Commencement Of Treatment Research Articles

Expression of B-cell activating factor (BAFF) in proliferative lupus nephritis, revisited

ABSTRACT Introduction Systemic Lupus Erythematosus, an autoimmune disease, can target various organs of the human body. Lupus nephritis (LN) is a major complication affecting almost half of all SLE patients, with classes “III and IV” being the most aggressive. The severity and prognosis of LN can be influenced by different biomarkers, some of which are used as therapeutic targets. One such target is the B-cell activating factor (BAFF), a key figure in the pathophysiology of SLE. New add-on treatments have emerged in the treatment of LN targeting BAFF as well as other pathways. Assortment of patients to suitable treatment combinations needs more precision using guiding markers. Methods This prospective study aims to explore BAFF-expression in patients with active-proliferative LN and its possible association with the response after induction therapy. Peripheral blood mononuclear cells (PBMC) and renal tissue samples (if applicable) were collected from participants before the initiation of induction treatment. RNA was extracted, and the expression levels of BAFF-mRNA were measured using quantitative real-time polymerase chain reaction. Clinical and laboratory data, including disease activity indices and renal functions, were recorded at baseline and 6-months after the commencement of the induction treatment. Results The study included 24 patients,14 responders and 10 non-responders. At baseline, median PBMC BAFF-mRNA expression was nearly identical in responders and non-responders. Renal BAFF-expression was found to be higher in non-responders, although non-significant (p = 0.21). Contrary to PBMC BAFF expression, renal BAFF-mRNA was negatively correlated with baseline glomerular filtration rate and with the primary endpoint of response, which was reduction of proteinuria to≥50% of baseline (p = 0.07). Conclusions Renal BAFF expression could be a better representative of severity and therapeutic response than blood expression. We acknowledge that the use of BAFF expression as a predictive for early refractoriness to therapy in LN is not yet conclusive.

Internet-Delivered Psychological Pain Management: A Prospective Cohort Study Examining Routine Care Delivery by a Specialist Regional Multidisciplinary Pain Service

Several clinical trials have demonstrated the effectiveness of internet-delivered psychological-based pain management programs (PMPs). However, to date, no large studies have reported the outcomes of PMPs when delivered by specialist multidisciplinary pain services in routine care. The present study reports (n = 653) the outcomes of an internet-delivered PMP provided as routine care by a specialist Australian regional pain service over a 6-year period. High levels of treatment commencement (85%) and completion (72%) were observed, with more than 80% of patients reporting they were satisfied with the intervention. Clinical improvements were observed from pretreatment to post-treatment (% change, 95% confidence intervals (CI)) in pain-related disability (8.8%; 4.5, 12.8), depression (28.4%; 23.0, 33.4), anxiety (21.9%; 14.6, 28.5), and pain intensity (7%; 3.5, 10.5), which were maintained to 3-month follow-up. At 3-month follow-up, 27% (23, 31), 46% (41, 51), 44% (39, 49), and 22% (19, 26) reported clinically meaningful (defined as ≥ 30%) improvements in pain-related disability, depression, anxiety, and pain intensity, respectively. These results were obtained with relatively little therapist time per patient (M = 30.0, (standard deviation) SD = 18.8) to deliver the intervention. The current findings highlight the potential of internet-delivered PMPs as part of the services provided by specialist pain services, particularly those servicing large geographical regions and for patients unable to travel to clinics for face-to-face care. PerspectiveThis study reports the outcomes of the routine delivery of an internet-delivered psychological PMP by a specialist pain service. The findings highlight the potential of this model of care when provided by specialist pain services, particularly for patients not unable to attend and not requiring intensive face-to-face care.

Temporal evolution of primary angiitis of the central nervous system (PACNS) on MRI following immunosuppressant treatment

PurposeTo systematically analyse the time course of vessel wall enhancement and associated stenosis in patients with primary angiitis of the central nervous system (PACNS) following immunosuppressive therapy.Material and methodsTwo neuroradiologists retrospectively analysed MRIs of patients with PACNS seen at the Bern University Hospital and the St. Gallen Cantonal Hospital between 2015 and 2020. MRIs were examined for the presence of vessel wall enhancement, length of vessel wall enhancement (mm), circumferential extent of enhancement (degree) and degree of stenosis (%). Descriptive statistics and measurements of interobserver reliability were obtained. To investigate the temporal profiles of the variables following the commencement of immunosuppressant treatment, four series of Bayesian generalised multi-level models were generated.ResultsA total of 23 patients with 43 affected vessels identified from 209 MRI exams were evaluated (mean follow-up: 715 days, standard deviation ± 487 days), leading to a complete dataset of 402 entries. Vessel wall enhancement and circumferential extent of enhancement decreased for approximately 1 year after the initiation of immunosuppressant therapy. Changes were more pronounced in younger patients. Disappearance of vessel wall enhancement (in at least one vessel) was seen in about half of patients after a median of 172 days interquartile range 113–244, minimum 54 days, maximum 627 days.ConclusionsThis study evaluated the typical time course of vessel wall enhancement in patients with PACNS. Our results could be a useful reference for radiologists and clinicians interpreting follow-up imaging in patients with PACNS.Critical relevance statementRoutine clinical exams can be interpreted with more confidence when radiologists are aware of the typical temporal evolution of vessel wall enhancement in patients with primary angiitis of the central nervous system after initiation of immunosuppressive therapy.Key PointsFew data exist for vessel wall imaging of primary angiitis of the central nervous system.Following immunosuppressant therapy, vessel wall enhancement decreases for approximately one year.These results may serve as a reference for radiologists performing follow-up imaging.Graphical

Time-to-treatment for metastatic non-small cell lung cancer in the era of biomarker testing.

e20623 Background: In 2011, the National Comprehensive Cancer Network (NCCN) recommended biomarker testing in patients with metastatic non-small cell lung cancer (mNSCLC) based on improved survival with targeted therapies and immunotherapy reported in clinical trials. The requirement for biomarker testing before the commencement of treatment could inadvertently contribute to delays in treatment initiation. We investigated the time to treatment for mNSCLC in the US general population in the era of advanced therapies for lung cancer. Methods: We obtained data from 32,518 adults with mNSCLC between 2004 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. We categorized time to treatment to < 1 month or ≥ 1 month, and period of diagnosis to 2004-2011 and 2012-2020. We used separate logistic regression models to investigate the relationship between time to treatment, period of diagnosis, and year of diagnosis, adjusting for age, sex, household income, residence, and race. Results: The mean age of the study population was 66 (SD 10) years, 41% Female and 76% White. The majority (84%) were Metropolitan dwellers. A total of 23,322 (76%) were diagnosed between 2004 and 2011, and 9,186 (28%) from 2012 to 2019. Overall, 40% of patients initiated cancer therapy within a month of diagnosis, with no significant difference between patients who commenced treatment between 2004-2011 (40.2%) and 2012-2019 (39.9) (chi2 = 0.3492 P = 0.555). In both logistic regression analyses, there was no significant relationship between time to treatment and period or year of diagnosis. However, race/ethnicity and age independently predicted the time to treatment. Compared to Whites, Blacks (Odds ratio (OR) 1.08, 95% CI 1.01- 1.16, p = 0.04) and Hispanics (OR 1.26, 95% CI 1.03-1.24, p 0.01) were more likely to initiate treatment ≥ 1 month from the time of diagnosis. The odds of initiating treatment ≥ 1 month also increased with age (Age/year OR 1.01 (95% CI 1.01-1.01). Conclusions: We did not identify delays in treatment initiation for mNSCLC in the current era of biomarker testing. Biomarker testing has become an essential diagnostic tool for mNSCLC, guiding targeted therapies that have been shown to improve treatment outcomes. However, some vulnerable populations continue to experience delays in treatment initiation, which could lead to poorer survival. Improvements in cancer therapeutics must be complemented by service delivery improvements to optimize treatment outcomes.

Predictors of time to diagnosis and treatment: A retrospective cohort study of patients with clinically localized prostate cancer in Nigeria.

e23123 Background: Equitable access to the management of early-stage prostate cancer is important for optimal outcome in the diagnostic and curative treatment pathway of patients. This study aimed to identify the predictors of time to treatment and time to diagnosis in these patients. Methods: This was a cohort study of 110 patients with clinically localized prostate cancer (T1-T3a, N0, M0) in three government-funded tertiary hospitals in Nigeria. Retrospective data on sociodemographic status, co-morbid conditions, clinical, pathological and radiological quality metrics, date of first presentation for cancer-related complaint in the tertiary hospital, date of diagnosis of prostate cancer, and the date of commencement of first cancer-directed treatment were collected. Primary endpoint was the time from diagnosis to treatment and the secondary endpoint was the time from presentation to diagnosis. Predictors were determined by Cox proportional hazards using Stata software, version 18.0 with a p-value of less than 0.05 considered significant. Results: Twelve percent (n = 13) of the patients had a family history of prostate cancer. Fifty-four percent (n = 59) had other co-morbid conditions. Nearly one-third, 29% (n = 32) had retired from their primary occupation and 10% (n = 11) were covered by health insurance. The overall median time to diagnosis was 30 (interquartile range (IQR) 10 - 48) days. The median time to treatment commencement was 32 (IQR 19 - 82) days for ADT; 57 (IQR 50 - 63) days for active surveillance; 45 (IQR 21 - 78) days for radical radiotherapy; and 100 (IQR 0 - 127) days for radical prostatectomy. Diagnostic PSA documentation independently predicted delayed time to diagnosis (adjusted HR = 0.22 with 95% CI [0.05,0.97]) while those with guideline concordant imaging investigations independently predicted longer time to treatment (adjusted HR = 0.63 with 95% CI [0.40,0.99]). Conclusions: The documentation of PSA level and use of guideline concordant imaging investigations were significantly associated with delayed time to care. Studies on interventions to reduce barriers associated with these factors is warranted to strengthen equitable access to care in this setting.

Stage IV renal cell carcinoma achieves pathologic complete response after two ipilimumab plus nivolumab courses despite severe immune-related adverse events: a case report

BackgroundIpilimumab (Ipi) plus nivolumab (Nivo) is the recommended first-line treatment for renal cell carcinoma (RCC). This report describes a case where pancreatic metastases disappeared after only two courses of Ipi + Nivo therapy. The primary tumor was cured by surgery, and a pathological Complete Response (pCR) was observed despite multiple serious immune-related Adverse Events (irAEs).Case presentationA 54-year-old woman with RCC and pancreatic metastasis at stage IV, diagnosed with intermediate risk according to the International Metastatic RCC Database Consortium classification, underwent initiation of Ipi + Nivo therapy. On day 26, she developed hyperthyroidism accompanied by tachycardia, leading to the commencement of metoprolol tartrate treatment. Following the resolution of tachycardia, a second course of Ipi + Nivo therapy was administered on day 50. By day 70, the patient exhibited Grade 3 hepatic dysfunction, followed by the onset of hypothyroidism on day 75, necessitating treatment with steroids and levothyroxine. After positive treatment, a Grade 3 skin disorder emerged on day 87 while tapering steroids, prompting treatment with methylprednisolone (mPSL) pulse therapy. The skin disorder responded to steroids, allowing for tapering. However, on day 113, a recurrence of Grade 3 skin disorder occurred, necessitating another mPSL pulse. The patient responded well to treatment, exhibiting improvement in her condition. On day 131, she presented at the hospital with complaints of respiratory distress, prompting a Computed Tomography (CT) scan that revealed interstitial pneumonia. By day 272, subsequent CT imaging showed the disappearance of pancreatic metastasis and shrinkage of the primary tumor. On day 294, she underwent a laparoscopic left nephrectomy. Pathological analysis confirmed a pCR in the primary tumor, indicating successful eradication of RCC through surgical intervention.ConclusionsThis case report presents a scenario where multiple severe irAEs appeared in a patient, yet metastases disappeared after only two courses of Ipi + Nivo therapy. The patient was ultimately cured by surgery and achieved a pCR. This case highlights that despite the occurrence of severe irAEs during RCC treatment with Ipi + Nivo therapy, they can be managed appropriately to maximize the therapeutic effects of checkpoint inhibitors.

Paraneoplastic syndromes in childhood neuroblastoma

INTRODUCTION: Neuroblastoma is a malignant tumor primarily affecting infants. Originating from embryonic cells of the sympathetic nervous system, NB commonly arises in the adrenal glands, followed by the abdomen, mediastinum, head, and neck. Clinical presentation varies depending on the tumor's location. General symptoms, if present, include fatigue, weight loss, and fever. The paraneoplastic syndrome refers to symptoms and disorders associated with malignant tumors but not directly caused by the tumor itself or its metastases. Opsoclonus-myoclonus syndrome and diarrhea are the most common paraneoplastic syndromes linked to neuroblastoma. REVIEW METHODS: The article was conducted using PubMed and Google Scholar data concerning paraneoplastic syndromes associated with neuroblastoma. THE STATE OF KNOWLEDGE: Opsoclonus-myoclonus syndrome is a neurological paraneoplastic syndrome that presents itself with characteristic eye movement disorder, short, involuntary, irregular twitches or spasms occurring in a muscle, sleep disturbance, and changes in behavior. Diarrhea resulting in hypokalemia may be also present as a paraneoplastic syndrome associated with neuroblastoma. Cushing’s syndrome is a rare condition in childhood, but it also may be linked to neuroblastoma. CONCLUSIONS: Neuroblastoma is one of the most common childhood cancers, Paraneoplastic syndromes associated with neuroblastoma are rare conditions. Diagnosing chronic diarrhea, OMS, and Cushing's syndrome should always lead to the exclusion of neuroblastoma. Heightened awareness among pediatricians regarding PNS could result in faster diagnosis, timely treatment commencement, and ultimately enhance patient prognosis.

Machine learning algorithms using national registry data to predict loss to follow-up during tuberculosis treatment

BackgroundIdentifying patients at increased risk of loss to follow-up (LTFU) is key to developing strategies to optimize the clinical management of tuberculosis (TB). The use of national registry data in prediction models may be a useful tool to inform healthcare workers about risk of LTFU. Here we developed a score to predict the risk of LTFU during anti-TB treatment (ATT) in a nationwide cohort of cases using clinical data reported to the Brazilian Notifiable Disease Information System (SINAN).MethodsWe performed a retrospective study of all TB cases reported to SINAN between 2015 and 2022; excluding children (< 18 years-old), vulnerable groups or drug-resistant TB. For the score, data before treatment initiation were used. We trained and internally validated three different prediction scoring systems, based on Logistic Regression, Random Forest, and Light Gradient Boosting. Before applying our models we splitted our data into training (~ 80% data) and test (~ 20%) sets, and then compared the model metrics using the test data set.ResultsOf the 243,726 cases included, 41,373 experienced LTFU whereas 202,353 were successfully treated. The groups were different with regards to several clinical and sociodemographic characteristics. The directly observed treatment (DOT) was unbalanced between the groups with lower prevalence in those who were LTFU. Three models were developed to predict LTFU using 8 features (prior TB, drug use, age, sex, HIV infection and schooling level) with different score composition approaches. Those prediction scoring systems exhibited an area under the curve (AUC) ranging between 0.71 and 0.72. The Light Gradient Boosting technique resulted in the best prediction performance, weighting specificity and sensitivity. A user-friendly web calculator app was developed (https://tbprediction.herokuapp.com/) to facilitate implementation.ConclusionsOur nationwide risk score predicts the risk of LTFU during ATT in Brazilian adults prior to treatment commencement utilizing schooling level, sex, age, prior TB status, and substance use (drug, alcohol, and/or tobacco). This is a potential tool to assist in decision-making strategies to guide resource allocation, DOT indications, and improve TB treatment adherence.

Abstract PO4-19-08: Randomized phase II study of talazoparib vs talazoparib plus atezolizumab for patients with premenopausal HR+/HER2- metastatic breast cancer harboring homologous recombination deficiency scar (Young-PALETTA, KCSG BR21-09)

Abstract Background Cyclin D kinase-4/6(CDK4/6) inhibitor combined with endocrine treatment have significantly increased progression free survival(PFS) and overall survival(OS) of patients with hormone receptor(HR)-positive/HER2-negative metastatic breast cancer, and currently is a standard 1st line endocrine treatment option. Homologous recombination deficiency(HRD) including germline(g) BRCA1/2 pathogenic mutation is known to be prevalent among young premenopausal patients. Recently several retrospective data suggested that patients with germline BRCA1/2 pathogenic mutation or HRD have poorer outcome with CDK4/6 inhibitor treatment, however there is no prospective evidence. Poly ADP-ribose polymerase(PARP) inhibitors have shown significant benefit over standard chemotherapy in patients with HER2-neg metastatic breast cancer and gBRCA1/2 pathogenic mutation in two Phase 3 trials. Since preclinical data suggested that PARP inhibitors play a role in anti-tumor immune modulation, immunotherapy combined with PARP inhibitors were explored and showed promising antitumor efficacy in several single arm trials. In this trial, we investigate talazoparib and atezolizumab combination compared with talazoparib monotherapy in premenopausal women with HR+/HER2- metastatic breast cancer with HRD-scar after failure with 1st line palbociclib and endocrine treatment combination. Methods This study is a multicenter, randomized, open-label phase II trial comparing talazoparib versus talazoparib with atezolizumab in premenopausal women with HR+/HER2- metastatic breast cancer harboring HRD scar whose disease have progressed with endocrine and palbociclib combination as the 1st-line endocrine treatment. Prior one line of cytotoxic chemotherapy other than platinum for metastatic setting is allowed, but prior palliative endocrine treatment is not allowed. Eligible patients will be pre-screened with tumor tissue biopsy and peripheral blood sampling before endocrine and palbociclib treatment commencement. HRD status is determined through targeted sequencing(SOLIDaccuTestTM by NGeneBio) of tumor tissue and germline HRD genes including BRCA1/2 variant test. Whole genome sequencing and RNA sequencing are performed for biomarker analyses. Patients harboring HRD scar will receive first line endocrine treatment with palbociclib plus aromatase inhibitor with ovarian suppression. After progression with 1L endocrine treatment, patients will be randomized to either talazoparib alone or talazoparib plus atezolizumab combination. Germline BRCA1/2 pathogenic mutation is a stratification factor. Primary endpoint is a progression free survival after randomization(PFS2). Secondary objectives are a composite of PFS1 and PFS2, PFS1, overall survival, patient reported outcome, and biomarkers for treatment response. A total of 178 subjects are required to detect hazard ratio of 0.62 (median PFS2 of at least 10.5 months with talazoparib and atezolizumab combination vs 6.5 months with talazoparib alone), to achieve 80% power at a two-sided a significance level at 10%, considering drop-out rate of 5%. The study period is expected to be 72 months overall(36 months for accrual and randomization and 24 months of follow-up for primary endpoint PFS2). Citation Format: Hee Kyung Ahn, Jieun Lee, Jee Hung Kim, Kyung-Hun Lee, Jee Hyun Kim, Min Hwan Kim, Minsuk Kwon, Han Jo Kim, Kyung Hae Jung, Yeon Hee Park. Randomized phase II study of talazoparib vs talazoparib plus atezolizumab for patients with premenopausal HR+/HER2- metastatic breast cancer harboring homologous recombination deficiency scar (Young-PALETTA, KCSG BR21-09) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-08.

What to do about recurrent urinary tract infections: A review of evidence behind emerging therapies.

Recurrent urinary tract infections (rUTIs) can be debilitating for patients and pose an increasing challenge in the primary care setting. An efficient approach enables timely access and effective carefor patients. Recent research and pharmaceutical developments have provided new avenues for treating this common condition. A narrative review was conducted to provide a targeted overview of contemporary management strategies in rUTIs to assist primary care physicians in managing patients with rUTIs efficiently and effectively. Recurrent urinary tract infections require investigation and risk factor identification. Appropriate patient education in the primary care setting, behavioural modifications and commencement of non-antibiotic treatment might reduce rUTI. Certain patients might require referral to a urologist for consideration of other treatment strategies and further investigation.

Prehabilitation: The underutilised weapon for chronic pain management.

Prehabilitation encompasses preparatory clinical intervention(s) delivered during the period between diagnosis and treatment commencement. Despite widespread successful usage preoperatively, psychological prehabilitation is neglected in outpatient chronic pain management. Although pain management waitlists are associated with treatment attrition and psychological and physical decline, this time window is underutilised in preventing escalation. Waitlists present an under-explored opportunity to 'prehabilitate' patients waiting for treatment. This topical review aimed to: (1) examine the effectiveness of psychological prehabilitation for pain services; (2) evaluate the psychological and physical decline associated with waiting for pain management; (3) highlight key psychological prehabilitative targets for increasing treatment engagement; (4) promote pain management psychological prehabilitation within personalised pain medicine, building recommendations for future interventions. Studies regarding the impact of waitlists and prehabilitation for chronic pain were reviewed. Findings demonstrated that the psychological constructs of patient expectations, health locus of control, self-efficacy and pain catastrophizing dynamically influence attrition, treatment engagement and outcomes while waiting. These constructs are amenable to change, emphasising their potential utility within a targeted waitlist intervention. Prehabilitating chronic pain patients towards treatment engagement could circumvent cycles of failed treatment seeking, preventing psychological and physical decline, and reducing healthcare utilisation. Utilising the waitlist to identify psychosocial risk factors (external health locus of control, low self-efficacy and high pain catastrophizing) would identify who requires additional support to prevent increased risk of treatment failure, enhancing personalised care before prescribed treatment is accessed. This review cements the urgent need for pain services to engage proactively with prehabilitation innovation.

Evaluation of post-operative complications and adjuvant treatments following immediate prepectoral versus subpectoral direct-to-implant breast reconstruction without acellular dermal matrix

BackgroundIn immediate breast reconstruction (IBR), it is unclear whether there is any difference in the complication rates between prepectoral versus subpectoral implant placement without acellular dermal matrix (ADM). AimTo compare the rates of early post-operative complications and time to initiation of adjuvant treatment in patients undergoing IBR between prepectoral and subpectoral implant placement without ADM for the two surgical procedure. MethodsWe retrospectively retrieved data of patients who underwent IBR with prepectoral versus subpectoral implant placement between January 1, 2020 and December 31, 2022 in a large cancer center in France. ResultsWe included 192 patients: 119 in the prepectoral and 73 in the subpectoral group. Their clinical characteristics were similar. Thirty patients (15.6%) received adjuvant chemotherapy, among them 27 (14.1%) received it within 12 weeks, and there was no difference between the groups (p = 0.12). In the prepectoral group, 39 patients (32.8%) received adjuvant radiotherapy versus 5 (6.8%) in the subpectoral group (p < 0.001), but there was no significant difference in time to treatment commencement. Overall, 35 patients (29.4%) in the prepectoral group and 17 (23.3%) in the subpectoral group experienced post-operative complications (p = 0.44). Using multivariable analysis, the only factor associated with post-operative complications was determined to be mastectomy weight (odds ratio 1.98 (1.10–3.59) for weight ≥500 g; p = 0.02). ConclusionPrepectoral implant placement without ADM can be proposed to patients undergoing IBR with an indication for adjuvant treatment. However, in our study, the reoperation rate with this technique was slightly higher (p = 0.008). This is partly due to the learning curve for surgeons using this new technique.

Risk of Venous Thromboembolism in Patients With Stage III and IV Non–Small-Cell Lung Cancer: Nationwide Descriptive Cohort Study

BackgroundVenous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non–small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments. Materials and MethodsA nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen–Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy. ResultsAmong the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis. ConclusionVTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.

Digital setup accuracy for moderate crowding correction with fixed orthodontic appliances: a prospective study

ObjectivesTo evaluate the accuracy of a semi-automatic 3D digital setup process in predicting the orthodontic treatment outcome achieved by labial fixed appliances.Subjects and MethodsTwenty-five adult patients (18 to 24 years old) with class I malocclusion and moderate crowding were prospectively enrolled and received treatment on both jaws through the straight-wire technique. Prior to treatment commencement, a semi-automatic digital setup simulating the predicted treatment outcome was performed for each patient through Orthoanalyzer software (3Shape®, Copenhagen, Denmark) to obtain the prediction model. This was compared to the final outcome model through 3D superimposition methods. Metric variables and inspection of color-coded distance maps were used to detect how accurately the digital setup predicts the actual treatment outcome.ResultsThe mean absolute distances (MAD) between the superimposed dental arches of the predicted and the final models were: 0.77 ± 0.13 mm following superimposition on the palate, 0.52 ± 0.06 mm following superimposition on the maxillary dental arch, and 0.55 ± 0.15 mm following superimposition on the mandibular dental arch. The MAD at the palatal reference area was 0.09 ± 0.04 mm. Visualization of color-coded distance maps indicated that the digital setup accurately predicted the final teeth position in a few cases. Almost half of the cases had posteriorly wider upper and lower dental arches and palatally/lingually positioned or inclined anterior teeth, whereas the rest still showed errors within 2–3 mm, distributed over the entire dental arches with no distinct pattern.ConclusionsThe accuracy of semi-automatic prediction of the labial fixed appliance treatment outcome in Class I cases with moderate crowding is not yet sufficient. While average measures showed deviations less than 1 mm, examination of individual color-coded distance maps revealed significant disparities between the simulated and the actual results.

Abstract LB098: Deep plasma proteome characterization in two independent clinical cohorts identifies clusters of biomarkers separating benign and malign tumors in women with suspicion of ovarian cancer

Abstract Early detection is essential for ovarian cancer survival but today’s biomarkers are not specific enough to clear benign from malignant tumors nor sensitive enough to be used in screening. Here we have used the proximity extension assay (PEA) Olink Explore HT to characterize 5416 plasma proteins. For a subset of the women, we have also characterized the transcriptional landscape in corresponding tumor tissue using total RNA-sequencing on the Illumina NovaSeq 6000 instrument. The plasma samples were from two independent Swedish clinical cohorts (N1 = 171, N2 = 233) and tumor RNA was extracted from 112 of the samples from the second cohort. Each cohort consisted of women who after suspicion of ovarian cancer were surgically diagnosed with either benign or malign tumors. All plasma samples were collected at time of diagnosis, before commencement of treatment. In the plasma protein analyses, the first cohort was used as a discovery and the second as replication. In the discovery cohort, we found a total of 328 plasma proteins differing significantly between women with benign tumors and; early stage (I-II), late stage (III-IV) or any stage(I-IV) malignant tumors. These associations were examined in the replication cohort, and were all found to have similar foldchange between women with benign and malignant tumors. 99.7% (327/328) differed significantly after adjustment for multiple hypothesis testing. The 328 associations corresponded to a total of 192 proteins out of which 26 (13.5%) were found to have a significant correlation with RNA-expression in the corresponding tumor. A correlation network analysis based on the 192 proteins identified 5 major clusters, consisting of 18 to 59 protein-protein couplings. 80% of these clusters contained proteins that are annotated with up to five major KEGG cancer pathways and several of these contained proteins correlating significantly with the tumor RNA-SEQ data. All except one cluster contained one or two proteins that are either currently approved FDA drug targets or listed as druggable in DrugBank by specific compounds. Ovarian cancer has a low 5-year survival and eludes the current treatment regimens if discovered late. By applying high-throughput proteomics in two independent cohorts, we identified a large number of affected proteins out of which only a few have corresponding changes in tumor RNA-expression. We also identified large highly co-regulated networks of proteins, suggesting large downstream systemic effects which could be a contributing factor to the difficulties in finding efficient treatments. Among these proteins, there are several druggable targets, however, not all the associated compounds are currently primarily used as anti-cancer drugs, highlighting the possibility of drug re-purposing for future use against ovarian cancer. Citation Format: Stefan Enroth, Mikaela Moskov, Julia Lindberg Hedlund, Svetlana Popova, Simn K. Forsberg, Klev Diamanti, Maria Lycke, Emma Ivansson, Anna Tolf, Karin Sundfeldt, Karin Stålberg, Ulf Gyllensten. Deep plasma proteome characterization in two independent clinical cohorts identifies clusters of biomarkers separating benign and malign tumors in women with suspicion of ovarian cancer [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 LB098.

A Case Study on the Ayurvedic Approach to Managing Psoriasis (Ek Kustha)

Ek-Kushta is similar to psoriasis. In the present era, this disease remains a matter of serious concern. These symptoms can be compared to Ek-Kushta. The digestive fire Agni also get Manda consuming red meat, non-veg food and drinks are more prone to get skin diseases like psoriasis or many auto immune disorders. The skin disease was referenced in the Kushta chapter of Charaka Samhita, along with other Samhitas, in our classical texts. For this many different Chikitsas like Shodana shaman, Virechana etc are explained in our classics. Here, a traditional Ayurvedic regimen was attempted to treat a 20 year old male. Methods: Samshodhana with Samshamana medication are the treatment for all varieties of Kushta. In this study, Virechana was administered first, followed by Samshamana medicine. Results: The evaluation of signs and symptoms was conducted prior to the commencement of treatment and subsequently after the completion of treatment. Following 4 weeks of scaling treatment, there was a reduction in the thickness of the skin, which had a sharply defined margin, was indurated, and presented as an erythematous plaque on the scalp, face, chest, abdomen, whole back, upper and lower limbs. Significant improvement in psychological and social behavior, which improved the quality of life of patients. After 4 weeks of treatment, the results of the Positive Auspitz's and candle grease sign were found to be negative. Conclusion: Virechana and Samshamana is effective in the management of Ek-Kushta (Psoriasis). After 4 weeks of observation, it appears Virechana and Samshamana can be used to decrease disease progression.

The effects of spatially-constrained treatment regions upon a model of wombat mange

The use of therapeutic agents is a critical option to manage wildlife disease, but their implementation is usually spatially constrained. We seek to expand knowledge around the effectiveness of management of environmentally-transmitted Sarcoptes scabiei on a host population, by studying the effect of a spatially constrained treatment regime on disease dynamics in the bare-nosed wombat Vombatus ursinus. A host population of wombats is modelled using a system of non-linear partial differential equations, a spatially-varying treatment regime is applied to this population and the dynamics are studied over a period of several years. Treatment could result in mite decrease within the treatment region, extending to a lesser degree outside, with significant increases in wombat population. However, the benefits of targeted treatment regions within an environment are shown to be dependent on conditions at the start (endemic vs. disease free), as well as on the locations of these special regions (centre of the wombat population or against a geographical boundary). This research demonstrates the importance of understanding the state of the environment and populations before treatment commences, the effects of re-treatment schedules within the treatment region, and the transient large-scale changes in mite numbers that can be brought about by sudden changes to the environment. It also demonstrates that, with good knowledge of the host-pathogen dynamics and the spatial terrain, it is possible to achieve substantial reduction in mite numbers within the target region, with increases in wombat numbers throughout the environment.

Comparing the Effects of Anti-TNF Agent and Ustekinumab on Small Bowel Inflammation in Crohn’s Disease: Inverse Probability Weighting With Stabilized Weights of Propensity Scores

Abstract Background Endoscopic mucosal healing serves as a critical predictor for achieving long-term remission in Crohn’s disease treatment. Recent data indicate that the effectiveness of healing varies based on the location of gastrointestinal inflammation. Additionally, reports suggest that antitumor necrosis factor-α (anti-TNF-α) agents exhibit reduced efficacy in treating small intestinal inflammation compared to colorectal inflammation. Conversely, limited research exists regarding the impact of the anti-IL12/23 agent ustekinumab (UST) on small intestinal inflammation. This study aimed to compare the effects of anti-TNF-α agents and UST on small intestinal inflammation using propensity score analysis. Methods This retrospective observational study involved 70 patients with Crohn’s disease who had inflammation in the small intestine and had initiated treatment with either anti-TNF agents or UST between March 2015 and August 2021. Endoscopic findings were evaluated before treatment commencement and at 1–2 years post-treatment initiation. The propensity score was employed to compare the efficacy of TNF agents and UST on small bowel inflammation. Results Ustekinumab exhibited greater improvement in the small intestinal endoscopy score than anti-TNF-α antibodies according to the propensity score analysis (inverse probability weighting; P = .0448). However, no significant disparity was observed in the overall improvement of endoscopic scores between UST and anti-TNF-α antibodies (P = .5938). Conclusions This study suggests that UST might be more effective than anti-TNF-α agents in treating small intestinal inflammation in Crohn’s disease.

Abstract 4814: Pediatric radiation treatment adherence in LMIC

Abstract Background: Radiation therapy plays a significant role in the treatment of pediatric cancer. However, there have been documented challenges and difficulties encountered by patients while accessing care for cancer and it has been postulated that travel distance contributes to treatment breaks and abandonment. Objectives: The objective of this study was to determine the prevalence of treatment breaks, assess the travel burden of patients receiving radiotherapy for pediatric cancers at a high-volume center in Nigeria and to determine the impact of travel burden on treatment breaks and treatment completion. Materials and Methods: A retrospective cross-sectional study design was utilized. Data was extracted from the electronic medical records of all pediatric patients referred to the center for radiation therapy between June 2019 and June 2023. Data was analyzed using Microsoft Excel and the results were presented in descriptive statistics. Association between data were analyzed using chi-square test with the level of significance (p) set at &amp;lt;0.05. Results: A total of 210 pediatric cancer patients were enrolled with an average age of 10.9 years. Children aged 0-14 years accounted for 69.05% while 30.95% were between the age of 15 and 19 years. Brain tumors were the most predominant diagnosis, representing 28.10% of cases. Treatment intent was predominantly radical or curative (81.69%). 61.43% (129) of the patient population came from the within the state with an average travel distance of 19.3 km. Of all the 210 patients, 44.29% of patients did not commence RT. The reasons for this were mostly financial constraints but were not explored in this study. Of those who did commence RT, 54.70% had breaks, and 45.30% did not have breaks. Also, 75.21% of patients completed their treatment; however, 24.79% were unable to complete their treatment. Travel distances varied, with the average distance to the treatment center being 165.3 km and the median at 28.5 km. The study categorized travel distance into quartiles: short (0-16 km), medium (&amp;gt;16 km to 28.5 km), long (&amp;gt;28.5 km to 302 km), and very long (&amp;gt;302 km to 1387 km). Chi-square test did not reveal a significant association between travel distance and treatment completion (p=0.57), nor between travel distance and treatment breaks (p=0.20). Conclusion: These findings highlight the complex interplay of demographic factors, disease profiles, and socioeconomic barriers affecting treatment continuity and completion among pediatric oncology patients in a resource-limited setting. These findings suggest that in this low - resource context, other variables such as socioeconomic status and financial barriers may play a more pivotal role than travel distance in treatment commencement, adherence and completion. As such, more detailed investigation of the obstacles through a comprehensive and targeted strategy could lead to more favorable outcomes in pediatric cancer radiation therapy adherence. Citation Format: Adedayo Joseph, Adeseye Akinsete, Ugonna Fakile, Chidiebere Agbakwuru, Lensa Keno, Omolola O. Adisa, Aishat Oladipo, Oluwafunmilayo Fagbemide, Muhammad Habeebu, Wilfred Ngwa. Pediatric radiation treatment adherence in LMIC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4814.

Abstract 2206: Obesity and cancer outcomes among patients with lung cancer and cutaneous melanoma treated with immune checkpoint inhibitors and EGFR inhibitors

Abstract Background: Obesity is a causal factor in cancer risk and progression. Immune checkpoint inhibitors (ICI) and EGFR inhibitors (EGFRi) are indicated for the treatment of several cancers, including non-small-cell lung cancer (NSCLC) and cutaneous melanoma (CM). Improved outcomes was observed with ICI in preclinical studies. We aimed to determine the association of obesity with progression-free survival (PFS) or overall survival (OS) among patients with NSCLC and CM treated with ICI or EGFRi. Methods: This was a retrospective study utilizing 2011-2019 SEER-Medicare data of Medicare Parts A and B enrolled patients ≥66 years diagnosed with NSCLC or CM who received ICI or EGFRi (NSCLC only) within 1-year post-diagnosis. Patients were followed from treatment commencement until death, loss to follow-up, or end of study. Descriptive statistics and survival analysis were used to achieve study objectives. Results: Among 2393 NSCLC patients receiving ICI, obese patients (N=281, 11.7%) were younger (73.4±5.2 yrs vs 74.4±5.9 yrs, p&amp;lt;0.01) with higher CCI scores (2 (IQR=1-4) vs 1 (IQR=0-2), p&amp;lt;0.0001) compared to non-obese patients (N=2,311, 89.2%). Time to progression(TTP) was 41% faster among obese patients (392 days (95% CI=330-468) vs 493 days (95% CI=464-525), p&amp;lt;0.01; HR=1.41 (1.13-1.76), p&amp;lt;0.01) with no significant difference in time to death (TTD) (443 days (404-488) vs 491 days (462-524), p=0.35). Among 880 CM patients, those with obesity (N=91, 10.3%)) were significantly younger (74.7±6.1 yrs vs 76.3±7.3 yrs, p=0.02) with higher CCI scores (2 (IQR=0-4) vs 0 (IQR=0-2), p&amp;lt;0.0001). TTP was 343 days (320-400). TTD was 1,409 days (1,107-2,136) with no association between obesity status and PFS or OS. Among 2,524 NSCLC patients receiving EGFRi, obese patients (126, 5.0%) were younger (73.7±6.1 yrs) vs 75.6±6.5 yrs, p&amp;lt;0.01), had higher CCI scores (2 (IQR=1-3) vs 0 (IQR=0-1), p&amp;lt;0.0001), and longer time to treatment (3 mths (IQR=1-7) vs 2 mths (IQR=1-6), p=0.02). A higher proportion were White (76.2% vs 61.3%, p&amp;lt;0.001). Risk of progression was 48% higher among obese patients (664 dys (496-778) vs 1,231 dys (1,127-1,379), p&amp;lt;0.0001; HR=1.48, 95% CI=1.11-1.97, p&amp;lt;0.01) with no significant difference in TTD (559 dys (440-763) vs 673 dys (639-707), p=0.35). Conclusion: Obesity with associated with PFS but not OS among patients with NSCLC with no association observed among patients with CM. Given that the link between obesity and NSCLC risk remains controversial, the observed association with PFS may be linked to the absence of the paradoxical effect of improve outcomes that may be seen with cancers caused by obesity such as CM. Citation Format: Sabina O. Nduaguba, Lori Hazlehurst. Obesity and cancer outcomes among patients with lung cancer and cutaneous melanoma treated with immune checkpoint inhibitors and EGFR inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2206.