicenter clinical trials. Evaluation of several DFOSq conjugates with antibodies and low molecular weight targeting agents in tumor mouse models gave PET images with high tumor uptake and low background. The promising preclinical results supported the translation of this chemistry to human clinical trials using two different radiolabeled antibodies. The potential clinical impact of these ongoing clinical trials is discussed.The use of DFOSq to radiolabel relatively low molecular weight targeting molecules, peptides, and peptide mimetics is also presented. Low molecular weight molecules typically clear the blood pool and accumulate in target tissue more rapidly than antibodies, so they are usually radiolabeled with positron-emitting radionuclides with shorter radioactive half-lives such as fluorine-18 (t1/2 ∼ 110 min) or gallium-68 (t1/2 ∼ 68 min). Radiolabeling peptides and peptide mimetics with zirconium-89, with its longer radioactive half-life (t1/2 = 78 h), could facilitate the centralized manufacture and distribution of radiolabeled tracers. In addition, the ability to image patients at later time points with zirconium-89 based agents (e.g. 4-24 h after injection) may also allow the delineation of small or low-uptake disease sites as the delayed imaging results in increased clearance of the tracer from nontarget tissue and lower background signal.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

Investigation of Basolateral Targeting Micelles for Drug Delivery Applications in Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a complex disorder characterized by uncontrolled renal cyst growth, leading to kidney function decline. The multifaceted nature of ADPKD suggests that single-pathway interventions using individual small molecule drugs may not be optimally effective. As such, a strategy encompassing combination therapy that addresses multiple ADPKD-associated signaling pathways could offer synergistic therapeutic results. However, severe off-targeting side effects of small molecule drugs pose a major hurdle to their clinical transition. To address this, we identified four drug candidates from ADPKD clinical trials, bardoxolone methyl (Bar), octreotide (Oct), salsalate (Sal), and pravastatin (Pra), and incorporated them into peptide amphiphile micelles containing the RGD peptide (GRGDSP), which binds to the basolateral surface of renal tubules via integrin receptors on the extracellular matrix. We hypothesized that encapsulating drug combinations into RGD micelles would enable targeting to the basolateral side of renal tubules, which is the site of disease, via renal secretion, leading to superior therapeutic benefits compared to free drugs. To test this, we first evaluated the synergistic effect of drug combinations using the 20% inhibitory concentration for each drug (IC20) on renal proximal tubule cells derived from Pkd1flox/-:TSLargeT mice. Next, we synthesized and characterized the RGD micelles encapsulated with drug combinations and measured their in vitro therapeutic effects via a 3D PKD growth model. Upon both IV and IP injections in vivo, RGD micelles showed a significantly higher accumulation in the kidneys compared to NT micelles, and the renal access of RGD micelles was significantly reduced after the inhibition of renal secretion. Specifically, both Bar+Oct and Bar+Sal in the RGD micelle treatment showed enhanced therapeutic efficacy in ADPKD mice (Pkd1fl/fl;Pax8-rtTA;Tet-O-Cre) with a significantly lower KW/BW ratio and cyst index as compared to PBS and free drug-treated controls, while other combinations did not show a significant difference. Hence, we demonstrate that renal targeting through basolateral targeting micelles enhances the therapeutic potential of combination therapy in genetic kidney disease.

Patient perspective on virtual prechemotherapy visits in gynecologic oncology

ObjectiveTo assess gynecologic oncology patients’ experiences with virtual prechemotherapy evaluation and determine preference for incorporating virtual visits into a chemotherapy schedule. MethodsFrom June-August 2023, a survey was distributed to patients with gynecologic malignancies who had both an in-person and virtual prechemotherapy visit at a tertiary comprehensive cancer center. Patient satisfaction and preference for incorporating virtual visits was elicited. Patients who preferred ≥ 50 % of prechemotherapy visits to be virtual were classified as “virtual-leaning” and those who preferred < 50 % virtual as “in-person-leaning.” ResultsOf 110 eligible patients, 93 agreed to participate and 73 completed the survey, yielding an overall 66.4% response rate and 78.5% (73/93) survey completion rate. Overall satisfaction with in-person and virtual visits were rated positively at similar rates (in-person 87.7%, virtual 87.2%). Sixty-four (88.4%) patients preferred some proportion of their visits to be virtual, 5 (7.0%) preferred no virtual care, and 4 (5.0%) had no preference. In a 6-cycle schedule of chemotherapy, the median number of preferred virtual visits was 3 (IQR 1.8–4.2). Forty-six (63.0%) patients were “virtual-leaning” and 23 (32.0%) were “in-person-leaning.” When comparing groups, there was no difference in age, race, category of residence, commute, experience with technical difficulty, primary disease site, disease stage, number of prior chemotherapy cycles, or number of prior virtual visits. ConclusionsMost patients are highly satisfied with virtual visits and prefer virtual care to be included when undergoing chemotherapy. A hybrid model should be offered to gynecological cancer patients undergoing chemotherapy, with patient preference dictating the cadence of virtual visits.

Peptide-conjugated Nanoparticle Platforms for Targeted Delivery, Imaging, and Biosensing Applications.

Peptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide-modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, and stimuli responsive behavior. Targeting peptides can direct the nanoparticles into specific tissues for targeted drug and gene delivery and imaging applications due to their specificity towards certain receptors. Furthermore, due to their stimuli-responsive features, they can offer controlled release of therapeutics into desired sites of disease. In addition, peptide-based biosensors and imaging agents can provide non-invasive detection and monitoring of diseases including cancer, infectious diseases, and neurological disorders. In this review, we covered the design and formulation of recent peptide-based NP platforms, as well as their utilization in in vitro and in vivo applications such as targeted drug and gene delivery, targeting, sensing, and imaging applications. In the end, we provided the future outlook to design new peptide conjugated nanomaterials for biomedical applications.

Evaluation of markers of immunity in different metastatic immune microenvironments suggests more suppression within breast to liver metastases in breast cancer

PurposeProgrammed death receptor ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are approved screening biomarkers for immune checkpoint inhibition (ICI) in advanced triple negative breast cancer. We examined these biomarkers along with characterization of the tumor microenvironment (TME) between breast tumors (BrTs), axillary metastases (AxMs), liver metastases (LvMs), non-axillary lymph node metastases, and non-liver metastases to determine differences related to site of metastatic disease.Methods3076 unpaired biopsies from breast cancer patients were analyzed using whole transcriptome sequencing and NextGen DNA depicting TMB within tumor sites. The PD-L1 positivity was determined with VENTANA PD-L1 (SP142) assay. The immune cell fraction within the TME was calculated by QuantiSeq and MCP-counter.ResultsCompared to BrT, more LvM samples had a high TMB (≥ 10 mutations/Mb) and fewer LvM samples had PD-L1+ expression. Evaluation of the TME revealed that LvM sites harbored lower infiltration of adaptive immune cells, such as CD4+, CD8+, and regulatory T-cells compared with the BrT foci. We saw differences in innate immune cell infiltration in LvM compared to BrT, including neutrophils and NK cells.ConclusionsLvMs are less likely to express PD-L1+ tumor cells but more likely to harbor high TMB as compared to BrTs. Unlike AxMs, LvMs represent a more immunosuppressed TME and demonstrate lower gene expression associated with adaptive immunity compared to BrTs. These findings suggest biopsy site be considered when interpreting results that influence ICI use for treatment and further investigation of immune composition and biomarkers expression by metastatic site.

Re-irradiation versus systemic therapy for the management of local-regionally recurrent head and neck cancer

PurposeThe optimal management of local-regionally recurrent head and neck cancer that is not amenable to surgical resection is uncertain. We sought to compare outcomes among patients treated with and without re-irradiation in this setting. Methods and MaterialsA review of institutional registries identified 65 patients with local-regionally recurrent squamous cell carcinoma of the head and neck who were ineligible for surgery. Forty patients (62 %) opted for re-irradiation with the remaining 25 patients (38 %) undergoing initial systemic therapy alone. All patients had measurable disease. Forty-three patients (66 %) were male and twenty-two (33 %) were female. The median age at the time of recurrence was 59 years (range, 39–84 years). The most common primary sites of disease were the oropharynx, (n = 25), oral cavity (N = 19), and nasopharynx (n = 11). The median interval from completion of prior radiation to the diagnosis of recurrent disease was 35 months (range, 2–102 months). ResultsRe-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local–regional control (39 % versus 3 %) compared to systemic therapy alone (p < 0.05, for both). The likelihood of developing any new grade 3+ toxicity was significantly higher among patients treated by re-irradiation compared to those treated by systemic therapy (53 % vs. 28 %, p < 0.001). There were 3 treatment-related fatalities, all of which occurred in the re-irradiation group. The incidence of grade 3+ late toxicity was 48 % and 12 % for patients in the re-irradiation and systemic therapy cohorts, respectively (p < 0.001). ConclusionAlthough re-irradiation improved overall survival compared to systemic therapy for appropriately selected patients with local-regionally recurrent head and neck cancer, the relatively high risk of toxicity must be considered.

Supramolecular Peptide Self-Assemblies Facilitate Oral Immunization.

Oral immunization is a promising strategy for preventing and treating gastrointestinal (GI) infections and diseases, as it allows for direct access to the disease site. To elicit immune responses within the GI tract, however, there are many obstacles that oral vaccines must surmount, including proteolytic degradation and thick mucus barriers. Here, we employed a modular self-assembling peptide nanofiber platform to facilitate oral immunization against both peptide and small molecule epitopes. Synthesizing nanofibers with d-amino acids rendered them resistant to proteases in vitro, whereas l-amino acid nanofibers were rapidly degraded. Additionally, the inclusion of peptide sequences rich in proline, alanine, and serine (PAS), increased nanofiber muco-penetration, and accelerated nanofiber transport through the GI tract. Oral immunization with PASylated nanofibers and mucosal adjuvant generated local and systemic immune responses to a peptide epitope but only for l-amino acid nanofibers. Further, we were able to apply this design to also enable oral immunization against a small molecule epitope and illustrated the therapeutic and prophylactic effectiveness of these immunizations in mouse models of colitis. These findings demonstrate that supramolecular peptide self-assemblies have promise as oral vaccines and immunotherapies.

Metastasis-Directed Stereotactic Body Radiotherapy in Prostate Cancer Patients Treated with Systemic Therapy and Undergoing Oligoprogression: Report on 11 Consecutive Cases

Background: Stereotactic body radiotherapy (SBRT) targeted at metastatic sites of disease progression is emerging as a potential therapeutic approach for managing oligoprogressive prostate cancer. However, a definitive benefit has yet to be demonstrated. Herein, we present our institution’s experience with this treatment approach. Methods: From April 2018 to March 2023, 11 patients affected by oligoprogressive prostate cancer were treated with SBRT targeting the nodal or bone sites of progression while maintaining the ongoing systemic therapy. Three patients were undergoing single-agent ADT (Androgen Deprivation Therapy), while the remaining eight were receiving a subsequent line of systemic therapy. All patients were evaluated with a pre-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT, which demonstrated between one and five localizations of disease. All the active sites were treated with SBRT in one (15–24 Gy) or three (21–27 Gy) fractions, except for one patient, who was treated in five fractions (35 Gy). PSA serum levels were tested at baseline, one month after RT and at least every three months; all patients underwent a post-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. The evaluated endpoints were PSA response, defined as a post-treatment decrease &gt;50% from baseline measured within 6 months, time to next-line systemic treatment (NEST), local control (LC), biochemical progression-free survival (bPFS), radiological progression-free survival (rPFS) and freedom from polymetastatic progression (FPP). Results: Nineteen lesions were treated (seven nodal and twelve bone). At a median follow-up of 19 months (7–63), 9 of the 11 patients had a PSA response; all patients had local control of the treated metastases. A total of six patients switched to a next-line systemic treatment, with a median NEST of 13 months. Six patients had polymetastatic progression with an FPP median time of 19 months. No patients died during the follow-up period. The SBRT-related toxicity was negligible. Conclusions: Our data support the use of SBRT targeting the sites of oligoprogressive disease before moving to a subsequent line of systemic treatment in patients with metastatic prostate cancer. Prospective studies to evaluate the potential impact of this approach on overall survival are warranted.

A double‐edged sword: The complex interplay between engineered nanoparticles and platelets

AbstractNanoparticles (NP) play a crucial role in nanomedicine, serving as carriers for localized therapeutics to allow for precise drug delivery to specific disease sites and conditions. When injected systemically, NP can directly interact with various blood cell types, most critically with circulating platelets. Hence, the potential activation/inhibition of platelets following NP exposure must be evaluated a priori due to possible debilitating outcomes. In recent years, various studies have helped resolve the physicochemical parameters that influence platelet‐NP interactions, and either emphasize nanoparticles' therapeutic role such as to augment hemostasis or to inhibit thrombus formation, or conversely map their potential undesired side effects upon injection. In the present review, we discuss some of the main effects of several key NP types including polymeric, ceramic, silica, dendrimers and metallic NPs on platelets, with a focus on the physicochemical parameters that can dictate these effects and modulate the therapeutic potential of the NP. Despite the scientific and clinical significance of understanding Platelet‐NP interactions, there is a significant knowledge gap in the field and a critical need for further investigation. Moreover, improved guidelines and research methodologies need to be developed and implemented. Our outlook includes the use of biomimetic in vitro models to investigate these complex interactions under both healthy physiological and disease conditions.

Abstract CT162: Trial in progress: A phase I, open-label, multicenter study of ZL-1218, an anti-CCR8 IgG1, as a single agent and as combination therapy with anti-PD-1 antibody to evaluate the safety, tolerability, and pharmacokinetics in subjects with advanced solid tumor

Abstract Background ZL-1218 is an anti-chemokine receptor 8 (CCR8) humanized IgG1 antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. CCR8 demonstrates a preferential expression in tumor-associated Tregs over peripheral Tregs. Thus, targeting CCR8 may allow for specific depletion of intratumoral Tregs without impacting peripheral Tregs/other immune cells. ZL-1218 is intended to decrease the intratumoral Tregs by binding to both high- and low-expressing CCR8+ cells and eliciting potent ADCC activity. ZL-1218 blocked CCR8 ligand CCL1 from binding to CCR8, and reduced Treg recruitment by blocking chemotaxis of CCR8+ cells (unpublished data). Additionally, ZL-1218 demonstrated enhanced antitumor activity in preclinical models in combination with anti-PD-1. Methods This is a Phase I study of ZL-1218 as a single agent and in combination with pembrolizumab (P) to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity in subjects with advanced solid tumor malignancies. The study consists of Part 1 Dose Escalation and Part 2 Cohort Expansion. In Part 1, subjects will be treated with escalating doses of ZL-1218 alone and in combination with a fixed dose of P to identify the maximum tolerated dose (MTD) and/or the recommended expansion dose (RD). The Bayesian optimal interval (BOIN) design is used and adopted with overdose control. Upon progression in the single agent group, a subject may enroll into combination therapy of ZL-1218 with P. Subjects will start at their respective single agent dose or the cleared combination dose level, whichever is lower. Part 2 will explore the combination with pembrolizumab in subjects with selected tumor types, with or without prior CPI therapy. Major inclusion criteria include: (1) Subjects must have histologically confirmed and documented diagnosis of locally advanced unresectable/metastatic advanced solid tumor that is refractory/intolerant to standard treatment, or for which no standard treatment exists, and no greater than 3 prior lines of therapy in the relapse/refractory setting (2). Subjects must have at least one target lesion as defined by RECIST v1.1 on CT, PET/CT, or MRI scan. (3) Subjects must have a site of disease which is not previously irradiated and is safe and amenable to biopsy. Major exclusion criteria include: (1) Prior exposure to CCR8 inhibitor, or severe hypersensitivity (≥ Grade 3) to P and/or any of its excipients. (2) Subjects with symptomatic or uncontrolled brain metastasis requiring concurrent treatment, impaired major organ functions, active autoimmune disease, or active infections. Part 1 Dose Escalation is ongoing in the US and EU. Citation Format: Elena Garralda, Valentina Boni, David Vincente Baz, Arvind Chaudhry, Ignacio Gil Bazo, Martin Gutierrez, Jyoti Malhotra, Casal Guzman Alonso, Valentina Gambardella, Michael Chisamore, Renke Zhou, Maria Tea, Deborah Doroshow. Trial in progress: A phase I, open-label, multicenter study of ZL-1218, an anti-CCR8 IgG1, as a single agent and as combination therapy with anti-PD-1 antibody to evaluate the safety, tolerability, and pharmacokinetics in subjects with advanced solid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT162.

Immunological effects of radiopharmaceutical therapy

Radiation therapy (RT) is a pillar of cancer therapy used in more than half of all cancer patients. Clinically, RT is mostly delivered as external beam radiation therapy (EBRT). However, the scope of EBRT is limited in the metastatic setting when all sites of disease need to be irradiated. Such limitation is attributed to radiation-induced toxicities including bone marrow and hematologic toxicities, ensuing from a large EBRT field. Radiopharmaceutical therapy (RPT) has emerged as an alternative to EBRT for the irradiation of all sites of metastatic disease. While RPT can reduce tumor burden, it can also impact the immune system and anti-tumor immunity. Understanding these effects is crucial for predicting and managing treatment-related hematological toxicities and optimizing their integration with other therapeutic modalities such as immunotherapies. Herein, we review the immunomodulatory effects of α- and β-particle emitter-based RPT on various immune cell lines including CD8+ and CD4+ T cells, natural killer (NK) cells, and regulatory T (Treg) cells. We briefly discuss Auger electron-emitter (AEE) based RPT and lastly, we highlight the combination of RPT with immune checkpoint inhibitors, which may offer potential therapeutic synergies for patients with metastatic cancers.

Citizens can help to map putative transmission sites for snail-borne diseases.

Schistosomiasis and fasciolosis are snail-borne diseases of great medical and veterinary health importance. The World Health Organization recommends complementing drug treatment with snail control and community involvement for disease elimination, but there is a general lack of snail experts and hence snail distribution data. Therefore, we adopted a citizen science approach and involved citizens in the monitoring of medically and veterinary important snail taxa. Snail data was collected weekly by 25 trained citizen scientists (CSs) at 76 sites around southern Lake Albert (Uganda) for 20 months. At each site, snails were searched for 30 minutes, sorted, target snail hosts identified to genus level, counted and data submitted through a smartphone application. The quality of this data was assessed by comparing it to monthly data collected by an 'expert' malacologist using the same sampling protocol. Generalised binomial logistic and linear mixed-effects models were used to analyse the variables for agreement between the CSs and expert. The binary agreement in presence/absence of Biomphalaria, Bulinus and Radix snails reported by the expert and CSs ranged between 70% and 86% (900 reports) with an average of 17% false negatives (sites wrongly defined as snail-free). The agreement for Biomphalaria and Radix increased with snail abundance, and false negatives decreased when the number of snails collected by citizens was aggregated per month. Site type significantly predicted binary agreement, which was lowest at lake sites (55%) and highest at spring sites (99%) with variations across genera. Similar temporal trends in snail abundance were recorded despite the expert reporting higher abundance. However, the relative abundance was consistent across site types. The match between the sites with highest Biomphalaria spp. abundance identified by CSs and expert was consistently high (~84.1%) and increased over time. Our results demonstrate the potential of citizen science to map putative schistosomiasis transmission sites. We therefore argue that this inclusive, powerful and cost-effective approach can be more sustainable than top-down monitoring and intervention campaigns.

Echo-intensity characterization at implant sites and novel diagnostic ultrasonographic markers for peri-implantitis.

To apply high-frequency ultrasound (HFUS) echo intensity for characterizing peri-implant tissues at healthy and diseased sites and to investigate the possible ultrasonographic markers of health versus disease. Sixty patients presenting 60 implants diagnosed as healthy (N = 30) and peri-implantitis (N = 30) were assessed with HFUS. HFUS scans were imported into a software where first-order greyscale outcomes [i.e., mean echo intensity (EI)] and second-order greyscale outcomes were assessed. Other ultrasonographic outcomes of interest involved the vertical extension of the hypoechoic supracrestal area (HSA), soft-tissue area (STA) and buccal bone dehiscence (BBD), among others. HFUS EI mean values obtained from peri-implant soft tissue at healthy and diseased sites were 122.9 ± 19.7 and 107.9 ± 24.7 grey levels (GL); p = .02, respectively. All the diseased sites showed the appearance of an HSA that was not present in healthy implants (area under the curve = 1). The proportion of HSA/STA was 37.9% ± 14.8%. Regression analysis showed that EI of the peri-implant soft tissue was significantly different between healthy and peri-implantitis sites (odds ratio 0.97 [95% confidence interval: 0.94-0.99], p = .019). HFUS EI characterization of peri-implant tissues shows a significant difference between healthy and diseased sites. HFUS EI and the presence/absence of an HSA may be valid diagnostic ultrasonographic markers to discriminate peri-implant health status.

Disparities in incidence and survival for patients with Ewing sarcoma in Florida.

Ewing sarcoma (ES) is a malignant bone tumor most commonly affecting non-Hispanic White (NHW) adolescent males, though recognition among Hispanic individuals is rising. Prior population-based studies in the United States (US), utilizing Surveillance, Epidemiology, and End Results (SEER) have shown higher all-cause mortality among White Hispanics, Blacks, and those of low socioeconomic status (SES). Florida is not part of SEER but is home to unique Hispanic populations including Cubans, Puerto Ricans, South Americans that contrasts with the Mexican Hispanic majority in other US states. This study aimed to assess racial/ethnic disparities on incidence and survival outcomes among this diverse Florida patient population. Our study examined all patients diagnosed with osseous ES (2005-2018) in Florida (n = 411) based on the state's population-based cancer registry dataset. Florida Age-adjusted Incidence Rates (AAIRs) were computed by sex and race-ethnicity and compared to the equivalent populations in SEER. Cause-specific survival disparities among Florida patients were examined using Kaplan-Meier analysis. Univariable and multivariable analyses using Cox regression were performed for race/ethnicity, with adjustment for age, sex, year of diagnosis, site of disease, staging, SES, and insurance type. There was a significantly higher incidence of osseous ES in Florida Hispanic males (AAIR 2.6/1,000,000); (95% CI: 2.0-3.2 per 1,000,000; n = 84) compared to the SEER Hispanic males (AAIR 1.2/1,000,000;1.1-1.4 per 1,000,000; n = 382). Older age, distant metastasis, lack of chemotherapy or surgical resection were statistically significant determinants of poor survival while SES, insurance status and race-ethnicity were not. However, among nonmetastatic ES, Florida Hispanics had an increased risk of death compared to Florida NHW (adjusted Hazard Ratio 2.32; 95%CI: 1.20-4.46; p = 0.012). Florida Hispanic males have a higher-than-expected incidence of osseous ES compared to the US. Hispanics of both sexes show remarkably worse survival for nonmetastatic disease compared to NHW. This disparity is likely multifactorial and requires further in-depth studies.

IJCM_150A: A profile of Head and Neck Cancer patients attending a tertiary cancer care centre in Southern Karnataka

Background: Overall, 57.5% of head and neck cancers (HNC) globally are from Asia. In India, HNC accounted for 30% of all cancers in males and 11 to 16% in females, of all sites of cancer. HNC in the low- and middle-income countries differ from those in the Western part of the globe in terms of age, site of disease, etiology, and molecular biology. Poverty, illiteracy, advanced stage at presentation, lack of access to affordable treatment facilities pose a major challenge in management of these cancers. Objective: To identify the socio-demographic and epidemiological factors influencing the cause of Head and neck cancer Methodology: A cross sectional study was conducted between February 2023 till November 2023, in Manipal Comprehensive Cancer Care Centre, Kasturba Hospital, Manipal. All the newly diagnosed Head and Neck cancer (HNC) patients aged above 18 years, from December 2022 were included in the study. The participants were interviewed with the structured questionnaire. Details of the socio-demographic characteristics, various risk factors of HNC, presenting symptoms, co-morbid conditions, anthropometric details, dietary habits, level of physical activity when they were healthy, tobacco, alcohol and betel quid use were taken. Institutional Ethics Committee Approval and informed consent from the participants were taken before the initiation of the study Results: The study found that 84% of the head and neck cancer patients were males. 78% of the cases had education only up to or less than 10th std. The middle class and lower class (according to BG prasad scale) constituted 62% of the cases. 70% reported the site of cancer as oral cavity. Conclusion: The study found that consumption of tobacco, alcohol andNon-vegetarian diet are more commonly seen in HNC cases. Also, males, age group of 51-70 years, belonging to middle-class SES, are more affected.

ACR-ARS Practice Parameter for the Performance of Proton Beam Therapy

Aim/Objectives/BackgroundThis practice parameter for the performance of proton beam radiation therapy was revised collaboratively by the American College of Radiology (ACR) and the American Radium Society (ARS). This practice parameter was developed to serve as a tool in the appropriate application of proton therapy in the care of cancer patients or other patients with conditions in which radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance (QA) standards, indications, and suggested documentation. MethodsThis practice parameter for the performance of proton beam radiation therapy was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters – Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. ResultsThe qualifications and responsibilities of personnel, such as the proton center Chief Medical Officer or Medical Director, Radiation Oncologist, Radiation Physicist, Dosimetrist and Therapist, are outlined, including the necessity for continuing medical education. Proton therapy standard clinical indications and methodologies of treatment management are outlined by disease site and treatment group (e.g. pediatrics) including documentation and the process of proton therapy workflow and equipment specifications. Additionally, this proton therapy practice parameter updates policies and procedures related to a quality assurance and performance improvement program (QAPI), patient education, infection control, and safety. ConclusionsAs proton therapy becomes more accessible to cancer patients, policies and procedures as outlined in this practice parameter will help ensure quality and safety programs are effectively implemented to optimize clinical care.

Oral Budesonide and low serum albumin levels at surgery are associated with a higher risk of postoperative intra-abdominal septic complications after primary ileocaecal resection for Crohn's disease: A retrospective analysis of 853 consecutive patients

Background and AimsThe terminal ileum is the most frequent site of Crohn's Disease (CD) that necessitates surgery. Of the postoperative complications (POCs) associated with ileocaecal resection for CD, intra-abdominal septic complications (IASCs) include anastomotic leak, abscesses, and entero-cutaneous fistula.We aimed to identify predictors of IASCs and severe POCs (Clavien-Dindo ≥3) after primary ileocaecal resection for CD. MethodsThis is a retrospective single-centre cohort study including all consecutive primary ileocaecal resection for CD in a tertiary IBD centre between 2004 and 2021. ResultsA total of 853 patients underwent primary ileocaecal resection for CD. 307 (36.6 %) patients were receiving antibiotics, 253 (29.8 %), systemic steroids, and 178 (21.0 %) oral budesonide at surgery. At 90 days, 260 (30.8 %) patients developed POCs, 62 (7.3 %) severe POCs, and 56 (6.6 %) IASCs. At multivariate analysis, severe POCs were associated with lower preoperative albumin levels (OR1.58, 95 %CI 1.02–2.50, p = 0.040) and a history of cardiovascular diseases (OR2.36, 95 %CI 1.08–7.84, p = 0.030). IASCs were associated with lower preoperative albumin levels (OR1.81, 95 %CI 1.15–2.94, p = 0.011) and oral budesonide (OR2.07, 95 %CI 1.12–3.83, p = 0.021) with a dose-dependent effect. ConclusionsThe independent association, dose-dependent effect, and biological plausibility of budesonide and IASCs suggest a robust causal effect. Oral budesonide should be carefully assessed before primary ileocaecal resection for CD.

Myeloid-derived suppressor cells attenuate the antitumor efficacy of radiopharmaceutical therapy using 90Y-NM600 in combination with androgen deprivation therapy in murine prostate tumors

RationaleAndrogen deprivation therapy (ADT) is pivotal in treating recurrent prostate cancer and is often combined with external beam radiation therapy (EBRT) for localized disease. However, for metastatic castration-resistant prostate cancer,...

Beclomethasone dipropionate-loaded colon-targeting UniORV® for effective treatment of colitis

This study was undertaken to develop novel colon-targeting UniORV® (cUO) of beclomethasone dipropionate (BDP) for strategic oral delivery to the disease site of colitis. BDP-loaded cUO (cUO/BDP) was characterized regarding morphology and dissolution behaviors. Plasma levels of beclomethasone 17-monopropionate (17-BMP), a metabolite of BDP, were measured after oral administration of BDP samples to rats. Anti-inflammatory effects of oral BDP samples (50 μg-BDP/kg) were assessed in a rat model of colitis. The cUO/BDP was found to be a 300 μm-sized spherical particle. Compared with crystalline BDP, cUO/BDP exhibited a marked improvement in dissolution behavior only under colonic conditions, and the dissolution of BDP from cUO was negligible under upper gastrointestinal conditions. Oral BDP solution (5 mg-BDP/kg) led to a rapid increase in the plasma 17-BMP level with a maximum plasma concentration (Cmax) as high as 620 ng/mL and time to Cmax of 0.9 h. In contrast, Cmax of oral cUO/BDP was below 5 ng/mL, suggesting suppressed upper gastrointestinal absorption and enhanced delivery to the colon. In the rat model of colitis, compared with BDP solution, oral cUO/BDP significantly attenuated neutrophilia in the colon. The use of cUO may be a promising strategy to enhance the efficacy of BDP against colitis.